WO2012017074A1 - Oral pharmaceutical formulations of esomeprazole in the form of mups (multi unit pellets system) tablets - Google Patents

Oral pharmaceutical formulations of esomeprazole in the form of mups (multi unit pellets system) tablets Download PDF

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Publication number
WO2012017074A1
WO2012017074A1 PCT/EP2011/063524 EP2011063524W WO2012017074A1 WO 2012017074 A1 WO2012017074 A1 WO 2012017074A1 EP 2011063524 W EP2011063524 W EP 2011063524W WO 2012017074 A1 WO2012017074 A1 WO 2012017074A1
Authority
WO
WIPO (PCT)
Prior art keywords
tablets
esomeprazole
pellets
cellulose
enteric
Prior art date
Application number
PCT/EP2011/063524
Other languages
English (en)
French (fr)
Inventor
Roberto Valducci
Serozh Avanessian
Tiziano Alighieri
Original Assignee
Valpharma S.P.A.
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 Valpharma S.P.A. filed Critical Valpharma S.P.A.
Priority to KR1020137005804A priority Critical patent/KR20140021985A/ko
Priority to EP11752137.7A priority patent/EP2600847A1/en
Publication of WO2012017074A1 publication Critical patent/WO2012017074A1/en

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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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core

Definitions

  • the present invention relates to the field of formulations of pharmaceutical compositions; in particular it relates to tablets of the MUPS type for oral administration of esomeprazole, and the method of preparation thereof.
  • Esomeprazole belongs to the class of proton pump inhibitors (PPI): drugs containing active ingredients discovered relatively recently, which have proved very effective in treating various gastrointestinal pathologies by reducing the acid secretion of the stomach.
  • PPI proton pump inhibitors
  • the enteric-coated tablets obtained by the conventional technique have long residence times in the stomach, sometimes unpredictable: there is an increased risk of degradation of the active ingredient, due to the residence time in the stomach and to microinfiltrations in the enteric coating.
  • the residence time in the stomach is short because the tablets or capsules disintegrate, releasing enteric-coated pellets having a diameter in the range 0.5-2.0 mm, which therefore pass through the stomach without stopping.
  • MUPS Multi Unit Pellet System
  • WO96/01623 describes tablets of the MUPS type, containing esomeprazole, in which, to avoid the aforementioned problems of compression, the pellets were coated with an enteric coating that contains a plasticizer in amounts from 20 to 50 wt.%, relative to the weight of the enteric coating.
  • a plasticizer in amounts from 20 to 50 wt.%, relative to the weight of the enteric coating.
  • the cores are isolated by applying neutral polymers characterized by low solubility owing to their high viscosity: it is therefore necessary to use dilute solutions, leading to lengthening of the covering times, made worse by the actual adhesiveness of the film.
  • concentrations used must be between 2 and 5% otherwise the viscosity becomes so great that spraying of the solutions is not possible.
  • the present invention thus solves the aforementioned problem by means of a method for preparation of tablets of the MUPS (Multi Unit Pellet System) type comprising esomeprazole, said method comprising the following steps:
  • step (iii) preparation of a mixture comprising enteric microgranules obtained from step (i) and the wet granulate obtained from step (ii);
  • step (iv) compression of the mixture obtained from step (iii) with a compression force equal to 1 .8-2.5 kN with lubricated punches.
  • the granulated excipients are mixed, wet as obtained without prior drying, with the enteric-coated pellets previously produced.
  • What distinguishes the present invention from other pharmaceutical formulations of the MUPS type containing esomeprazole magnesium dihydrate already on the market is the use of a much lower compression force, so that the enteric coating of the pellets is not damaged during compression.
  • the tablets obtained disintegrate when in contact with the fluids and release the protected granules that they contain.
  • the presence of a water content of approx. 10% in the wet granulate of tableting excipients surprisingly makes it possible to obtain tablets having high hardness and low friability while applying a minimal compression force equal to approx. 2kN.
  • the tablets obtained by the aforementioned method have suitable hardness (above 15kp) and friability for withstanding the usual subsequent steps of film coating and packaging.
  • the tablets can then be coated with ordinary excipients for film coating in an aqueous medium.
  • the tablets lose the water added in the step of granulation of the tableting excipients.
  • the finished tablets thus produced display, surprisingly, a further increase in hardness at the end of the film coating cycle.
  • the present invention also relates to enteric microgranules containing esomeprazole that are particularly simple and convenient to be prepared and which, even if they do not possess particularly high mechanical strength and must not be submitted to high pressures during compression, can be used particularly advantageously in the aforementioned method; said microgranules each comprising:
