WO2021112548A1 - Composition pharmaceutique - Google Patents

Composition pharmaceutique Download PDF

Info

Publication number
WO2021112548A1
WO2021112548A1 PCT/KR2020/017442 KR2020017442W WO2021112548A1 WO 2021112548 A1 WO2021112548 A1 WO 2021112548A1 KR 2020017442 W KR2020017442 W KR 2020017442W WO 2021112548 A1 WO2021112548 A1 WO 2021112548A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
tablet
weight
esomeprazole
cellulose
Prior art date
Application number
PCT/KR2020/017442
Other languages
English (en)
Korean (ko)
Inventor
최재준
김민환
노현경
서정민
Original Assignee
진양제약 주식회사
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
Application filed by 진양제약 주식회사 filed Critical 진양제약 주식회사
Publication of WO2021112548A1 publication Critical patent/WO2021112548A1/fr

Links

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
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer

Definitions

  • the present invention relates to pharmaceutical compositions containing esomeprazole.
  • Omeprazole exists in two isomers, the R-isomer and the S-isomer. It is known that the S-isomer is superior to the R-isomer in terms of therapeutic effects and side effects.
  • esomeprazole is (S)-5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H-benzoimidazole, indigestion, indigestion It is a representative proton pump inhibitor (PPI) used in the treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome.
  • PPI proton pump inhibitor
  • Esomeprazole is susceptible to decomposition or transformation in acidic and neutral media, is promoted by acidic compounds, and is also affected by moisture, heat, organic solvents and light.
  • Korean Patent No. 10-0100996 proposed a method of mixing beta-cyclodextrin as a stabilizing component in esomeprazole
  • Korean Patent No. 10-2006777 proposed a method of adding sodium hydrogen carbonate to esomeprazole.
  • the present inventors performed an experiment by selecting various candidates capable of increasing the stability of esomeprazole while reducing the content of related substances, and as a result, when magnesium hydroxide, which is one of the substances used as a stabilizer and an alkalizer, is added, the above It was confirmed that it has bioequivalence with the commercially available Nexium tablet along with the stability improvement of esomeprazole.
  • Another object of the present invention is to provide a solid preparation comprising the pharmaceutical composition.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising esomeprazole or a pharmaceutically acceptable salt thereof, and magnesium hydroxide.
  • the magnesium hydroxide is included in the total composition in an amount of 2 to 10% by weight.
  • the present invention also provides a solid formulation comprising the pharmaceutical composition.
  • the solid formulation is a tablet, and the tablet has a humidity of 75% at 45°C and an open state, and the content of the total related substances after 28 days from the initial is 2% by weight or less, and the content reduction rate under the same conditions is 4.5% by weight is below.
  • the pharmaceutical composition according to the present invention can manufacture a tablet with improved convenience and patient compliance while having bioequivalence compared to the Nexium tablet.
  • the tablet of the present invention has a low water absorption rate and can improve formulation stability by minimizing the generation and content reduction rate of related substances even under severe conditions, and thus can be used as an alternative drug to the currently marketed Nexium tablet.
  • the present invention discloses a method in which stability can be improved by limiting the composition and content of a stabilizing agent or an alkalizing agent to esomeprazole in the preparation of a pharmaceutical composition comprising esomeprazole.
  • Esomeprazole is a compound represented by the following formula (1).
  • Esomeprazole of Formula 1 is named as (S)-5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H-benzoimidazole.
  • Nexium tablets which are currently marketed esomeprazole, are formulated into tablets by preparing a pellet containing esomeprazole magnesium salt, enteric coating it, and adding an excipient.
  • the Nexium tablet had an unsatisfactory problem in terms of stability, and in particular, as a result of being left in an atmosphere at 45°C and 75% humidity was maintained, the generation of related substances increased, and the content of esomeprazole in the formulation was severely reduced.
  • the present invention discloses a method capable of securing excellent stability even in a harsh environment while having bioequivalence compared to the existing Nexium tablet, which is easy to manufacture and has stability.
