WO2025068971A1

WO2025068971A1 - Compositions containing cabazitaxel and lipids for oral administration

Info

Publication number: WO2025068971A1
Application number: PCT/IB2024/059471
Authority: WO
Inventors: Shoukath M. Ali; Paul Chen; Ateeq Ahmad; Saifuddin Sheikh; Moghis U. Ahmad; Imran Ahmad
Original assignee: Jina Pharmaceuticals Inc
Current assignee: Jina Pharmaceuticals Inc
Priority date: 2023-09-27
Filing date: 2024-09-27
Publication date: 2025-04-03
Anticipated expiration: 2026-03-27

Abstract

The invention relates to compositions of cabazitaxel and administering compositions of cabazitaxel. Embodiments provide compositions comprising cabazitaxel with at least one lipid and/or guggulsterol, and/or guggulsterol derivatives, and/or sodium cholesteryl sulfate, in tablet or capsule forms, and administering the compositions in a subject.

Description

DESCRIPTION

TITLE OF THE INVENTION: COMPOSITIONS CONTAINING CABAZITAXEL AND LIPIDS FOR ORAL ADMINISTRATION

FIELD OF THE INVENTION

The invention relates to compositions comprising cabazitaxel and lipids. The invention further relates to compositions comprising cabazitaxel, guggulsterol and/or guggulsterol derivatives and/or sodium cholesteryl sulfate. In some embodiments, the invention relates to composition comprising cabazitaxel, lipids including phosphatidylcholine, phosphatidylglycerol. In preferred embodiments, the invention relates to compositions comprising cabazitaxel, phosphatidylcholine, and guggulsterol or guggulsterol derivatives or sodium cholesteryl sulfate. In certain embodiments, the invention also relates to composition comprising cabazitaxel and excipients in a tablet or capsule. The invention further relates administering composition to a mammal subject in the treatment or prevention of diseases. Compositions according to the present invention are suitable for practice on an industrial manufacturing scale, and may be practiced, e.g., as a continuous method.

BACKGROUND OF THE INVENTION

The taxanes have emerged as a major class of chemotherapeutic agents as shown by their extensive use as single agent and in combination with other drugs to treat wide variety of solid malignancies. Cabazitaxel is a novel second generation, semi-synthetic derivative of a natural taxoid. The mechanism of action of cabazitaxel is like that of paclitaxel and docetaxel. It binds the N-terminal amino acids of the P-tubulin subunit and promotes microtubule polymerization and inhibits microtubule cell division, thereby arresting the tumor cell cycle and tumor proliferation. Cabazitaxel is superior to paclitaxel and docetaxel because of its poor affinity to P-glycoprotein due to presence of the extra methyl groups. This enables it to be effective in docetaxel-resistant tumors. Cabazitaxel is marketed as Jevtana® and is approved for patients with hormone- refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen. The individual dosage of cabazitaxel is based on calculation of the Body Surface Area (BSA) and is 25 mg/m² administered as a one-hour intravenous infusion every three weeks in combination with oral prednisone 10 mg.

Jevtana® is supplied as a sterile non-aqueous concentrate for solution for infusion containing cabazitaxel 60 mg/1.5ml polysorbate 80 packaged in a glass vial, and an additional solvent for dilution of the Concentrate. The solvent is a sterile, non-pyrogenic 13% w/w aqueous solution of ethanol. The concentrate and the solvent are intended for the preparation of a premix solution of cabazitaxel at 10 mg/ml prior to dilution with 0.9% saline or 5% dextrose solution in an infusion bag.

The taxanes including cabazitaxel are highly lipophilic and practically insoluble in water. Due to its insolubility, various solubilizers such as polysorbate 80, Cremophore EL, and ethanol were successfully exploited to formulate taxanes for intravenous administration. However, hypersensitivity reactions and infusion related toxicities are associated with the use of Polysorbate 80, Cremophore EL, and ethanol, and to reduce the risk of these side effects, patients are routinely premedicated with corticosteroids prior to the treatment of taxane drugs.

Further, all taxanes are cytotoxic in nature. The main dose-limiting toxicity of cabazitaxel is fatal febrile neutropenia, hence complete blood count should be monitored weekly and prior to each treatment cycle and supplement with G-CSF treatment of required. Other toxicities include nausea and vomiting.

To circumvent the toxic effect of cabazitaxel and the excipients in the current marketed intravenous product, new compositions of cabazitaxel for oral route of administration is warranted.

SUMMARY OF THE INVENTION

This invention provides compositions containing cabazitaxel. In some embodiments, the composition comprises phosphatidylcholine. In some embodiments, the composition further comprises one or more of guggulsterol, guggulsterol derivatives, and/or sodium cholesteryl sulfate. In some preferred embodiments, the composition further comprises other excipients. Certain embodiments comprise a composition comprising cabazitaxel and administering the composition to a subject. In certain embodiments, the subject is a mammal. In preferred embodiments, the subject is human.

In some embodiments, this invention provides compositions comprising cabazitaxel and phosphatidylcholine for oral delivery to a subject. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human. In some embodiments, the composition for oral delivery is in the form of tablet or capsule. In preferred embodiments, the tablets and/or capsules comprise enteric coating.

In certain embodiments compositions of the present invention comprises cabazitaxel and phosphatidylglycerol for oral delivery to a subject. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human. In some embodiments, the composition for oral delivery is in the form of tablet or capsule. In preferred embodiments, the tablets and/or capsules comprise enteric coating.

Provided herein in some embodiments are compositions comprising cabazitaxel and guggulsterol for oral delivery to a subject. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human. In some embodiments, the composition for oral delivery is in the form of tablet or capsule. In preferred embodiments, the tablets and/or capsules comprise enteric coating.

The invention in some embodiments provides compositions comprising cabazitaxel and a guggulsterol derivative for oral delivery to a subject. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human. In some embodiments, oral delivery is in the form of tablet or capsule. In more preferred embodiments, the tablets and/or capsules comprise enteric coating. The invention in some embodiments provides compositions comprising cabazitaxel and sodium cholesteryl sulfate for oral delivery to a subject. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human. In some embodiments, the oral delivery is in the form of tablet or capsule. In more preferred embodiments, the tablets and/or capsules comprise enteric coating.

The invention in some embodiments provides compositions comprising cabazitaxel, phosphatidylcholine, and sodium cholesteryl sulfate for oral delivery to a subject. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human. In some embodiments, the oral delivery is in the form of tablet or capsule. In more preferred embodiments, the tablets and/or capsules comprise enteric coating.

