[go: up one dir, main page]

WO2025137749A1 - Procédé de solubilisation d'olopatadine et son utilisation - Google Patents

Procédé de solubilisation d'olopatadine et son utilisation Download PDF

Info

Publication number
WO2025137749A1
WO2025137749A1 PCT/BR2024/050504 BR2024050504W WO2025137749A1 WO 2025137749 A1 WO2025137749 A1 WO 2025137749A1 BR 2024050504 W BR2024050504 W BR 2024050504W WO 2025137749 A1 WO2025137749 A1 WO 2025137749A1
Authority
WO
WIPO (PCT)
Prior art keywords
olopatadine
fact
solubilization
solvent
added
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/BR2024/050504
Other languages
English (en)
Portuguese (pt)
Inventor
Carolina FALASCHI SAPONI
George SERRATO GUALBERTO
Luiz Felipe DE OLIVEIRA FARIA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eurofarma Laboratorios Ltda
Original Assignee
Eurofarma Laboratorios Ltda
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from BR102023027572-9A external-priority patent/BR102023027572A2/pt
Application filed by Eurofarma Laboratorios Ltda filed Critical Eurofarma Laboratorios Ltda
Publication of WO2025137749A1 publication Critical patent/WO2025137749A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/14—Decongestants or antiallergics