  • an optimal effect can be achieved when magnesium hydroxide used as a stabilizing agent (or alkalizing agent) is used, but the content thereof is limited in the entire composition.
  • Stabilizer is a substance added to prevent decomposition by acid, moisture, light, etc., magnesium oxide, magnesium hydroxide, sodium hydrogen carbonate, calcium carbonate, magnesium carbonate, calcium silicate, meglumine, sodium carbonate, Various compositions are known, such as sodium bicarbonate, potassium carbonate, potassium bicarbonate, magnesium carbonate, sodium citrate, and potassium citrate.
  • the content of esomeprazole is used in the range of 1 to 40% by weight, 5 to 35% by weight, and 10 to 30% by weight based on the total amount of the solid preparation.
  • the pharmaceutical composition of the present invention further comprises a pharmaceutically acceptable excipient.
  • the pharmaceutically acceptable additive may be at least one selected from a diluent, a disintegrant, a binder, and a lubricant.
  • the diluent refers to a substance used to increase the total weight of the solid preparation, L-arginine, mannitol, microcrystalline cellulose, lactose, lactose hydrate, lactose anhydride, cellulose and its derivatives, dibasic or tribasic calcium phosphate, erythritol, It may be at least one selected from the group consisting of low-substituted hydroxypropyl cellulose, starch, pregelatinized starch, sorbitol, and xylitol. According to one embodiment, the diluent may be lactose hydrate, lactose anhydride, and low-substituted hydroxypropyl cellulose.
  • the content of the diluent may be 1 to 80% by weight, 5 to 75% by weight, or 10 to 70% by weight based on the total amount of the solid formulation, and outside this range, the desired effect due to the addition of the diluent may not be obtained.
  • L-arginine and microcrystalline cellulose are used together, but each of them is used in the range of 10 to 60% by weight and 20 to 60% by weight.
  • the disintegrant is a composition that can be easily decomposed to maintain the appropriate hardness of the solid preparation and to absorb the drug when administered orally, croscarmellose sodium, corn starch, crospovidone, low-substituted hydroxypropyl cellulose, and It may be at least one selected from the group consisting of pregelatinized starch.
  • the disintegrant may be crospovidone.
  • the content of the disintegrant may be 1 to 40% by weight, 5 to 30% by weight, or 10 to 25% by weight based on the total amount of the solid preparation, and outside this range, the desired effect due to the addition of the disintegrant cannot be obtained.
  • a binder is a material capable of improving the productivity, uniformity and dissolution rate of a solid preparation by binding each composition, for example, hydroxypropyl cellulose, copovidone (copovidone, a copolymer of vinylpyrrolidone with other vinyl derivatives) , hydroxypropyl methyl cellulose, polyvinylpyrrolidone (povidone), pregelatinized starch, and at least one selected from the group consisting of low-substituted hydroxypropyl cellulose, hypromellose, pregelatinized starch, and polyvinylacetic acid.
  • the binder is povidone.
  • the content of the binder may be 0.01 to 10% by weight, 0.1 to 7% by weight, or 0.3 to 5% by weight based on the total amount of the solid formulation, and outside this range, the desired effect may not be obtained due to the addition of the binder. .
  • Lubricants are used to improve the tableting process, for example, stearic acid, metal salts of stearate (eg, calcium stearate, magnesium stearate, sodium stearate, etc.), talc, colloidal silica, sucrose fatty acid ester, hydrogenated vegetable It may be at least one selected from the group consisting of oils, waxes, glyceryl fatty acid esters, and glycerol dibehenate. According to one embodiment, the lubricant is sodium stearyl fumarate.
  • the content of the lubricant may be 0.01 to 10% by weight, 0.1 to 7% by weight, or 0.3 to 5% by weight based on the total amount of the solid formulation, and outside this range, the desired effect due to the addition of the lubricant may not be obtained. .
  • additives such as a fluidizing agent, a stabilizer, a brightening agent, a surfactant, an antioxidant, a preservative, and a colorant may be further included.
  • composition comprising the composition as described above can be formulated into an orally administrable dosage form.
  • the orally administrable dosage form is not particularly limited whether it is a solid preparation or a non-solid preparation, but is preferably a solid preparation.
  • solid formulation refers to a formulation made by molding or encapsulating a drug in a certain shape.