  • microgranules preferably having an average diameter between 500 and 800 ⁇ ;
  • said layer (b) containing esomeprazole does not contain alkaline substances
  • said coating layer (d) can also contain plasticizers but in amounts such as not to endow said coating with sufficient mechanical strength to preserve enteric characteristics during dry compression.
  • the isolating layer (c) constituted of mannitol, applied simply in aqueous solution, makes it possible to obtain pellets with very fast production times and with excellent results. With the same operating conditions with respect to the neutral polymers used in the aforementioned patents, there is an approximately five-fold decrease in production times.
  • microgranules can be used, as well as for preparation of tablets of the MUPS type according to the method of the present invention, for the preparation of capsules filled with said microgranules.
  • tablette excipients means the inert additives, known and mentioned in the various pharmacopoeias, which are generally added to active ingredients, or to granules containing them, to facilitate their compression to tablets; in particular, for preparation of tablets of the MUPS type, disintegrating tableting excipients are used, for example microcrystalline cellulose, carboxymethyl starch, croscarmellose, crospovidone, pregelatinized starch and others.
  • the esomeprazole is esomeprazole magnesium dihydrate.
  • the pellets according to the present invention have an average diameter between 500 and 800 ⁇ .
  • the pellets according to the invention are prepared by fluidized bed technology.
  • the layer containing the active ingredient further comprises usual excipients, preferably polysorbate, povidone or PEG and mixtures thereof.
  • the layer of active ingredient does not comprise alkalizing substances.
  • the layer containing the active ingredient is applied on the inert (neutral) cores using an aqueous suspension of the components of the layer in which the active ingredient is contained at 15-25 wt.%, more preferably at approx. 20%.
  • the active ingredient is contained in larger amounts than is known in the prior art, in which suspensions are used at 6-10 wt.% of active ingredient. It has now been discovered that it is also possible to work with higher concentrations (up to 15- 25 wt.%) when said aqueous suspension is prepared and maintained at a temperature not above 20 °C, preferably between 10 and 20 °C; in fact, by carrying out homogenization of the suspension at this temperature, it is possible to prevent gelation thereof and make the spraying operation possible.
  • the isolating layer of mannitol is preferably applied by means of fluidized bed technology using a solution of mannitol in water preferably at a concentration by weight below 50%, more preferably at 10-30%.
  • Said solution of mannitol is preferably at pH 9-10, said pH preferably being obtained by adding a 1 N solution of NaOH.
  • the pellets according to the invention are made resistant to the gastric environment using suitable films for this purpose, known and referred to in the various pharmacopoeias; among these, preferably the following can be used: Eudragit L100- 55, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate, cellulose acetate phthalate, hydroxypropylmethylcellulose succinate, polyvinyl acetate.
  • the enteric coating can further comprise other usual excipients, for example glyceryl monostearate, triethyl citrate, talc, paraffin and mixtures thereof.
  • any plasticizers present are in amounts below 25 wt.% relative to the enteric polymers. The aforementioned amount of plasticizer is not sufficient to endow the pellets with the necessary mechanical strength in dry compression. The pellets are preserved, however, when compressed with wet granulate of tableting excipients according to the method of the present invention.
  • the pellets according to the invention or others selected for example from those known in the prior art are mixed with the tableting excipients and then compressed. It is convenient for the purposes of the present method to use the microgranules according to the present invention because they are easier to prepare while maintaining the desired enteric characteristics and release at neutral or slightly alkaline pH.
  • the granulate of the tableting excipients comprises cellulose and preferably further comprises an alditol of general formula H[CH(OH)] n H where n is between 5 and 12.
  • Said tableting excipients are advantageously constituted of cellulose or of mixtures of cellulose and an alditol of general formula H[CH(OH)] n H where n is between 5 and 12, preferably selected from mannitol, lactitol, isomalt, maltitol, sorbitol or xylitol.
  • the aforementioned mixture of cellulose+alditol preferably comprises 70-90 wt.% of cellulose and the remaining 10-30% of alditol.
  • the aforementioned cellulose+alditol mixture is preferably obtained by co-spray drying.
  • the tableting excipients are granulated with addition of water, to obtain a wet granulate with a water content preferably of 7-13%, more preferably 9-1 1 % (based on the weight of the excipients).
  • the water content was evaluated by testing for weight loss on drying.
  • the water used for preparation of the granulate of tableting excipients is preferably acidified beforehand to pH 3-5, preferably using hydrochloric acid.