Definitions

  • Figure 8 shows the qualitative evaluation of the crystallization tendency of olopatadine hydrochloride from samples prepared with different pH values and heating time after storage in the refrigerator (2-8 °C) for 7 days.
  • Topical corticosteroids of the present invention are selected from the group comprising flunisolide, fluticasone furoate, mometasone furoate, fluticasone propionate, cortisol, budesonide, beclomethasone dipropionate, triamcinolone acetonide, ciclesonide, their prodrugs, salts, polymorphs and stereoisomers.
  • the topical corticosteroid is fluticasone, as disclosed in document US4335121 , incorporated herein by reference.
  • the excipients are separated into three different groups: the first group comprises the excipients that make up the solvent/co-solvent system, added in step (a) of the process and defined below.
  • the second group of excipients are those that act as solubilization adjuvants, added in step (b) of the process and defined below.
  • the excipients added in step (f), as well as the excipients added after obtaining the aqueous solution that is incorporated into a pharmaceutical composition, defined below are those that will be part of the final product, without the specific function of assisting in the olopatadine solubilization process.
  • Solubilization and recrystallization processes induced by successive heating-cooling cycles can be used to control crystallization parameters, such as morphology, particle size distribution and polymorphism. Smaller crystals are eliminated by heating and the remaining crystals function as nuclei for crystal growth and optimization of the desired parameter. Complete elimination of nuclei is usually obtained at higher temperatures and longer heating times. Thus, the temperature and heating time are also fundamental parameters for the solubilization of a drug.
  • step (a) a solvent and co-solvent system composed of at least two excipients is added, the solvent being water and the co-solvent selected from the group comprising glycerin, propylene glycol, polyethylene glycol, pentylene glycol, ethyl alcohol, propylene carbonate, sorbitol, maltitol or a combination thereof.
  • the solvent:co-solvent ratio is in the range of 1:1 to 1:30.
  • a solvent/co-solvent system composed of water and glycerin in the ratio of 1:16 is added.
  • solubilization adjuvants are added to the solvent/cosolvent system in the commercially available physical state, these adjuvants being selected from the group comprising chelating agents, sweeteners, cosolvents, buffers and solubilization agents.
  • the chelating agent is selected from the group comprising EDTA salts and pentetic acid
  • the sweetener is selected from the group comprising xylitol, maltitol, sorbitol, aspartame, neotame, saccharin, sucralose, acesulfame, glucose, dextrose, polydextrose or a combination thereof
  • the cosolvent is selected from the group comprising polyethylene glycol, sodium chloride, potassium chloride or combinations thereof
  • the solubilizing agent is selected from the group comprising betacyclodextrin, alphacyclodextrin, gammacyclodextrin or their derivatives or a combination thereof
  • the buffer is selected from the group comprising sodium citrate/citric acid, dibasic sodium phosphate/basic sodium phosphate, sodium acetate/acetic acid.
  • the chelating agent is disodium EDTA
  • the sweetener is xylitol
  • the cosolvent is polyethylene glycol
  • the most suitable buffer is composed of sodium citrate/citric acid and the solubilizing agent is betacyclodextrin.
  • step (b) the chelating agent is added in an amount ranging from 0.005% to 0.1% m/v, the sweetener is added in an amount ranging from 0.05% to 10% m/v, the co-solvent is added in an amount ranging from 0.01% to 70% m/v, the solubilizing agent is added in an amount ranging from 0.1% to 25% m/v, and the buffer is added in an amount ranging from 0.1% to 5.0% m/v.
  • chelating agent 0.5% m/v sweetener, 5.0% m/v of co-solvent, 0.6% m/v of solubilizing agent, and 1.5% m/v of buffer are added.
  • heating occurs until reaching a temperature above 50 °C and below 90 °C, preferably above 60 °C and below 90 °C, preferably above 70 °C and below 90 °C, preferably between 80 °C and 90 °C. In embodiments preferred, heating occurs until a temperature between 80 °C and 85 °C is reached. In yet another embodiment, heating in step (c) occurs under mechanical stirring at a speed between 200 and 400 rpm.
  • step (d) olopatadine is added in the form of a salt, keeping the mixture heated.
  • an amount of between 0.1 to 1.5% m/v of olopatadine in its hydrochloride form is added to a solution at a temperature above 50 °C and below 90 °C, preferably above 60 °C and below 90 °C, preferably above 70 °C and below 90 °C, preferably between 80 °C and 90 °C.
  • heating occurs until a temperature between 80 °C and 85 °C is reached.