  • the solid preparation may be any solid preparation for oral use prepared as wet granules or may include wet granules, for example, dry syrup, granules, tablets (including single-layered tablets, double-layered tablets, inner core tablets, etc.), pellets, Or it may be formulated as a capsule, etc., but is not limited thereto.
  • the solid formulation may be one in which wet granules are filled in the form of tablets, pellets, or capsules.
  • the tablets, pellets, and capsules may be those commonly used in the art.
  • the capsule may be a hard capsule or a soft capsule.
  • the capsule When the oral solid combination preparation is a capsule, the capsule may be in a form including granules or tablets therein.
  • the solid formulation may be a tablet including wet granules.
  • the oral solid formulation is a tablet.
  • the solid preparation of the present invention can be used as a representative proton pump inhibitor used in the treatment of indigestion, peptic ulcer disease, gastroesophageal reflux disease, Zollinger-Ellison syndrome, and the like.
  • the dosage of the solid preparation is, for example, in the range of 1 mg to 200 mg for adults, 5 mg to 100 mg, 5 mg to 90 mg, 5 mg to 80 mg, 5 mg to 75 mg, 5 mg to 70 mg. Or 5 mg - 60 mg are preferable, and 15 mg - 60 mg are still more preferable.
  • the administration may be administered once a day, multiple times a day, or once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks to once a year.
  • the solid formulation may be administered at 50 mg per day once a day in the morning or dividedly administered at 50 mg per day at 25 mg twice a day twice a day in the morning and in the evening.
  • the solid preparation according to the present invention may be formulated in a tablet form by mixing esomeprazole and magnesium hydroxide, but by tableting with a pharmaceutical additive.
  • Tableting is a process of manufacturing tablets by applying a certain level of compression pressure, and is a process of binding particles by creating a bonding force between particles using a tableting machine. Specific steps are not particularly limited in the present invention.
  • a tableting machine is an equipment for molding powder or granules under strong pressure with punches and dies of various shapes, and may vary depending on the size and shape of the punches and dies.
  • Tablets may vary in shape, for example oval, triangular, almond, peanut, parallelogram, circular, pentagonal, hexagonal and trapezoidal. Preferred shapes are circular, oval and parallelogram shapes.
  • a coating process may be further performed after the additionally prepared tableting.
  • coated tablets Tablets manufactured after the coating process are called coated tablets, and compressed tablets (eg, uncoated tablets) containing esomeprazole or a pharmaceutically acceptable salt thereof, and magnesium hydroxide are coated in a single layer or multiple layers using a coating base. .
  • the coating base used in the coating process may include a general coating agent used for tablets, preferably one that is difficult to dissolve in the intestinal pH environment and can promote dissolution of the active ingredient.
  • the base examples include cellulose derivatives such as hypromellose (hydroxypropylmethyl cellulose), hydroxypropyl cellulose, ethyl cellulose, and methyl cellulose; polyvinyl compounds such as polyvinyl alcohol, povidone (polyvinylpyrrolidone), polyvinylacetal diethylaminoacetate, and vinyl acetate resin; acrylic acid derivatives such as aminoalkyl methacrylate copolymer RS and ethyl acrylate/methyl methacrylate copolymer dispersion; sugars such as sucrose and mannitol used for coating sugar; Polyethylene glycol and the like are possible, and these may be used alone or in combination of two or more.
  • cellulose derivatives such as hypromellose (hydroxypropylmethyl cellulose), hydroxypropyl cellulose, ethyl cellulose, and methyl cellulose
  • polyvinyl compounds such as polyvinyl alcohol, povidone (polyvinylpyrrolidone), polyvin
  • the coating agent is Pharmacoat (Pharmacoat), Methocel (Methocel), Sepifilm (Sepifilm), Viscontran (Viscontran), Opadry (Opadry), Etocell, Aquacoat (Aquacoat),
  • a coating base having a trade name such as Surelease, Viscontran, Tylopur, or Methocel may be used, but is not limited thereto.
  • the tablet of the present invention is a small preparation.
  • the small size is a concept compared to the size of the existing esomeprazole capsules or core granules, which means that the size is small compared to conventionally known pharmaceuticals, and preferably, the weight of the tablet is 400 mg or less. It has a small size compared to the weight of about 540 mg of the conventional Nexium tablet.
  • Esomeprazole is a prescription frequently used for chronic patients such as gastric ulcer, duodenal ulcer, and gastritis. When formulated in a small size, ease of administration and patient compliance can be increased.
