WO2005051348A2 - Comprimes de pantoprazole a enrobage enterique - Google Patents

Comprimes de pantoprazole a enrobage enterique Download PDF

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Publication number
WO2005051348A2
WO2005051348A2 PCT/HU2004/000111 HU2004000111W WO2005051348A2 WO 2005051348 A2 WO2005051348 A2 WO 2005051348A2 HU 2004000111 W HU2004000111 W HU 2004000111W WO 2005051348 A2 WO2005051348 A2 WO 2005051348A2
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WO
WIPO (PCT)
Prior art keywords
weight
pantoprazole
water
disintegrant
active ingredient
Prior art date
Application number
PCT/HU2004/000111
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English (en)
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WO2005051348A3 (fr
Inventor
Pál FEKETE
Zsuzsa SZLÁVYNÉ SZÉLL
Cecília BURESNÉ PAPP
Éva FURDYGA
Original Assignee
EGIS Gyógyszergyár Rt.
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
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Application filed by EGIS Gyógyszergyár Rt. filed Critical EGIS Gyógyszergyár Rt.
Publication of WO2005051348A2 publication Critical patent/WO2005051348A2/fr
Publication of WO2005051348A3 publication Critical patent/WO2005051348A3/fr

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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
    • A61K9/28—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
    • 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
    • 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
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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 invention relates to enteric-coated tablets containing pantoprazole as active ingredient and a process for the preparation thereof.
  • Pantoprazole (5- (difluoromethoxy) -2 ⁇ [ (3,4-di- methox ⁇ -2-p ⁇ ridinyl) -methyl] -sulphinyl ⁇ -lH-benz- imidazole) of the formula (I)
  • Said core may be formulated into granules, pellets, tablets or fillers of capsules. In case of tablets polyvinylpyrrolidone or hydroxypropyl cellulose is used as excipient.
  • a water-soluble interim film coating which separates theticiancore" from the acidic coating material. This may also contain an alkaline component, or it may be the shell of the capsule .
  • a film coating resistant to gastric acid dissolving in the small intestine (enterosolvent) . Its material contains acid groups .
  • pellet used throughout - this- specification relates . to nearly. • - spherical agglomerates* 0.3-2.0 mm in diameter.
  • the first patent application concerned with the preparation of a pantoprazole composition is International patent WO 92/22284.
  • the number of the corresponding Hungarian patent is 219,247.
  • compositions containing acid- sensitive benzimidazole derivatives described in EP 244,380 contain several components incompatible with pantoprazole.
  • lactose, microcrystalline cellulose and hydroxypropyl cellulose being present in the composition cause an increased decomposition of the pantoprazole.
  • polyvinylpyrrolidone and/or hydroxypropyl-methyl cellulose are used as excipients, and mannitol is applied as an" optional inert filler.
  • mannitol is applied as an" optional inert filler.
  • pharmaceutical compositions of favourable stability can be produced.
  • Hungarian patent specification No. 219,247 it is described that whenever mannitoli is used as filler, the use of an appropriate polymeric binder is also' required. '-•.*
  • pantoprazole compositions being on the market are prepared as contemplated in Hungarian patent No. 219,247.
  • said compositions are identical with the enterosolvent tablet described in Example 1 of the patent specification.
  • the above composition which is provided in Hungarian patent No. 219,247 ensures that the stability of the composition containing pantoprazole as active ingredient is suitable even if the humidity content of the composition is between 5 and 8% by weight, contrary to the maximum value of 1.5% by weight raised as a requirement ' i ' n " Hungarian ' patent specification No. 198,385. Meeting said requirement would demand expensive technical measures (e.g. drying;, • air with a ' low humidity content cooled below -15 °C, tabletting and packing room with 20% relative humidity content) .
  • the aim of the present invention was to elaborate a film-coated . enterosolvent.
  • . tablet- containing pantoprazole which comprises a core containing the stabilized----active ingredient- of suitable mechanical stability, a separating layer surrounding the core and an enterosolvent coating, which tablet keeps its favourable dissolution characteristics under storage • and thus ensures the proper delivery of the active ingredient.
