WO2025026423A1

WO2025026423A1 - Compositions, their use and manufacture for treatment of gastrointestinal conditions

Info

Publication number: WO2025026423A1
Application number: PCT/CN2024/109451
Authority: WO
Inventors: Lian Wang; Shun Chen; Jing SHAO; Zeren Wang; Xiaoyan Zhou
Original assignee: Shenzhen Pharmacin Co Ltd
Current assignee: Shenzhen Pharmacin Co Ltd
Priority date: 2023-08-02
Filing date: 2024-08-02
Publication date: 2025-02-06
Anticipated expiration: 2026-02-02

Abstract

Provided herein are compositions and methods for treating gastrointestinal conditions comprising clofazimine or its derivatives. Further provided herein are compositions and methods for ameliorating symptoms associated with gastrointestinal conditions, including ulcerative colitis.

Description

COMPOSITIONS, THEIR USE AND MANUFACTURE FOR TREATMENT OF GASTROINTESTINAL CONDITIONS

CROSS-REFERENCE

This application claims the benefit of PCT Application No. PCT/CN2023/110745 filed August 2, 2023, which is incorporated by reference herein in its entirety.

BACKGROUND OF THE DISCLOSURE

Gastrointestinal (GI) conditions are disorders of the digestive system that can result in painful and irritating symptoms in subjects. Standard course of treatment for GI conditions, such inflammatory bowel diseases (IBD) , includes 5-aminosalicylic acid (5-ASA, also referred to in the generic form as mesalamine) , corticosteroid and thiopurines. The efficacy of 5-ASA is limited, however, as it is often administrated at a large dose for an extended period of time. Corticosteroids and thiopurines are associated with long term safety concerns, and are often tapered after achieving clinical remission. For advanced patients, biologics therapies and some new small molecules such as JAK inhibitors are used in clinic. However, the high cost of biologics and safety concerns with these options limited their general use. Thus, there is a need for treatment of gastrointestinal conditions with improved safety and efficacy.

SUMMARY

Provided herein are methods for treatment of a gastrointestinal condition, comprising: administering to a subject having a gastrointestinal condition a composition, wherein the composition comprises a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein: each of R¹, R², and R³ is independently selected from the group consisting of: a phenyl, chlorophenyl, a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of the R¹, R², and R³ is independently optionally substituted; R⁴ is a hydrogen or halogen atom; and R⁵ is a hydrogen or halogen atom.

Provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition comprising administering to a subject having a gastrointestinal condition a composition, wherein the composition comprises a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein, each of R¹, R² and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted; R⁴ represents a hydrogen or halogen atom; and R⁵ represents a hydrogen or halogen atom.

Provided herein are compositions, wherein the composition is in the form of a suppository, and wherein the composition comprises: a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein, each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted; R⁴ represents a hydrogen or halogen atom; and R⁵ represents a hydrogen or halogen atom; and a pharmaceutically acceptable excipient.

Provided herein are compositions, wherein the composition is in the form of an amorphous solid dispersion, and wherein the composition comprises: a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

Provided herein are methods of treating a gastrointestinal condition, comprising administering to a subject the compositions described herein.

BRIEF DESCRIPTION OF THE FIGURES

The features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which:

FIGURE 1 is a bar plot showing change rate of body weight (%) of mice fed with purified water after 13 days of intraperitoneal injection of saline (Blank control) or with 2.5 %DSS in drinking water after 13 days of intraperitoneal injection of 5 %P188 (w/w) , 30 %HS15 (v/v) , and saline (DSS model control) , oral administration of 150 mg per kg (mpk) mesalazine via intragastric gavage (Positive control) , oral administration of 25 mpk clofazimine via intragastric gavage (Condition 1) , or intraperitoneal injection of 5 mpk clofazimine (Condition 2) . The Y axis corresponds to the change rate of body weight (%) of mice from each group, whereas the X axis indicates the name of each group. *Indicated significant differences compared to the model group, *represents p<0.05, **represents p<0.01 and ***represents p<0.001. #Indicates significant differences compared to the mesalazine group, ###represents p<0.001, ##represents p<0.01.

FIGURES 2A-2B are a bar plot (FIG. 2A) and photos (FIG. 2B) showing the colon length of mice fed with purified water after 13 days of intraperitoneal injection of saline (Blank control) , or fed with 2.5 %DSS in drinking water after 13 days of intraperitoneal injection of 5 %P188 (w/w) , 30 %HS15 (v/v) , and saline (DSS model control) , oral administration of 150 mpk mesalazine via intragastric gavage (Positive control) , oral administration of 25 mpk clofazimine via intragastric gavage (Condition 1) , or intraperitoneal injection of 5 mpk clofazimine (Condition 2) . In FIG. 2A, the Y axis represents the colon length of mice from each group. The X axis represents the name of each group. *Indicated significant differences compared to the model group, *represents p<0.05, and ***represents p<0.001; #Indicated significant differences compared to the mesalazine group, ##represents p<0.01 ###represents p<0.001. FIG. 2B provides photograph images taken from the colon of mice under the stated conditions.

FIGURE 3 is a bar plot showing the DAI score of each group of mice fed with purified water after 13 days of intraperitoneal injection of saline (Blank control) or fed with 2.5 %DSS in drinking water after 13 days of intraperitoneal injection of saline, 5 %P188 (w/w) , 30 %HS15 (v/v) , and saline (DSS model control) , oral administration of 150 mpk mesalazine via intragastric gavage (Positive control) , oral administration of 25 mpk clofazimine via intragastric gavage (Condition 1) , or intraperitoneal injection of 5 mpk clofazimine (Condition 2) . The Y axis corresponds to the DAI score of mice from each group, whereas the X axis indicates the name of each group. *Indicates significant differences compared to the model group, *represents p<0.05, and ***represents p<0.001; #Indicates significant differences compared to the mesalazine group, ##represented p<0.01.

FIGURES 4A-4B are plots showing the change of body weight of mice fed with purified water after 13 days of administration of saline (Blank control) or fed with 3 %DSS in drinking water after 13 days of administration of 100%HS15 (DSS model control) , 150 mpk mesalamine (Positive control) in 20 %Soluplus (w/w) aqueous solution, 25 mpk clofazimine dissolved in 100 %HS15 (Condition 1) , or 25 mpk clofazimine suspended in 0.5 %CMC aqueous solution (Condition 2) ( “condition 1 and 2 are the “Gavage group” ) . In FIG. 4A, The Y axis corresponds to the body weight of mice from each group, whereas the X axis indicates the name of each group. In FIG. 4B, The Y axis corresponds to the change rate of body weight (%) of mice from each group, whereas the X axis indicates the name of each group. *Indicates significant differences compared to the DSS model control, *represents p<0.05, **represents p<0.01 and ***represents p<0.001.

FIGURES 5A-5B are bar plots (FIG. 5A) and photos (FIG. 5B) showing the colon length of mice from the Gavage group. In FIG. 5A, the Y axis represents the colon length of mice from each group. The X axis represents the name of each group. *Indicates significant differences compared to the DSS model control, ***represents p<0.001. FIG. 5B provides photograph images taken from the colon of mice under the stated conditions.

FIGURES 6A-6B are bar plots showing the DAI score of mice with DSS-induced UC from the Gavage group on day 4 (FIG. 6A) and day 8 (FIG. 6B) . The Y axis corresponds to the DAI score of mice from each group, whereas the X axis indicates the name of each group.

FIGURE 7 shows photograph images of the Hematoxylin &Eosin (HE) staining of colon tissue of mice with DSS-induced UC from the Gavage group mice described in FIGURE 4.

FIGURE 8 are bar plots showing the level of IL-1, IL-6, and keratoconus (KC) of mice with DSS-induced UC from the Gavage groups. The Y axis corresponds to the level of IL-1 (left) , IL-6 (middle) , or KC (right) of mice from each group, whereas the X axis indicates the name of each group.

FIGURES 9A-9B are bar plots (FIG. 9A) and photograph images (FIG. 9B) showing the colon length of mice fed with 3%DSS in drinking water after administration of solvent (Condition 3, 5 %P188 + 30 %HS15 in saline) or 25 mpk clofazimine in 5 %P188 and 30 %HS15 in saline (Condition 4) (Condition 3 and Condition 4 are the “Enema group” ) . In FIG. 9A, the Y axis represents the colon length of mice from each group. The X axis represents the name of each group. FIG. 9B provides photograph images taken from the colon of mice under the stated conditions.

FIGURE 10 is a photo showing the HE staining of colon tissue of mice with DSS-induced UC from the Enema group.

FIGURE 11 is a plot showing the body weight of mice fed with purified water after 13 days administration of saline (Blank control) or fed with 3.5 %DSS in drinking water after 13 days of administration of 100 %HS15 (DSS model control) , 150 mpk mesalamine in 20 %Soluplus (w/w) aqueous solution (Positive control) , 25 mpk clofazimine in 100 %HS15 (Condition 1) , 25 mpk clofazimine in 0.5 %CMC aqueous solution (Condition 2) , or 5 mpk Tofacitinib (Condition 3) . The Y axis corresponds to the body weight of mice from each group, whereas the X axis indicates the name of each group.

FIGURE 12 is a bar plot showing the change rate of body weight (%) of mice fed with purified water after 13 days of administration of saline (Blank control) , or fed with 3.5%DSS in drinking water after 13 days of administration of 5 %P188 (w/w) , 30 %HS15 (v/v) , and saline (DSS model control) , 150 mpk mesalamine dissolved in 20%Soluplus (w/w) aqueous solution (Positive control) , 25 mpk clofazimine in 100 %HS15 (Condition 1) , 25 mpk clofazimine suspended in 0.5 %CMC aqueous solution (Condition 2) , or 5 mpk Tofacitinib (Condition 3) . The Y axis corresponds to the change rate of body weight (%) of mice from each group, whereas the X axis indicates the name of each group.

FIGURES 13A-13B are bar plots (FIG. 13A) and photograph images (FIG. 13B) showing the colon length of mice fed with purified water after administration of saline (Blank control) , or fed with 3.5 %DSS in drinking water after administration of 5 %P188 (w/w) +30 %HS15 (v/v) + saline (DSS model control) , 150 mpk mesalamine in 20 %Soluplus (w/w) aqueous solution (Positive control) , 25 mpk clofazimine dissolved in 100%HS15 (Condition 1) , 25 mpk clofazimine suspended in 0.5 %CMC aqueous solution (Condition 2) , or 5 mpk Tofacitinib (Condition 3) . In FIG. 13A, the Y axis corresponds to the colon length of mice from each group, whereas the X axis indicates the name of each group. FIG. 13B provides photograph images taken from the colon of mice under the stated conditions.

FIGURE 14 is a bar plot showing the DAI score for the mice fed with purified water after receiving saline (Blank control) or with 3.5 %DSS in drinking water after receiving 5 %P188 (w/w) , 30 %HS15 (v/v) and saline (DSS model control) , 150 mpk mesalamine in 20%Soluplus (w/w) aqueous solution (positive control) , 25 mpk clofazimine in 100 %HS15 (Condition 1) , 25 mpk clofazimine suspended in 0.5 %CMC aqueous solution (Condition 2) , or 5 mpk Tofacitinib (Condition 3) . The Y axis corresponds to the DAI score of mice from each group, whereas the X axis indicates the name of each group.

FIGURE 15 shows photograph images of HE staining of colon tissue of mice fed with purified water after receiving saline (Blank control) , or fed with 3.5 %DSS in drinking water after receiving 5 %P188 (w/w) , 30 %HS15 (v/v) , and saline (DSS model control) , 150 mpk mesalamine in 20 %Soluplus (w/w) aqueous solution (positive control) , 25 mpk clofazimine dissolved in 100 %HS15 (Condition 1) , 25 mpk clofazimine suspended in 0.5 %CMC aqueous solution (Condition 2) , or 5 mpk Tofacitinib (Condition 3) .

FIGURES 16A-16B are bar plots (FIG. 16A) and photograph images (FIG. 16B) showing the colon length of mice administered with purified water (Blank control) , 0.5 %CMC-Na/water (Model control) , 150 mpk 5-ASA in 20%Soluplus, 1.5 mpk, 4.0 mpk, 10 mpk, or 25 mpk clofazimine suspended in 0.5 %CMC-Na/water. In FIG. 16A, the Y axis corresponds to the colon length of mice from each group, whereas the X axis indicates the name of each group. FIG. 16B provides photograph images taken from the colon of mice under the stated conditions.

FIGURE 17 shows photograph images of HE staining of colon tissue of mice administered with purified water (Blank control) , 0.5 %CMC-Na/water (Model control) , 150 mpk 5-ASA in 20%Soluplus, 1.5 mpk, 4.0 mpk, 10 mpk, or 25 mpk clofazimine suspended in 0.5 %CMC-Na/water.

FIGURE 18 is a plot showing the DAI scores of mice administered with purified water (Blank control) , 0.5 %CMC-Na/water (Model control) , 150 mpk 5-ASA in 20%Soluplus, 1.5 mpk, 4.0 mpk, 10 mpk, or 25 mpk clofazimine suspended in 0.5 %CMC-Na/water. The Y axis corresponds to the DAI score of mice from each group, whereas the X axis indicates the date after administration.

FIGURES 19A-19C are bar plots (FIGs. 19A-19B) , photograph images (FIG. 19C) showing the colon length and colon weight of mice without any treatment (Blank control) , administered with blank suppositoryNAI 25 A (model control) , 5-ASA (Mesalamine suppository) , 17 mpk, 6.5 mpk, or 2.2 mpk clofazimine suspended in NAI 25 A. In FIG. 19A, the Y axis corresponds to the colon length of mice from each group, whereas the X axis indicates the name of each group. FIG. 19B provides photograph images taken from the colon of mice under the stated conditions.

FIGURE 20 shows photograph images of HE staining of colon tissue of mice without any treatment (Blank control) , administered with blank suppositoryNAI 25 A (model control) , 5-ASA (Mesalamine suppository) , 17 mpk, 6.5 mpk, or 2.2 mpk clofazimine suspended inNAI 25 A.

DETAILED DESCRIPTION

The present disclosure is generally directed to compositions and methods for treating gastrointestinal conditions. In particular, provided herein are compositions and methods for treating gastrointestinal conditions comprising administering to a subject in need thereof a composition comprising clofazimine or its derivatives. Also provided herein are methods for ameliorating symptoms associated with gastrointestinal conditions comprising administering to a subject in need thereof a composition comprising clofazimine or its derivatives. Clofazimine or its derivatives can be formulated in many dosage forms, such as liquid, capsule, table, powder suppository, or dispersions. In some embodiments, the dispersion comprises an amorphous solid dispersion.

The following description and examples illustrate embodiments of the present disclosure in detail. It is to be understood that this disclosure is not limited to the particular embodiments described herein and as such can vary. Those of skill in the art will recognize that there are numerous variations and modifications of this disclosure, which are encompassed within its scope.

All terms are intended to be understood as they would be understood by a person skilled in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure pertains.

The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

Although various features of the present disclosure may be described in the context of a single embodiment, the features can also be provided separately or in any suitable combination. Conversely, although the present disclosure may be described herein in the context of separate embodiments for clarity, the present disclosure can also be implemented in a single embodiment.

Definitions

The following definitions supplement those in the art and are directed to the current application and are not to be imputed to any related or unrelated case, e.g., to any commonly owned patent or application. Although any methods and materials similar or equivalent to those described herein can be used in the practice for testing of the present disclosure, the preferred materials and methods are described herein. Accordingly, the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that, as used in the specification, the singular forms “a, ” “an” and “the” include plural referents unless the context clearly dictates otherwise. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “include” , “includes, ” and “included, ” is not limiting.