The invention in some embodiments provides compositions comprising cabazitaxel, phosphatidylcholine, and guggulsterol for oral delivery to a subject. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human. In some embodiments, the oral delivery is in the form of tablet or capsule. In more preferred embodiments, the tablets and/or capsules comprise enteric coating.

The invention in some embodiments provides compositions comprising cabazitaxel, phosphatidylcholine, and guggulsterol derivative for oral delivery to a subject. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human. In some embodiments, the oral delivery is in the form of tablet or capsule. In more preferred embodiments, the tablets and/or capsules comprise enteric coating.

In some embodiments, a cabazitaxel composition of present invention is coadministered with other drugs. Drugs that can be co-administered along with cabazitaxel composition include but are not limited to anticancer drugs such as doxorubicin, epirubicin, methotrexate, mitoxantrone, capecitabine, carboplatin, cisplatin, etoposide, 5-flurouracil, cyclophosphamide, bendamustine, daunomycin, bleomycin, gemcitabine, irinotecan, SN-38, mitoxantrone, cytrabine, erlotinib, imatinib, ibrutinib, palbociclib, bortezomib, abiraterone, bicalutamide, flutamide, temozolomide, etc.; antihypertensive agents, such as dihydropyridines, antidepressants, antiallergic agents, etc.; corticosteroids drugs such as prednisone, methylprednisolone, dexamethasone, budesonide, hydrocortisone, etc.; antihistamine drugs such as diphenhydramine, chlorpheniramine, dexchlorpheniramine, cetirizine, levocetrizine, loratadine, desloratadine, etc. drugs for treating acid reflux such as cimetidine, ranitidine, famotidine, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, etc.

The amount of cabazitaxel included in a cabazitaxel composition according to present invention is not limited to any particular amount or percentage (by weight) of the final composition or weight. In some embodiments, the proportion of cabazitaxel is about 1% to about 90% of the total weight, preferably about 2% to about 75% of the total weight, more preferably about 5% to about 50% of the total weight.

The amount of phosphatidylcholine or phosphatidylglycerol included in a cabazitaxel composition according to present invention is not limited to any particular amount or percentage (by weight) of the final composition or weight. In some embodiments, the proportion of phosphatidylcholine is between about 1% to about 90% of the total weight, preferably about 2% to about 80% of the total weight, more preferably about 3% to about 50% of the total weight.

The amount of guggulsterol or guggulsterol derivative or sodium cholesteryl sulfate included in a cabazitaxel composition according to present invention is not limited to any particular amount or percentage (by weight) of the final composition or weight. In some embodiments, the proportion of guggulsterol or guggulsterol derivative or cholesteryl sulfate is about 0.1% to about 90% of the total weight, preferably about 0.1% to about 50% of the total weight, more preferably about 0.1% to about 25% of the total weight.

DEFINITIONS

To facilitate an understanding of the present invention, a number of terms and phrases are defined below:

As used herein, the term “composition” “preparation” or “formulation” refers to the combination of an active agent (e.g., an active pharmaceutical compound) with a carrier, inert or active, excipients, making the composition especially suitable for diagnostic or therapeutic use in vitro, in vivo, or ex vivo. As used herein, the term “active” as used in reference to an agent, composition, or compound, refers to an agent that, upon administration or application, causes a beneficial, desired, or expected result. The administration may be in one or more administrations, applications, dosages and is not intended to be limited to a particular formulation or administration route. The term is not limited to any particular level of activity. For example, a formulation of an active agent need not have the same level of activity as a different formulation of an active agent, so long as the active agent in the formulation is sufficiently active that an effective amount of the active agent can be administered by administration of the formulation of the agent.

The terms “agent” and “compound” are used herein interchangeably to refer to any atom, molecule mixture or more complex composition having an attributed feature. For example, an ‘active agent” or “active compound” refers to any atom, molecule, preparation mixture, etc. that, upon administration or application, causes beneficial, desired, or expected result.

As used herein, the term “administration” or “administering” refers to the act of giving a drug, or active agent, or therapeutic treatment (e.g., composition of the present invention) to a physiological system (e.g., a subject or in vivo, in vitro, or ex vivo cells, tissues, and organs). Exemplary routes of administration to the subject, for example, a mammal can be through mouth (oral), skin (transdermal), eyes (ophthalmic), nose (nasal), and the like. Administration may be in one or more administrations, applications, or dosages, and is not intended to be limited to a particular administration route.

As used herein, the term “co-administration” refers to the administration of at least two agents(s) (e.g., two separate compositions, containing different active agents) or therapies to a subject. In some embodiments, the co-administration of two or more agents or therapies are concurrent. In other embodiments, a first agent/therapy is administered prior to a second agent/therapy. Those of skill in the art understand that the formulations and/or routes of administration of the various agents or therapies used may vary. The appropriate dosage for co-administration can be readily determined by one skilled in the art.

As used herein, the term “excipient” refers to an inactive ingredient (i.e. not pharmaceutically active) added to the preparation of active ingredient The disintegrates, antiadherants, binders, plasticizers, fillers, coatings, lubricants, preservatives, glidants, flavors, colors, sorbents, sweeteners, antioxidants, permeation enhancer, humectant, emulsifying agent, ointment base, acidifying and/or alkalizing and/or buffering agent, gelling and protective agents described herein may be referred to generally as “excipients”.

As used herein, the term “disease” refers to a state, signs, and/or symptoms that are associated with any impairment of the normal state of a living animal or any of its organs or tissues that interrupts or modifies the performance of normal functions and may be a response to environmental factors.

As used herein, the term “treatment” or grammatical equivalents encompasses the improvement and/or reversal of the symptoms of disease (e.g., cancer), or reduction of risk of occurrence of disease. A compound which causes an improvement in any parameter associated with disease when used in the screening methods of the instant invention may thereby be identified as a therapeutic compound. The term “treatment” refers to therapeutic treatment. For example, those who may benefit from treatment with compositions of the present invention include those already with a disease and/or disorder (e.g., cancer, or symptoms or pathologies consistent with cancer).

As used herein, the term “mammal” refers to a group of vertebrate animals that produces or secrete milk from mammary glands to feed their offspring. Examples of mammals herein include humans, dogs, cats, horses, whales, and dolphins.