  • the solid formulation according to the present invention was tested under severe stability conditions among stability conditions, and as a result, the moisture absorption rate was low, the generation of related substances was small, and the content reduction rate was low.
  • the harsh stability conditions are based on temperature 45°C and humidity 75%, and left in an open state, the content of total related substances after 28 days compared to the initial time is 2% by weight or less, 1.9% by weight or less, 1.8% by weight or less, 1.7% by weight or less, 1.6 wt% or less, 1.5 wt% or less, 1.3 wt% or less.
  • compositions of Tables 1 and 2 were mixed, and a lubricant was added and mixed, followed by tableting to prepare uncoated tablets.
  • Example 1 Example 2
  • Example 3 Example 4
  • Example 5 esomeprazole magnesium 15.03 15.03 15.03 15.03 15.03 L-Arginine 25.34 25.34 25.34 25.34 25.34 25.34 stabilizer magnesium hydroxide 1.01 2.53 5.07 7.60 15.20 Microcrystalline Cellulose 44.59 43.07 40.54 38.01 30.41 D-mannitol 1.52 1.52 1.52 1.52 povidone 5.07 5.07 5.07 5.07 5.07 crospovidone 5.07 5.07 5.07 5.07 5.07 5.07 5.07 Sodium Stearyl Fumarate 2.36 2.36 2.36 2.36 2.36 2.36 2.36 2.36 2.36 2.36 2.36 2.36 2.36 2.36
  • Example 1 Example 2
  • Example 3 Example 4
  • Example 5 Comparative Example 1 1 hours 3.6 2.6 0.9 0.7 0.9 2 hours 4.2 3.1 1.5 1.4 1.3 1.5 4 hours 5.4 4.3 2.5 2.4 2.4 2.6 8 hours 5.3 5.0 3.5 3.2 3.3 4.2 24 hours 5.2 4.8 3.3 3.2 3.2 4.7
  • Table 3 is a primary evaluation of tablet stability, and the weight of the tablet increased by absorbing moisture in the air over time, but as the content of magnesium oxide increased, the stability to moisture showed a tendency to improve.
  • the tablet of Comparative Example 1 has a large increase in weight, so that the addition of magnesium hydroxide can further improve the stability to moisture during tablet manufacture.
  • the uncoated tablets of Examples and Comparative Examples were dissolved in Opadry II (85F18422), Opadry Acrylic (93A18597) and Opadry II (85F15458) in purified water and sequentially coated to prepare the tablets of Examples and Comparative Examples.
  • the mass of the unit dosage form of the final manufactured tablet was 380 mg.
  • the tablets of Examples and Comparative Examples were stored for 28 days under accelerated conditions (40° C., 75 % RH), and the reduction rate of esomeprazole content at the initial, 7th, 14th, 21st, and 28th days was measured.
  • the content reduction rate was evaluated by dissolving the tablet in 50% methanol and measuring the absorbance at 305 nm with an ultraviolet absorbance spectrophotometer to evaluate the content of esomeprazole.
  • Example 1 Example 2
  • Example 3 Example 4
  • Control Example 1 Early 103.1 103.9 103.5 103.6 103.8 101.95 Day 7 102.83 102.55 101.57 103.2 101.44 102.31 Day 14 101.8 101.51 100.51 101.45 100.29 104.21 Day 21 100.89 100.76 100.28 101.04 100.31 95.14 Day 28 99.58 99.98 101.62 100.99 99.18 93.05 content reduction rate 3.41 3.77 1.81 2.52 4.45 8.73
  • Each tablet of Example 3 has a total weight of about 380 mg, and in the case of a commercially available Nexium tablet, about 540 mg, it can be seen that the size of the tablet according to the present invention is small. These small-sized tablets bring excellent results in convenience of administration and patient preference in Experimental Example 5 below.
  • the patients were randomly assigned to group 1 as 10 patients, and then each group was instructed to take each tablet.
  • the degree of ease of swallowing the tablet when swallowing was scored using a scoring method of 1: very hard / 2: hard / 3: normal / 4: easy / 5: very easy.
  • the average value was calculated.
  • the test results are shown in the table below.
  • Example 1 (Nexium Tablet)
  • Example 3 Example 4 Convenience of taking 2.3 4.8 4.7 patient preference 6 people 15 people 9 people
  • Example 3 had the highest score for convenience in taking. It was confirmed that the tablet of Example 3 reduced the unit dosage form (about 540 mg) of Nexium tablet marketed in a unit dosage form of 380 mg by about 30%, thereby improving patient convenience and preference.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention présente : une composition pharmaceutique contenant de l'ésoméprazole qui présente une excellente stabilité en raison de la génération d'une petite quantité de substances apparentées et ayant un faible taux de réduction de contenu même dans des atmosphères hostiles; et une formulation solide le comprenant.
PCT/KR2020/017442 2019-12-06 2020-12-02 Composition pharmaceutique WO2021112548A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020190161219A KR20210071242A (ko) 2019-12-06 2019-12-06 제약 조성물
KR10-2019-0161219 2019-12-06