Reference in the specification to “some embodiments, ” “an embodiment, ” “one embodiment” or “other embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least some embodiments, but not necessarily all embodiments, of the present disclosure.

As used in this specification and claim (s) , the words “comprising” (and any form of comprising, such as “comprise” and “comprises” ) , “having” (and any form of having, such as “have” and “has” ) , “including” (and any form of including, such as “includes” and “include” ) or “containing” (and any form of containing, such as “contains” and “contain” ) are inclusive or open-ended and do not exclude additional, un-recited elements or method steps. It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the present disclosure, and vice versa. Furthermore, compositions of the present disclosure can be used to achieve methods of the present disclosure.

Unless specifically stated or obvious from context, as used herein, the term “about” in reference to a number or range of numbers is understood to mean the stated number and numbers +/-10 %thereof.

Compositions

Provided herein are compositions, comprising a compound according to Formula (I) ,

wherein each of R¹, R², and R³ is independently selected from the group consisting of: a phenyl, chlorophenyl, lower alkylphenyl and lower alkoxyphenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of the R¹, R², and R³ is independently optionally substituted; R⁴ is a hydrogen or halogen atom; and R⁵ is a hydrogen or halogen atom. In some embodiments, R¹ is phenyl, chlorophenyl, lower alkylphenyl, or lower alkoxyphenyl. In some embodiments, R³ is phenyl, chlorophenyl, lower alkylphenyl, or lower alkoxyphenyl. In some embodiments, both R¹ and R³ are selected from phenyl, chlorophenyl, lower alkylphenyl, and lower alkoxyphenyl, wherein the phenyl, chlorophenyl, lower alkylphenyl, and lower alkoxyphenyl is substituted or unsubstituted. In some embodiments, each of R¹ and R³ is independently an ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl radical. In some embodiments, R² is an ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group. In some embodiments, R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl group. In some embodiments, each of R⁴ and R⁵ is hydrogen. In some embodiments, the compound is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, 2-anilino-3-cyclohexylimino-5-phenyl-3, 5-dihydrophenazine. In some embodiments, each of R¹, R², and R³ is independently selected from the group consisting of: a phenyl or a chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of the R¹, R², and R³ is independently optionally substituted; R⁴ is a hydrogen or halogen atom; and R⁵ is a hydrogen or halogen atom. In some embodiments, R¹ is phenyl or chlorophenyl. In some embodiments, R³ is phenyl or chlorophenyl. In some embodiments, the compound is clofazimine.

Also provided herein are pharmaceutical compositions, comprising a composition described herein. In some embodiments, the pharmaceutical composition is formulated as a neutral or a salt form. In some embodiments, the pharmaceutical composition comprises a salt. In some embodiments, the pharmaceutical composition comprises a pharmaceutically acceptable salt. In some embodiments, the salt is a pharmaceutically acceptable salt. Pharmaceutically acceptable salts include those formed with free amino groups such as those derived from hydrochloric, phosphoric, acetic, oxalic, or tartaric acids, and those formed with free carboxyl groups such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine, or procaine. In some embodiments, a salt or a pharmaceutically acceptable salt can comprise a hydrochloric acid (HCl) salt, an ascorbic acid salt, a mandelic acid salt, an aspartic acid salt, a carbonic acid salt, a citric acid salt, a formic acid salt, a glutamic acid salt, a lactic acid salt, a lauric acid salt, a maleic acid salt, a palmitic acid salt, a phosphoric acid salt, or any combination thereof. In some embodiments, a salt or a pharmaceutically acceptable salt can include, but is not limited to, a metal salt such as sodium salt, potassium salt, cesium salt and the like; an alkaline earth metal salt such as calcium salt, magnesium salt and the like; an organic amine salt such as a triethylamine salt, a pyridine salt, a picoline salt, an ethanolamine salt, a triethanolamine salt, a dicyclohexylamine salt, an N, N’ -dibenzylethylenediamine salt and the like; an inorganic acid salt such as hydrochloride, hydrobromide, phosphate, sulphate and the like; an organic acid salt such as citrate, lactate, tartrate, maleate, fumarate, mandelate, acetate, dichloroacetate, trifluoroacetate, oxalate, formate and the like; a sulfonate such as methanesulfonate, benzenesulfonate, p-toluenesulfonate and the like; and/or an amino acid salt such as arginate, asparginate, glutamate and the like.

In some embodiments, described herein is a composition comprising a compound or a pharmaceutically acceptable salt thereof present in an amount from about 0.01 %to about 25 %of the total weight of the composition. In some embodiments, a compound or a pharmaceutically acceptable salt thereof described herein is present in an amount of about 0.01%to about 0.1 %, about 0.01 %to about 1 %, about 0.01 %to about 5 %, about 0.01 %to about 10 %, about 0.01 %to about 15 %, about 0.01 %to about 20 %, about 0.01 %to about 25 %, about 0.1 %to about 1 %, about 0.1 %to about 5 %, about 0.1 %to about 10 %, about 0.1 %to about 15 %, about 0.1 %to about 20 %, about 0.1 %to about 25 %, about 0.5 %to about 1 %, about 0.5 %to about 5 %, about 0.5 %to about 10 %, about 0.5 %to about 15 %, about 0.5 %to about 20 %, about 0.5 %to about 25 %, about 1 %to about 5 %, about 1 %to about 10 %, about 1 %to about 15 %, about 1 %to about 20 %, about 1 %to about 25 %, about 5 %to about 10 %, about 5 %to about 20 %, about 5 %to about 25 %, about 10 % to about 20 %, or about 20 %to about 25 %of the total weight of a composition or a pharmaceutical composition described herein. In some embodiments, a compound or a pharmaceutically acceptable salt thereof described herein is present in an amount of about 0.01 %, about 0.02 %, about 0.03 %, about 0.04 %, about 0.05 %, about 0.06 %, about 0.07 %, about 0.08%, about 0.09 %, about 0.1 %, about 0.2 %, about 0.3 %, about 0.4 %, about 0.5 %, about 0.6 %, about 0.7 %, about 0.8 %, about 0.9 %, about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 11 %, about 12 %, about 13 %, about 14 %, about 15 %, about 16 %, about 17 %, about 18 %, about 19 %, about 20 %, about 21 %, about 22 %, about 23 %, about 24 %, or about 25 %of the total weight of a composition or a pharmaceutical composition described herein.

In some embodiments, a composition or a pharmaceutical composition described herein comprises an excipient. In some embodiments, the excipient is a pharmaceutically acceptable excipient. Non-limiting examples of excipients include a solvent, a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a chelator, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, a coloring agent, or a suspending agent. In some embodiments, the excipient is a solvent. In some embodiments, the solvent comprises polyoxyethylene ester, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG, sold under the trade name Soluplus) , or poloxamer 188 (P188) , . In some embodiments, the solvent comprises polyoxyethylene esters of 12-hydroxystearic acid (HS15) . In some embodiments, the solvent comprises about: 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, 50 %, 55 %, 60 %, 65 %, 70 %, 75 %, 80 %, 85 %, 90 %, 95 %, or 100 %HS15 (volume/volume (v/v) ) . In some embodiments, the solvent comprises 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, 50 %, 55 %, 60 %, 65 %, 70 %, 75 %, 80 %, 85 %, 90 %, 95 %, or 100 %HS15 (v/v) . In some embodiments, the solvent comprises 30 %v/v HS15. In some embodiments, the solvent comprises 30 %HS15 (v/v) . In some embodiments, the solvent comprises up to 100 %v/v HS15. In some embodiments, the solvent is 100 %v/v HS15. In some embodiments, the solvent is PVAc-PVCap-PEG. In some embodiments, the solvent comprises about: 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, or 50 %PVAc-PVCap-PEG (weight/weight (w/w) ) . In some embodiments, the solvent comprises 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, or 50 %PVAc-PVCap-PEG (w/w) . In some embodiments, the solvent comprises about 20 %PVAc-PVCap-PEG (w/w) . In some embodiments, the solvent comprises 20 %PVAc-PVCap-PEG (w/w) . In some embodiments, the solvent is Poloxamer 188 (P188) . In some embodiments, the solvent comprises about: 1 %, 2 %, 3 %, 4 %, 5 %, 6 %, 7 %, 8 %, 9 %, or 10 %P188 (w/w) . In some embodiments, the solvent comprises 1 %, 2 %, 3 %, 4 %, 5 %, 6 %, 7 %, 8 %, 9 %, or 10 %P188 (w/w) . In some embodiments, the solvent comprises about 5%P188. In some embodiments, the solvent comprises 5 %P188 . In some embodiments, the solvent comprises saline. In some embodiments, a composition or a pharmaceutical composition described herein comprises P188, HS15, and saline. In some embodiments, a composition or a pharmaceutical composition described herein comprises 5 %P188 (w/w) , 30 %HS15 (v/v) , and saline. In some embodiments, the excipient is a suspending agent. In some embodiments, the suspending agent comprises CMC. In some embodiments, the suspending agent comprises about: 0.1 %, 0.2 %, 0.3 %, 0.4 %, 0.5 %, 0.6 %, 0.7 %, 0.8 %, 0.9 %, or 1.0 %CMC. In some embodiments, the suspending agent comprises 0.1 %, 0.2 %, 0.3 %, 0.4 %, 0.5 %, 0.6 %, 0.7 %, 0.8 %, 0.9 %, or 1.0 %CMC. In some embodiments, the suspending agent comprises about 0.5%CMC. In some embodiments, the suspending agent comprises 0.5 %CMC.

In some embodiments, a composition or a pharmaceutical composition disclosed herein comprise a preservative. Exemplary preservatives include antibacterial or antifungal compounds. Examples of preservatives include but are not limited to octadecyldimethylbenzyl ammonium chloride, hexamethonium chloride, benzalkoniurn chloride (amixture of alkylbenzyldimethylammonium chlorides in which the alkyl groups are long-chain compounds) , and benzethonium chloride.

In some embodiments, a composition or a pharmaceutical composition disclosed herein is formulated to be compatible with its intended route of administration. Examples of routes of administration include, but are not limited to, topical, systemic, parenteral, intravenous, intradermal, subcutaneous, oral, intranasal, intratumoral, transdermal, transmucosal, and rectal administration. In some embodiments, a pharmaceutical composition described herein is formulated for delivery to the colon. In some embodiments, a pharmaceutical composition described herein is formulated for rectal administration. In some embodiments, a pharmaceutical composition described herein is formulated as a suppository. In further embodiments, a composition or a pharmaceutical composition described herein is formulated in a sterile solution.

In some embodiments, a composition or a pharmaceutical composition described herein comprises a surfactant. Surfactants can lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid. The surfactant can be a detergent, a wetting agent, an emulsifier, a foaming agent, a dispersant, or any combination thereof. In some embodiments, the surfactant comprises a polysorbate-type emulsifier. In some embodiments, the polysorbate is a PEG (polyethylene glycol) -ylated sorbitan esterified with one or more fatty acids. In some embodiments, the surfactant is selected from: Polysorbate 20 (polyoxyethylene 20 sorbitan monolaurate) , Polysorbate 60, Polysorbate 80, or any combination thereof.

In some embodiments, a pharmaceutical composition provided herein is administered to a subject in need thereof in an oral form, an enema form, a transdermal form, an oil formulation, an aqueous dispersion, an emulsion, an oil-in-water emulsion, a water-in-oil emulsion, a solution, a suspension, an elixir, a gel, a syrup, an aerosol, a mist, a powder, a pill, a tablet, a lozenge, a gel, a lotion, a paste, a formulated stick, a balm, a cream, an ointment, or comprised in a bandage, a dressing, or a suppository.

In some embodiments, a pharmaceutical composition described herein is prepared as a suppository. In some embodiments, the suppository comprises a suppository base. In some embodiments, the suppository base is a hydrophilic suppository base or a lipophilic suppository base. In some embodiments, the suppository base is lipophilic suppository base. In some embodiments, the suppository base has a melting point of from about 30 degrees Celsius to about 38 degrees Celsius. In some embodiments, the suppository base has a melting point of about 30 degrees Celsius, about 30.5 degrees Celsius, about 31 degrees Celsius, about 31.5 degrees Celsius, about 32 degrees Celsius, about 32.5 degrees Celsius, about 33 degrees Celsius, about 33.5 degrees Celsius, about 34 degrees Celsius, about 34.5 degrees Celsius, about 35 degrees Celsius, about 35.5 degrees Celsius, about 36 degrees Celsius, about 36.5 degrees Celsius, about 37 degrees Celsius, about 37.5 degrees Celsius, or about 38 degrees Celsius. In some embodiments, the lipophilic suppository base comprises a fatty base material. Fatty base materials as used herein include, but are not limited to: fatty oils, hard fats, waxes, and fatty acids. Examples of fatty oils and hard fats include, but are not limited to: cocoa butter, palm oil, coconut oil, or lard. In some embodiments, the suppository comprises a hard fat. In some embodiments, the hard fat is commercially available. In some embodiments, the hard fat comprises mono-, di-and triglyceride esters of fatty acids. In some embodiments, the fatty acids comprises a chain length of 10 to 18 carbon atoms. In some embodiments, the hard fat comprises more triglyceride esters of fatty acids than mono-or diglyceride esters of fatty acids. In some embodiments, the hard fat comprises: A, AIML, AM, AML, AP, AS2, AS2X, NA, NA0, NA15, NAI 25 A, NAI 50, NAIS 90, NAS 50, andNAS 55 (manufactured by Gattefosse Inc. ) , “Isocacao” (manufactured by Kao Corp. ) , H-5, H-15, H-35, W-25, W-35, S-55 andS-58 (all manufactured by Huls AG) , NissanB-115 or NissanN-145 (all from Nippon Oil &Fats Co., Ltd. ) . In some embodiments, the hard fat comprisesNAI 25 A.

In some embodiments, a composition described herein comprises a weight ratio of a hard fat to a compound described herein from about 2: 1 to about 200: 1. In some embodiments, the weight ratio of the hard fat to the compound is about 2.5: 1 to about 100: 1, about 3: 1 to about 50: 1, about 4: 1 to about 25: 1, or about 5: 1 to about 10: 1. In some embodiment, the weight ratio of the hard fat to the compound is about 2: 1 to about 3: 1, about 2.5: 1 to about 3.5: 1, about 3: 1 to about 4: 1, about 3.5: 1 to about 4.5: 1, about 4: 1 to about 5: 1, about 4.5: 1 to about 5.5: 1, about 5: 1 to about 6: 1, about 5.5: 1 to about 6.5: 1, about 6: 1 to about 7: 1, about 6.5: 1 to about 7.5: 1, about 7: 1 to about 8: 1, about 7.5: 1 to about 8.5: 1, about 8:1 to about 10: 1, about 9: 1 to about 15: 1, about 10: 1 to about 20: 1, about 15: 1 to about 25: 1, about 20: 1 to about 50: 1, about 25: 1 to about 100: 1, or about 50: 1 to about 100: 1. In some embodiments, the weight ratio of the hard fat to the compound is about 3.3: 1. In some embodiments, the weight ratio of the hard fat to the compound is about 10: 1. In some embodiments, the weight ratio of the hard fat to the compound is about 25: 1. In some embodiments, the weight ratio of the hard fat to the compound is about 100: 1.