  • heating occurs under mechanical stirring at a speed between 200 and 400 rpm.
  • 0.665% of olopatadine hydrochloride is added to the solubilizing system in step (d).
  • step (e) after the addition of olopatadine, in step (e), the mixture obtained in step (d) is kept under heating and stirring for a determined period. Specifically, in this step, heating is maintained at a temperature above 50 °C and below 90 °C, preferably above 60 °C and below 90 °C, preferably above 70 °C and below 90 °C, preferably between 80 °C and 90 °C. In preferred embodiments, heating occurs until a temperature between 80 °C and 85 °C is reached, under mechanical stirring at a speed between 200 and 400 rpm, for a period of time ranging from 15 to 85 minutes, preferably 45 minutes. Additionally, in another embodiment of step (e), optionally, purified water can be added to the mixture obtained to maintain the volume of the solution. This step is optional as it will only be necessary if high water loss due to evaporation is observed during heating.
  • olopatadine Over a wide pH range, olopatadine has a chemical structure with two polar centers with opposite charges (zwitterionic form) that, under certain conditions, interact and form an insoluble complex. This situation is also characteristic in the solubilization process, in which if If there is an adequate supply of energy to the process, in the form of heating, solubilization occurs partially, leading to subsequent precipitation of the drug. Although heating can lead to structural changes and consequent degradation of the active ingredient, what the inventors observed here is that the degradation of the olopatadine molecule in the solution also depends on the time of exposure to heating. Thus, the heating time and temperature are decisive in obtaining a stable system without degradation of the drug.
  • suitable system should be understood as one that has all additive materials solubilized, available to interact with the drug, enhancing its solubility in aqueous medium and at the target temperature, specifically, 80 - 85 °C for a period of 45 minutes.
  • the addition of other drugs can be carried out in a secondary stage, involving prior solubilization in a suitable solvent/co-solvent and incorporation into the system after incorporation of olopatadine and/or incorporation directly into the system if it is insoluble in aqueous medium, being dispersed in the final product at room temperature.
  • step (f) the solution is cooled until it reaches a temperature below or equal to 50 °C, for example, between 50 °C and 30 °C, between 50 °C and 40 °C, preferably between 50 °C and 45 °C.
  • cooling can be done by removing the heat source and in industrial reactors, or by circulating ice-cold water. The impact of cooling is not significant for the process as long as it is maintained under constant agitation.
  • viscosity agents selected from the group comprising microcrystalline cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polycarbophil, carboxymethyl cellulose, pectin, gum guar gum, xanthan gum, carrageenan gum, agar gum, tragacanth gum or a combination thereof.
  • two viscosity agents are added: microcrystalline cellulose and methyl cellulose.
  • the viscosity agents are added in an amount ranging from 0.01 to 5.00% m/v, preferably 0.3% m/v. In the system formed by the two preferred agents, the proportion between them is 1:20, 1:15, preferably 1:10.
  • the addition of the viscosity agents occurs under conventional mechanical stirring by a naval propeller with an increase in speed to improve homogenization.
  • step (g) the mixture is left to cool under ambient conditions until it reaches room temperature, for example, a temperature of at most 30 °C; for example, between 20 °C and 30 °C; preferably, between 25 °C and 30 °C.
  • room temperature for example, a temperature of at most 30 °C; for example, between 20 °C and 30 °C; preferably, between 25 °C and 30 °C.
  • the mixture is kept under constant stirring and, at the end, homogenization is carried out under high shear.
  • the olopatadine solubilization process of the present invention comprises the steps of:
  • solubilization adjuvants in the physical state available commercially, these adjuvants being selected from the group comprising chelating agents, sweeteners, co-solvents, buffers and solubilization agents, the chelating agent being disodium EDTA in an amount of 0.025% m/v, the sweetener being xylitol in an amount of 0.5% m/v, the co-solvent being polyethylene glycol in an amount of 5.0% m/v, the solubilization agent being betacyclodextrin in an amount of 0.6% m/v, and the buffer being composed of sodium citrate/citric acid in an amount of 1.5% m/v, respectively;
  • Example 1 Dissolution tests of olopatadine hydrochloride in aqueous solution at a concentration of 0.665% (m/v).