The use of terms “a” and “an” and “the” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising”, “including”, “having”, and “containing” are to be construed as open-ended terms (i.e., meaning “including but limited to”) unless otherwise noted. The use of any and all examples, or exemplary language (e.g., ‘such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specifications should be constructed as indicating any non-claimed element as essential to the practice of the invention. BRIEF DESCRIPTION OF DRAWING

[FIG. 1] FIG. 1 is a graph showing the blood concentration of cabazitaxel over a period of time in mice (Example 8).

[Fig. 1] FIG. 2 is a graph showing blood concentration of cabazitaxel over a period of time after oral or IV administration in patients (Example 11).

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to a composition comprising cabazitaxel formulation. In some embodiment, the invention comprises administrating a cabazitaxel composition to a subject, e.g., to treat a disease. In some embodiments, the composition comprising cabazitaxel comprises lipids, for example, phosphatidylcholine or phosphatidylglycerol. In certain embodiments, the composition comprising cabazitaxel comprises guggulsterol or a guggulsterol derivative or sodium cholesteryl sulfate. In other embodiments, the composition comprises phosphatidylcholine or phosphatidylglycerol and/or guggulsterol, a guggulsterol derivative, or sodium cholesteryl sulfate. In preferred embodiments the subject is a mammal and in more preferred embodiments, the subject is human.

Embodiments of the invention are described in the Summary, and in this Detailed Description of the Invention. Although the invention has been described in connection with specific embodiments, the invention as claimed should not be unduly limited to such specific embodiments.

Examples of phosphatidylcholine suitable for use in the composition of the present invention include soy phosphatidylcholine (SPC), hydrogenated soy phosphatidylcholine (HSPC), dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC). Examples of phosphatidylglycerol include dimyristoylphosphatidylglycerol (DMPG), distearoylphosphatidylglycerol (DSPG), dipalmitoylphosphatidylglycerol (DMPG). Examples of guggulsterol derivatives suitable for use in the composition of the present invention include guggulsteryl laurate, guggulsteryl myristate, guggulsteryl palmitate, guggulsteryl stearate, guggulsteryl oleate, guggulsteryl linoleate, guggulsteryl linoleneate.

In some embodiments, the composition of the present invention comprises antioxidants and or stabilizers. Examples of antioxidants suitable for use in the composition of present invention include, alpha-tocopherol (Vitamin E), alpha-tocopherol polyethylene glycol succinate (TPGS), ascorbic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), sodium metabisulfite (SMB), propyl gallate, cysteine, citric acid.

The present invention provides compositions comprising cabazitaxel and delivering such compositions to a subject, e.g., a human subject. Any suitable amount of cabazitaxel sufficient to produce a desired effect, e.g., a therapeutic effect, can be used. In preferred embodiments, suitable amounts of cabazitaxel are those amounts that can be suitably incorporated into a tablet, capsule, of the present invention.

In preferred embodiments, amount of cabazitaxel in a tablet or capsule containing cabazitaxel and excipients is in between 10 mg and 2000 mg such as in between 10 mg and 1000 mg or 10 mg and 700 mg. In preferred embodiments, the quantity of cabazitaxel in a tablet or capsule containing cabazitaxel and excipients is in between 10 mg and 500 mg.

In some embodiments, the amount of lipid in a tablet or capsule containing cabazitaxel, lipid, and excipients is in between 10 mg and 5000 mg such as in between 10 mg and 3000 mg or 10 mg and 2000 mg and 10 mg and 1000 mg. In preferred embodiments, the quantity of lipid in a tablet or capsule containing cabazitaxel and excipients is in between 10 mg and 500 mg.

In some embodiments, the amount of guggulsterol or guggulsterol derivative or sodium cholesteryl sulfate in a tablet or capsule containing cabazitaxel, guggulsterol or guggulsterol derivative or sodium cholesteryl sulfate and excipients is in between 1 mg and 500 mg such as in between 1 mg and 300 mg or 1 mg and 200 mg and 1 mg and 100 mg. In preferred embodiments, the quantity of guggulsterol or guggulsterol derivative or sodium cholesteryl sulfate in a tablet or capsule containing cabazitaxel and excipients is between 1 mg and 500 mg. Guggulsterol or guggulsterol derivative in the present invention is in the form of Z- isomer or E-isomer or mixture of Z- and E- isomer. In more preferred embodiments, guggulsterol or guggulsterol derivative is in the form Z-isomer.

In some embodiments, a cabazitaxel composition contains disintegrants. Disintegrants expand and dissolve when wet, causing the tablets to break apart in the digestive tract, releasing the active ingredients for absorption. Examples of disintegrants that find use in the present invention include but are not limited to crosslinked polymers such as crosslinked sodium carboxymethylcellulose (also known as cross carmellose or croscarmellose), crosslinked polyvinylpyrrolidone (also known as cross povidone or crospovidone); starches, clays, cellulose, and sodium starch glycolate.

In some embodiments, a cabazitaxel composition contains binders. A binder holds the ingredients in a tablet together and improves free flow qualities by formulation of granules to desired hardness and size. Examples of binders that find use in the present invention include but are not limited to cellulose, microcrystalline cellulose, methyl cellulose, hydroxypropylcellulose, hydroxypropyl methyl cellulose (HPMC), carboxymethylcellulose, polyvinylpyrrolidone, polypropylene-polyethylene copolymer, magnesium aluminometasilicate (Neuselin US2) sodium lauryl sulfate, glucose, sucrose, lactose, povidone, starch, gelatin, sugar alcohols such as xylitol, sorbitol, maltitol.

In some embodiments, a cabazitaxel composition contains lubricants. Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Examples of lubricants that find use in the present invention include but are not limited to stearic acid, magnesium stearate, calcium stearate, surfactants, polyethylene glycol, vegetable oil.

In some embodiments, a cabazitaxel composition contains absorption enhancers. Enhancer increases the absorption by promoting diffusion or the drug solubility of an active ingredient. Example of absorption enhancers that find use in the present invention include but are not limited to Vitamin E-PEG1000 succinate (TPGS), silicified microcrystalline cellulose (SMCC HD90), polyethylene glycol-polypropylene glycol-polyethylene glycol polymer (Poloxamers), stearic acid, oleic acid, magnesium stearate, calcium stearate, surfactants, propylene glycol, polyethylene glycol, vegetable oil.