In some embodiments, the hard fat is present in an amount from about 0.10 g to about 10.00 g. In some embodiments, the hard fat is present in an amount of about 0.10 g, 0.11 g, 0.12 g, 0.13 g, 0.14 g, 0.15 g, 0.16 g, 0.17 g, 0.18 g, 0.17 g, 0.19 g, 0.20 g, 0.21 g, 0.22 g, 0.23 g, 0.24 g, 0.25 g, 0.26 g, 0.27 g, 0.28 g, 0.29 g, 0.30 g, 0.31 g, 0.32 g, 0.33 g, 0.34 g, 0.35 g, 0.36 g, 0.37 g, 0.38 g, 0.39 g, 0.40 g, 0.41 g, 0.42 g, 0.43 g, 0.44 g, 0.45 g, 0.46 g, 0.47 g, 0.48 g, 0.49 g, 0.50 g, 0.51 g, 0.52 g, 0.53 g, 0.54 g, 0.55 g, 0.56 g, 0.57 g, 0.58 g, 0.59 g, 0.60 g, 0.61 g, 0.62 g, 0.63 g, 0.64 g, 0.65 g, 0.66 g, 0.67 g, 0.68 g, 0.69 g, 0.70 g, 0.71 g, 0.72 g, 0.73 g, 0.74 g, 0.75 g, 0.76 g, 0.77 g, 0.78 g, 0.79 mg, 0.80 g, 0.81 g, 0.82 g, 0.83 g, 0.84 g, 0.85 g, 0.86 g, 0.87 g, 0.88 g, 0.89 g, 0.90 mg, 0.91 g, 0.92 g, 0.93 g, 0.94 g, 0.95 g, 0.96 g, 0.97 g, 0.98 g, 0.99 g, 1.00 g, 1.50 g, 2.00 g, 2.50 g, 3.00 g, 3.50 g, 4.00 g, 4.50 g, 5.00 g, 5.50 g, 6.00 g, 6.50 g, 7.00 g, 7.50 g, 8.00 g, 8.50 g, 9.00 g, 9.50 g, or 10.00 g.

In some embodiments, a compound described herein is present in a suppository composition described herein in an amount of up to 2500 mg. In some embodiments, a compound described herein is present in a suppository described herein in an amount of up to 2000 mg. In some embodiments, a compound described herein is present in a suppository described herein in an amount of up to 1000 mg. In some embodiments, a compound described herein is present in a suppository described herein in an amount of up to 600 mg. In some embodiments, a compound described herein is present in a suppository described herein in an amount of up to 250 mg. In some embodiments, a compound described herein is present in a suppository described herein in an amount of up to 200 mg. In some embodiments, a compound described herein is present in a suppository in an amount of up to 100 mg. In some embodiments, a compound described herein is present in a suppository described herein in an amount of about 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, 470 mg, 480 mg, 490 mg, 500 mg, 510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg.600 mg, 610 mg, 620 mg, 630 mg, 640 mg, 650 mg, 670 mg, 680 mg, 690 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, or 2500 mg. In some embodiments, the compound described herein is present in a suppository described herein is in an amount of about 60 mg. In some embodiments, a compound described herein is present in a suppository described herein is in an amount of 60 mg. In some embodiments, the compound described herein is present in a suppository described herein is in an amount of about 160 mg. In some embodiments, the compound described herein is present in a suppository described herein is in an amount of 160 mg. In some embodiments, the compound described herein is present in a suppository described herein is in an amount of about 600 mg. In some embodiments, the compound described herein is present in a suppository described herein is in an amount of 600 mg. In some embodiments, the compound described herein is present in a suppository described herein is in an amount of about 2100 mg. In some embodiments, the compound described herein is present in a suppository described herein is in an amount of 2100 mg. In some embodiments, the compound described herein is a compound encompassed by Formula I. In some embodiments, the compound is clofazimine or a pharmaceutically acceptable salt thereof.

In some embodiments, a composition or a pharmaceutical composition provided herein is formulated in a form of an enema formulation. In some embodiments, a compound described herein is present in an enema composition described herein in an amount of up to 2500 mg. In some embodiments, a compound described herein is present in an enema formulation described herein in an amount of up to 2000 mg. In some embodiments, a compound described herein is present in an enema formulation described herein in an amount of up to 1000 mg. In some embodiments, a compound described herein is present in an enema formulation described herein in an amount of up to 600 mg. In some embodiments, a compound described herein is present in an enema formulation described herein in an amount of up to 250 mg. In some embodiments, a compound described herein is present in an enema formulation described herein in an amount of up to 200 mg. In some embodiments, a compound described herein is present in an enema formulation in an amount of up to 100 mg. In some embodiments, a compound described herein is present in an enema formulation described herein in an amount of about 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, 470 mg, 480 mg, 490 mg, 500 mg, 510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg. 600 mg, 610 mg, 620 mg, 630 mg, 640 mg, 650 mg, 670 mg, 680 mg, 690 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, or 2500 mg. In some embodiments, the compound described herein is present in an enema formulation described herein is in an amount of about 60 mg. In some embodiments, a compound described herein is present in an enema formulation described herein is in an amount of 100 mg. In some embodiments, the compound described herein is present in a suppository described herein is in an amount of about 160 mg. In some embodiments, the compound described herein is present in an enema formulation described herein is in an amount of 320 mg. In some embodiments, the compound described herein is present in an enema formulation described herein is in an amount of about 600 mg. In some embodiments, the compound described herein is present in an enema formulation described herein is in an amount of 600 mg. In some embodiments, the compound described herein is present in an enema formulation described herein is in an amount of about 2100 mg. In some embodiments, the compound described herein is present in an enema formulation described herein is in an amount of 2100 mg. In some embodiments, the compound described herein is a compound encompassed by Formula I. In some embodiments, the compound is clofazimine or a pharmaceutically acceptable salt thereof.

In some embodiments, a composition or a pharmaceutical composition provided herein is formulated in a form of a dispersion. In some embodiments, a composition or a pharmaceutical composition provided herein comprises a solid dispersion. In some embodiments, a composition or a pharmaceutical composition provided herein are formulated in the form of a solid dispersion. In some embodiments, the solid dispersion is an amorphous solid dispersion. In some embodiments, the amorphous solid dispersion described herein comprises the compound described herein, and a high-molecular weight material. In some embodiments, the high-molecular weight material is a hydrophilic high-molecular weight material. In some embodiments, the high-molecular weight material comprises at least one of polyvinylpyrrolidone (povidone) (e.g., PVP-K30) , vinylpyrrolidone-vinyl acetate copolymer (copovidone or PVP-VA64, e.g., sold under the trade nameVA 64) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or Hypromellose; e.g., HPMC-E5) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMC AS) , Hypromellose phthalate (HPMCP) , polyethylene glycol (PEG) , polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG, e.g., sold under the trade name Soluplus) , polysaccharide, polymethacrylates, or a combination thereof. In some embodiments, the hydrophilic high-molecular weight material is polyvinylpyrrolidone (PVP) , copovidone, crospovidone, HPMC, or a combination thereof. In some embodiments, the high-molecular weight material comprises HPMC and crospovidone. In some embodiments, the high-molecular weight material comprises HPMC and PVP. In some embodiments, the high-molecular weight material comprises HPMC and copovidone. In some embodiments, the high-molecular weight material comprises Hypromellose phthalate (HPMCP) . In some embodiments, the high-weight material comprises polymethacrylates (e.g., sold under the trade name) . In some embodiments, the high-molecular weight material comprises HPMC AS.

In some embodiments, the high-molecular weight material is present in a disclosed amorphous solid dispersion and/or a disclosed pharmaceutical composition in an amount of at least 10 mg, at least 20 mg, at least 25 mg, at least 30 mg, at least 40 mg, at least 50 mg, at least 60 mg, at least 70 mg, at least 75 mg, at least 80 mg, at least 90 mg, at least 100 mg, at least 110 mg, at least 120 mg, at least 125 mg, at least 130 mg, at least 140 mg, at least 150 mg, at least 160 mg, at least 170 mg, at least 175 mg, at least 180 mg, at least 190 mg, or at least 200 mg. In some embodiments, the high-molecular weight material is present in a disclosed amorphous solid dispersion and/or a disclosed pharmaceutical composition in an amount of at most 30 mg, at most 35 mg, at most 40 mg, at most 45 mg, at most 50 mg, at most 55 mg, at most 60 mg, at most 65 mg, at most 70 mg, at most 75 mg, at most 80 mg, at most 90 mg, at most 100 mg, at most 105 mg, at most 110 mg, at most 115 mg, at most 120 mg, at most 125 mg, at most 130 mg, at most 135 mg, at most 140 mg, at most 145 mg, at most 150 mg, at most 155 mg, at most 160 mg, at most 165 mg, at most 170 mg, at most 175 mg, at most 180 mg, at most 185 mg, at most 190 mg, at most 195 mg, at most 200 mg, at most 210 mg, at most 220 mg, at most 230 mg, at most 240 mg, at most 250 mg, at most 260 mg, at most 270 mg, at most 280 mg, at most 290 mg, or at most 300 mg. In some embodiments, the high-molecular weight material is present in a disclosed amorphous solid dispersion and/or a disclosed pharmaceutical composition in an amount of about 10 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about 210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, about 245 mg, or about 250 mg. In some embodiments, the high-molecular weight material is present in an amorphous solid dispersion and/or a pharmaceutical composition disclosed herein in an amount of from 10 mg to 1000 mg. In some embodiments, the high-molecular weight material is present in an amount of from about 50 mg to about 150 mg, from about 55 mg to about 150 mg, from about 60 mg to about 150 mg, from about 65 mg to about 150 mg, from about 70 mg to about 150 mg, from about 75 mg to about 150 mg, from about 80 mg to about 150 mg, from about 85 mg to about 150 mg, from about 90 mg to about 150 mg, from about 95 mg to about 150 mg, from about 100 mg to about 150 mg, from about 105 mg to about 150 mg, from about 110 mg to about 150 mg, from about 115 mg to about 150 mg, from about 120 mg to about 150 mg, from about 125 mg to about 150 mg, from about 130 mg to about 150 mg, from about 135 mg to about 150 mg, from about 140 mg to about 150 mg, from about 145 mg to about 150 mg, from about 50 mg to about 145 mg, from about 50 mg to about 140 mg, from about 50 mg to about 130 mg, from about 50 mg to about 135 mg, from about 50 mg to about 125 mg, from about 50 mg to about 120 mg, from about 50 mg to about 115 mg, from about 50 mg to about 110 mg, from about 50 mg to about 105 mg, from about 50 mg to about 100 mg, from about 50 mg to about 95 mg, from about 50 mg to about 90 mg, from about 50 mg to about 85 mg, from about 50 mg to about 80 mg, from about 50 mg to about 75 mg, from about 50 mg to about 70 mg, from about 50 mg to about 65 mg, from about 50 mg to about 60 mg, or from about 50 mg to about 55 mg. In some embodiments, the high-molecular weight material is present in an amount of 20 mg to 500 mg, 20 mg to 400 mg, 20 mg to 300 mg, 25 mg to 250 mg, 30 mg to 200 mg, 50 mg to 200 mg, 50 mg to 150 mg, 50 mg to 125 mg, 75 mg to 200 mg, 75 mg to 150 mg, 100 mg to 125 mg, or 100 mg to 150 mg. In some embodiments, the high-molecular weight material comprises PVP, HPMC, copovidone, crospovidone, or a combination thereof. In some embodiments, the amorphous solid dispersion comprises about 100 mg of HPMC AS.

In some embodiments, the high-molecular weight material is present in an amount from about 1.0 mg to about 1000 mg, including but not limited to about: 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28 mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 31.5 mg, 32 mg, 32.5 mg, 33 mg, 33.5 mg, 36 mg, 36.5 mg, 37 mg, 37.5 mg, 38 mg, 38.5 mg, 39 mg, 39.5 mg, 40 mg, 40.5 mg, 41 mg, 41.5 mg, 42 mg, 42.5 mg, 43 mg, 43.5 mg, 44 mg, 44.5 mg, 45 mg, 45.5 mg, 46 mg, 46.5 mg, 47 mg, 47.5 mg, 48 mg, 48.5 mg, 49 mg, 49.5 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, 155 mg, 160 mg, 165 mg, 170 mg, 175 mg, 180 mg, 185 mg, 190 mg, 200 mg, 205 mg, 210 mg, 215 mg, 220 mg, 225 mg, 230 mg, 235 mg, 240 mg, 245 mg, 250 mg, 255 mg, 260 mg, 265 mg, 270 mg, 275 mg, 280 mg, 285 mg, 290 mg, 295 mg, 300 mg, 305 mg, 310 mg, 315 mg, 320 mg, 325 mg, 326 mg, 326.5 mg, 327 mg, 327.5 mg, 328 mg, 328.5 mg, 329 mg, 329.5 mg, 330 mg, 330.5 mg, 331 mg, 331.5 mg, 332 mg, 332.5 mg, 333 mg, 333.5 mg, 334 mg, 334.5 mg, 335 mg, 335.5 mg, 336 mg, 336.5 mg, 337 mg, 337.5 mg, 338 mg, 338.5 mg, 339 mg, 339.5 mg, 340 mg, 340.5 mg, 341 mg, 341.5 mg, 342 mg, 342.5 mg, 343 mg, 343.5 mg, 344 mg, 344.5 mg, 345 mg, 345.5 mg, 346 mg, 346.5 mg, 347 mg, 347.5 mg, 348 mg, 348.5 mg, 349 mg, 349.5 mg, 350 mg, 350.5 mg, 351 mg, 351.5 mg, 352 mg, 352.5 mg, 353 mg, 353.5 mg, 354 mg, 354.5 mg, 355 mg, 355.5 mg, 356 mg, 356.5 mg, 357 mg, 357.5 mg, 358 mg, 358.5 mg, 359 mg, 359.5 mg, 360 mg, 360.5 mg, 361 mg, 361.5 mg, 362 mg, 362.5 mg, 363 mg, 363.5 mg, 364 mg, 364.5 mg, 365 mg, 365.5 mg, 366 mg, 366.5 mg, 367 mg, 367.5 mg, 368 mg, 369.5 mg, 370 mg, 370.5 mg, 371 mg, 371.5 mg, 372 mg, 372.5 mg, 373 mg, 373.5 mg, 374 mg, 374.5 mg, 375 mg, 375.5 mg, 376 mg, 376.5 mg, 377 mg, 377.5 mg, 378 mg, 378.5 mg, 379 mg, 379.5 mg, 380 mg, 380.5 mg, 381 mg, 381.5 mg, 382 mg, 382.5 mg, 383 mg, 383.5 mg, 384 mg, 384.5 mg, 385 mg, 385.5 mg, 386 mg, 386.5 mg, 387 mg, 387.5 mg, 388 mg, 388.5 mg, 389 mg, 389.5 mg, 390 mg, 390.5 mg, 391 mg, 391.5 mg, 392 mg, 392.5 mg, 393 mg, 393.5 mg, 394 mg, 394.5 mg, 395 mg, 395.5 mg, 396 mg, 396.5 mg, 397 mg, 397.5 mg, 398 mg, 398.5 mg, 399 mg, 399.5 mg, 400 mg, 405 mg, 410 mg, 415 mg, 420 mg, 425 mg, 430 mg, 435 mg, 440 mg, 445 mg, 450 mg, 455 mg, 460 mg, 465 mg, 470 mg, 475 mg, 480 mg, 485 mg, 490 mg, 495 mg, 500 mg, 505 mg, 510 mg, 515 mg, 520 mg, 525 mg, 530 mg, 535 mg, 540 mg, 545 mg, 550 mg, 555 mg, 560 mg, 565 mg, 570 mg, 575 mg, 580 mg, 585 mg, 590 mg, 595 mg, 600 mg, 605 mg, 610 mg, 615 mg, 620 mg, 625 mg, 630 mg, 635 mg, 640 mg, 645 mg, 650 mg, 655 mg, 660 mg, 665 mg, 675 mg, 680 mg, 685 mg, 690 mg, 695 mg, 700 mg, 705 mg, 710 mg, 715 mg, 720 mg, 725 mg, 730 mg, 735 mg, 740 mg, 745 mg, 750 mg, 755 mg, 760 mg, 765 mg, 770 mg, 775 mg, 780 mg, 785 mg, 790 mg, 795 mg, 800 mg, 805 mg, 810 mg, 815 mg, 820 mg, 825 mg, 830 mg, 835 mg, 840 mg, 845 mg, 850 mg, 855 mg, 860 mg, 865 mg, 870 mg, 875 mg, 880 mg, 885 mg, 890 mg, 895 mg, 900 mg, 905 mg, 910 mg, 915 mg, 920 mg, 925 mg, 930 mg, 935 mg, 940 mg, 945 mg, 950 mg, 955 mg, 960 mg, 965 mg, 970 mg, 975 mg, 980 mg, 985 mg, 990 mg, 995 mg, or 1000 mg.