  • the wet granulate is mixed with the enteric-coated pellets previously produced without carrying out drying.
  • the mixture thus obtained is compressed using conventional tableting presses, equipped for obtaining tablets of the desired shape and dosage.
  • the punches must be lubricated at the time of compression.
  • a tableting machine equipped with automatic distribution of a lubricant is used.
  • the lubricant is preferably selected from sodium stearyl fumarate, stearic acid, magnesium stearate, talc, purified silica, kaolin.
  • the amount of lubricant to use for lubricating the punches is preferably 0.2-3.0 wt.% relative to the total of the tableting mixture.
  • the enteric-coated pellets are mixed with the wet granulate of tableting excipients in the presence of a lubricant as well, which preferably is the same as is used for lubricating the punches.
  • a lubricant as well, which preferably is the same as is used for lubricating the punches.
  • the lubricant is preferably partly applied directly on the punches and partly mixed with the pellets and the tableting excipients.
  • the mixture for tableting, on lubricated punches has the following percentage composition by weight:
  • the mixture comprises:
  • the neutrals are introduced into the fluidized bed with Wurster insert, and spraying of the suspension (prepared and maintained at 20 °C) containing esomeprazole, polysorbate 80, povidone PEG and purified water in the following amounts, is begun:
  • Air inlet temperature 90 °C
  • Air outlet temperature 40-50 °C
  • the pellets thus obtained are forced through a vibrating screen equipped with a screen with holes 650 micron in diameter.
  • pellets are coated, still in the fluidized bed equipped with Wurster insert, with an aqueous solution based on mannitol in the following amounts:
  • pellets are additionally coated in a fluidized bed equipped with Wurster insert with an aqueous solution based on Eudragit L100-55 with the following composition: Eudragit L100-55 61 14 g 19.86%
  • Air inlet temperature 45 °C
  • Air outlet temperature 25-30 °C
  • a proportion of the pellets of example 1 is mixed with cellulose+mannitol (marketed by Avicel with the name HFE-102, it is a co-spray dried mixture with content of microcrystalline cellulose and mannitol of 83 wt.% and 17 wt.% respectively) in the following amounts:
  • tablets are formed at a dosage of 43.38 mg of esomeprazole magnesium dihydrate, having an average weight of 700 mg/tablet and hardness 1 1 kp obtained with compression force applied equal to 4.5 kN.
  • the aforementioned tablets have the following release profile:
  • a proportion of cellulose+mannitol (Avicel HFE-102) is granulated in an automatic pan, soaking the powder with water acidified to pH 4 using hydrochloric acid, in the following amounts: Cellulose+mannitol 10000 g
  • tablets are formed at a dosage of 43.38 mg of esomeprazole magnesium dihydrate having an average weight of 724 mg/tablet and hardness 16 kp obtained with a compression force equal to 3.5 kN.
  • the aforementioned tablets are dried in an automatic pan.
  • a proportion of cellulose+mannitol (Avicel HFE-102) is granulated in an automatic pan, soaking the powder with water acidified to pH 4 using hydrochloric acid, in the following amounts:
  • tablets are formed at a dosage of 43.38 mg of esomeprazole magnesium dihydrate having an average weight of 748 mg/tablet and hardness 20 kp obtained by applying a compression force equal to 2.0 kN.
  • the aforementioned tablets are dried in an automatic pan.
  • the tablets produced in example 4 are put in an automatic pan and coated with a colouring suspension with the following composition: HPMC 5cps 202.3 g 5%
  • Air inlet temperature 50 °C
  • Air outlet temperature 25-30 °C
  • the neutrals are introduced into the fluidized bed with Wurster insert, and spraying of the suspension (prepared and maintained at 20 °C) containing esomeprazole, polysorbate 80, povidone, PEG and purified water in the following amounts is begun:
  • Air inlet temperature 90 °C
  • Air outlet temperature 40-50 °C
  • the pellets thus obtained are forced through a vibrating screen equipped with a screen having holes with diameter of 650 micron.
  • pellets are coated, still in the fluidized bed equipped with Wurster insert, with an aqueous solution based on mannitol in the following amounts:
  • Air inlet temperature 70°C
  • Air outlet temperature 40-45 °C
  • pellets are additionally coated in a fluidized bed equipped with Wurster insert with an aqueous solution based on Eudragit L100-55 with the following composition:
  • Air inlet temperature 45 °C
  • Air outlet temperature 25-30°C
  • a proportion of the pellets of example 6 is mixed with microcrystalline cellulose in the following amounts:
  • tablets are formed at a dosage of 43.38 mg of esomeprazole magnesium dihydrate having an average weight of 700 mg/tablet and hardness 10 kp obtained with a compression force equal to 5.0 kN.
  • the aforementioned tablets have the following release profile:
  • microcrystalline cellulose is granulated in an automatic pan, soaking the powder with water acidified to pH 4 using hydrochloric acid, in the following amounts: Microcrystalline cellulose l OOOO g
  • tablets are formed at a dosage of 43.38 mg of esomeprazole magnesium dihydrate having an average weight of 724 mg/tablet and hardness 14 kp obtained with a compression force equal to 3.5 kN.
