WO2022075760A1 - Composition pharmaceutique comprenant de l'aprémilast - Google Patents
Composition pharmaceutique comprenant de l'aprémilast Download PDFInfo
- Publication number
- WO2022075760A1 WO2022075760A1 PCT/KR2021/013750 KR2021013750W WO2022075760A1 WO 2022075760 A1 WO2022075760 A1 WO 2022075760A1 KR 2021013750 W KR2021013750 W KR 2021013750W WO 2022075760 A1 WO2022075760 A1 WO 2022075760A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- apremilast
- acid
- tablet
- oral pharmaceutical
- Prior art date
Links
Images
Classifications
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
-
- 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
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates to a pharmaceutical composition
- a pharmaceutical composition comprising apremilast or a pharmaceutically acceptable salt thereof. More specifically, by using a specific excipient, it is possible to provide a pharmaceutical composition with significantly improved disintegration and dissolution delay over time.
- Apremilast increases the intracellular level of cAMP by inhibiting the intracellular enzyme PDE4 (Phosphodiesterase-4), thereby increasing TNF- ⁇ , IL- 23 and modulates the inflammatory response by modulating other inflammatory mediators.
- PDE4 Phosphodiesterase-4
- apremilast when administered orally, apremilast has a bioavailability of about 73% and is a poorly soluble substance that is difficult to dissolve in water belonging to BCS class IV. Disintegration time and dissolution rate may be lowered due to cross-linking, etc., so the stability of the formulation should not change during distribution and storage so that it exerts a certain medicinal effect. For this purpose, it is necessary to select the crystalline form of apremilast, the main ingredient, or to reduce the particle size or to mix with appropriate additives.
- the dosage form of Otezla tablet currently on sale is disclosed in Korean Patent Registration No. 2035362 and Korean Patent Application No. 10-2019-7030218, which is a divisional application thereof. Due to the various characteristics of the active drug substance to be formulated, the dosage form is typically Disclosed are formulations using 50-65% by weight of lactose hydrate of the total composition as filler, stating that pharmaceutical excipients uniquely adapted to the active drug substance are required to achieve advantageous physical and pharmaceutical properties.
- Patent Document 1 Registered Patent Publication No. 10-0997001
- Patent Document 2 Registered Patent Publication No. 10-2035362
- Patent Document 3 Patent Publication No. 10-2019-0120418
- the present inventors studied a method for improving the disintegration and dissolution delay of current commercial products containing apremilast as a main component when exposed to temperature and humidity.
- the surface and internal matrix structure of the tablet cross-link or harden more densely.
- the ability to dissolve the main ingredient is reduced due to the decrease in the ability to penetrate into the tablet, the swelling of the tablet, the decrease in wetting power, and as a result, the disintegration time is delayed.
- the present invention aims to provide an oral formulation containing apremilast as a main component, and contains apremilast, and among low-substituted hydroxypropyl cellulose and mannitol, sorbitol, and pregelatinized starch. It is a specific problem to provide an oral formulation using one or more selected excipients.
- the present invention discloses the following means.
- apremilast or a pharmaceutically acceptable salt thereof low-substituted hydroxypropyl cellulose; And it provides an oral pharmaceutical composition comprising one or more excipients selected from mannitol, sorbitol, and pregelatinized starch.
- the low-substituted hydroxypropyl cellulose may be 3% to 40% of the total weight of the total composition.
- the mannitol may be 10% to 50% of the total weight of the total composition.
- the sorbitol may be 10% to 50% of the total weight of the total composition.
- the pregelatinized starch may be 5% to 50% of the total weight of the total composition.
- the oral pharmaceutical composition may further include one or more additives selected from a filler, a disintegrant, a lubricant, an adsorbent, and a coating agent.
- the oral pharmaceutical composition of the present invention may be a tablet used for preventing and treating diseases that are improved by inhibiting TNF- ⁇ production or inhibiting PDE4.
- the oral pharmaceutical composition comprising apremilast or a pharmaceutically acceptable salt thereof of the present invention does not delay disintegration and dissolution even when exposed to high temperature and humidity as time elapses after tablet preparation by using a specific excipient. It has the characteristic of solving the problems of commercial products.
- 1 is a graph showing the results of the initial dissolution test of the stability test.
- 2 is a graph showing the results of the dissolution test after 8 weeks of storage in the stability test.
- the present invention relates to an oral pharmaceutical composition
- an oral pharmaceutical composition comprising apremilast or a pharmaceutically acceptable salt thereof as a main component.