In some embodiments, the high-molecular weight material is present in the amorphous solid dispersion in an amount of 5%to 80%of a total weight of the amorphous solid dispersion. In some embodiments, the high-molecular weight material is present in an amount of from about 10%to about 60%, from about 30%to about 50%, from about 5%to about 60%, from about 20%to about 50%, from about 20%to about 40%, from about 25%to about 35%, from about 28%to about 32%, from about 25%to about 30%, or from about 20%to about 30%of a total weigh of the amorphous solid dispersion. In some embodiments, the high-molecular weight material comprises from about 20%to about 50%of the total weight of the amorphous solid dispersion. In some embodiments, the high-molecular weight material comprises from about 20%to about 40%of the total weight of the amorphous solid dispersion. In some embodiments, the high-molecular weight material is present in an amount of about 20 %, about 21 %, about 22 %, about 23 %, about 24 %, about 25 %, about 26 %, about 27 %, about 28 %, about 29 %, about 30 %, about 31 %, about 32 %, about 33 %, about 34 %, about 35 %, about 36 %, about 37 %, about 38 %, about 39 %, or about 40 %of a total weigh of the amorphous solid dispersion. In some embodiments, the high-molecular weight material is present in an amount of about 28 %of a total weight of the amorphous solid dispersion.

In some embodiments, to form an amorphous solid dispersion, a compound and a high-molecular weight material described herein are first dissolved to form a solution. The solution is then introduced into a spray dryer via flash atomization. After collection, the particles are placed into a convection tray dryer to form powders. In some embodiments, to form an amorphous solid dispersion, the compound and the high-molecular weight material are first dissolved into a polar solvent. In some embodiments, the polar solvent is selected from the group consisting of methanol, chloroform, N-methylpyrrolidone, tetrahydrofuran, ethyl acetate, acetone, dimethylformamide, dimethylacetamide, acetonitrile, dimethyl sulfoxide, propylene carbonate, dichloromethane, and mixtures thereof. In some embodiments, the polar solvent comprises a mixture of dichloromethane and methanol.

In some embodiments, the high-molecular weight material is present in the amorphous solid dispersion in an amount of 5 %to 8 0%of a total weigh of the amorphous solid dispersion. In some embodiments, the high-molecular weight material is present in an amount of from about 10 %to about 60 %, from about 30 %to about 50 %, from about 5 %to about 60 %, from about 20 %to about 50 %, from about 20%to about 40%, from about 25 %to about 35 %, from about 28 %to about 32 %, from about 25 %to about 30 %, or from about 20%to about 30 %of a total weigh of the amorphous solid dispersion. In some embodiments, the high-molecular weight material comprises from about 20 %to about 50 %of the total weight of the amorphous solid dispersion. In some embodiments, the high-molecular weight material comprises from about 20 %to about 40 %of the total weight of the amorphous solid dispersion. In some embodiments, the high-molecular weight material is present in an amount of about 20 %, about 21 %, about 22 %, about 23 %, about 24 %, about 25 %, about 26 %, about 27 %, about 28 %, about 29 %, about 30 %, about 31 %, about 32 %, about 33 %, about 34%, about 35%, about 36%, about 37%, about 38 %, about 39 %, or about 40 %of a total weigh of the amorphous solid dispersion. In some embodiments, the high-molecular weight material is present in an amount of about 28 %of a total weigh of the amorphous solid dispersion.

In some embodiments, the high-molecular weight material is present in the disclosed pharmaceutical composition in an amount of 5 %to 80 %of a total weigh of the pharmaceutical composition. In some embodiments, the high-molecular weight material is present in an amount of from about 10 %to about 60 %, from about 30 %to about 50 %, from about 5 %to about 60 %, from about 20 %to about 50 %, from about 20 %to about 40 %, from about 25 %to about 35 %, from about 28 %to about 32 %, from about 25 %to about 30 %, or from about 20 %to about 30 %of a total weight of the pharmaceutical composition. In some embodiments, the high-molecular weight material comprises from about 20 %to about 50 %of the total weight of the pharmaceutical composition. In some embodiments, the high-molecular weight material comprises from about 20 %to about 40 %of the total weight of the pharmaceutical composition. In some embodiments, the high-molecular weight material is present in an amount of about 20 %, about 21 %, about 22 %, about 23 %, about 24 %, about 25 %, about 26 %, about 27 %, about 28 %, about 29 %, about 30 %, about 31 %, about 32 %, about 33 %, about 34 %, about 35 %, about 36 %, about 37 %, about 38 %, about 39 %, or about 4 0%of a total weight of the pharmaceutical composition.

In some embodiments, the high-molecular weight material is present in the disclosed composition or pharmaceutical composition as an excipient. In some embodiments, a high-molecular weight material is present in the disclosed pharmaceutical composition as an excipient of the amorphous solid dispersion in an amount of about 0.10 %to about 20 %by weight, including about 0.1 %to about 10 %, about 3 %to about 8 %, about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %or about 10 %by weight of the pharmaceutical composition. In some embodiments, a high-molecular weight material is present in the disclosed pharmaceutical composition as an excipient of the amorphous solid dispersion in an amount of about 5 %by weight of the pharmaceutical composition.

In some embodiments, the weight ratio of the high-molecular weight material to the compound in an amorphous solid dispersion is from about 0.1: 1 to about 10: 1. In some embodiments, the weight ratio of the high-molecular weight material to the compound in an amorphous solid dispersion is from about 0.5: 1 to about 5: 1, from about 0.5: 1 to about 4: 1, from about 0.5: 1 to about 3: 1, from about 0.6: 1 to about 4: 1, from about 0.7: 1 to about 3: 1, from about 0.8: 1 to about 2: 1, from about 0.9: 1 to about 1.1: 1, from about 1: 1 to about 3: 1, from about 1: 1 to about 4: 1, from about 1: 1 to about 5: 1, or from about 1: 1 to about 6: 1. In some embodiments, the weight ratio of the high-molecular weight material to the compound is in an amorphous solid dispersion about 3: 1.

In some embodiments, the high-molecular weight material is present in an amount of from 30 mg to 300 mg, and the compound is present in an amount of from 10 mg to 100 mg. In some embodiments, the high-molecular weight material is present in in an amount of about 240 mg and the compound is present in an amount of about 80 mg. In some embodiments, the high-molecular weight material is present in in an amount of about 187.5 mg and the compound is present in an amount of about 62.5 mg. In some embodiments, the high-molecular weight material is present in in an amount of about 67.5 mg and the compound is present in an amount of about 22.5 mg. In some embodiments, the high-molecular weight material comprises HPMC AS. In some embodiments, the compound described herein is a compound encompassed by Formula I. In some embodiments, the compound is clofazimine or a pharmaceutically acceptable salt thereof.

In some embodiments, a composition or a pharmaceutical composition described herein is formulated in the form of a suppository comprising an amorphous solid dispersion described herein and a suppository base described herein. Also provided here are methods for preparing or forming a composition described herein comprising a suppository. In some embodiments, to form a suppository with the amorphous solid dispersion described herein, the suppository base is melted, mixed with the amorphous solid dispersion described herein, and the mixture is then cooled to from a suppository. In some embodiments, the weight ratio of the suppository base described herein to the amorphous solid dispersion described herein is from about 08: 1 to about 15: 1. In some embodiments, the weight ratio of the suppository base described herein to the amorphous solid dispersion described herein is about 0.8: 1, about 1.0: 1, about 1.1: 1, about 1.2: 1, about 1.3: 1, about 1.4: 1, about 1.5: 1, about 1.6: 1, about 1.7: 1, about 1.8: 1, about 1.9: 1, about 2.0: 1, about 2.1: 1, about 2.2: 1, about 2.3: 1, about 2.4: 1, about 2.5: 1, about 2.6: 1, about 2.7: 1, about 2.8: 1, about 2.9: 1, about 3.0: 1, about 3.1: 1, about 3.2: 1, about 3.3: 1, about 3.4: 1, about 3.5: 1, about 3.6: 1, about 3.7: 1, about 3.8: 1, about 3.9: 1, about 4.0: 1, about 4.5: 1, about 5.0: 1, about 5.5: 1, about 6.0: 1, about 6.5: 1, about 7.0: 1, about 7.5: 1, about 8.0: 1, about 8.5: 1, about 9.0: 1, about 9.5: 1, about 10.0: 1, about 10.5: 1, about 11.0: 1, about 11.5: 1, about 12.0: 1, about 12.5: 1, about 13: 1, about 13.5: 1, about 14: 1, about 14.5: 1, or about 15: 1.

In some embodiments, the suppository comprises 4 g of a suppository base described herein and 320 mg of an amorphous solid dispersion described herein. In some embodiments, the suppository comprises 8 g of a suppository base described herein and 320 mg of an amorphous solid dispersion described herein. In some embodiments, the suppository comprises 240 mg of a suppository base described herein and 90 mg of an amorphous solid dispersion described herein. In some embodiments, the suppository comprises 250 of a suppository base described herein and 250 mg of an amorphous solid dispersion described herein.

Methods of Treatment

Provided herein are methods of treating a disease or condition comprising administering to a subject a composition or a pharmaceutical composition described herein. In some embodiments, the disease or condition is a gastrointestinal disease or condition, an autoimmune disease or condition, an intestinal or colon-associated condition, or a symptom associated with any of these. In some embodiments, the gastrointestinal disease or condition is a chronic disease or condition. In some embodiments, the gastrointestinal disease or condition is an acute disease or condition. In some embodiments, the gastrointestinal disease or condition is gastrointestinal spasms, irritable bowel syndrome (IBS) , hemorrhoids, anal fissures, perianal abscesses, anal fistula, diverticular disease, colon polyps and cancer, colitis, and inflammatory bowel diseases (IBD) . Examples of colitis include, but are not limited to, infectious colitis, ulcerative colitis, Ischemic colitis, and radiation colitis. In some embodiments, the gastrointestinal disease or condition is ulcerative colitis. In some embodiments, the gastrointestinal disease or condition is IBD. In some embodiments, the subject is a mammal. In some embodiments, the mammal is a dog, cat, sheep, llama, pig, goat, sheep, horse, cow, human, or non-human primate. In some embodiments, the subject is a human. In some embodiments, the subject is a patient in need thereof. In some embodiments, the human is 10 years old or less. In some embodiments, the human is 21 years old or less. In some embodiments, the human is 21 years old or more. In some embodiments, the human is 30 years old or more. In some embodiments, the human is 40 years old or more. In some embodiments, the human is 50 years old or more.

Also provided herein are methods for ameliorating symptoms associated with gastrointestinal conditions comprising administering to a subject a composition or a pharmaceutical composition described herein. Examples of a symptom associated with gastrointestinal conditions include but are not limited to diarrhea, dehydration, nausea, constipation, bloating, rectal bleeding, abdominal pain, cramping, rectal pain, headache, malaise, rash, conjunctivitis, pruritus, weight loss, fatigue, and fever.

In some embodiments, a composition or pharmaceutical composition described herein, when administered to a subject, preserve the integrity of the gastrointestinal tract. In some embodiments, a composition or pharmaceutical composition described herein, when administered, preserve the integrity of the colon. In some embodiments, a composition or pharmaceutical composition described herein, when administered, preserve the integrity of the large intestine. In certain instances, gastrointestinal conditions lead to reduced integrity of the gastrointestinal tract and/or damaged mucosal layer. In some cases, damaged mucosal layer is shown by epithelia cells shedding, loss of crypt structure, a large number of lymphocyte infiltration and crypt abscess (accumulation of inflammatory cells within the crypts of the gastrointestinal tract) . In some embodiments, the administration of a composition or pharmaceutical composition described herein to a subject in need thereof improves colonic mucosal integrity in large intestine of the subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein to a subject in need thereof reduces intestinal mucosal damage in the subject as compared to an untreated subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein to a subject in need thereof reduces epithelia cell shedding in the subject as compared to an untreated subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein to a subject in need thereof maintains the integrity of crypt structure in the subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein to a subject in need thereof reduces the loss of crypt structure in the subject as compared an untreated subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein to a subject in need thereof reduces lymphocyte infiltration in large intestine of the subject as compared to an untreated subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein to a subject in need thereof reduces crypt abscess in large intestine of the subject as compared to an untreated subject. In some embodiments, the administration maintains the number of goblet cell and epithelial cell in large intestine of the subject as compared to an untreated subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein to a subject in need thereof reduces colon atrophy in large intestine of the subject as compared to an untreated subject. In some embodiments, the integrity of the gastrointestinal tract, colon/large intestine, is measured by a change in length, inflammatory markers, mucosal layer, and/or epithelial barrier leakiness and/or cell-cell junction tightness.

Upregulation of inflammatory molecules is often associated with gastrointestinal conditions. In some embodiments, the administration of a composition or a pharmaceutical composition described herein reduces inflammation in a subject. In some instances, the administration of a composition or a pharmaceutical composition described herein inhibits the production of inflammatory molecules. In some embodiments, the administration a composition or a pharmaceutical composition described herein inhibits the production of inflammatory molecules in colon tissue. Non-limiting examples of inflammatory molecules include cytokines, chemokines, inflammasomes, bradykinin, histamine, and prostaglandins. In some embodiments, the administration of a composition or a pharmaceutical composition described herein inhibits the production of inflammatory cytokines in large intestine of the subject as compared to an untreated subject. In some embodiments, the inflammatory molecules can be IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12P70, INF gamma, TNF alpha, or keratoconus (KC) .

In some embodiments, the administration of a composition or a pharmaceutical composition described herein reduces the production of IL-2 in large intestine of the subject as compared to an untreated subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein reduces the production of IL-2 by about: 5 %, 10 %, 15 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 85 %, 90 %, 91 %, 92 %, 93 %, 94 %, or 95 %.

In some embodiments, the administration of a composition or a pharmaceutical composition described herein reduces the production of IL-6 in large intestine of the subject as compared to an untreated subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein reduces the production of IL-6 by about: 5 %, 10 %, 15 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 85 %, 90 %, 91 %, 92 %, 93 %, 94 %, or 95 %.

In some embodiments, the administration of a composition or a pharmaceutical composition described herein reduces the production of KC in large intestine of the subject as compared to an untreated subject. In some embodiments, the administration of a composition or a pharmaceutical composition described herein described herein reduces the production of KC by about: 5 %, 10 %, 15 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 85 %, 90 %, 91 %, 92 %, 93 %, 94 %, or 95 %.