  • Tests 1 to 4 were performed in aqueous solution with the pH value adjusted by adding a few drops of 1 M HCl solution until pH 2.8 was reached. The temperature was maintained at 25 °C in test 1, 40 °C in test 2 and 80 °C in tests 3 and 4 for the subsequent addition of olopatadine hydrochloride. It was found that the higher the temperature of the solution before the addition of olopatadine, the better the dissolution of the drug. However, even under heating to 80 °C and the apparently immediate dissolution of olopatadine, when the sample was kept at room conditions for a period of 24 hours, the inventors were able to observe the presence of crystals of the drug by optical microscopy, as shown in Figure 1.
  • Test 7 was performed under the same conditions as tests 5 and 6, with the difference that there was no pH adjustment. Before the addition of olopatadine, the pH of the solution was adjusted to 9.0 with the addition of Na2PC and NaCI and, after the addition, it equilibrated at around 6.6. It was therefore observed that the The addition of olopatadine promoted a reduction in pH. A sample of the solution was evaluated by microscopy, and a high degree of crystallization was observed, as shown in Figure 2.
  • the crystals precipitated in test 7 were characterized by X-ray diffraction (XRD), which allowed the characterization of the trihydrate zwitterionic form of olopatadine, different from the form A of olopatadine hydrochloride used as the starting material.
  • XRD X-ray diffraction
  • test 10 consists of reproducing test 5 as taught in the prior art, using heating of the solution to 80 °C for subsequent addition of olopatadine. Even after seven days, the presence of crystals was not verified in the sample kept at room conditions, a fact that contradicts what is expected during processes that employ high temperatures for a long time.
  • the steps of the processes employed in these tests are revealed here and comprise the steps of:
  • the olopatadine content was evaluated by high performance liquid chromatography (HPLC), using a method developed by the Owner, after the samples had been stored for 7 days under ambient conditions.
  • HPLC high performance liquid chromatography
  • the method involves filtering the samples and diluting the supernatant in a pH 3 buffer solution.
  • the buffer was prepared with 1 g of sodium lauryl sulfate to 1 L of ultrapurified water and adding phosphoric acid until the pH was corrected to 3.
  • Standard and confirmation solutions were prepared at the same concentration of olopatadine hydrochloride, also using the buffer as a diluent.
  • a Symmetry C18 column (4.6 pm x 150 pm x 5 pm) was used, injection volume of 10 pL, flow rate of 1.2 mL/minute, detection at 237 nm, run of 20 minutes with detection of the olopatadine peak in approximately 7 minutes.
  • the column temperature was 25 °C and the sampler temperature was 20 °C.
  • a gradient mobile phase was used, with phase A being acetonitrile and phase B being a 90:10 mixture of pH 3.0 buffer and acetonitrile. The gradient is described in Table 4.
  • Example 3 Comparison of the solubilization efficiency of the process of the present invention and the process disclosed in example 9 of document US8399508.
  • composition prototype has the following aspects:
  • the rheological system is the same as that reported in document BR 10 20220068550, of the same title as the present invention, the teachings of which are incorporated herein in their entirety.
  • the drug delivery platform via the nasal route has pseudoplastic behavior, obtained by combining several excipients. Methylcellulose was initially chosen, since it has the greatest hydrophobicity and the ability to exhibit thermogelling behavior with increasing temperature (25 to 35 °C), even at low concentrations.
  • Figure 8 presents a proposed flow for the production of the prototype pharmaceutical composition comprising olopatadine hydrochloride and fluticasone propionate.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pulmonology (AREA)
  • Otolaryngology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention, intitulée « Procédé de solubilisation d'olopatadine et son utilisation », concerne un procédé de solubilisation d'olopatadine en milieu aqueux pour l'obtention de compositions aqueuses stables à haute teneur en olopatadine isolée, ou en association avec d'autres agents pharmaceutiques. Plus particulièrement, le procédé de solubilisation permet l'obtention de compositions aqueuses présentant des propriétés appropriées, notamment le pH, pour administration par voie nasale et oculaire, utiles pour le traitement d'affections allergiques.
PCT/BR2024/050504 2023-12-27 2024-11-05 Procédé de solubilisation d'olopatadine et son utilisation Pending WO2025137749A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
BR102023027572-9A BR102023027572A2 (pt) 2023-12-27 Processo de solubilização de olopatadina e seu uso
BR1020230275729 2023-12-27