- the apremilast is (+)-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-4-acetylaminoisoindoline-1 having the following structure ,3-dione is a known substance and can be prepared according to a known method.
- the pharmaceutically acceptable salts include conventional acid addition salts, for example, maleic acid, fumaric acid, benzoic acid, ascorbic acid, succinic acid, acetic acid, formic acid, oxalic acid, propionic acid, tartaric acid, salicylic acid, citric acid, gluconic acid, lactic acid, mandelic acid.
- the salt may be in the form of a conventional metal salt, for example, an alkali metal salt such as lithium, sodium, or potassium; alkaline earth metal salts such as calcium or magnesium salts; or chromium salts.
- an excipient is further included in addition to the main ingredient, apremilast.
- Such an excipient may be a material selected from at least one selected from mannitol, sorbitol, and pregelatinized starch along with low-substituted hydroxypropyl cellulose.
- the low-substituted hydroxypropyl cellulose is 3% to 40% of the total weight of the composition
- the mannitol is 10% to 50% of the total weight of the composition
- the sorbitol is 10% to 50% of the total weight of the composition
- the pregelatinized starch may be included in an amount of 5% to 50% of the total weight of the total composition.
- the pharmaceutical composition of the present invention may be prepared according to a commonly used formulation method by adding a pharmaceutically acceptable additive.
- additives may include excipients, disintegrants, lubricants, glidants, coating agents, and the like.
- the excipient may include microcrystalline cellulose and the like, and may be included in an amount of 10% to 50% of the total weight of the total composition.
- the disintegrant may include corn starch, crospovidone, low-substituted hydroxypropyl cellulose (L-HPC), croscarmellose sodium, and the like. Preferably, it is croscarmellose sodium, and may be included in 1% to 5% of the total weight of the total composition.
- the lubricant may include talc, polyethylene glycol, calcium behenate, calcium stearate, hydrogenated castor oil, magnesium stearate, and the like. Preferably it is magnesium stearate, and may be included in 0.5% to 3% of the total weight of the total composition.
- Colloidal silicon dioxide may be used as the fluidizing agent, and may be included in 1% to 5% of the total weight of the total composition.
- the coating agent may include hypromellose, polyvinyl alcohol, polyethylene glycol, talc, and the like. Preferably, it is a combination of polyvinyl alcohol, polyethylene glycol, and talc, and may be included in an amount of 30-50 wt%, 10-30 wt%, and 10-20 wt%, respectively, of the total coating agent.
- the coating agent may further include a colorant, and may include, but is not limited to, titanium dioxide and iron oxide. Suitable colorants may be mixed to obtain the desired color of the coating formulation.
- a more preferred embodiment of the present invention provides an excipient other than apremilast, which is the main component, of a three-component system of low-substituted hydroxypropyl cellulose, mannitol, and pregelatinized starch, or low-substituted hydroxypropyl cellulose, sorbitol, and pregelatinized starch. It may be a three-component system. By substituting the above three-component system instead of using lactose, the effect on disintegration and dissolution rate over time is minimized.
- the oral pharmaceutical composition of the present invention is a solid preparation for oral administration, tablets, granules, capsules, liquid preparations for oral administration, and may be in the form of suspensions, internal solutions, emulsions, syrups, and the like. Preferably, it may be in the form of a tablet.
- the oral pharmaceutical composition of the present invention may be prepared by a method well known in the pharmaceutical field. Specifically, it may be prepared by a direct tableting method, a dry granulation method, or a wet granulation method.
- the preferred dosage of the oral pharmaceutical composition of the present invention varies depending on the patient's condition and weight, the degree of disease, drug form, administration route and period, but may be appropriately selected by those skilled in the art. However, for desirable effects, the oral pharmaceutical composition of the present invention may be administered in an amount of 10 to 100 mg per day. Administration may be administered once a day, or may be administered in several divided doses. The above dosage does not limit the scope of the present invention in any way.
- the oral pharmaceutical composition of the present invention is useful for preventing and treating diseases that are improved by inhibiting TNF- ⁇ production or inhibiting PDE4.
- diseases include depression, asthma, allergic rhinitis, inflammation, chronic lung inflammatory disease, inflammatory skin disease, psoriasis, psoriatic arthritis, atopic dermatitis, contact dermatitis, rheumatoid arthritis, arthritis-related disorders, osteoarthritis, systemic lupus erythematosus , chronic obstructive pulmonary disease, chronic pulmonary inflammatory disease, inflammatory bowel disease, Crohn's disease, Behcet's disease, ulcerative colitis, colitis, chronic obstructive pulmonary disease, myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), etc.