Routes of Administration

The routes of administration of a composition or a pharmaceutical composition described herein depend on the condition of the subject and the nature of the disease. In some embodiments, a composition or a pharmaceutical composition described herein is administered parenterally, transdermally, mucosally, nasally, buccally, sublingually, rectally, or orally. In some embodiments, a composition or a pharmaceutical composition described herein is administered orally. In some embodiments, a composition or a pharmaceutical composition described herein can be administered with food. In some embodiments, a composition or a pharmaceutical composition described herein can be administered without food. In some embodiments, a composition or a pharmaceutical composition described herein is administered rectally. In some embodiments, a composition or a pharmaceutical composition described herein is administered via intragastric gavage. In some embodiments, a composition or a pharmaceutical composition described herein is administered via an enema.

Dosing Schedule

In some embodiments, the composition or the pharmaceutical composition is administered at a dose that comprises about 10 mg to about 250 mg of the compound. In some embodiments, the composition or the pharmaceutical composition is administered at a dose that comprises about 10 mg to about 20 mg, about 20 mg to about 30 mg, about 30 mg to about 40 mg, about 40 mg to about 50 mg, about 50 mg to about 60 mg, about 60 mg to about 70 mg, about 70 mg to about 80 mg, about 80 mg to about 90 mg, about 90 mg to about 100 mg, about 110 mg to about 120 mg, about 120 mg to about 130 mg, about 130 mg to about 140 mg, about 140 mg to about 150 mg, about 150 mg to about 160 mg, about 160 mg to about 170 mg, about 170 mg to about 180 mg, about 180 mg to about 190 mg, about 190 mg to about 200 mg, about 200 mg to about 210 mg, about 210 mg to about 220 mg, about 220 mg to about 230 mg, about 230 mg to about 240 mg, or about 240 mg to about 250 mg of the compound.

In some embodiments, a composition or a pharmaceutical composition described herein is administered at a dose that comprises about 1 milligram per kilogram (mpk) , about 1.5 mpk, about 2 mpk, about 2.5 mpk, about 3 mpk, about 3.5 mpk, about 4 mpk, about 4.5 mpk, about 5 mpk, about 5.5 mpk, about 6 mpk, about 6.5 mpk, about 7 mpk, about 7.5 mpk, about 8 mpk, about 8.5 mpk, about 9 mpk, about 9.5 mpk, about 10 mpk, about 10.5 mpk, about 11 mpk, about 11.5 mpk, about 12 mpk, about 12.5 mpk, about 13 mpk, about 13.5 mpk, about 14 mpk, about 14.5 mpk, about 15 mpk, about 15.5 mpk, about 16 mpk, about 16.5 mpk, about 17 mpk, about 17.5 mpk, about 18 mpk, about 18.5 mpk, about 19 mpk, about 19.5 mpk, about 20 mpk, about 20.5 mpk, about 21 mpk, about 21.5 mpk, about 22 mpk, about 22.5 mpk, about 23 mpk, about 23.5 mpk, about 24 mpk, about 24.5 mpk, about 25 mpk, about 25.5 mpk, about 26 mpk, about 26.5 mpk, about 27 mpk, about 27.5 mpk, about 28 mpk, about 28.5 mpk, about 29 mpk, about 29.5 mpk, or about 30 mpk of the composition or the pharmaceutical composition described herein.

In some embodiments, a composition or a pharmaceutical composition described herein is administered to the subject as a single dose or multiple doses. In some embodiments, a composition or a pharmaceutical composition described herein is administered up to two times a day, or up to three times a day. In some embodiments, a composition or a pharmaceutical composition described herein is administered daily. In some embodiments, a composition or a pharmaceutical composition described herein is administered every other day. In some embodiments, a composition or a pharmaceutical composition described herein is administered to the subject over a period of 1, 2, 3, 4, 5, 6, 7 or more days or weeks. In certain embodiments, a composition or a pharmaceutical composition described herein is administered over a period of about 1 week to about 2 weeks, about 2 weeks to about 3 weeks, about 3 weeks to about 4 weeks, about 4 weeks to about 5 weeks, about 6 weeks to about 7 weeks, about 7 weeks to about 8 weeks, about 8 weeks to about 9 weeks, about 9 weeks to about 10 weeks, about 10 weeks to about 11 weeks, about 11 weeks to about 12 weeks, about 12 weeks to about 24 weeks, about 24 weeks to about 48 weeks, about 48 weeks or about 52 weeks, or longer. The frequency of administration of a composition or a pharmaceutical composition described herein is, in certain instances, once daily, twice daily, once every week, once every three weeks, once every four weeks (or once a month) , once every 8 weeks (or once every 2 months) , once every 12 weeks (or once every 3 months) , or once every 24 weeks (once every 6 months) . In some embodiments of the methods disclosed herein, a composition or a pharmaceutical composition described herein is administered, independently, in an initial dose for a first period of time, an intermediate dose for a second period of time, and a low dose for a third period of time. In some embodiments, the initial dose is higher than the intermediate dose and the intermediate dose is higher than the high dose. In some embodiments, the first, second, and third periods of time are, independently, about 1 week to about 2 weeks, about 2 weeks to about 3 weeks, about 3 weeks to about 4 weeks, about 4 weeks to about 5 weeks, about 6 weeks to about 7 weeks, about 7 weeks to about 8 weeks, about 8 weeks to about 9 weeks, about 9 weeks to about 10 weeks, about 10 weeks to about 11 weeks, about 11 weeks to about 12 weeks, about 12 weeks to about 24 weeks, about 24 weeks to about 48 weeks, about 48 weeks or about 52 weeks, or longer.

In some embodiments, the composition or the pharmaceutical composition is administered up to two times a day, or up to three times a day. In some embodiments, the composition or the pharmaceutical composition is administered daily. In some embodiments, the composition or the pharmaceutical composition is administered every other day. In some embodiments, the composition or the pharmaceutical composition is administered two times a day for about 1 to 6 weeks in an initiation phase or exacerbation phase followed by administration once a day, once every other day, once a week or as needed in a maintenance phase.

EXEMPLARY EMBODIMENTS

wherein: each of R¹, R², and R³ is independently selected from the group consisting of: a phenyl, chlorophenyl, a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of the R¹, R², and R³ is independently optionally substituted; R⁴ is a hydrogen or halogen atom; and R⁵ is a hydrogen or halogen atom. Further provided herein are methods for treatment of a gastrointestinal condition, wherein R¹ is phenyl or chlorophenyl. Further provided herein are methods for treatment of a gastrointestinal condition, wherein R³ is phenyl or chlorophenyl. Further provided herein are methods for treatment of a gastrointestinal condition, wherein R² is an ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group. Further provided herein are methods for treatment of a gastrointestinal condition, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl group. Further provided herein are methods for treatment of a gastrointestinal condition, wherein each of R⁴ and R⁵ is hydrogen. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, 2-anilino-3-cyclohexylimino-5-phenyl-3, 5-dihydrophenazine. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the gastrointestinal condition is a chronic condition. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the gastrointestinal condition is ulcerative colitis. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the gastrointestinal condition is inflammatory bowel diseases. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is present in an effective amount to inhibit the production of inflammatory cytokines in the subject. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is present in an effective amount to reduce intestinal mucosal structural damage in the subject. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition further comprises a solvent. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the solvent comprises polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the solvent comprises: 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the solvent comprises 30%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the solvent comprises 100%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the solvent comprises polyoxyethylene ester, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG) . Further provided herein are methods for treatment of a gastrointestinal condition, wherein the solvent comprises 20%PVAc-PVCap-PEG. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the solvent comprises Poloxamer 188 (P188) . Further provided herein are methods for treatment of a gastrointestinal condition, wherein the solvent comprises 5%P188. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition further comprises a suspending agent. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the suspending agent comprises carboxymethylcellulose (CMC) . Further provided herein are methods for treatment of a gastrointestinal condition, wherein the suspending agent comprises 0.5%CMC. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is in a dosage form of a liquid, capsule, tablet, powder, or suppository. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is in a dosage form of a suppository. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition comprises a lipophilic suppository base. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the lipophilic suppository base is a hard fat. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the hard fat has a melting point of about 33 degrees Celsius to about 35 degrees Celsius. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the hard fat comprises mono-, di-, and triglyceride esters of fatty acids comprising a carbon chain length of 10 to 18. Further provided herein are methods for treatment of a gastrointestinal condition, wherein a weight ratio of the hard fat to the compound is from about 2: 1 to about 100: 1. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the weight ratio of the hard fat to the compound is about 2: 1, about 3: 1, about 3.3: 1, about 5: 1, about 10: 1, about 25: 1, about 50:1, or about 100: 1. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is in the form of a dispersion. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the dispersion is an amorphous solid dispersion. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the amorphous solid dispersion comprises a high-molecular weight material. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the high-molecular weight material vinylpyrrolidone-vinyl acetate copolymer (copovidone) , polyvinylpyrrolidone (PVP or povidone) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or hypromellose) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMCAS) , polyethylene glycol (PEG) , polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVAc-PVCap-PEG) , or a combination thereof. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the high-molecular weight material is HPMC. Further provided herein are methods for treatment of a gastrointestinal condition, wherein a weight ratio of the high-molecular weight material to the compound is from about 1: 1 to about 5: 1. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the weight ratio of the high-molecular weight material to the compound is about 3: 1. Further provided herein are methods for treatment of a gastrointestinal condition, wherein composition is administered in a suppository dosage form. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered in an oral dosage form. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered in an enema dosage form. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered parenterally, transdermally, mucosally, nasally, buccally, sublingually, rectally, or orally. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered rectally. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is formulated for delivery to the colon. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered via an enema. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the subject is a mammal. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the subject is a human. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the compound is present in an amount of up to 200 mg. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the compound is present in an amount of up to 100 mg. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the compound is present in an amount of about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, or 150 mg. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered once a day from 10 mg/kg to 25 mg/kg. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered once a day at 10 mg/kg, 17 mg/kg, or 25 mg/kg. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered up to two times a day, or up to three times a day. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the composition is administered daily or every other day. Further provided herein are methods for treatment of a gastrointestinal condition, wherein the pharmaceutical composition is administered two times a day for about 1 to 6 weeks in an initiation phase or exacerbation phase followed by administration once a day, once every other day, once a week, or as needed in a maintenance phase.

wherein, each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted; R⁴ represents a hydrogen or halogen atom; and R⁵ represents a hydrogen or halogen atom. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein R¹ is phenyl or chlorophenyl. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein R³ is phenyl or chlorophenyl. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein R² is an ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl group. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein each of R⁴ and R⁵ is hydrogen. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, 2-anilino-3-cyclohexylimino-5-phenyl-3, 5-dihydrophenazine. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, the compound is clofazimine or a pharmaceutically acceptable salt thereof. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the symptom comprises: diarrhea, rectal bleeding, abdominal pain, cramping, rectal pain, weight loss, fatigue, fever, malaise, or pruritis. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is present in an effective amount to inhibit production of inflammatory cytokines in large intestine of the subject as compared to an untreated subject. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is present in an effective amount to protect intestinal mucosal structural integrity in large intestine of the subject as compared to an untreated subject. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is present in an effective amount to reduce epithelia cells shedding in large intestine of the subject as compared to an untreated subject. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is present in an effective amount to reduce a loss of crypt structure in large intestine of the subject as compared to an untreated subject. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is present in an effective amount to reduce lymphocyte infiltration in large intestine of the subject as compared to an untreated subject. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is present in an effective amount to reduce crypt abscess in large intestine of the subject as compared to an untreated subject. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is in a dosage form of a liquid, capsule, table, or suppository. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition further comprises a solvent. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the solvent comprises polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the solvent comprises 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the solvent comprises 30%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the solvent comprises 100%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the solvent comprises polyoxyethylene ester, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG) . Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the solvent comprises 20%PVAc-PVCap-PEG. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the solvent comprises Poloxamer 188 (P188) . Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the solvent comprises 5%P188. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition further comprises a suspending agent. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the suspending agent comprises carboxymethylcellulose (CMC) . Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the suspending agent comprises 0.5%CMC. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is in a dosage form of an enema. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is in a dosage form of a suppository. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition comprises a lipophilic suppository base. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the lipophilic suppository base comprises a hard fat. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the hard fat has a melting point of about 33 degrees Celsius to about 35 degrees Celsius. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the hard fat comprises a mixture of mono-, di-and triglyceride esters of fatty acids comprising a carbon chain length of 10 to 18. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein a weight ratio of the hard fat to the compound is from about 2: 1 to about 100: 1. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein a weight ratio of the hard fat to the compound is about 2: 1, about 3: 1, about 3.3: 1, about 5: 1, about 10: 1, about 25: 1, about 50: 1, or about 100: 1. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is in the form of a dispersion. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the dispersion is an amorphous solid dispersion. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the amorphous solid dispersion comprises a high-molecular weight material. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the high-molecular weight material vinylpyrrolidone-vinyl acetate copolymer (copovidone) , polyvinylpyrrolidone (PVP or povidone) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or hypromellose) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMC AS) , polyethylene glycol (PEG) , polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVAc-PVCap-PEG) , or a combination thereof. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the high-molecular weight material is HPMC AS. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein a weight ratio of the high-molecular weight material to the compound is from about 1: 1 to about 5: 1. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the weight ratio of the high-molecular weight material to the compound is about 3: 1. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered in a suppository dosage form. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered in an oral dosage form. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered in an enema dosage form. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered parenterally, transdermally, mucosally, nasally, buccally, sublingually, rectally, or orally. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered rectally. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is formulated for delivery to the colon. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered via an enema. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the subject is a mammal. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the subject is a human. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the compound is present in an amount of up to 200 mg. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the compound is present in an amount of up to 100 mg. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the compound is present in an amount of about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, or 150 mg. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered once a day from 10 mg/kg to 25 mg/kg. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered once a day at 10 mg/kg, 17 mg/kg, or 25 mg/kg. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered up to two time a day, or up to three times a day. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered daily or every other day. Further provided herein are methods for ameliorating a symptom associated with a gastrointestinal condition, wherein the composition is administered up to two times a day for about 1 to 6 weeks in an initiation phase or exacerbation phase followed by administration once a day, once every other day, once a week, or as needed in a maintenance phase.