  • the aforementioned tablets are dried in an automatic pan.
  • a proportion of the microcrystalline cellulose is granulated in an automatic pan, soaking the powder with water acidified to pH 4 preferably using hydrochloric acid, in the following amounts:
  • tablets are formed at a dosage of 43.38 mg of esomeprazole magnesium dihydrate having an average weight of 748 mg/tablet and hardness 16 kp obtained with a compression force equal to 2.0 kN.
  • the aforementioned tablets are dried in an automatic pan.
  • Air inlet temperature 50°C
  • Air outlet temperature 25-30 °C
  • Temperature of cores 25-30 °C Spray this suspension on the tablets until a weight increase of 25 mg/tablet is obtained. Once the predetermined average weight is reached, dry the tablets in an automatic pan.
  • the neutrals are introduced into the fluidized bed with Wurster insert, and spraying of the suspension (prepared and maintained at 20 °C) containing esomeprazole, polysorbate 80, povidone, PEG and purified water in the following amounts is begun:
  • Air inlet temperature 90 °C
  • the pellets thus obtained are forced through a vibrating screen equipped with a screen having holes with diameter of 650 micron.
  • these pellets are coated, still in the fluidized bed equipped with Wurster with an aqueous solution based on mannitol in the following amounts:
  • pellets are additionally coated in a fluidized bed equipped with Wurster insert with an aqueous solution based on Eudragit L1 00-55 with the following composition:
  • a proportion of the pellets of example 1 1 is mixed with cellulose+mannitol (Avicel HFE-102) in the following amounts:
  • tablets are formed at a dosage of 21 .69 mg of esomeprazole magnesium dihydrate having an average weight of 350 mg/tablet and hardness 7 kp obtained with a compression force equal to 5.0 kN.
  • a proportion of the cellulose+mannitol (Avicel HFE-102) is granulated in an automatic pan, soaking the powder with water acidified to pH 4 using hydrochloric acid, in the following amounts: Cellulose+mannitol 10000 g
  • the aforementioned tablets are dried in an automatic pan.
  • a proportion of the cellulose+mannitol (Avicel HFE-102) is granulated in an automatic pan, soaking the powder with water acidified to pH 4 using hydrochloric acid, in the following amounts:
  • Air inlet temperature 50 °C
  • Air outlet temperature 25-30 °C
  • Air inlet temperature 90 °C
  • Air outlet temperature 40-50 °C
  • the pellets thus obtained are forced through a vibrating screen equipped with a screen having holes with diameter of 650 micron.
  • pellets are coated, still in the fluidized bed equipped with Wurster insert, with an aqueous solution based on mannitol in the following amounts:
  • Air inlet temperature 70 °C
  • Air outlet temperature 40-45 °C
  • pellets are additionally coated in a fluidized bed equipped with Wurster insert with an aqueous solution based on Eudragit L100-55 with the following composition: Eudragit L100-55 61 14 g 19.86%
  • Air inlet temperature 45 °C
  • a proportion of the pellets of example 16 is mixed with microcrystalline cellulose in the following amounts:
  • tablets are formed at a dosage of 21 .69 mg of esomeprazole magnesium dihydrate having an average weight of 350 mg/tablet and hardness 5 kp obtained with a compression force equal to 5.0 kN.
  • the aforementioned tablets have the following release figures: Release in the first 2 hours in HCI 0.1 12.6%
  • a proportion of the microcrystalline cellulose is granulated in an automatic pan, soaking the powder with water acidified to pH 4 using hydrochloric acid, in the following amounts:
  • tablets are formed at a dosage of 21 .69 mg of esomeprazole magnesium dihydrate having an average weight of 362 mg/tablet and hardness 13 kp obtained with a compression force equal to 3.5 kN.
  • the aforementioned tablets are dried in an automatic pan.
  • a proportion of the microcrystalline cellulose is granulated in an automatic pan, soaking the powder with water acidified to pH 4 using hydrochloric acid, in the following amounts:
  • tablets are formed at a dosage of 21 .69 mg of esomeprazole magnesium dihydrate having an average weight of 748 mg/tablet and hardness 20 kp obtained with a compression force equal to 2.3 kN.
  • the aforementioned tablets are dried in an automatic pan.
  • Air inlet temperature 50 °C
  • Air outlet temperature 25-30°C
  • Cellulose+mannitol/water cellulose + mannitol granulated with water
  • Microcrystalline cellulose/water microcrystalline cellulose granulated with water 21 .69 mg of esomeprazole magnesium dihydrate
  • Cellulose+mannitol/water cellulose + mannitol granulated with water
  • Microcrystalline cellulose/water microcrystalline cellulose granulated with water Tablet hardness was assessed using the Erweka durometer model TBH 225 TD.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/EP2011/063524 2010-08-06 2011-08-05 Oral pharmaceutical formulations of esomeprazole in the form of mups (multi unit pellets system) tablets WO2012017074A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
KR1020137005804A KR20140021985A (ko) 2010-08-06 2011-08-05 Mups (다중단위 펠릿 시스템) 태블릿 형태의 경구형 에소메프라졸 약학 제형
EP11752137.7A EP2600847A1 (en) 2010-08-06 2011-08-05 Oral pharmaceutical formulations of esomeprazole in the form of mups (multi unit pellets system) tablets