  • Summary of the invention The invention is based on the recognition that by using appropriately chosen excipients compatible with the active ingredient it is not necessary to use a polymeric binder in order to prepare pantoprazole tablets possessing mechanical characteristics suitable for the formation of a film coating, and the -dissolution of the active ingredient from said tablets following storage meets even the strictest pharmacopoeial requirements.
  • enteric-coated tablets containing pantoprazole that is 5- (difluoro-
  • ⁇ methoxy) -2 ⁇ [ (3,4-dimethoxy-2-pyridinyl) -ritiethyl] - sulphinyl ⁇ -lH-benzlmidazole as active ingredient which comprise • a.) a core consisting of 20-50% by weight (related to the weight of the tablet core) of the active ingredient, spray-dried or granulated mannitol having an average particle size between
  • an alkalizing substance 100 ⁇ m and 500 ⁇ m, an alkalizing substance, a disintegrant and a lubricant generally applied in the pharmaceutical industry; b.) a water-soluble separating film coating; c.) an enterosolvent film coating insoluble in gastric juices; and d.) an optional water-soluble protecting film coating.
  • the film-coated enterosolvent tablet containing pantoprazole as active ingredient comprises a.) a core consisting of 20-50% by weight (related to the weight of the tablet core) of the active ingredient, 30-75% by weight of spray-dried or granulated mannitol having an ⁇ : average particle size between 100 ⁇ m and 500 ⁇ m, 2-20% by weight of an alkalizing substance, a disintegrant and a lubricant usually applied in the pharmaceutical industry; b.) a water-soluble separating film coating; c.) an enterosolvent film coating insoluble in gastric juices; and d.) an optional wa-ter.-s ⁇ l ⁇ blev • protecting .film coating. • ' ⁇ • .. ,
  • the film-coated enterosolvent tablet containing pantoprazole as active ingredient comprises a.) a core consisting of 20-50% by weight (related to the weight of the tablet core) , preferably- - 25-35%. by weight-, of the sodium-, salt of pantoprazole ' , . 30- ⁇ -75% by ". ⁇ wei,ght.> preferably -30-55%- by ' weight , -- more' - pre erably- • 30 ⁇ -40%..
  • the tablet according to the invention contains as active ingredient pantoprazole, preferably the sodium salt of pantoprazole. . , more, preferably the sesquihydrate ⁇ of the - sodium salt ⁇ of pantoprazole.
  • the tablet according to the invention contains as alkalizing substance an alkali hydroxide, an alkali carbonate, an alkali hydrocarbonate or mixtures thereof, preferably an alkali hydro- carbonate, more preferably sodium hydroxide, sodium ca bonate,, ., . sodi ⁇ m hydrocarbonate or a mixture thereof.
  • alkalizing substance an alkali hydroxide, an alkali carbonate, an alkali hydrocarbonate or mixtures thereof, preferably an alkali hydro- carbonate, more preferably sodium hydroxide, sodium ca bonate,, ., . sodi ⁇ m hydrocarbonate or a mixture thereof.
  • the most, .preferable is the application of sodium carbona ⁇ e . , *.
  • the tablet according to the invention contains sodium carboxymethyl starch, sodium carboxymethyl cellulose, potassium carboxymethyl cellulose, crospovidone or a mixture thereof. The most preferable is the application of crospovidone.
  • anti-friction agent and lubricant stearic acid hydrogenated vegetable oils, paraffme or alkali earths stearates, preferably magnesium or potassium stearate, more preferably potassium stearate can be used.
  • a preferred embodiment of the film-coated tablet according to the invention containing pantoprazole as active ingredient contains, on the surface of the tablet core, 5-20% by weight (related to the total weight of the composition) of a water-soluble coating, on the outer surface of said coating 5-20 % by weight of an enteric coating insoluble in gastric acid and, if desired, 0,5-5% by weight of a further coating soluble in water.
  • a process for the preparation of enteric-coated tablets containing pantoprazole as active ingredient which comprises a.) providing a tablet core consisting of 20 - 50% by weight of the active ingredient, spray- dried or granulated mannitol having a particle size between 100 ⁇ m and 500 ⁇ m, an alkalizing agent and optionally other auxiliary agents generally applied in the pharmaceutical industry; b.) applying to the core a water-soluble film- coating; c.) applying an enterosolvent film coating insoluble in gastric juices; and optionally d*. ) applying a -water-soluble protecting film coating.