wherein, each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted; R⁴ represents a hydrogen or halogen atom; and R⁵ represents a hydrogen or halogen atom; and a pharmaceutically acceptable excipient. Further provided herein are compositions, wherein R¹ is phenyl or chlorophenyl. Further provided herein are compositions, wherein R³ is phenyl or chlorophenyl. Further provided herein are compositions, wherein R² is an: ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group. Further provided herein are compositions, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl group. Further provided herein are compositions, wherein each of R⁴ and R⁵ is hydrogen. Further provided herein are compositions, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, 2-anilino-3-cyclohexylimino-5-phenyl-3, 5-dihydrophenazine. Further provided herein are compositions, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof. Further provided herein are compositions, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of from 10 mg to 3000 mg. Further provided herein are compositions, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of about 20 mg, 60 mg, 160 mg, 600 mg, 2100 mg. Further provided herein are compositions, wherein the excipient comprises a lipophilic suppository base. Further provided herein are compositions, wherein the lipophilic suppository base comprises a wax, cocoa butter, or a hard fat. Further provided herein are compositions, wherein the hard fat has a melting point of from about 33 degrees Celsius to about 35 degrees Celsius. Further provided herein are compositions, wherein the hard fat comprises at least one ester. Further provided herein are compositions, wherein the hard fat comprises a mixture of mono-, di-, and triglyceride esters of fatty acids comprising a carbon chain length of 10 to 18. Further provided herein are compositions, wherein a weight ratio of the hard fat to the compound is from about 2: 1 to about 100: 1. Further provided herein are compositions, wherein a weight ratio of the hard fat to the compound is about 2: 1, about 3: 1, about 3.3: 1, about 5: 1, about 10: 1, about 25: 1, about 50: 1, or about 100: 1. Further provided herein are compositions, wherein the hard fat is present in an amount of from 0.1 g to 10 g. Further provided herein are compositions, wherein the hard fat is present in an amount of about 0.24 g, about 0.25 g, about 4 g, about 6 g, about 7 g, or about 8 g. Further provided herein are compositions, wherein the composition further comprises a dispersion comprising the compound. Further provided herein are compositions, wherein the dispersion is an amorphous solid dispersion. Further provided herein are compositions, wherein the amorphous solid dispersion further comprises a high-molecular weight material. Further provided herein are compositions, wherein the high-molecular weight material vinylpyrrolidone-vinyl acetate copolymer (copovidone) , polyvinylpyrrolidone (PVP or povidone) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or hypromellose) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMCAS) , polyethylene glycol (PEG) , polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVAc-PVCap-PEG) , or a combination thereof. Further provided herein are compositions, wherein the high-molecular weight material is HPMC. Further provided herein are compositions, wherein a weight ratio of the high-molecular weight material to the compound is from about 1: 1 to about 5: 1. Further provided herein are compositions, wherein the weight ratio of the high-molecular weight material to the compound is about 3: 1. Further provided herein are compositions, wherein HPMC is present in an amount of from 30 mg to 300 mg, and the compound is present in an amount of from 10 mg to 100 mg. Further provided herein are compositions, wherein HPMC is present in in an amount of about 240 mg and the compound is present in an amount of about 80 mg. Further provided herein are compositions, wherein HPMC is present in in an amount of about 187.5 mg and the compound is present in an amount of about 62.5 mg. Further provided herein are compositions, wherein HPMC is present in in an amount of about 67.5 mg and the compound is present in an amount of about 22.5 mg. Further provided herein are compositions, wherein a weight ratio of the suppository base to the amorphous solid dispersion is from about 0.8: 1 to about 15: 1. Further provided herein are compositions, wherein the weight ratio of the suppository base to the amorphous solid dispersion is about 1: 1, about 2: 1, about 2.5: 1, or about 12.5: 1. Further provided herein are compositions, wherein the suppository base is present in an amount of from 0.20 g to about 10 g. Further provided herein are compositions, wherein the suppository base is present in an amount of about 0.24 g, about 0.25 g, about 4 g, or about 8 g. Further provided herein are methods of treating a gastrointestinal condition, comprising administering to a subject the compositions described herein. Further provided are methods of treating a gastrointestinal condition, wherein the gastrointestinal condition comprises ulcerative colitis.

wherein, each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted; R⁴ represents a hydrogen or halogen atom; and R⁵ represents a hydrogen or halogen atom; and a pharmaceutically acceptable excipient. Further provided herein are compositions, wherein R¹ is phenyl or chlorophenyl. Further provided herein are compositions, wherein R³ is phenyl or chlorophenyl. Further provided herein are compositions, wherein R² is an: ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group. Further provided herein are compositions, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl radical. Further provided herein are compositions, wherein each of R⁴ and R⁵ is hydrogen. Further provided herein are compositions, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, 2-anilino-3-cyclohexylimino-5-phenyl-3, 5-dihydrophenazine. Further provided herein are compositions, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof. Further provided herein are compositions, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of from 10 mg to 100 mg. Further provided herein are compositions, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of about 22.5 mg, 62.5 g, or 80 mg. Further provided herein are compositions, wherein the excipient comprises a high-molecular weight material. Further provided herein are compositions, wherein the high-molecular weight material vinylpyrrolidone-vinyl acetate copolymer (copovidone) , polyvinylpyrrolidone (PVP or povidone) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or hypromellose) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMCAS) , polyethylene glycol (PEG) , polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVAc-PVCap-PEG) , or a combination thereof. Further provided herein are compositions, wherein the high-molecular weight material is HPMC. Further provided herein are compositions, wherein a weight ratio of the high-molecular weight material to the compound is from about 1: 1 to about 5: 1. Further provided herein are compositions, wherein the weight ratio of the high-molecular weight material to the compound is about 3: 1. Further provided herein are compositions, wherein HPMC is present in an amount of about 240 mg and the compound is present in an amount of about 80 mg. Further provided herein are compositions, wherein HPMC is present in an amount of about 67.5 mg and the compound is present in an amount of about 22.5 mg. Further provided herein are compositions, wherein HPMC is present in an amount of about 187.5 mg and the compound is present in an amount of about 62.5 mg.

Provided herein are compositions, wherein the composition is in the form of an enema, and wherein the composition comprises: a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein, each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted; R⁴ represents a hydrogen or halogen atom; and R⁵ represents a hydrogen or halogen atom; and a pharmaceutically acceptable excipient. Further provided herein are compositions, wherein R¹ is phenyl or chlorophenyl. Further provided herein are compositions, wherein R³ is phenyl or chlorophenyl. Further provided herein are compositions, wherein R² is an: ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group. Further provided herein are compositions, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl radical. Further provided herein are compositions, wherein each of R⁴ and R⁵ is hydrogen. Further provided herein are compositions, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, 2-anilino-3-cyclohexylimino-5-phenyl-3, or 5-dihydrophenazine. Further provided herein are compositions, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof. Further provided herein are compositions, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of from 10 mg to 100 mg. Further provided herein are compositions, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of about 22.5 mg, 62.5 g, or 80 mg. Further provided herein are compositions, wherein the pharmaceutically acceptable solvent comprises polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are compositions, wherein the pharmaceutically acceptable solvent comprises 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are compositions, wherein the pharmaceutically acceptable solvent comprises 30%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are compositions, wherein the pharmaceutically acceptable solvent comprises 100%polyoxyethylene esters of 12-hydroxystearic acid. Further provided herein are compositions, wherein the pharmaceutically acceptable solvent comprises polyoxyethylene ester, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer or (PVAc-PVCap-PEG) . Further provided herein are compositions, Further provided herein are compositions, wherein the pharmaceutically acceptable solvent comprises 20%PVAc-PVCap-PEG. Further provided herein are compositions, wherein the pharmaceutically acceptable solvent comprises Poloxamer 188 (P188) . Further provided herein are compositions, wherein the pharmaceutically acceptable solvent comprises 5%P188. Further provided herein are compositions, wherein the composition further comprises a suspending agent. Further provided herein are compositions, wherein the suspending agent comprises carboxymethylcellulose (CMC) . Further provided herein are compositions, wherein the suspending agent comprises 0.5%CMC.

Provided herein are methods of treating a gastrointestinal condition, comprising administering to a subject the compositions described herein. Further provided are methods of treating a gastrointestinal condition, wherein the gastrointestinal condition comprises ulcerative colitis. Further provided are methods of treating a gastrointestinal condition, wherein the gastrointestinal condition comprises inflammatory bowel disease (IBD) .

EXAMPLES

Example 1. Effects of Clofazimine in a DSS-Induced Model in Mice

Ameliorative effect of clofazimine on UC was determined in a DSS-induced mouse model. Briefly, 5 groups of 6-8 week old C57BL/6J male mice were treated once daily with: (1) saline (Blank Control) , (2) 5 %P188 (w/w) +30 %HS15 (v/v) + saline (DSS Model Control) , (3) 150 mpk mesalamine (Positive Control) , (4) 25 mpk clofazimine (Condition 1) , or (5) 5 mpk clofazimine (Condition 2) . The detailed animal grouping and treatment information is shown in Table 3. All mice except the blank control group were freely fed with 2.5 %dextran sodium sulfate (DSS) in drinking water during the duration of the experiment. The test drug or mesalamine was dissolved in the solvent as shown in Table 3.

Table 1. Animal Grouping and Treatment Information for Testing the Efficacy of Clofazimine

Note:

1. i.g. Intragastric gavage; i. p. peritonea injection;

2. The dose of mesalamine to mice was calculated and converted from human dose.

As shown in FIG. 1, mice in DSS model control group experienced significant weight loss after 13 days of treatment (about 18 %) , while clofazimine treated mice from Condition 1 and Condition 2 maintained a relatively stable weight. More particularly, mice treated with 25 mpk clofazimine via intragastric gavage (Condition 1) only lost about 2 %of body weight, whereas mice treated with 5 mpk clofazimine via intraperitoneal injection (Condition 2) lost about 11%of body weight, which is comparable to the positive control.

After 13 days of treatment, the proximal colon from cecum to anus from each group was dissected and the length was measured. The colon length of clofazimine treated mice was significantly longer than that of model mice (FIGS. 2A-2B) . In particular, the average colon length of mice treated with 25 mpk clofazimine was about 80%longer than that of mice in DSS model control group. Thus, clofazimine could effectively inhibit DSS-induced intestinal mucosal damage and colon atrophy in mice.

The disease activity index (DAI) scoring system was used to evaluate the overall efficacy of clofazimine or positive control in mice with DSS-induced UC based on the body weight loss, fecal state and fecal occult blood test (FOBT) . FOBT is a diagnostic test to assess for hidden (occult) blood in the stool. Due to damage and bleeding of the intestinal mucosa, iron ions in blood will react with benzidine and hydrogen peroxide to produce color reaction. The appearance of blue color indicates blood positive reaction, and the appearance of brown color indicates blood negative reaction. The anus of mice was stimulated and an appropriate amount of feces were collected and placed on a glass slide. 1-2 drops of physiological saline were added to moisten the feces and then excessive amount of benzidine and hydrogen peroxide were added and mixed well with the feces. After about 5 min, color appearance was observed and recorded. The body weight loss, fecal state, and bleeding situation were evaluated at 0-5 scale according to the DAI scoring criteria in Table 2. As shown in FIG. 3, the DSS model control group has the highest DAI score as compared to the blank control group, mesalazine or clofazimine treated group. Clofazimine-treated groups (Condition 1 and Condition 2) had lower DAI score as compared to mesalazine-treated group. Specifically, the DAI scores of clofazimine treated mice in Condition 1 and Condition 2 were 1.33 and 2.2, respectively, whereas the DAI scores of DSS model control and positive control were 6.66 and 4, respectively. Thus, the DAI score showed that clofazimine could effectively reduce the severity of diseases caused by DSS damage (reduced by about 70%as compared to the DSS model control) .

Table 2. DAI Scoring Criteria

The above results shows that clofazimine has therapeutic effect in DSS-induced UC model. Compared to DSS model control and positive control, the body weights of clofazimine-treated mice could be maintained relatively stable whereas the body weights of the model group and positive control group decreased significantly during the study. The clofazimine gavage group had longer colon length and better DAI scores compared to the model and positive control groups. The overall results show the potential therapeutic effects of clofazimine on UC in a DSS-induced model.

Example 2. Comparisons of Effects of Clofazimine Oral or Rectal Administration in a DSS-induced Mouse Model

Comparisons of effects of clofazimine oral or rectal administration was determined in a DSS-induced mouse model. Briefly, mice were divided into two groups, gavage group and enema group. More specifically, mice in the gavage group were further divided into five groups, and mice in the enema group were further divided into two groups, as shown in Table 3. All mice except the blank control group were freely fed with 3.0 %DSS in drinking water during the experiment stage. Except for Condition 2 and positive control in which the test drugs were suspended in solvents, the test drugs in other groups were all dissolved insolvents. The detailed animal grouping and treatment information is shown in Table 3. The results of gavage and enema groups were shown separately for two reasons. First, because feces excretion would obstruct enema administration, the food intake was limited for mice in the enema group. Therefore, the body weights of mice in the enema groups dropped significantly from early experiment. Second, the mice in the enema group excreted less feces, and had clofazimine solution stuck to the feces, which would also affected FOBT results. Therefore, the enema group mice did not undergo FOBT. To obtain HE stain of colon tissue, some tissues from the distal colon of mice were cut and soaked in tissue fixative. To perform Luminex cytokine test, some tissues from the distal colon of mice were cut and stored at -80 ℃ before testing.

Table 3. Animal Grouping and Treatment Information via Oral vs. Rectal Administration

Note: i.g. intragastric gavage, p.r. enema route.

As shown in FIG. 4A, mice in the gavage model control group started to show weight loss on day 7, while clofazimine treated mice via intragastric gavage maintained a relatively stable weight change. FIG. 4B shows that the change rate of body weight for clofazimine treated mice (Condition 1 and Condition 2) were significantly smaller than that of the DSS model control (untreated) . Specifically, on day 11, model mice lost over 20 %of body weight while clofazimine treated mice in both Condition 1 and Condition only lost less than 10 %of body weight. Moreover, as shown in FIGS. 5A-5B, the colon length of clofazimine treated mice was more than 1 cm longer than that of the DSS model control (untreated) . The DAI scores for the clofazimine treated mice were also lower than that of the DSS model control on Day 4 and Day 8 (FIGS. 6A-6B) . On Day 4, the DAI scores for Condition 1 and Condition 2 were 2.1 and 1.2, respectively, while the DAI scores for the DSS model was 3.4. On Day 8, the DAI scores for Condition 1 and Condition 2 were still lower than that for the DSS model. The DAI scores for Condition 1 and Condition 2 were 4.2 and 3.4, respectively, while the DAI score for the DSS model was 5.5, suggesting the disease severity of mice treated with 25 mpk clofazimine via intragastric gavage was reduced by about 23%. HE stain results (FIG. 7) show that the mucosal layer of the DSS treated mice was severely damaged, as shown by epithelial cells shedding, loss of crypt structure, a large number of lymphocyte infiltration and crypt abscess. On the contrary, such damages were much less severe in clofazimine treated mice. Therefore, clofazimine administration protected mice from mucosal damage.

At the end of the assay, tissues fromthe distal colon were collected to test inflammatory molecules, including IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, INF gamma, TNF alpha and KC on a multiplex chip. The expression levels were measured by Luminex method. Only cytokines exhibiting significant changes between blank control group and the DSS model group were shown in FIG. 8. The expression of IL-1, IL-6 and KC were upregulated in colon tissue of DSS model mice, while clofazimine effectively inhibited the production of some inflammatory cytokines in colon tissue.

Similar results were observed in the Enema group. As shown in FIGS. 9A-9B, the colon length was about 1 cm longer for mice treated with clofazimine rectally via enema route (Condition 4) as compared to untreated (Condition 3) . The HE staining of colon tissue of mice from Condition 3 and Condition 4 showed mice treated with clofazimine (Condition 4) maintained the integrity of crypt structure, while disruption of the integrity of crypt structure was observed from the HE staining of colon tissue of the untreated mice (Condition 3) . Additionally, more goblet cells and epithelial cells were observed in the colonic tissue of mice treated with clofazimine rectally as compared to untreated mice (Condition 3) (FIG. 10) . Therefore, rectal administration of clofazimine solution maintained the colon length and reduced damage to intestinal mucosal structures by DSS in mice.

The results showed that clofazimine can maintain body weight, colon length and reduce colon bleeding. HE stain showed that clofazimine, when administrated either orally or rectally, improved mice colonic mucosa integrality by maintaining the integrity of crypt structure and the number of goblet cell and epithelial cell, and reducing inflammatory cells infiltration. The expression of IL-1, IL-6 and KC were upregulated in colon tissue of DSS model mice, while clofazimine reduced the expression of these cytokines. The test confirmed that both oral and rectal administration are effective in reducing the symptoms of DSS-induced UC model.