Publications (1)

Publication Number Publication Date
WO2025137749A1 true WO2025137749A1 (fr) 2025-07-03

Family

ID=96216237

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/BR2024/050504 Pending WO2025137749A1 (fr) 2023-12-27 2024-11-05 Procédé de solubilisation d'olopatadine et son utilisation

Country Status (1)

Country Link
WO (1) WO2025137749A1 (fr)

Citations (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999051273A1 (fr) * 1998-04-07 1999-10-14 Alcon Laboratories, Inc. Compositions ophtalmiques gelifiantes, contenant de la gomme de xanthanne
WO2001054687A1 (fr) * 2000-01-25 2001-08-02 Alcon Universal Ltd. Compositions ophtalmiques anti-allergiques appropriees pour etres utilisees avec des lentilles de contact
WO2008015695A2 (fr) * 2006-05-15 2008-02-07 Sun Pharmaceutical Industries Limited Complexe d'inclusion
US20090312724A1 (en) * 2007-06-28 2009-12-17 Cydex Pharmaceuticals, Inc. Nasal and Ophthalmic Delivery of Aqueous Corticosteroid Solutions
WO2011008923A2 (fr) * 2009-07-17 2011-01-20 Alcon Research, Ltd. Schéma posologique pour l'administration d'olopatadine en pulvérisation nasale à des enfants
WO2012159064A1 (fr) * 2011-05-19 2012-11-22 Alcon Research, Ltd. Composition ophtalmique à concentration élevée en olopatadine
CN102885767A (zh) * 2012-11-02 2013-01-23 江苏吉贝尔药业有限公司 一种新的盐酸奥洛他定滴眼液及其制备方法
US8399508B2 (en) * 2001-06-27 2013-03-19 Alcon Pharmaceuticals Ltd. Olopatadine formulations for topical nasal administration
CN103202833A (zh) * 2012-12-25 2013-07-17 常州市亚邦医药研究所有限公司 一种奥洛他定或其盐的药用组合物及其制备方法
WO2013119974A1 (fr) * 2012-02-10 2013-08-15 Alcon Research, Ltd. Composition pharmaceutique aqueuse à stabilité améliorée
IN2010DE01281A (fr) * 2010-06-02 2013-10-18
IN2011CH04301A (fr) * 2011-12-09 2014-04-25
CN103830219A (zh) * 2012-11-20 2014-06-04 深圳大佛药业有限公司 一种稳定的奥洛他定组合物
JP2014214085A (ja) * 2013-04-22 2014-11-17 ロート製薬株式会社 オロパタジン含有水性組成物
WO2015036902A1 (fr) * 2013-09-13 2015-03-19 Glenmark Pharmaceuticals Ltd Composition pharmaceutique stable à dose fixe comprenant de la mométasone et de l'azélastine
EP3037094A1 (fr) * 2014-12-23 2016-06-29 Poifa Warszawa SA Composition pharmaceutique ophtalmique
CN106256351A (zh) * 2015-06-18 2016-12-28 江苏吉贝尔药业股份有限公司 盐酸奥洛他定凝胶滴眼液及其制备方法
US20170105930A1 (en) * 2015-05-20 2017-04-20 Gavis Pharmaceuticals Aqueous ophthalmic solution of olopatadine
CN107823124A (zh) * 2017-11-09 2018-03-23 广州博济医药生物技术股份有限公司 一种盐酸奥洛他定外用组合物及其乳膏剂
CN109806224A (zh) * 2019-03-15 2019-05-28 江苏长泰药业有限公司 一种奥洛他定组合物及其制备方法
CN112603884A (zh) * 2020-12-24 2021-04-06 苏州工业园区天龙制药有限公司 一种含盐酸奥洛他定的滴眼液及其制备方法
US20230018472A1 (en) * 2019-12-06 2023-01-19 Toko Yakuhin Kogyo Co., Ltd. Rhinenchysis composition containing olopatadine
CN115887367A (zh) * 2022-11-21 2023-04-04 山东诺明康药物研究院有限公司 一种盐酸奥洛他定原位凝胶滴眼液及其制备方法和应用
CN114099505B (zh) * 2021-12-07 2023-10-27 湖北远大天天明制药有限公司 一种眼用组合物及其制备方法与应用

Patent Citations (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999051273A1 (fr) * 1998-04-07 1999-10-14 Alcon Laboratories, Inc. Compositions ophtalmiques gelifiantes, contenant de la gomme de xanthanne
WO2001054687A1 (fr) * 2000-01-25 2001-08-02 Alcon Universal Ltd. Compositions ophtalmiques anti-allergiques appropriees pour etres utilisees avec des lentilles de contact
US8399508B2 (en) * 2001-06-27 2013-03-19 Alcon Pharmaceuticals Ltd. Olopatadine formulations for topical nasal administration
WO2008015695A2 (fr) * 2006-05-15 2008-02-07 Sun Pharmaceutical Industries Limited Complexe d'inclusion
US20090312724A1 (en) * 2007-06-28 2009-12-17 Cydex Pharmaceuticals, Inc. Nasal and Ophthalmic Delivery of Aqueous Corticosteroid Solutions
WO2011008923A2 (fr) * 2009-07-17 2011-01-20 Alcon Research, Ltd. Schéma posologique pour l'administration d'olopatadine en pulvérisation nasale à des enfants
IN2010DE01281A (fr) * 2010-06-02 2013-10-18
WO2012159064A1 (fr) * 2011-05-19 2012-11-22 Alcon Research, Ltd. Composition ophtalmique à concentration élevée en olopatadine
IN2011CH04301A (fr) * 2011-12-09 2014-04-25
WO2013119974A1 (fr) * 2012-02-10 2013-08-15 Alcon Research, Ltd. Composition pharmaceutique aqueuse à stabilité améliorée
CN102885767A (zh) * 2012-11-02 2013-01-23 江苏吉贝尔药业有限公司 一种新的盐酸奥洛他定滴眼液及其制备方法
CN103830219A (zh) * 2012-11-20 2014-06-04 深圳大佛药业有限公司 一种稳定的奥洛他定组合物
CN103202833A (zh) * 2012-12-25 2013-07-17 常州市亚邦医药研究所有限公司 一种奥洛他定或其盐的药用组合物及其制备方法
JP2014214085A (ja) * 2013-04-22 2014-11-17 ロート製薬株式会社 オロパタジン含有水性組成物
WO2015036902A1 (fr) * 2013-09-13 2015-03-19 Glenmark Pharmaceuticals Ltd Composition pharmaceutique stable à dose fixe comprenant de la mométasone et de l'azélastine
EP3037094A1 (fr) * 2014-12-23 2016-06-29 Poifa Warszawa SA Composition pharmaceutique ophtalmique
US20170105930A1 (en) * 2015-05-20 2017-04-20 Gavis Pharmaceuticals Aqueous ophthalmic solution of olopatadine
CN106256351A (zh) * 2015-06-18 2016-12-28 江苏吉贝尔药业股份有限公司 盐酸奥洛他定凝胶滴眼液及其制备方法
CN107823124A (zh) * 2017-11-09 2018-03-23 广州博济医药生物技术股份有限公司 一种盐酸奥洛他定外用组合物及其乳膏剂
CN109806224A (zh) * 2019-03-15 2019-05-28 江苏长泰药业有限公司 一种奥洛他定组合物及其制备方法
US20230018472A1 (en) * 2019-12-06 2023-01-19 Toko Yakuhin Kogyo Co., Ltd. Rhinenchysis composition containing olopatadine
CN112603884A (zh) * 2020-12-24 2021-04-06 苏州工业园区天龙制药有限公司 一种含盐酸奥洛他定的滴眼液及其制备方法
CN114099505B (zh) * 2021-12-07 2023-10-27 湖北远大天天明制药有限公司 一种眼用组合物及其制备方法与应用
CN115887367A (zh) * 2022-11-21 2023-04-04 山东诺明康药物研究院有限公司 一种盐酸奥洛他定原位凝胶滴眼液及其制备方法和应用