- MDS myelodysplastic syndrome
- MPD myeloproliferative disease
- the present invention is not limited thereto.
- the present invention inhibits TNF- ⁇ production comprising administering the oral pharmaceutical composition according to the above in a therapeutically effective amount to mammals, including humans, or by inhibiting PDE4 to prevent disease or It relates to treatment methods.
- the present invention relates to the use of an oral pharmaceutical composition for preventing or treating a disease that is improved by inhibiting TNF- ⁇ production or inhibiting PDE4.
- tablets containing apremilast as a main component were prepared. Specifically, a tablet was prepared by mixing a component other than magnesium stearate among the following components, mixing magnesium stearate with the mixture, and then compressing it into a single-layer tablet using a tablet press.
- Example 1 Example 2
- Example 3 Example 4
- Example 5 Raw material name mg/tablet % mg/tablet % mg/tablet % mg/tablet % mg/tablet % apremilast 30 10.0% 30 10.0% 30 10.0% 30 10.0% 30 10.0% 30 10.0% mannitol 150 50.0% 30 10.0% - - - - - - sorbitol - - - 150 50.0% 30 10.0% - - Low-substituted hydroxypropyl cellulose 39 13.0% 93.9 31.3% 39 13.0% 93.9 31.3% 33.9 11.3% pregelatinized starch - - - - - - - - 150 50.0% Microcrystalline Cellulose 58.5 19.5% 123.6 41.2% 58.5 19.5% 123.6 41.2% 63.6 21.2% Croscarmellose Sodium 9 3.0% 9 3.0% 9 3.0% 9 3.0% 9 3.0% 9 3.0% colloidal silicon dioxide 9 3.0% 9 3.0% 9 3.0% 9 3.0% 9 3.0% 9 3.0% magnesium
- tablets containing apremilast as a main component were prepared. Specifically, a tablet was prepared by mixing a component other than magnesium stearate among the following components, mixing magnesium stearate with the mixture, and then compressing it into a single-layer tablet using a tablet press.
- Example 6 Example 7
- Example 8 Example 9
- Example 10 Raw material name mg/tablet % mg/tablet % mg/tablet % mg/tablet % mg/tablet % apremilast 30 10.0% 30 10.0% 30 10.0% 30 10.0% 30 10.0% 30 10.0% 30 10.0% 30 10.0% 30 10.0% mannitol - - 90 30.0% 90 30.0% - - - - sorbitol - - - - - 90 30.0% 90 30.0% Low-substituted hydroxypropyl cellulose 108.9 36.3% 33.9 11.3% 10 3.3% 33.9 11.3% 10 3.3% pregelatinized starch 15 5.0% 35.1 11.7% 35.1 11.7% 35.1 11.7% 35.1 11.7% Microcrystalline Cellulose 123.6 41.2% 88.5 29.5% 112.4 37.5% 88.5 29.5% 120.65 40.2% Croscarmellose Sodium 9 3.0% 9 3.0% 9 3.0% 9 3.0% 9 3.0% 9 3.0% colloidal silicon dioxide 9 3.0% 9 3.0%
- tablets containing apremilast as a main component were prepared. Specifically, among the following components, components except for a part of magnesium stearate are mixed, the mixture is dry granulated, the dry granulated material is sized, and the magnesium stearate remaining in the sized product is mixed and lubricated, followed by a single-layer tablet using a tableting machine Tablets were prepared by tableting with
- tablets containing apremilast as a main component were prepared. Specifically, a tablet was prepared by mixing a component other than magnesium stearate among the following components, mixing magnesium stearate with the mixture, and then compressing it into a single-layer tablet using a tableting machine.
- the tablets prepared in Examples 1 to 10, the tablets prepared in Comparative Examples 1 to 6, and the commercially available Otezla tablets 30mg and 20mg were used as Comparative Examples 7 and 8, respectively, and packaged in PTP, and then stored at 60° C. and at the beginning of the stability test.
- the disintegration time after 8 weeks was compared. Specifically, the disintegration time evaluation using a disintegration tester was performed according to the disintegration test method of the Korean Pharmacopoeia general test method. The time at which more than 80% of the disintegration was measured as the disintegration time, and the results are shown in Tables 6 and 7.