In some embodiments, a cabazitaxel composition contains glidant. Glidants are used commonly to improve the flow characteristics of a powder mixture by reducing friction between particles. Examples of glidants that find use in the present invention include but are not limited to colloidal silicone dioxide such as fumed silica, Aerosil®, corn starch, and magnesium carbonate.

In some embodiments, a cabazitaxel composition contains diluents or fillers. Diluents or fillers normally make up the bulk of solid unit dosage forms when the drug itself is inadequate to produce the bulk. Examples of diluents or fillers that find use in the present invention include but are not limited to dextrose, lactose, starches, sorbitol, mannitol, microcrystalline cellulose, dibasic calcium phosphate, calcium carbonate, and magnesium stearate.

In some embodiments, a cabazitaxel composition contains plasticizers. Plasticizers are added to produce elasticity and flexibility to the coating materials in the case of tablets, determine hardness of capsule shell in case of soft gelatin capsule and impart softness. Examples of plasticizers that find use in the present invention include but are not limited to diacetylated monoglycerides, castor oil, polyethylene glycol, polypropylene glycol, triethyl citrate, and triacetin.

In some embodiments, a cabazitaxel composition coating material. The coatings of tablets or capsules protect ingredients from deterioration from moisture present in the air. Examples of coating materials that find use in the present invention include but are not limited to hydroxypropyl methyl cellulose (HMPC), synthetic polymers, polysaccharides, povidone, ethyl cellulose, gelatin, and shellac.

In some embodiments, a cabazitaxel composition further contains enteric coating materials. Enteric coatings control the rate of drug release and determine where the drug will be released in the digestive tract. Examples of enteric coating materials that find use in the present invention include but not limited to hydroxypropyl methylcellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), poly (methacrylic acid-co-methyl methacrylate, cellulose acetate trimellitate (CAT), polyvinyl acetate phthalate (PVAP), esters of aleurtic acid (shellac), ethyl cellulose, Opadri® enteric, methacrylic acid-methyl methacrylate copolymer or Eudragit®, and Acryl-EZE®.

In some embodiments, a cabazitaxel composition contains coloring agents. Colors are added to improve the appearance and identification of a product. Examples of coloring agents that find use in the present invention include but are not limited to FD and C, D, and C dyes and lakes.

Pharmaceutical preparations that find use with the composition of the present invention include but are not limited to tablets, capsules, pills, and suspensions. For the oral mode of administration, preferred forms of formulation include tablets, capsules, lozenges, and powders.

When desired, a composition containing cabazitaxel or cabazitaxel, phosphatidylcholine and or guggulsterol, or a guggulsterol derivative or sodium cholesteryl sulfate formulation can be encapsulated in enteric-coated tablets or enteric coated-capsules to protect it from acids in the stomach. The term “enteric” refers to a small intestine, and enteric coatings prevent release of medication before it reaches the small intestine. Most enteric coatings work by presenting a surface that is stable at acidic pH but breaks down rapidly at higher pH.

In some embodiments, cabazitaxel, guggulsterol, a guggulsterol derivative or sodium cholesteryl sulfate are mixed with one or more excipients such as cross carmellose sodium, polyvinylpyrrolidone, microcrystalline cellulose, and fumed silica (Aerosil) and passed through sieve to form granules. In some embodiments, the granules may further contain phosphatidylcholine. In some embodiments these granules are mixed with lubricants such as steric acid and compressed into tablets. In preferred embodiments, the tablets are seal coated, e.g., with polymers such as hydroxypropyl methylcellulose. In particularly preferred embodiments, the seal coated tablets are further enteric coated with polymers such as methacrylic acid copolymer (Acryl-EZE®), or hydroxypropyl methyl cellulose polymer (Opadry®) enteric).

In some embodiments, cabazitaxel, guggulsterol, a guggulsterol derivative or sodium cholesteryl sulfate are mixed with one or more excipients such as microcrystalline cellulose, and aerosol and passed through sieve to form granules. In some embodiments, the granules further contain phosphatidylcholine. In some embodiments, these granules are mixed with microcrystalline cellulose, croscarmellose sodium, lactose, and poloxamer 188 and compressed into tablets. In preferred embodiments, the tablets are seal coated with polymers such as hydroxypropyl methylcellulose (HPMC), ethyl cellulose, or Opadry®. In particularly preferred embodiments, the seal coated tablets are further enteric coated with polymers such as methacrylic acid copolymer, Acryl-EZE®, functional polymers such as methacrylic acid- methyl methacrylate copolymer, Eudragit®.

In some embodiments, compositions of the present invention include antioxidants. Examples of antioxidants include but are not limited to alpha-tocopherol (Vitamin E), alpha-tocopherol polyethylene glycol succinate (TPGS), ascorbic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), sodium metabisulfite (SMB), propyl gallate, cysteine, citric acid, etc.

In some embodiments, compositions of the present invention contain cabazitaxel about 0.1% to about 90% of the total weight, preferably about 0.5% to about 75% of the total weight, more preferably about 1% to about 50% of the total weight.

In some embodiments, the amount of cabazitaxel in a single tablet or capsule is between 10 mg and 2000 mg, preferably between 10 mg and 1000 mg and more preferable between 10 mg and 500 mg.

In some embodiments, a composition of the present invention contains lipid about 1% to about 90% of the total weight, preferably about 2% to about 80% of the total weight, more preferably about 3% to about 50% of the total weight.

In some embodiments, a composition of the present invention comprises guggulsterol about 0.1% to about 90% of the total weight, preferably about 0.1% to about 75% of the total weight, more preferably about 0.1% to about 50% of the total weight.

In some embodiments, a composition of the present invention comprises a guggulsterol derivative about 0.1% to about 90% of the total weight, preferably about 0.1% to about 75% of the total weight, more preferably about 0.1% to about 50% of the total weight.

In some embodiments, a composition of the present invention comprises sodium cholesteryl sulfate about 0.1% to about 90% of the total weight, preferably about 0.1% to about 75% of the total weight, more preferably about 0.1% to about 50% of the total weight. The composition of the present invention may be administered in any dosage form and via any system that delivers the active compound cabazitaxel in vivo. In some embodiments, a composition of the present invention is delivered in a dosage form selected from tablets, chewable tablets, capsules, soft gelatin capsules. In some embodiments, the composition is formulated into a desired dosage form to achieve immediate release profile, extended-release profile, or delayed release profile in vivo upon administration.