Similar Documents

Publication Publication Date Title
JP6487452B2 (ja) ブリンゾラミドを含む医薬組成物
BRPI0618661A2 (pt) composições de inibidores de lipoxigenase
CN106459137A (zh) 用于治疗眼部病症的膜附着性自组装体系
US12440470B2 (en) Liquid tasimelteon formulations and methods of use thereof
JP7494230B2 (ja) 無菌眼用水性プロピオン酸フルチカゾンａ型ナノ結晶懸濁液の調製方法
WO2025137749A1 (fr) Procédé de solubilisation d'olopatadine et son utilisation
BR102023027572A2 (pt) Processo de solubilização de olopatadina e seu uso
JP2006519811A (ja) ５−メチル−２−（２’−クロロ−６’−フルオロアニリノ）フェニル酢酸を含む医薬組成物
ES2858573T3 (es) Composiciones acuosas que comprenden bilastina y mometasona
CA3160578A1 (fr) Composition medicale contenant un compose steroidique et de l'olopatadine
US20170157108A1 (en) Liquid formulation comprising montelukast or pharmaceutically acceptable salt thereof and method for preparing same
CN106714803B (zh) 眼用混悬液制剂
JP2024528195A (ja) ブラジキニンｂ２受容体拮抗薬を経口投与するための脂質ベースの組成物
EP2827838B1 (fr) Composition pharmaceutique ophtalmique contenant un inhibiteur d'anhydrase carbonique et procédé pour sa préparation
KR20220163961A (ko) 고체 깊은 공융 용매 제형 플랫폼
CN114980881A (zh) 包含奥洛他定的鼻用组合物
CN111989102A (zh) 水性混悬液型药物制剂
WO2023193074A1 (fr) Utilisation de la prednisolone ou de ses sels pharmaceutiques actifs dans une composition pharmaceutique, composition pharmaceutique, son procédé de préparation et son utilisation
HK40088043B (en) Lipid-based composition for oral administration of bradykinin b2-receptor antagonists
HK40088043A (en) Lipid-based composition for oral administration of bradykinin b2-receptor antagonists
CN111989101A (zh) 具有受控溶出的水性悬浮液型药物制剂
AU2023221541A2 (en) Bilastine composition for once-daily parenteral administration
HK1234413A1 (en) Membrane-adherent self-assembled systems for treatment of ocular disorders
HK1234413B (zh) 用於治療眼部病症的膜附著性自組裝體系
HK1233540A1 (en) Ophthalmic suspension formulation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24909249

Country of ref document: EP

Kind code of ref document: A1