- Example 1 Example 2
- Example 3 Example 4
- Example 5 Example 6
- Example 7 Example 8
- Example 9 Example 10
- Example 5 Early 52'' 59'' 57'' 53'' 1'02'' 57'' 51'' 56'' 52'' 56'' after 8 weeks 5'22'' 5'39'' 5'27'' 4'58'' 5'09'' 4'57'' 4'39'' 4'46'' 4'41'' 4'48'' division Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Early 1'12'' 1'09'' 1'02'' 57'' 59' 56'' 1'19'' 1'03' after 8 weeks 12'28'' 12' 12'16'' 11'12''' 8'07'' 10'29'' 8'13'' 13'15'' 10'03'''
- the tablets prepared in Examples 1 to 10, the tablets prepared in Comparative Examples 1 to 6, and the commercially available Otezla tablets 30mg and 20mg were used as Comparative Examples 7 and 8, respectively, and packaged in PTP, and then stored at 60° C. and at the beginning of the stability test.
- the dissolution test was compared after 8 weeks. Specifically, the test was performed at 50 rpm for 60 minutes using 900 mL of 37 °C water test solution containing 0.3% SLS, and samples were collected at 15 minutes, 30 minutes, and 60 minutes and analyzed by HPLC. The results are shown in Tables 8 and 9 and FIGS. 1 and 2 .
- Example 1 0 39.6 51.8 62.5
- Example 2 0 42.9 54.1 64.1
- Example 3 0 40.9 52.7 62.9
- Example 4 0 43.5 56.7 64.0
- Example 5 0 43.9 57.5 64.0
- Example 6 0 45.2 58.6 65.2
- Example 7 0 48.9 62.1 70.9
- Example 8 0 44.8 58.4 66.3
- Example 9 0 48.5 62.4 69.1
- Example 10 0 44.5 57.9 66.5 Comparative Example 1 0 16.8 34.7 48.3 Comparative Example 2 0 18.5 36.7 52.4 Comparative Example 3 0 17.5 36.9 53.8 Comparative Example 4 0 22.3 42.9 56.8 Comparative Example 5 0 18.9 39.8 55.2 Comparative Example 6 0 21.4 42.1 55.3 Comparative Example 7 0 17.4 35.4 50.3 Comparative Example 8 0 21.5 40.2 52.9
- the oral pharmaceutical composition comprising apremilast or a pharmaceutically acceptable salt thereof of the present invention is used for the treatment of diseases related to inflammatory reactions, in particular, the prevention of psoriasis, psoriatic arthritis, dermatitis, sarcoidosis, and Behcet's disease. Or, since it exhibits a therapeutic effect, it can be used as a drug in the pharmaceutical industry and medical field.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne une composition pharmaceutique orale comprenant de l'aprémilast ou un sel pharmaceutiquement acceptable correspondant et peut fournir une composition pharmaceutique orale présentant une biodisponibilité améliorée à l'aide d'un excipient spécifique pour résoudre, à la différence des formulations sur le marché, des retards dans le temps de désintégration et le taux de dissolution qui se produisent en raison du durcissement et de la réticulation se produisant au cours du temps lorsqu'elle est soumise à l'action de la température et de l'humidité.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2020-0130621 | 2020-10-08 | ||
KR1020200130621A KR20220047105A (ko) | 2020-10-08 | 2020-10-08 | 아프레밀라스트를 함유하는 약학 조성물 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022075760A1 true WO2022075760A1 (fr) | 2022-04-14 |
Family
ID=81126995
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2021/013750 WO2022075760A1 (fr) | 2020-10-08 | 2021-10-07 | Composition pharmaceutique comprenant de l'aprémilast |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR20220047105A (fr) |
WO (1) | WO2022075760A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114948888A (zh) * | 2022-05-30 | 2022-08-30 | 江苏知原药业股份有限公司 | 一种阿普米司特片的制备方法和由该方法制备的阿普米司特片 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104523574A (zh) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | 一种阿普斯特固体分散体及其制备方法 |
CN107115310A (zh) * | 2017-04-12 | 2017-09-01 | 广州艾格生物科技有限公司 | 一种阿普斯特口服固体制剂及其制备方法 |
KR20180097623A (ko) * | 2015-12-24 | 2018-08-31 | 지앙수 헨그루이 메디슨 컴퍼니 리미티드 | 아프레밀라스트 서방형 제제 |
WO2019073477A1 (fr) * | 2017-10-10 | 2019-04-18 | Mankind Pharma Ltd. | Composition pharmaceutique d'aprémilast à libération prolongée |
US20200261416A1 (en) * | 2017-10-13 | 2020-08-20 | Unichem Laboratories Ltd | Pharmaceutical compositions of apremilast |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6962940B2 (en) | 2002-03-20 | 2005-11-08 | Celgene Corporation | (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof |
CN104136003A (zh) | 2011-12-27 | 2014-11-05 | 细胞基因公司 | (+)-2-[1-(3-乙氧基-4-甲氧基-苯基)-2-甲磺酰基-乙基]-4-乙酰氨基异二氢吲哚-1,3-二酮的制剂 |
-
2020
- 2020-10-08 KR KR1020200130621A patent/KR20220047105A/ko active Search and Examination
-
2021
- 2021-10-07 WO PCT/KR2021/013750 patent/WO2022075760A1/fr active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104523574A (zh) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | 一种阿普斯特固体分散体及其制备方法 |
KR20180097623A (ko) * | 2015-12-24 | 2018-08-31 | 지앙수 헨그루이 메디슨 컴퍼니 리미티드 | 아프레밀라스트 서방형 제제 |
CN107115310A (zh) * | 2017-04-12 | 2017-09-01 | 广州艾格生物科技有限公司 | 一种阿普斯特口服固体制剂及其制备方法 |
WO2019073477A1 (fr) * | 2017-10-10 | 2019-04-18 | Mankind Pharma Ltd. | Composition pharmaceutique d'aprémilast à libération prolongée |
US20200261416A1 (en) * | 2017-10-13 | 2020-08-20 | Unichem Laboratories Ltd | Pharmaceutical compositions of apremilast |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114948888A (zh) * | 2022-05-30 | 2022-08-30 | 江苏知原药业股份有限公司 | 一种阿普米司特片的制备方法和由该方法制备的阿普米司特片 |
Also Published As
Publication number | Publication date |
---|---|
KR20220047105A (ko) | 2022-04-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20220168255A1 (en) | Pharmaceutical composition containing dimethyl fumarate for administration at a low daily dose | |
KR100866720B1 (ko) | 항치매 약물의 안정화 방법 | |
CA2569683C (fr) | Compositions pharmaceutiques antimicrobiennes orales | |
NO20121414A1 (no) | Farmasoytiske sammensetninger omfattende hydromorfon og nalokson | |
WO2019108021A2 (fr) | Composition pharmaceutique comprenant du tofacitinib | |
EA031395B1 (ru) | Состав с модифицированной кинетикой высвобождения | |
WO2022075760A1 (fr) | Composition pharmaceutique comprenant de l'aprémilast | |
US20230018600A1 (en) | Controlled release formulations comprising drotaverine or salt thereof | |
WO2019066555A1 (fr) | Composition pharmaceutique comprenant un comprimé sphéroïdal à unités multiples contenant de l'ésoméprazole et un sel de qualité pharmaceutique de celui-ci, et procédé de préparation de la composition pharmaceutique | |
WO2012148181A2 (fr) | Composition à libération contrôlée de médicaments | |
WO2016013795A1 (fr) | Preparation a liberation prolongee | |
WO2021118026A1 (fr) | Formulation de comprimé à noyau contenant un inhibiteur de la pompe à protons et du mosapride | |
WO2020171404A1 (fr) | Composition pharmaceutique | |
WO2018143511A1 (fr) | Comprimé oral triple à libération prolongée contenant de la prégabaline | |
WO2019160243A1 (fr) | Composition pharmaceutique à libération prolongée contenant du lacosamide | |
WO2012077968A2 (fr) | Formulation complexe contenant de l'hydrochlorure de lercanidipine et du valsartan et son procédé de préparation | |
Kauss et al. | Development of rectodispersible tablets and granulate capsules for the treatment of serious neonatal sepsis in developing countries | |
WO2013032206A1 (fr) | Composition orale à libération prolongée contenant du chlorhydrate d'itopride, et procédé de préparation associé | |
US20100272794A1 (en) | Pharmaceutical composition of memantine | |
WO2017116031A1 (fr) | Composition pharmaceutique contenant du géfitinib, pouvant être administrée à des patients présentant une intolérance au lactose, et présentant une commodité de dosage améliorée | |
WO2021107370A1 (fr) | Préparation de comprimé à cœur comprenant un inhibiteur de la pompe à protons et mosapride | |
WO2015163689A1 (fr) | Composition contenant le principe actif (i) et procédé pour préparer celle-ci | |
WO2019199134A1 (fr) | Composition pharmaceutique comprenant du lénalidomide | |
WO2016195377A2 (fr) | Composition de préparation solide contenant du pranlukast à biodisponibilité améliorée et procédé pour sa préparation | |
WO2019199132A1 (fr) | Composition de comprimé oral de lénalidomide dans diverses quantités |
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: 21878010 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21878010 Country of ref document: EP Kind code of ref document: A1 |