EXPERIMENTAL EXAMPLES

EXAMPLE 1

TPGS 1000 (5.0 g) and hydrogenated soy phosphatidylcholine (HSPC) (15.0 g) were dissolved in alcohol (230 mL). Cabazitaxel (25.0 g) was then mixed and warmed to 30°C- 35°C. Separately Prosolve SMCC HD90 (30.0 g) and Neusilin US2 (10.0 g) were mixed and loaded into Top spray assembly bowl of fluid bed processor. The mixture was granulated using cabazitaxel-HSPC solution with top spray process at inlet temperature of 50°C-60 °C and bed temperature up to 27°C-35 °C. After completion of spray, granules were dried and sifted through #30 mesh sieve and mixed with 330 mesh passed extra granular Neusilin US2 (6.0 g), croscarmellose sodium (12.5 g), sodium lauryl sulfate (2.5 g), polaxamer 188 (12.5 g), hydrophilic fumed silica (Aerosil) (1.2 g) in blender for 5 mins. The blend was lubricated with magnesium stearate for 5 mins before compressing the lubricated blend into tablets.

HPMC 3 CPS (12.0 g) was dispersed in isopropyl alcohol (140 mL) and dichloromethane (90 mL) was added and stirred for 25 minutes. With this mixture, the seal coating was performed in an auto coater at inlet temperature 40°C-45°C and bed temp. 30°C- 35 °C. The tablets were dried for 30 minutes at 35°C-40 °C bed temperature.

Acryl EZE white (23.0 g) was dispersed in purified water and stirred for 30 mins. Using this mixture, enteric coating was done in an auto coater at inlet temperature 45°C-55 °C and bed temp. 35°C-40 °C. The tablets were dried for 20 mins at 35°C-40 °C bed temperature. EXAMPLE 2

TPGS 1000 (5.0 g) and Guggulsterol (15.0 g) were dissolved in alcohol (230 mL). Cabazitaxel (25.0 g) was then mixed and warmed to 30°C-35°C. Separately Prosolve SMCC HD90 (30.0 g) and Neusilin US2 (10.0 g) were mixed and loaded into Top spray assembly bowl of fluid bed processor. The mixture was granulated using cabazitaxel-guggulsterol solution with top spray process at inlet temperature of 50°C-60 °C and bed temperature up to 27°C-35 °C. After completion of spray, granules were dried and sifted through #30 mesh sieve and mixed with 330 mesh passed extra granular Neusilin US2 (6.0 g), croscarmellose sodium (12.5 g), sodium lauryl sulfate (2.5 g), polaxamer 188 (12.5 g), hydrophilic fumed silica (Aerosil) (1.2 g) in blender for 5 mins. The blend was lubricated with magnesium stearate for 5 mins before compressing the lubricated blend into tablets.

Acryl EZE white (23.0 g) was dispersed in purified water and stirred for 30 mins. Using this mixture, enteric coating was done in an auto coater at inlet temperature 45°C-55 °C and bed temp. 35°C-40 °C. The tablets were dried for 20 mins at 35°C-40 °C bed temperature.

EXAMPLE 3

TPGS 1000 (5.0 g) and guggulsteryl laurate (15.0 g) were dissolved in alcohol (230 mL). Cabazitaxel (25.0 g) was then mixed and warmed to 30°C-35°C. Separately, Prosolve SMCC HD90 (30.0 g) and Neusilin US2 (10.0 g) were mixed and loaded into Top spray assembly bowl of fluid bed processor. The mixture was granulated using cabazitaxel-guggul laurate solution with top spray process at inlet temperature of 50°C-60 °C and bed temperature up to 27°C-35 °C. After completion of spray, granules were dried and sifted through #30 mesh sieve and mixed with 330 mesh passed extra granular Neusilin US2 (6.0 g), croscarmellose sodium (12.5 g), sodium lauryl sulfate (2.5 g), poloxamer 188 (12.5 g), hydrophilic fumed silica (Aerosil) (1.2 g) in blender for 5 mins. The blend was lubricated with magnesium stearate for 5 mins before compressing the lubricated blend into tablets.

HPMC 3 CPS (12.0 g) was dispersed in isopropyl alcohol (140 mb) and dichloromethane (90 mL) was added and stirred for 25 minutes. With this mixture, the seal coating was performed in an auto coater at inlet temperature 40°C-45°C and bed temp. 30°C- 35 °C. The tablets were dried for 30 minutes at 35°C-40 °C bed temperature.

EXAMPLE 4

TPGS 1000 (10.0 g) and sodium cholesteryl sulfate (5.0 g) were dissolved in alcohol (470 mL). Hydrogenated soy phosphatidylcholine (HSPC) (25.0 g) was added until it dissolved completely. Cabazitaxel (50.0 g) was then mixed and warmed to 30°C-35°C. Separately, Prosolve SMCC HD90 (60.0 g) and Neusilin US2 (20.0 g) were mixed and loaded into Top spray assembly bowl of fluid bed processor. The mixture was granulated using cabazitaxel-HSPC-sod. Cholesteryl sulfate solution with top spray process at inlet temperature of 50°C-60 °C and bed temperature up to 27°C-35 °C. After completion of spray, granules were dried and sifted through #30 mesh sieve and mixed with 330 mesh passed extra granular Neusilin US2 (13.0 g), croscarmellose sodium (25.0 g), sodium lauryl sulfate (5.0 g), poloxamer 188 (25.0 g), hydrophilic fumed silica (Aerosil) (2.5 g) in blender for 5 mins. The blend was lubricated with magnesium stearate for 5 mins before compressing the lubricated blend into tablets.

HPMC 3 CPS (25.0 g) was dispersed in isopropyl alcohol (280 mL) and dichloromethane (190 mL) was added and stirred for 25 minutes. With this mixture, the seal coating was performed in an auto coater at inlet temperature 40°C-45°C and bed temp. 30°C- 35 °C. The tablets were dried for 30 minutes at 35°C-40 °C bed temperature. Acryl EZE white (45.0 g) was dispersed in purified water and stirred for 30 mins. Using this mixture, enteric coating was done in an auto coater at inlet temperature 45°C-55 °C and bed temp. 35°C-40 °C. The tablets were dried for 20 mins at 35°C-40 °C bed temperature.