Publications (1)

Publication Number Publication Date
WO2021112548A1 true WO2021112548A1 (fr) 2021-06-10

Family

ID=76221845

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2020/017442 WO2021112548A1 (fr) 2019-12-06 2020-12-02 Composition pharmaceutique

Country Status (2)

Country Link
KR (1) KR20210071242A (fr)
WO (1) WO2021112548A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102432084B1 (ko) * 2021-11-16 2022-08-12 알리코제약(주) S-오메프라졸을 함유하는 안정성이 개선되고 소형화된 정제

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20060134124A (ko) * 2004-03-26 2006-12-27 에자이 알앤드디 매니지먼트 가부시키가이샤 용출 제어 제제 및 그의 제조 방법
CN103845734A (zh) * 2014-03-20 2014-06-11 辽宁亿灵科创生物医药科技有限公司 埃索美拉唑药物组合物及其制剂
KR20160082169A (ko) * 2014-12-31 2016-07-08 한미약품 주식회사 비스테로이드성 항염증제 및 프로톤 펌프 저해제를 포함하는 경구용 서방성 복합제제
KR20160124368A (ko) * 2015-04-17 2016-10-27 대원제약주식회사 프로피온산 계열의 비스테로이드성 항염증 약물(nsaid) 및 프로톤 펌프 저해제(ppi)를 함유하는 생체이용률이 증진된 약제학적 조성물
KR101723266B1 (ko) * 2014-08-13 2017-04-05 영남대학교 산학협력단 비스테로이드성 항염증약물 및 프로톤 펌프 저해제를 포함하는 경구용 속방형 조성물 및 그 제조방법

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102006777B1 (ko) 2018-01-29 2019-10-08 주식회사 종근당 에스오메프라졸 및 탄산수소나트륨을 포함하는 약제학적 제제