Example 3. Comparisons of Effects of Clofazimine vs JAK Inhibitors in a DSS-induced Mouse Model

Effects of clofazimine vs a JAK inhibitor on UC were determined in a DSS-induced model. 6 groups of 6-8 week old C57BL/6J male mice were treated with: (1) purified water (Blank control) , (2) 100 %HS15 (DSS model control) , (3) 150 mpk mesalamine (positive control) , (4) 25 mpk clofazimine in 100 %HS15, (5) 15 mpk clofazimine in 0.5 %CMC aqueous solution, or (6) 5 mpk Tofacitinib in water. All mice except the Blank control group were freely fed with 3.5 %DSS in drinking water during the experiment stage. Except for Condition 2 and Positive control in which the test drugs were suspended in solvents, the test drugs in other groups were dissolved in solvents. The detailed grouping and treatment information is shown in Table 4. The doses of positive control and tofacitinib were calculated and converted from human doses a. All drugs were orally administered via intragastric gavage.

Table 4. Administration Information for Comparing the Efficacy of Clofazimine vs. JAK Inhibitor

As shown in FIG. 11-12, both clofazimine and Tofacitinib treated mice reduced weight loss caused by DSS. Specifically, on day 13, model mice lost over above 25 %weight, while clofazimine treated mice in Condition 1 and Condition 2 only lost about 15 %weight and Tofacitinib treated mice in Condition 3 lost about 19 %weight. As suggested by the colon length shown in FIGS. 13A-13B, clofazimine and Tofacitinib could also effectively reduce DSS-induced intestinal mucosal damage and colon atrophy in model mice. The colon length of clofazimine treated mice in Condition 1, Condition 2, and Condition 3 is 6.35 cm, 6.51 cm, and 5.60 cm, respectively, while the colon length of the DSS model mice is 4.99 cm. Moreover, clofazimine and tofacitinib treatment decreased disease severity caused by high concentrations of DSS (FIG. 14) . On day 5, the DAI score for the clofazimine treated mice in Condition 1 and Condition 2 is about 1.7 and 0.8, respectively, while the DAI score of DSS model control is 2.1. Thus, the disease severity of mice treated with 25 mpk clofazimine via intragastric gavage is reduced by up to about 62%. Additionally, clofazimine treatment showed better results as compared to tofacitinib (DAI score is 2.0) . The HE staining of colon tissue showed that both clofazimine and tofacitinib administration protected mice from mucosal damage. In general, clofazimine and tofacitinib treated mice showed less epithelial cells shedding, loss of crypt structure, lymphocyte infiltration and crypt abscess.

Therefore, clofazimine show effects in UC mice model at higher concentration of DSS. Clofazimine, when administered orally or rectally in solution or suspension to DSS treated mice, can reduce (1) weight loss; (2) colon bleeding; (3) mucosal damage and colon atrophy; and (4) inflammation.

Example 4. Clofazimine Formulation I

To prepare suppository formulation of clofazimine, the matrixNAI was melted at about 75 degrees Celsius, then clofazimine was added to the meltedNAI and mixed together. The mixture was then cooled to generate a suppository formulation. The amount of clofazimine andNAI are listed in Table 5.

Table 5. Clofazimine Formulation II

Example 5. Clofazimine Formulation II

Suppository formulations of clofazimine were made according to the following procedure:

Step 1: Amorphous solid dispersion (ASD) preparation: clofazimine and hydroxypropyl methylcellulose acetate succinate (HPMC AS) were dissolved into solvent mixture of dichloromethane and methanol (3/7, V/V) to obtain a clear solution, the solution was then spray dried using a spray dryer (Labplant D-06AG, UK) to generate clofazimine ASD. The spay drying parameters were set as: feed rate 3.0-5.0 rpm, inlet temperature 50 to 70 degrees Celsius, outlet temperature 30-50 degrees Celsius, and atomization pressure 2.0-3.0 bar. After collection, the particles were placed into a convection tray dryer.

Step 2: The matrix Suppocire NAI was melted at about 75 degrees Celsius.

Step 3: The ASD powder of from Step 1 was added to Step 2 and mixed together.

Step 4: The mixture of step 3 was added to the suppository model preheated to 40 degrees Celsius and cooled.

Table 6. Suppository Formulation II

Example 6. Clofazimine Suspension Formulation Pharmacological Assay in DDS-Induced UC Mice

Effects of clofazimine at different doses was determined in DSS-induced model. 7 groups of 6-8 week old C57BL/6J male mice weighing around 20g were freely fed with purified water or 3.5% (w/v) DSS solution for 14 days before they were orally administered with (1) purified water (Blank control) , (2) 100 %HS15 (Model control) , (3) 150 mpk mesalamine (5-ASA) , (4) 1.5 mpk clofazimine in 0.5 %CMC aqueous solution, (5) 4.0 mpk clofazimine in 0.5 %CMC aqueous solution, (6) 10 mpk clofazimine in 0.5 %CMC aqueous solution, or (7) 25 mpk clofazimine in 0.5 %CMC aqueous solution. All mice except the Blank control group were freely fed with 3.5 %DSS in drinking water during the assay. The treatment schedule is shown in Table 7.

Table 7. Treatment Schedule of Clofazimine Suspension

As shown in FIGS. 16A-16B, the average colon length of mice treated with clofazimine at 1.5 mg/kg, 4.0 mg/kg, 10 mg/kg, 25 mg/kg are 6.1 cm, 5.7 cm, 6.3 cm, 6.9 cm, respectively, which are all longer than that of mice treated with model control (4.9 cm) or 5-ASA (5.5 cm) . The colon length of mice treated with 25 mg/kg of clofazimine is 1.45 times longer than model control, suggesting clofazimine suspension effectively reduced DSS-induced intestinal mucosal damage.

As suggested in FIG. 17, clofazimine at 1.5 and 4.0 mg/kg have the effects of inhibiting intestinal atrophy, promoting colon tissue reconstruct, and inhibiting intestinal bleeding in UC mice. The effect of 4.0 mg/kg is similar to that of 5-ASA. Mice treated with 10 and 25 mg/kg clofazimine showed a more promising therapeutic effect on UC mice. Among them, 10 mg/kg showed a significant effect in promoting colon tissue repair, while 25 mg/kg showed a significant reduction in rectal bleeding in the early stage of the experiment. As shown in FIG. 18, the DAI score for mice treated with 10 mg/kg or 25 mg/kg clofazimine on day 13 is 1.89 and 2.05, respectively, both are significantly lower than the other groups (about 49%lower than that of model control) . Therefore, mice treated with 10 and 25 mg/kg clofazimine showed the best results in reducing the symptoms of DSS-induced UC model.

Example 7. Pharmacological Effects of Clofazimine Suppository in a TNBS-induced UC Rat Model

Pharmacological effects of clofazimine suppository were evaluated in a TNBS-induced UC rat model. Briefly, 7-9 week old Sprague–Dawley (SD) male rats, weighing around 200 g, were treated with 2.5%TNBS in 50%ethanol at a dose of 125 mg/kg to induce an acute TNBS-induced UC model. All rats were fasted for 12 hours intrarectally injected with 2.5%TNBS solution and maintained in supine position for 10 min to prevent leakage of the intracolonic injection. Then, rats were fasted again for another 6 hours and the loss of body weight, mental state and fecal status were evaluated 24 hours after TNBS administration. Qualified rats were randomly divided and treated with suppositories once a day for 7 consecutive days as listed in Table 8. The grouping and administration information are shown in Table 8.

Table 8. Grouping and Treatment of Clofazimine Suppository

As shown in FIG. 19A and 19C, the colon length of rats treated with clofazimine suppositories at various doses were generally longer than that of model control or rats treated with 5-ASA. In particular, the colon length of rats treated with 4%, 1.3%and 0.4%clofazimine suspension suppositories were 16.7 cm, 17.0 cm, and 15.1 cm, respectively, as compared to 14.1 cm and 15.1 cm for the model control and rats treated with 5-ASA, respectively. Administration of 4%clofazimine suppository showed the best effect in restoring colon length (up to about 30%longer than that of model control) . Additionally, as shown in FIG. 19B, the colon weight of rats treated with 4% (17 mpk) clofazimine suspension suppository is higher than that in model control, treated with 5-ASA, or at lower doses of clofazimine.

Additionally, as shown in FIG. 20, TNBS causes severe damage to the colonic mucosa, making it very difficult for the colon to peristalsis and defecate normally. After treatment, the intestinal mucosa is repaired, and black scabs were excreted. The excretion of black scabs at concentrations of 4%and 1.3%is faster than that at concentration of 0.4%. 1.3%clofazimine suppository has the best effect on repairing colon mucosa and restoring intestinal peristalsis, while 4.0%clofazimine suppository inhibits intestinal mucosal fibrosis weaker than 1.3%.

The foregoing description and accompanying drawings set forth a number of representative embodiments at the present time. Various modifications, additions, and alternative designs will, of course, become apparent to those skilled in the art in light of the foregoing teachings without departing from the scope hereof, which is indicated by the following claims rather than by the foregoing description. All changes and variations that fall within the meaning and range of equivalency of the claims are to be embraced within their scope.

Claims

A method for treating a gastrointestinal condition, comprising:

administering to a subject having a gastrointestinal condition a composition, wherein the composition comprises a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein:

each of R¹, R², and R³ is independently selected from the group consisting of: a phenyl, chlorophenyl, a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of the R¹, R², and R³ is independently optionally substituted;

R⁴ is a hydrogen or halogen atom; and

R⁵ is a hydrogen or halogen atom.
The method of claim 1, wherein R¹ is phenyl or chlorophenyl.
The method of claim 1, wherein R³ is phenyl or chlorophenyl.
The method of claim 1, wherein R² is an ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group.
The method of claim 1, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl group.
The method of claim 1, wherein each of R⁴ and R⁵ is hydrogen.
The method of claim 1, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, or 2-anilino-3-cyclohexylimino-5-phenyl-3, 5-dihydrophenazine.
The method of claim 1, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof.
The method of claim 1, wherein the gastrointestinal condition is a chronic condition.
The method of claim 1, wherein the gastrointestinal condition is ulcerative colitis.
The method of claim 1, wherein the gastrointestinal condition is inflammatory bowel diseases.
The method of claim 1, wherein the composition is present in an effective amount to inhibit the production of inflammatory cytokines in the subject.
The method of claim 1, wherein the composition is present in an effective amount to reduce intestinal mucosal structural damage in the subject.
The method of claim 1, wherein the composition further comprises a solvent.
The method of claim 14, wherein the solvent comprises polyoxyethylene esters of 12-hydroxystearic acid.
The method of claim 15, wherein the solvent comprises: 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%polyoxyethylene esters of 12-hydroxystearic acid.
The method of claim 15, wherein the solvent comprises 30%polyoxyethylene esters of 12-hydroxystearic acid.
The method of claim 15, wherein the solvent comprises 100%polyoxyethylene esters of 12-hydroxystearic acid.
The method of claim 14, wherein the solvent comprises polyoxyethylene ester, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG) .
The method of claim 19, wherein the solvent comprises 20%PVAc-PVCap-PEG.
The method of claim 14, wherein the solvent comprises Poloxamer 188 (P188) .
The method of claim 21, wherein the solvent comprises 5%P188.
The method of any of claims 1 to 13, wherein the composition further comprises a suspending agent.
The method of claim 23, wherein the suspending agent comprises carboxymethylcellulose (CMC) .
The method of claim 24, wherein the suspending agent comprises 0.5%CMC.
The method of any one of claims 14 to 24, wherein composition is in a dosage form of an enema.
The method of claim 1, wherein the composition is in a dosage form of a liquid, capsule, tablet, powder, or suppository.
The method of claim 1, wherein the composition is in a dosage form of a suppository.
The method of claim 28, wherein the composition comprises a lipophilic suppository base.
The method of claim 29, wherein the lipophilic suppository base is a hard fat.
The method of claim 30, wherein the hard fat has a melting point of about 33 degrees Celsius to about 35 degrees Celsius.
The method of claim 31, wherein the hard fat comprises mono-, di-, and triglyceride esters of fatty acids comprising a carbon chain length of 10 to 18.
The method of any one of claims 30 to 32, wherein a weight ratio of the hard fat to the compound is from about 2: 1 to about 100: 1.
The method of claim 33, wherein the weight ratio of the hard fat to the compound is about 2: 1, about 3: 1, about 3.3: 1, about 5: 1, about 10: 1, about 25: 1, about 50: 1, or about 100: 1.
The method of any one of claims 1 to 25, wherein the composition is in the form of a dispersion.
The method of claim 35, wherein the dispersion is an amorphous solid dispersion.
The method of claim 36, wherein the amorphous solid dispersion comprises a high-molecular weight material.
The method of claim 37, wherein the high-molecular weight material vinylpyrrolidone-vinyl acetate copolymer (copovidone) , polyvinylpyrrolidone (PVP or povidone) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or hypromellose) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMC AS) , Hypromellose phthalate (HPMCP) , polyethylene glycol (PEG) , polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVAc-PVCap-PEG) , polymethacrylates or a combination thereof.
The method of claim 37, wherein the high-molecular weight material is HPMC AS.
The method of any one of claims 37 to 39, wherein a weight ratio of the high-molecular weight material to the compound is from about 1: 1 to about 5: 1.
The method of claim 40, wherein the weight ratio of the high-molecular weight material to the compound is about 3: 1.
The method of claim 1, wherein the composition is administered in a suppository dosage form.
The method of claim 1, wherein the composition is administered in an oral dosage form.
The method of claim 1, wherein the composition is administered in an enema dosage form.
The method of claim 1, wherein the composition is administered parenterally, transdermally, mucosally, nasally, buccally, sublingually, rectally, or orally.
The method of claim 1, wherein the composition is administered rectally.
The method of claim 1, wherein the composition is formulated for delivery to the colon.
The method of claim 47, wherein the composition is administered via an enema.
The method of any one of claims 1 to 48, wherein the subject is a mammal.
The method of claim 49, wherein the subject is a human.
The method of any one of claims 1 to 50, wherein the compound is present in an amount of up to 300 mg.
The method of any one of claims 1 to 50, wherein the compound is present in an amount of up to 100 mg.
The method of any one of claims 1 to 50, wherein the compound is present in an amount of about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, or 150 mg.
The method of any one of claims 1 to 50, wherein the composition is administered once a day from 10 mg/kg to 25 mg/kg.
The method of any one of claims 1 to 50, wherein the composition is administered once a day at 10 mg/kg, 17 mg/kg, or 25 mg/kg.
The method of any one of claims 1 to 53, wherein the composition is administered up to two times a day, or up to three times a day.
The method of any one of claims 1 to 53, wherein the composition is administered daily or every other day.
The method of any one of claims 1 to 53, wherein the composition is administered two times a day for about 1 to 6 weeks in an initiation phase or exacerbation phase followed by administration once a day, once every other day, once a week, or as needed in a maintenance phase.
A method for ameliorating a symptom associated with a gastrointestinal condition comprising administering to a subject having a gastrointestinal condition a composition, wherein the composition comprises a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein,

each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted;