EXAMPLE 5

TPGS 1000 (10.0 g) and guggulsterol (5.0 g) were dissolved in alcohol (470 mL). Hydrogenated soy phosphatidylcholine (HSPC) (25.0 g) was added until it dissolved completely. Cabazitaxel (50.0 g) was then mixed and warmed to 30°C-35°C. Separately, Prosolve SMCC HD90 (60.0 g) and Neusilin US2 (20.0 g) were mixed and loaded into Top spray assembly bowl of fluid bed processor. The mixture was granulated using cabazitaxel- HSPC-guggulsterol solution with top spray process at inlet temperature of 50°C-60 °C and bed temperature up to 27°C-35 °C. After completion of spray, granules were dried and sifted through #30 mesh sieve and mixed with 330 mesh passed extra granular Neusilin US2 (13.0 g), croscarmellose sodium (25.0 g), sodium lauryl sulfate (5.0 g), poloxamer 188 (25.0 g), hydrophilic fumed silica (Aerosil) (2.5 g) in blender for 5 mins. The blend was lubricated with magnesium stearate for 5 mins before compressing the lubricated blend into tablets.

HPMC 3 CPS (25.0 g) was dispersed in isopropyl alcohol (280 mL) and dichloromethane (190 mL) was added and stirred for 25 minutes. With this mixture, the seal coating was performed in an auto coater at inlet temperature 40°C-45°C and bed temp. 30°C- 35 °C. The tablets were dried for 30 minutes at 35°C-40 °C bed temperature.

Acryl EZE white (45.0 g) was dispersed in purified water and stirred for 30 mins. Using this mixture, enteric coating was done in an auto coater at inlet temperature 45°C-55 °C and bed temp. 35°C-40 °C. The tablets were dried for 20 mins at 35°C-40 °C bed temperature.

EXAMPLE 6

TPGS 1000 (10.0 g) and guggulsteryl laurate (5.0 g) were dissolved in alcohol (470 mL). Hydrogenated soy phosphatidylcholine (HSPC) (25.0 g) was added until it dissolved completely. Cabazitaxel (50.0 g) was then mixed and warmed to 30°C-35°C. Separately, Prosolve SMCC HD90 (60.0 g) and Neusilin US2 (20.0 g) were mixed and loaded into Top spray assembly bowl of fluid bed processor. The mixture was granulated using cabazitaxel- HSPC-guggul laurate solution with top spray process at inlet temperature of 50°C-60 °C and bed temperature up to 27°C-35 °C. After completion of spray, granules were dried and sifted through #30 mesh sieve and mixed with 330 mesh passed extra granular Neusilin US2 (13.5 g), croscarmellose sodium (25.0 g), sodium lauryl sulfate (5.0 g), poloxamer 188 (25.0 g), hydrophilic fumed silica (Aerosil) (2.5 g) in blender for 5 mins. The blend was lubricated with magnesium stearate for 5 mins before compressing the lubricated blend into tablets.

HPMC 3 CPS 12.50 g) was dispersed in isopropyl alcohol (280 mL) and dichloromethane (190 mL) was added and stirred for 25 minutes. With this mixture, the seal coating was performed in an auto coater at inlet temperature 40°C-45°C and bed temp. 30°C- 35 °C. The tablets were dried for 30 minutes at 35°C-40 °C bed temperature.

Acryl EZE white (22.50 g) was dispersed in purified water and stirred for 30 mins. Using this mixture, enteric coating was done in an auto coater at inlet temperature 45°C-55 °C and bed temp. 35°C-40 °C. The tablets containing 50 mg cabazitaxel per tablet were dried for 20 mins at 35°C-40 °C bed temperature.

EXAMPLE 7

TPGS 1000 (40.0 g) and guggulsteryl laurate (20.0 g) were dissolved in alcohol (1.9 L). Hydrogenated soy phosphatidylcholine (HSPC) (100.0g) was added until it dissolved completely. Cabazitaxel (200.0 g) was then mixed and warmed to 30°C-35°C. Separately, Prosolve SMCC HD90 (240.0 g) and Neusilin US2 (80.0 g) were mixed and loaded into Top spray assembly bowl of fluid bed processor. The mixture was granulated using cabazitaxel- HSPC-guggul laurate solution with top spray process at inlet temperature of 50°C-60 °C and bed temperature up to 27°C-35 °C. After completion of spray, granules were dried and sifted through #30 mesh sieve and mixed with 330 mesh passed extra granular Neusilin US2 (54.0 g), croscarmellose sodium (100.0 g), sodium lauryl sulfate (20.0 g), poloxamer 188 (100.0 g), hydrophilic fumed silica (Aerosil) (10.0 g) in blender for 5 mins. The blend was lubricated with magnesium stearate for 5 mins before compressing the lubricated blend into tablets. HPMC 3 CPS (100.0 g) was dispersed in isopropyl alcohol (1.14 L) and dichloromethane (760 mL) was added and stirred for 25 minutes. With this mixture, the seal coating was performed in an auto coater at inlet temperature 40°C-45°C and bed temp. 30°C- 35 °C. The tablets were dried for 30 minutes at 35°C-40 °C bed temperature.

Acryl EZE white (180.0 g) was dispersed in purified water and stirred for 30 mins. Using this mixture, enteric coating was done in an auto coater at inlet temperature 45°C-55 °C and bed temp. 35°C-40 °C. The tablets containing 50 mg cabazitaxel per tablet were dried for 20 mins at 35°C-40 °C bed temperature.

All publications and patents mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described compositions of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, the invention should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in the relevant arts are intended to be within the scope of the following claims.

EXAMPLE 8

Pharmacokinetics of Cabazitaxel Tablets Following an Oral Administration in ICR (CD- 1) Mice

ICR (CD-I) mice at the age of 5-6 weeks were provided with 19% protein Rodent Diet and water ad libitum. Mice were acclaimed in the facility for at least 7 days before use. There were 4 mice for each post-dose time point and 2 for pre-dose. A total of 5 time points (0.0, 0.5, 1.0, 2.0, 4.0 and 6.0 hr.) were taken at pre-dose and post dose.

Cabazitaxel tablet (50 mg) was weighed, crushed, and pulverized with a glass mortar and pestle until no chunks were visible in the powder. Powder was suspended in purified water at 2 mg cabazitaxel/mL suspension. The suspension was sonicated for 2-3 min to ensure that a homogeneous dosing formulation was achieved before administration. Dosing volume was calculated based on body weight of individual animal at 20 mL/kg.