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20060134124A (ko) * 2004-03-26 2006-12-27 에자이 알앤드디 매니지먼트 가부시키가이샤 용출 제어 제제 및 그의 제조 방법
CN103845734A (zh) * 2014-03-20 2014-06-11 辽宁亿灵科创生物医药科技有限公司 埃索美拉唑药物组合物及其制剂
KR101723266B1 (ko) * 2014-08-13 2017-04-05 영남대학교 산학협력단 비스테로이드성 항염증약물 및 프로톤 펌프 저해제를 포함하는 경구용 속방형 조성물 및 그 제조방법
KR20160082169A (ko) * 2014-12-31 2016-07-08 한미약품 주식회사 비스테로이드성 항염증제 및 프로톤 펌프 저해제를 포함하는 경구용 서방성 복합제제
KR20160124368A (ko) * 2015-04-17 2016-10-27 대원제약주식회사 프로피온산 계열의 비스테로이드성 항염증 약물(nsaid) 및 프로톤 펌프 저해제(ppi)를 함유하는 생체이용률이 증진된 약제학적 조성물

Also Published As

Publication number Publication date
KR20210071242A (ko) 2021-06-16

Similar Documents

Publication Publication Date Title
US6605303B1 (en) Oral pharmaceutical extended release dosage form
JP3878669B2 (ja) プロトンポンプ抑制剤を含有する複数単位の製剤
US20090208575A1 (en) Pharmaceutical Composition Of Acid Labile Substances
US20090274756A1 (en) Stabilized composition
WO2019147094A1 (fr) Formulation pharmaceutique comprenant de l'ésoméprazole et du bicarbonate de sodium
KR20130010044A (ko) 콜린 알포세레이트 또는 이의 약학적으로 허용되는 염을 포함하는 서방형 약학 조성물 및 이의 제조방법
WO2019108021A2 (fr) Composition pharmaceutique comprenant du tofacitinib
WO2019004770A9 (fr) Composition pour préparation solide à usage oral comprenant un inhibiteur de pompe à protons, préparation solide à usage oral la comprenant, et son procédé de préparation
WO2022050670A1 (fr) Compositions pharmaceutiques sous forme de comprimé comprenant de l'oméprazole, de l'ésoméprazole, ou un sel de qualité pharmaceutique de ceux-ci et leurs processus de préparation
EP1837016A2 (fr) Composition pharmaceutique en multiple-unité
EP3648745A1 (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
WO2021112548A1 (fr) Composition pharmaceutique
WO2021118026A1 (fr) Formulation de comprimé à noyau contenant un inhibiteur de la pompe à protons et du mosapride
WO2020171404A1 (fr) Composition pharmaceutique
WO2017084680A1 (fr) Composition pharmaceutique contenant un médicament anti-inflammatoire non stéroïdien et un inhibiteur de pompe à protons
WO2015108392A1 (fr) Petit comprimé pharmaceutique contenant de l'ésoméprazole
WO2013157841A1 (fr) Comprimé à libération prolongée contenant de la lévodropropizine et procédé pour préparer celui-ci
WO2021091188A1 (fr) Composition pharmaceutique à libération prolongée pour une administration orale, contenant du rebamipide ou un sel pharmaceutiquement acceptable de celui-ci
US9040564B2 (en) Stabilized composition
WO2019199134A1 (fr) Composition pharmaceutique comprenant du lénalidomide
CN115209875A (zh) 用于口服施用的药物组合物
KR20220126426A (ko) 안정성이 향상된 라베프라졸을 유효성분으로 포함하는 경구용 속방형 제제 및 이의 제조방법
WO2018203636A1 (fr) Composition ayant une solubilité dans l'eau et une biodisponibilité améliorées
WO2006111853A2 (fr) Formes posologiques solides stables d'un medicament labile en milieu acide
WO2021075926A1 (fr) Composition pharmaceutique comprenant un inhibiteur de la pompe à protons et un antiacide

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: 20896329

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: 20896329

Country of ref document: EP

Kind code of ref document: A1