  • the process according to the invention for the preparation of enteric-coated tablets containing pantoprazole as active ingredient comprises a.) providing a tablet core consisting of 20-50% by weight, preferably 25-35% by weight of the active ingredient, 30-75% by* weight, preferably30-50% by weight, more preferably ..30-40% by- weight of spray-dried mannitol having an average particle size between 100 ⁇ m and 500 ⁇ m, 2-20% by weight, preferably 5-10% by weight of an alkalizing agent, 2-20% by weight, preferably 10-20% by weight of a disintegrant and 1-5% by weight, preferably 2-4% by weight of- a lubricant, b.) applying to the core 5-20% by weight (related to the final weight of the composition) a water-soluble film-coating; c.) applying 5-20% by weight (related to the final weight of the composition) of an enteric film coating insoluble in gastric juices; and optionally d.) applying 0,5-5 % by weight
  • the film-coated tablet according to the invention containing pantoprazole can also be prepared as follows.
  • First a tablet core is provided by granulating a mixture of 20-50% by weight (related to the ' weight, of the tablet core) of the active ingredient, a disintegrant.and an alkalizing agent with an aqueous . solution: of .mannitol- and the alkalizing- agent, optionally drying the .granulate, ' ., adding to the granulate spray-dried mannitol . having an average particle size between 100 ⁇ m and 500 ' ⁇ m, optionally a disintegrant and a lubricant and compressing the homogenizate to tablets.
  • the thus-obtained tablets are then coated first with a water- soluble coating, then with an enterosolvent coating resistant to gastric acid and finally 18 and optionally with a water-soluble film coating.
  • the film-coated tablet according to the invention containing pantoprazole can also be prepared as follows: the mixture of 20-50% by weight, preferably 25- 35% by -weight -.(related ••to" -the --weight- , of the tablet core) of the active- ingredient, . ⁇ 2-20% by weight, preferably 10-20% by weight of a disintegrant and' 2-20 % .by weight, preferably 5- 10% by weight of an alkalizing agent is granulated with an aqueous solution of 2-20% by weight of mannitol and 1-3% by weight of an alkalizing agent, the granulate is.
  • pantoprazole preferably the sodium salt of pantoprazole, more particularly the sesquihydrate of the . sodium salt of pantoprazole is used.
  • alkalizing agent an alkali hydroxide, an alkali carbonate, an alkali hydrocarbonate or mixtures thereof, preferably an alkali hydrocarbonate-, more preferably, .sodium: hydroxide, - sodium carbonate,., sodium hydrocarbonate or a mixture thereof .
  • alkali hydroxide preferably an alkali hydrocarbonate-, more preferably, .sodium: hydroxide, - sodium carbonate,., sodium hydrocarbonate or a mixture thereof .
  • The. ost. preferable is the application of sodium carbonate. - - •
  • sodium carboxymethyl starch sodium carboxymethyl cellulose, potassium carboxymethyl cellulose, crospovidone, or a mixture thereof.
  • the most preferable is the application of crospovidone.
  • lubricant stearic acid hydrogenated vegetable oils, paraf ine or alkali earths stearates, preferably magnesium or potassium stearate, more preferably potassium stearate can be used.
  • pantoprazole compositions can be prepared which are much more favourable in respect of the dissolution requirements than those prepared according to the state of the art.
  • Pantoprazole used as active ingredient for the composition according to the invention is known from the European patent No. 166,287.
  • physiologically acceptable salts of pantoprazole provided in the same patent the use of the sodium salt is particularly preferable.
  • Granulated . or ..spray-dried mannitol having an average particle size of -100 ⁇ m or -above used for the preparation of the tablet core belongs to the so-called direct compressing auxiliary? agents. These substances are characterized by favourable flow properties resulted by the particle size of 100 ⁇ m or above, the nearly symmetric or spherical shape of the granules'?:-; furthermore by a good compressibility.
  • Such * substances comprising mannitol are: marketed by' the firm Roquette under the name Pearlitol (e.g.