A single oral dose at 40 mg cabazitaxel/kg body weight was administered orally to each animal using a 22-gauge stainless gavage needle. After dose administration, blood samples were collected by retro-orbital bleeding (under CO2 anesthesia) into pre-labeled, Micro-tainer tubes containing K2EDTA. Each mouse was bled once. Immediately after collection, the blood sample was gently inverted several times to ensure complete mixing with the anticoagulant, and then kept in 2-8 °C refrigerator. Plasma was separated after centrifugation (10 min at 2000xg) and stored in cryo-vials in the freezer (-20°C or colder) before analysis.

The concentration of cabazitaxel in the plasma was quantified (Figure 1) using Cl 8 reverse-phase HPLC with UV detector.

EXAMPLE 9

Subacute Toxicity of Orally Administered Cabazitaxel Tablets in ICR (CD-I) Mice

ICR (CD-I) mice (at the age of 5-6 weeks were provided with 19% protein Rodent Diet and water ad libitum. Mice were acclaimed in the facility for at least 7 days before use. A total of 48 animals (24 male and 24 female) were randomized into 4 groups (Table 1): A (control), B (low-dose), C (mid-dose) and D (high-dose). Mice in the control group were administered with water. Mice in treatment groups were administered with daily dose of cabazitaxel for 5 days. All mice were sacrificed for organ weight and gross pathology on day 29.

Table 1. Dose groups

Cabazitaxel tablets were weighed and crushed into powder before study initiation and stored in 2-8 °C. An aliquot of the powder was weighed each dosing day and suspended at 3 mg cabazitaxel/mL in water as dosing formulation for mice in high-dose group. For mid- and low-dose group, the suspension was diluted into 2 mg/mL and 1 mg/mL, respectively. Cabazitaxel was administered by oral gavage with 22-g stainless steel gavage needle. The mortality, clinical signs, body/organ weight, gross pathology, hematology, and blood chemistry were evaluated. Mortality: There was no mortality in control and low-dose groups throughout the study period. A total of 3 male mice were found dead or moribund on day 8. Two male mice in high- dose group and one male mouse in mid-dose group were found dead. A total of 3 female mice between day 8 and day 11 were also found dead in high dose group.

Clinical Signs: Male mice in mid-dose and high-dose groups showed clinical signs including rough coats, dehydration and hunched posture started from day 5. By day 10, all surviving mice showed no clinical signs. No clinical signs were observed in male mice from low-dose and control groups. Female mice in high-dose group showed clinical signs including rough coats, dehydration and hunched posture started from day 5. By day 10, all surviving mice showed no clinical signs. No clinical signs were observed in female mice from low-dose, mid-dose, and control groups.

Body Weights: For female mice, maximum body weight loss (average 20% loss from day 1) was found in those from high-dose group on day 8. Small body weight loss (7.1% loss from day 1) was also found in those from mid-dose mice on day 5. For male mice, the maximum of 14.8% and 11.5% body weight loss was found in mice from high- and mid-dose groups, respectively. The body weight of all remaining mice treated with cabazitaxel was comparable to those in the control group at the end of study.

Organ Weight: The weights of animal organs including liver, kidneys, heart, lungs, and spleen were recorded upon necropsy on Day 29 and were normalized to 20 g of mouse body weight. All organ weights are comparable to those in the control group.

Gross Pathology: There were no lesions or abnormal changes found in any major organs.

Hematology and Blood Chemistry: There were no abnormal changes found in hematology and blood chemistry of all groups. EXAMPLE 10

Efficacy of Orally Administered Cabazitaxel Tablets on Survival of Mice Bearing P388 Leukemia

The in vivo P388-bearing CD2F1 mouse leukemia model has been used extensively for preclinical evaluation of anti-leukemic activity of test compounds (Dykes, D. J. et al. 2008). In this model, the untreated control mice will only survive for about 9-11 days. Depending on the efficacy on the treatments, the treated mice will survive longer than the control ones. The prolonged survival can be used as an endpoint for the efficacy testing.

CD2F1 mice at the age of 4-6 weeks on study day 1 were provided with 19% protein Rodent Diet and water ad libitum. Mice were acclaimed in the facility for at least 7 days before use.

Mouse leukemia cell line P388 (log phase cells) were transferred from culture flask to a sterile test tube and centrifuged at 200 xg (approx. 1000 rpm), 2-8 °C for 5 min. Cells were washed twice with 10 mL cold PBS and re-suspended in 5 mL cold PBS. Cell counts were counted using a hemocytometer after staining with trypan blue stain. 5xlO⁶/mL cells were suspended in PBS. On Day 0, I xlO⁶ cells/mouse in 0.2 mL were administered intraperitoneally.

Cabazitaxel Tablet (50 mg) was crushed and pulverized with a glass mortar and pestle until no chunks were visible in the powder. Powder was suspended in purified water at 2 mg cabazitaxel /mL. The suspension was sonicated for 2-3 min to ensure that a homogeneous suspension was achieved before dose administration for dose level of 40 mg/kg per day. Dilution was made with purified water to achieve 1 mg cabazitaxel/mL for dose level of 20 mg/kg per day. Dosing volumes were calculated based on body weight of individual animal at 20 mL/kg.

Result: Treatment with oral cabazitaxel at cumulative dose of 120 mg/kg resulted in a significant increase in survival of P388-bearing leukemic mice compared to non-treatment control group (Table 2). Table 2. Summary of Dose Levels, Dosing Schedule, and Median Survival

EXAMPLE 11

Maximum Tolerated Dose (MTD) and Pharmacokinetics of Oral Cabazitaxel Tablet in Patients with Advanced Solid Tumors Who Have Failed Conventional Therapy

An open label, non-randomized, multicentric, dose escalating, single dose study was conducted in patients with advanced solid tumors who had failed conventional therapy. Patients received a single oral dose of cabazitaxel Lipid tablet (50, 100, 200 and 300 mg, corresponding to 1, 2, 4 and 6 tablets, respectively). The tablets were prepared according to Examples 6 and 7. Patients were first enrolled in the lowest dose group followed by a higher dose group. At different time point blood, urine and fecal samples were collected for PK analysis.

Diagnosis and Main Criteria for Inclusion: Patients with histopathologically/cytologically confirmed primary advanced solid tumors like breast cancer, head and neck, lung, melanoma, gastric, colon or prostate for which cabazitaxel monotherapy was a viable treatment option or patients with advanced solid malignancies refractory to conventional treatment and with an ECOG performance status of 0-2 with an adequate bone marrow, renal and hepatic function were included in the study. A total of 15 patients (3 patients in each dose group of 50 mg, 100 mg, 200 mg and 6 patients in dose group of 300 mg) were enrolled.