R⁴ represents a hydrogen or halogen atom; and

R⁵ represents a hydrogen or halogen atom.
The method of claim 59, wherein R1 is phenyl or chlorophenyl.
The method of claim 59, wherein R³ is phenyl or chlorophenyl.
The method of claim 59, wherein R² is an ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group.
The method of claim 59, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl group.
The method of claim 59, wherein each of R⁴ and R⁵ is hydrogen.
The method of claim 59, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, or 2-anilino-3-cyclohexylimino-5-phenyl-3, 5-dihydrophenazine.
The method of claim 59, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof.
The method of claim 59, wherein the symptom comprises: diarrhea, rectal bleeding, abdominal pain, cramping, rectal pain, weight loss, fatigue, fever, malaise, or pruritis.
The method of claim 59, wherein the composition is present in an effective amount to inhibit production of inflammatory cytokines in large intestine of the subject as compared to an untreated subject.
The method of claim 59, wherein the composition is present in an effective amount to increase intestinal mucosal structural integrity in a large intestine of the subject as compared to an untreated subject.
The method of claim 59, wherein the composition is present in an effective amount to reduce epithelia cells shedding in a large intestine of the subject as compared to an untreated subject.
The method of claim 59, wherein the composition is present in an effective amount to reduce a loss of crypt structure in a large intestine of the subject as compared to an untreated subject.
The method of claim 59, wherein the composition is present in an effective amount to reduce lymphocyte infiltration in a large intestine of the subject as compared to an untreated subject.
The method of claim 59, wherein the composition is present in an effective amount to reduce crypt abscess in a large intestine of the subject as compared to an untreated subject.
The method of claim 59, wherein the composition is in a dosage form of a liquid, capsule, table, enema, or suppository.
The method of claim 59, wherein the composition further comprises a solvent.
The method of claim 75, wherein the solvent comprises polyoxyethylene esters of 12-hydroxystearic acid.
The method of claim 76, wherein the solvent comprises 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%polyoxyethylene esters of 12-hydroxystearic acid.
The method of claim 77, wherein the solvent comprises 30%polyoxyethylene esters of 12-hydroxystearic acid.
The method of claim 77, wherein the solvent comprises 100%polyoxyethylene esters of 12-hydroxystearic acid.
The method of claim 75, wherein the solvent comprises polyoxyethylene ester, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG) .
The method of claim 81, wherein the solvent comprises 20%PVAc-PVCap-PEG.
The method of claim 75, wherein the solvent comprises Poloxamer 188 (P188) .
The method of claim 82, wherein the solvent comprises 5%P188.
The method of claim 83, wherein the composition further comprises a suspending agent.
The method of claim 84, wherein the suspending agent comprises carboxymethylcellulose (CMC) .
The method of claim 85, wherein the suspending agent comprises 0.5%CMC.
The method of any one of claims 75 to 86, wherein the composition is in a dosage form of an enema.
The method of any one of claims 59 to 74, wherein the composition is in a dosage form of a suppository.
The method of claim 88, wherein the composition comprises a lipophilic suppository base.
The method of claim 89, wherein the lipophilic suppository base comprises a hard fat.
The method of claim 90, wherein the hard fat has a melting point of about 33 degrees Celsius to about 35 degrees Celsius.
The method of claim 91, wherein the hard fat comprises a mixture of mono-, di-and triglyceride esters of fatty acids comprising a carbon chain length of 10 to 18.
The method of claim 92, wherein a weight ratio of the hard fat to the compound is from about 2: 1 to about 100: 1.
The method of claim 92 or 93, wherein a weight ratio of the hard fat to the compound is about 2: 1, about 3: 1, about 3.3: 1, about 5: 1, about 10: 1, about 25: 1, about 50: 1, or about 100: 1.
The method of any one of claims 59 to 69, wherein the composition is in the form of a dispersion.
The method of claim 95, wherein the dispersion is an amorphous solid dispersion.
The method of claim 96, wherein the amorphous solid dispersion comprises a high-molecular weight material.
The method of claim 97, wherein the high-molecular weight material vinylpyrrolidone-vinyl acetate copolymer (copovidone) , polyvinylpyrrolidone (PVP or povidone) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or hypromellose) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMC AS) , polyethylene glycol (PEG) , polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVAc-PVCap-PEG) , or a combination thereof.
The method of claim 97, wherein the high-molecular weight material is HPMC AS.
The method of any one of claims 97 to 99, wherein a weight ratio of the high-molecular weight material to the compound is from about 1: 1 to about 5: 1.
The method of any one of claims 97 to 100, wherein the weight ratio of the high-molecular weight material to the compound is about 3: 1.
The method of claim 59, wherein composition is administered in a suppository dosage form.
The method of claim 59, wherein the composition is administered in an oral dosage form.
The method of claim 59, wherein the composition is administered in an enema dosage form.
The method of claim 59, wherein the composition is administered parenterally, transdermally, mucosally, nasally, buccally, sublingually, rectally, or orally.
The method of claim 59, wherein the composition is administered rectally.
The method of claim 59, wherein the composition is formulated for delivery to the colon.
The method of claim 107, wherein the composition is administered via an enema.
The method of any one of claims 59 to 108, wherein the subject is a mammal.
The method of claim 109, wherein the subject is a human.
The method of any one of claims 59 to 110, wherein the compound is present in an amount of up to 300 mg.
The method of any one of claims 59 to 110, wherein the compound is present in an amount of up to 100 mg.
The method of any one of claims 59 to 110, wherein the compound is present in an amount of about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, or 150 mg.
The method of any one of claims 59 to 110, wherein the composition is administered once a day from 10 mg/kg to 25 mg/kg.
The method of any one of claims 59 to 110, wherein the composition is administered once a day at 10 mg/kg, 17 mg/kg, or 25 mg/kg.
The method of any one of claims 59 to 113, wherein the composition is administered up to two time a day, or up to three times a day.
The method of any one of claims 59 to 113, wherein the composition is administered daily or every other day.
The method of any one of claims 59 to 116, wherein the composition is administered up to two times a day for about 1 to 6 weeks in an initiation phase or exacerbation phase followed by administration once a day, once every other day, once a week, or as needed in a maintenance phase.
A composition, wherein the composition is in the form of a suppository, and wherein the composition comprises:

a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein,

each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted;

R⁴ represents a hydrogen or halogen atom; and

R⁵ represents a hydrogen or halogen atom; and

a pharmaceutically acceptable excipient.
The composition of claim 119, wherein R¹ is phenyl or chlorophenyl.
The composition of claim 119, wherein R³ is phenyl or chlorophenyl.
The composition of claim 119, wherein R² is an: ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group.
The composition of claim 119, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl group.
The composition of claim 119, wherein each of R⁴ and R⁵ is hydrogen.
The composition of claim 119, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, or 2-anilino-3-cyclohexylimino-5-phenyl-3, 5-dihydrophenazine.
The composition of claim 119, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof.
The composition of claim 126, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of from 10 mg to 3000 mg.
The composition of claim 126, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of about 20 mg, 60 mg, 160 mg, 600 mg, or 2100 mg.
The composition of any one of claims 119 to 128, wherein the excipient comprises a lipophilic suppository base.
The composition of claim 129, wherein the lipophilic suppository base comprises a wax, cocoa butter, or a hard fat.
The composition of claim 130, wherein the hard fat has a melting point of from about 33 degrees Celsius to about 35 degrees Celsius.
The composition of claims 130 or 131, wherein the hard fat comprises at least one ester.
The composition of claim 132, wherein the hard fat comprises a mixture of mono-, di-, and triglyceride esters of fatty acids comprising a carbon chain length of 10 to 18.
The composition of claim 133, wherein a weight ratio of the hard fat to the compound is from about 2: 1 to about 100: 1.
The composition of claim 134, wherein a weight ratio of the hard fat to the compound is about 2: 1, about 3: 1, about 3.3: 1, about 5: 1, about 10: 1, about 25: 1, about 50: 1, or about 100: 1.
The composition of any one of claims 129 to 135, wherein the hard fat is present in an amount of from 0.1 g to 10 g.
The composition of any one of claims 129 to 135, wherein the hard fat is present in an amount of about 0.24 g, about 0.25 g, about 4 g, about 6 g, about 7 g, or about 8 g.
The composition of any one of claims 119 to 135137, wherein the composition further comprises a dispersion comprising the compound.
The composition of claim 138, wherein the dispersion is an amorphous solid dispersion.
The composition of claim 139, wherein the amorphous solid dispersion further comprises a high-molecular weight material.
The composition of claim 140, wherein the high-molecular weight material vinylpyrrolidone-vinyl acetate copolymer (copovidone) , polyvinylpyrrolidone (PVP or povidone) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or hypromellose) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMC AS) , polyethylene glycol (PEG) , polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVAc-PVCap-PEG) , or a combination thereof.
The composition of claim 141, wherein the high-molecular weight material is HPMC AS.
The composition of any one of claims 140 to 142, wherein a weight ratio of the high-molecular weight material to the compound is from about 1: 1 to about 5: 1.
The composition of claim 143, wherein the weight ratio of the high-molecular weight material to the compound is about 3: 1.
The composition of claim 142, wherein HPMC AS is present in an amount of from 30 mg to 300 mg, and the compound is present in an amount of from 10 mg to 100 mg.
The composition of claim 142, wherein HPMC AS is present in in an amount of about 240 mg and the compound is present in an amount of about 80 mg.
The composition of claim 142, wherein HPMC AS is present in in an amount of about 187.5 mg and the compound is present in an amount of about 62.5 mg.
The composition of claim 142, wherein HPMC AS is present in in an amount of about 67.5 mg and the compound is present in an amount of about 22.5 mg.
The composition of any one of claims 138 to 144, wherein a weight ratio of the suppository base to the amorphous solid dispersion is from about 0.8: 1 to about 15: 1.
The composition of claim 149, wherein the weight ratio of the suppository base to the amorphous solid dispersion is about 1: 1, about 2: 1, about 2.5: 1, or about 12.5: 1.
The composition of any one of claims 138 to 144, wherein the suppository base is present in an amount of from 0.20 g to about 10 g.
The composition of any one of claims 138 to 144, wherein the suppository base is present in an amount of about 0.24 g, about 0.25 g, about 4 g, or about 8 g.
A composition, wherein the composition is in the form of an amorphous solid dispersion, and wherein the composition comprises:

a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein,

each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted;

R⁴ represents a hydrogen or halogen atom; and

R⁵ represents a hydrogen or halogen atom; and

a pharmaceutically acceptable excipient.
The composition of claim 153, wherein R¹ is phenyl or chlorophenyl.
The composition of claim 153, wherein R³ is phenyl or chlorophenyl.
The composition of claim 153, wherein R² is an: ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group.
The composition of claim 153, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl radical.
The composition of claim 153, wherein each of R⁴ and R⁵ is hydrogen.
The composition of claim 153, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, 2-anilino-3-cyclohexylimino-5-phenyl-3, or 5-dihydrophenazine.
The composition of claim 153, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof.
The composition of claim 160, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of from 10 mg to 100 mg.
The composition of claim 160, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of about 22.5 mg, 62.5 g, or 80 mg.
The composition of any one of claims 153 to 162, wherein the excipient comprises a high-molecular weight material.
The composition of claim 163, wherein the high-molecular weight material vinylpyrrolidone-vinyl acetate copolymer (copovidone) , polyvinylpyrrolidone (PVP or povidone) , polyvinyl alcohol (PVA) , polysaccharide, hydroxypropyl methylcellulose (HPMC or hypromellose) , hydroxyethyl cellulose (HEC) , hydroxypropyl cellulose (HPC) , polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD) , sulfobutylether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMC AS) , polyethylene glycol (PEG) , polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVAc-PVCap-PEG) , or a combination thereof.
The composition of claim 163, wherein the high-molecular weight material is HPMC AS.
The composition of any one of claims 163 to 165, wherein a weight ratio of the high-molecular weight material to the compound is from about 1: 1 to about 5: 1.
The composition of claim 166, wherein the weight ratio of the high-molecular weight material to the compound is about 3: 1.
The composition of claim 165, wherein HPMC AS is present in an amount of about 240 mg and the compound is present in an amount of about 80 mg.
The composition of claim 165, wherein HPMC AS is present in an amount of about 67.5 mg and the compound is present in an amount of about 22.5 mg.
The composition of claim 165, wherein HPMC AS is present in an amount of about 187.5 mg and the compound is present in an amount of about 62.5 mg.
A composition, wherein the composition is in the form of an enema, and wherein the composition comprises:

a compound or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I) ,

wherein,

each of R¹, R², and R³ is independently selected from the group consisting of phenyl or chlorophenyl; a C₁-C₁₂ alkyl; a C₃-C₈ cycloalkyl; or a C₁-C₁₁ heteroalkyl, wherein each of R¹, R², and R³ is substituted or unsubstituted;

R⁴ represents a hydrogen or halogen atom; and

R⁵ represents a hydrogen or halogen atom; and

a pharmaceutically acceptable solvent.
The composition of claim 171, wherein R¹ is phenyl or chlorophenyl.
The composition of claim 171, wherein R³ is phenyl or chlorophenyl.
The composition of claim 171, wherein R² is an: ethyl, propyl, butyl, pentyl, hexyl, heptyl, decyl, cyclohexyl, or cycloheptyl group.
The composition of claim 171, wherein R² is an ethyl, n-propyl, 1-methylethyl (i-propyl) , n-butyl, heptyl, 1, 3-dimethylbutyl, sec-butyl, 1, 1-dimethylethyl (t-butyl) , 3, 5, 5-trimethylpentyl, n-dodecyl, n-decyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3, 5-dimethylcyclohexyl, or cycloheptyl radical.
The composition of claim 171, wherein each of R⁴ and R⁵ is hydrogen.
The composition of claim 171, wherein the compound or the pharmaceutically acceptable salt thereof is clofazimine, 2- (p-chlor-anilino) -3-cyclohexylimino-5- (p-chlorophenyl) -3, 5-dihydro-phenazine, 2-anilino-3-cyclohexylimino-5-phenyl-3, or 5-dihydrophenazine.
The composition of claim 171, wherein the compound is clofazimine or a pharmaceutically acceptable salt thereof.
The composition of claim 171, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of from 10 mg to 100 mg.
The composition of claim 171, wherein the clofazimine or a pharmaceutically acceptable salt thereof is present in an amount of about 22.5 mg, 62.5 g, or 80 mg.
The composition of claim 171, wherein the pharmaceutically acceptable solvent comprises polyoxyethylene esters of 12-hydroxystearic acid.
The composition of claim 181, wherein the pharmaceutically acceptable solvent comprises 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%polyoxyethylene esters of 12-hydroxystearic acid.
The composition of claim 181, wherein the pharmaceutically acceptable solvent comprises 30%polyoxyethylene esters of 12-hydroxystearic acid.
The composition of claim 181, wherein the pharmaceutically acceptable solvent comprises 100%polyoxyethylene esters of 12-hydroxystearic acid.
The composition of claim 171, wherein the pharmaceutically acceptable solvent comprises polyoxyethylene ester, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG) .
The composition of claim 185, wherein the pharmaceutically acceptable solvent comprises 20%PVAc-PVCap-PEG.
The composition of claim 171, wherein the pharmaceutically acceptable solvent comprises Poloxamer 188 (P188) .
The composition of claim 187, wherein the pharmaceutically acceptable solvent comprises 5%P188.
The composition of claim 171, wherein the composition further comprises a suspending agent.
The composition of claim 189, wherein the suspending agent comprises carboxymethylcellulose (CMC) .
The composition of claim 190, wherein the suspending agent comprises 0.5%CMC.
A method of treating a gastrointestinal condition, comprising administering to a subject the composition of any one of claims 119 to 191.
The method of claim 192, wherein the gastrointestinal condition comprises ulcerative colitis.
The method of claim 192, wherein the gastrointestinal condition comprises inflammatory bowel disease (IBD) .