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITFI2010A000175 2010-08-06
ITFI2010A000175A IT1401284B1 (it) 2010-08-06 2010-08-06 Nuove formulazioni farmaceutiche idonee per la somministrazione orale di esomeprazolo magnesio diidrato, in forma di compresse mups (multi unit pellets system).

Publications (1)

Publication Number Publication Date
WO2012017074A1 true WO2012017074A1 (en) 2012-02-09

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PCT/EP2011/063524 WO2012017074A1 (en) 2010-08-06 2011-08-05 Oral pharmaceutical formulations of esomeprazole in the form of mups (multi unit pellets system) tablets

Country Status (4)

Country Link
EP (1) EP2600847A1 (ko)
KR (1) KR20140021985A (ko)
IT (1) IT1401284B1 (ko)
WO (1) WO2012017074A1 (ko)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013122554A1 (en) 2012-02-14 2013-08-22 Mahmut Bilgic Pellet formulations comprising esomeprazole
WO2013122553A1 (en) * 2012-02-14 2013-08-22 Mahmut Bilgic A pharmaceutical formulation comprising an atp-ase inhibitor and method for this formulation
US10076494B2 (en) 2016-06-16 2018-09-18 Dexcel Pharma Technologies Ltd. Stable orally disintegrating pharmaceutical compositions
US10736855B2 (en) 2016-02-25 2020-08-11 Dexcel Pharma Technologies Ltd. Compositions comprising proton pump inhibitors
US11077055B2 (en) 2015-04-29 2021-08-03 Dexcel Pharma Technologies Ltd. Orally disintegrating compositions