For pharmacokinetic evaluations, a total of 20 blood samples (each of 05 mL) and 07 urine samples were collected from each patient in each dose groupat the time points specified in the protocol. Fecal samples were collected at pre-dose and all the fecal samples were collected till 24 hours from each patient in each dose group. The pharmacokinetic parameters were calculated for cabazitaxel using non-compartmental model of Phoenix® WinNonlin® Version 8.3 (Certara L.P.).

Plasma: Cmax, AUCO-t, AUCO-oo, Tmax, AUC_%Extrap_obs, Xz, Vd, Cl and tl/2 Urine: Ae0-72h, Rmax, Tmax, R

Fecal: Ae0-24h

The plasma concentration of cabazitaxel - time profiles are shown in Figure 2. The pharmacokinetic parameters for cabazitaxel are summarized in the following tables.

Table 3. Descriptive Statistics of Pharmacokinetics of Cabazitaxel (Plasma)

Table 4. Descriptive Statistics of Pharmacokinetics of Cabazitaxel (Urine)

Table 5. Descriptive Statistics of Pharmacokinetics of Cabazitaxel (Fecal)

The pharmacokinetic profile of cabazitaxel was well characterized in plasma for all dose levels. Non-linear behavior was observed at higher dose levels after 200 mg single dose. After singledose administration, median time to achieve peak plasma concentration of cabazitaxel ranged from 3 to 7 hours with mean terminal half-life ranging from ~ 79 to 203 hours. A minimal amount (i.e. <0.1%) of the administered drug eliminated through urine over 72 hours post single dose. The amount excreted through feces ranged from ~ 4 to 22%.

Most importantly, a single dose of oral cabazitaxel lipid tablet results in an average AUC of 889, 1187 or 1110 ng h/mL at a dose level of 100, 200 or 300 mg, respectively. Meanwhile, the average AUC of 991 ng h/mL can be achieved by intravenously administered cabazitaxel at the recommended dose of 25 mg/m² (Jevtana® Prescribing Information).

Safety variables included adverse events (AEs), clinical laboratory parameters, vital signs, physical examinations. All AEs reported during the study were included in the safety analysis. AEs were classified by system organ class, by preferred term from the MedDRA version 24.0. The MTD for cabazitaxel Lipid tablet was established as 300 mg.

REFERENCES

1. Nightingale, G. and Ryu, J. Drug Forecast (2012), Vol. 37; 8:440-448.

2. Paller, C.J. and Antonarakis, E.S. Drug Des. Devel. Ther. (2011), 5;117-124.

3. Palepu, N. US 2012/0065255 Al.

4. Jevtana® (Cabazitaxel) Injection for Intravenous Use- Prescribing information

5. Mita, A.C., Figlin, R., Mita, M.M. (2012), Clin. Cancer Res. 18(24): 6574-6579. Abidi, A. J. Pharmacology and Pharmcotherapeutics, (2013), 4:230-237. Cal cagno, F., Nguyen, T., Dobi, E., Villanueva, C., Curtit, E., Kim, S., Montcuquet, P., Kleinclauss, F., Pivot, X., Thiery-Vuillemin, A., Clinical Medicine Insights: Oncology (2013), 7: 1-12. Schwartzberg, L.S., Navari, R.M. Adv. Ther. (2018). 35:754-767. Dykes, D.J. and Waud, W.R. Murine L1210 and P388 Leukemias, Tumor Models in Cancer Research (2008), Edited by: B. A. Teicher © Humana Press Inc., Totowa, NJ

Claims

CLAIMS What is claimed is:

1. A composition comprising cabazitaxel and at least one lipid and/or guggulsterol or guggulsterol derivative or sodium cholesteryl sulfate in a seal coated and or enteric coated tablet or capsule.

2. The composition of claim 1, wherein said at least one lipid is selected from the group consisting of soy phosphatidylcholine (SPC), hydrogenated soy phosphatidylcholine (HSPC), dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidylcholine

(DPPC), disteroylphosphatidylglycerol (DSPG), dipalmitoylphosphatidylglycerol (DMPG), cholesterol (Choi), cholesterol sulfate and its salts.

3. The composition of claim 1 wherein, the guggulsterol derivative is selected from a group consisting of guggulsteryl laurate, guggulsteryl myrstate, guggulsteryl palmitate, guggulsteryl stearate, guggulsteryl oleate, guggulsteryl linoleate, and guggulsteryl linolenate.

4. The composition of claim 1 , further contains one or more excipients selected from magnesium aluminometasilicate, tocopherol polyethylene glycol succinate, silicified microcrystalline cellulose, magnesium stearate, cross carmellose sodium, sodium lauryl sulfate, polyethylene glycol-polypropylene glycol-polyethylene glycol polymer, poloxamer 188, hydrophilic fumed silica, aerosol, citric acid.

5. The composition of claim 1, wherein said seal coating comprises one or more polymers selected from hydroxymethyl propyl cellulose, methyl hydroxyethylcellulose, ethyl cellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, povidone, sodium carboxy methylcellulose, acrylate polymer, and polyethylene glycol.

6. The composition of claim 1, wherein said enteric coating comprises one or more polymers selected from hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate, acrylate polymers, and polyvinyl acetate phthalate, methacrylic acid- methyl methacrylate copolymers.

7. The composition of claim 1, wherein the amount of said cabazitaxel in a single tablet or capsule is at least in the range 20 mg to 1000 mg.

8. The composition of claim 1, wherein the amount of said lipid in a single tablet or capsule is at least in the range 10 mg to 1000 mg.

9. The composition of claim 1, wherein the amount of said guggulsterol or guggul derivative is in a single tablet or capsule is at least 2 mg to 500 mg.

10. The composition of claim 1, wherein the amount of said sodium cholesteryl sulfate is in a single tablet or capsule is at least 2 mg to 500 mg.

11. The composition of claim 1 , wherein said composition is a tablet or capsule and said administering comprises oral administration.

12. The composition of claim 1, wherein said composition comprises oral administration in a subject.

13. The composition of claim 12, wherein said subject is a mammal.

14. The composition of claims 12 & 13, wherein the subject is a human.