  • the particle size of the active ingredient or the excipient used for the composition e.g. sodium carbonate, crospovidone
  • the amount of the granulated 48 e.g. sodium carbonate, crospovidone
  • mannitol having a particle size of 100 ⁇ m or above being present in the tablet core
  • granulation may be carried out with an aqueous solution Of mannitol-.' The amount of mannitol used- for the granulation - may ⁇ be ⁇ between 2 ' and 20%-by ' weight related to the total weight of the tablet core;"” Granulation can be carried out ⁇ ⁇ either by kneading or by fluidization spraying methods.
  • dislntegrants are also used in order to ensure a '1" quick decomposition of the tablet core in an aqueous .. medium r . -and a quick and " complete dissolution "- ' of * --the active*-*- -ingredient: " As diajlntegrant " it .'is- " expedient to.- ' use* a «» ' s-o-called mecanicant", such as sodium carboxymethyl starch, sodium carboxymethyl cellulose, potassium carboxymethyl cellulose or crospovidone (cross-linked polyvinylpyrrolidone) .
  • the quantity of the disintegrants in the composition may be 2-20% by weight. As these substances can absorb a considerable amount of water, it is expedient to use these substances in the smallest possible quantity in order to decrease water-uptake of the compositions during storage.
  • the pH of the tablet core is to be raised to a value above pH 7 in order to ensure the chemical stability Of pantoprazole-.
  • "--'As -alkalizing 'a'gent sodium • hydroxide,• • potassium Tydroxidey • ⁇ ⁇ sodium hydrogen carbonate or sodium carbonate may ' be us.ed.- These substances may be admixed- with the active ingredient and the mannitol in powdered form, or may be applied in the form of solutions. In the composition preferably sodium carbonate is applied.
  • the amount of the alkalizing agents in the tablet core is 2-20% by weight.
  • a part, of • he alkalizing agent may -ais' - be- applied together "with -the aqueou-s.-.-solution of the ...mannitol . " "...-- ' * ' ⁇ ⁇ ,--- . ⁇ "... -* ⁇ -.- .,,, ,-,-*>'. ⁇ ;,• ....-•-
  • a lubricant that is an anti-friction substance for the preparation of the tablet core.
  • the role of this substance is to decrease the friction and adhesion between the tablet core and the compressing dies.
  • substances generally used for the manufacture of tablets such as stearic acid, hydrogenated vegetable oils, paraffine or alkaline earth stearates, preferably magnesium or potassium stearate, more preferably potassium stearate are used in an amount between 1-5% related to the weight of the composition.
  • the water-soluble ' separating, layer applied on the tablet ⁇ .core . may ' ' contain film-forming substances generally used for the preparation of film-coated tablets.
  • Such water-soluble film- forming substance is e.g. hydroxypropyl-methyl cellulose, which is suggested to be used as a substance for the separating layer in compositions . containing benzimidazole derivatives in several publications according to the state of the -art (e"". " g. ' European .patent No. 244,380, Hungarian patent No..- - 247 , ' 9-83) v.
  • plasticizers such as polyethylene glycol
  • optionally further additives e.g. titanium ⁇ dioxide, talc
  • the separating coating should be relatively thick in order to provide an effective protection for the active ingredient in the core against the acidic, film- forming polymer resistant to gastric acid. That 48
  • the amount of the separating layer is between 5 and 20% by weight related to the total amount of the composition.
  • coating substance preferably ready-made coating substances, such as the product under the trademark Opadry can be used.
  • the gastric acid resistant enteric coating may contain film-forming substances known for the persons skilled in the art. Such substances are e.g. cellulose acetate phtalate, polyvinyl- acetate phtalate, hydroxypropyl-methyl cellulose phtalate, hydroxypropyl-methyl cellulose acetate succinate, ethylacrylate methacrylic acid copolymer, methylmethacrylate methacrylic acid copolymer, shellac. These polymers may be used as organic solutions or preferably as aqueous dispersions, and optionally plasticizers, e.g. triacetine or triethyl citrate may be added to them.
  • plasticizers e.g. triacetine or triethyl citrate may be added to them.
  • This coating should also be relatively thick in order to ensure the intact character of the film-coated tablet while the composition is in the stomach, and thus to ensure an efficient protection for the active ingredient in the core against the decomposing effect of the acidic gastric juice. That is why the amount of the separating layer is 5 to 20% by weight related to the total weight of the composition.