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20230086439A (ko) 2021-12-08 2023-06-15 주식회사 다산제약 에스오메프라졸 또는 이의 약학적으로 허용가능한 염을 포함하는 약학 제제 및 이의 제조 방법

Citations (7)

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Publication number Priority date Publication date Assignee Title
WO1996001623A1 (en) 1994-07-08 1996-01-25 Astra Aktiebolag Multiple unit tableted dosage form i
WO2002072071A1 (en) * 2001-03-09 2002-09-19 Astrazeneca Ab Method to obtain microparticles containing a h+, k+ -atp-ase inhibitor
EP1452172A2 (en) * 1994-07-08 2004-09-01 AstraZeneca AB Multiple unit pharmaceutical preparation
WO2005034924A1 (en) 2003-10-14 2005-04-21 Natco Pharma Limited Enteric coated pellets comprising esomeprazole, hard gelatin capsule containing them, and method of preparation
WO2006002077A2 (en) 2004-06-15 2006-01-05 Teva Pharmaceutical Industries Ltd. Stable pharmaceutical formulations of benzimidazole compounds
WO2008006534A2 (en) * 2006-07-11 2008-01-17 Lek Pharmaceuticals D.D. Multiple unit tablets
WO2010041276A1 (en) * 2008-10-06 2010-04-15 Jubilant Organosys Limited Pharmaceutical compositions comprising amorphous esomeprazole, dosage forms and process thereof

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996001623A1 (en) 1994-07-08 1996-01-25 Astra Aktiebolag Multiple unit tableted dosage form i
EP1452172A2 (en) * 1994-07-08 2004-09-01 AstraZeneca AB Multiple unit pharmaceutical preparation
WO2002072071A1 (en) * 2001-03-09 2002-09-19 Astrazeneca Ab Method to obtain microparticles containing a h+, k+ -atp-ase inhibitor
WO2005034924A1 (en) 2003-10-14 2005-04-21 Natco Pharma Limited Enteric coated pellets comprising esomeprazole, hard gelatin capsule containing them, and method of preparation
WO2006002077A2 (en) 2004-06-15 2006-01-05 Teva Pharmaceutical Industries Ltd. Stable pharmaceutical formulations of benzimidazole compounds
WO2008006534A2 (en) * 2006-07-11 2008-01-17 Lek Pharmaceuticals D.D. Multiple unit tablets
WO2010041276A1 (en) * 2008-10-06 2010-04-15 Jubilant Organosys Limited Pharmaceutical compositions comprising amorphous esomeprazole, dosage forms and process thereof

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013122554A1 (en) 2012-02-14 2013-08-22 Mahmut Bilgic Pellet formulations comprising esomeprazole
WO2013122553A1 (en) * 2012-02-14 2013-08-22 Mahmut Bilgic A pharmaceutical formulation comprising an atp-ase inhibitor and method for this formulation
US11077055B2 (en) 2015-04-29 2021-08-03 Dexcel Pharma Technologies Ltd. Orally disintegrating compositions
US11986554B2 (en) 2015-04-29 2024-05-21 Dexcel Pharma Technologies Ltd. Orally disintegrating compositions
US10736855B2 (en) 2016-02-25 2020-08-11 Dexcel Pharma Technologies Ltd. Compositions comprising proton pump inhibitors
US10076494B2 (en) 2016-06-16 2018-09-18 Dexcel Pharma Technologies Ltd. Stable orally disintegrating pharmaceutical compositions
US10835488B2 (en) 2016-06-16 2020-11-17 Dexcel Pharma Technologies Ltd. Stable orally disintegrating pharmaceutical compositions

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Publication number Publication date
KR20140021985A (ko) 2014-02-21
IT1401284B1 (it) 2013-07-18
ITFI20100175A1 (it) 2012-02-07
EP2600847A1 (en) 2013-06-12

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