  • the outer protecting layer serving to prevent the film-coated tablets from sticking together during storage at higher temperatures may also contain water-soluble film-forming substances generally applied for the manufacture of film- coated tablets .
  • water-soluble film-forming substances are e.g. hydroxypropyl-methyl cellulose.
  • film-forming polymer optionally further excipients, plasticizers , e.g. polyethylene glycol may be used in the coating.
  • This protecting layer is relatively thin, it is used in an amount between 0,5 and 5% by weight related, to the total weight of the composition.
  • coating substance ready-made coating systems such as the substances marketed under the trade name Opadry can preferably be applied. • . . ' ⁇ . - • ... • .
  • a particularly advantage of the enteric-coated tablets according to the invention over other enterosolvent, pantoprazole-containing film- coated tablets according to the state of the art is that the rate of the dissolution of the active ingredient does not drop off during storage of the film-coated tablets in a room having a relative humidity content of 75%, as the tablet core does not contain hygroscopic, hydrofil polymeric binders, such as polyvinylpyrrolidone or hydroxymethyl cellulose, and at the same time the amount of the highly hygroscopic disintegrant is considerably lower.
  • the tablet core according to the invention contains 16.1% by weight of hygroscopic crospovidone, while the tablet core of the composition according to the literature contains 32.2% by weight of crospovidone and further 2,6% by weight of povidone K90 polymer, which is also a hygroscopic substance.
  • This latter polymer may increase the strength of the binding between the granules in the. tablet core ' having a high humidity content due to further ' physical changes, which may finally lead to " ' a slow dissolution of the active ingredient.
  • the homogen-izate is compressed into tablets weighting 155 mg on a tabletting machine of Manesty B3B ' "-type using-.le ⁇ tifi ⁇ rm- dies" of' -8 -itim*- In- . diameter . --,
  • the ; tablet- cores " are coated- ' first ' •' with a - ' -dispersion of 2.6-0 :-.P -,.g, of Opardy I-. in- 2300.
  • a fluidization granulating machine of Glatt GPCG 1 type 676.5 g of pantoprazole 540.5 g of mannitol, 120.0 g of sodium carbonate and 400 g of crospovidone are introduced, and the mixture of the ingredients is granulated with a solution of 60.0 g of Povidon K90, 100.0 g of mannitol and 30.0 g of sodium carbonate in 750 g of water.
  • the granulate is dried until the humidity content has decreased below 3%, and then 350.0 g of crospovidone - and-- 48.0 g of -potassium stearate are . mixed to- it.
  • the homogenizate is compressed into tablets weighting 155 mg on a tabletting machine of Manesty B3B type using lentiform dies of 8 mm in diameter.
  • the tablet cores are coated first with a coating dispersion prepared from 237.5 g of 3 cP hydroxypropyl-methyl cellulose (Pharmacoat 603), 4,8 g of Povidon K 25, 4.2 g of titanium dioxide, 53.1 g of propylene glycol and 2130. 1 of water, then with a coating dispersion prepared from an aqueous .dispersion of 682.0 g of Eudragit L 30D containing 204.6 g of Eudragit -55 and 20.4 g of triethyl citrate in 1330 g of water.
  • the homogenizate is compressed to tablets weighting 155 mg on a tabletting machine of EXI type using len-tiform dies of 8 mm in diameter.
  • the tablet cores are coated as specified in Example 1 in a coating apparatus of Glatt GC 250 type first with a dispersion of 1.10.8 g of Opadry I in 1000 g of water, then with a coating dispersion prepared from 17 . 7.3 g of an aqueous Eudragit L .30D dispersion containing -53.2 g of Eudragit '. L-55 , 15.5 g of triethyl citrate, 38.2 g of talc and ' 3.9 g of ' ween 80.
  • Protecting layer Opadry clear 1.00 mg 2.00 mg 0.064 kg 0.20 kg ( Hydroxypropyl - methyl cellulose , polyethylene glycol 400 ) Purified 0.58 kg 1.80 kg water

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  • Health & Medical Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Comprimés à enrobage entérique contenant du pantoprazole en tant que principe actif et procédé de préparation desdits comprimés. Les comprimés selon la présente invention comprennent (a) un noyau constitué de l'ingrédient actif à raison de 20 à 50 % en poids (par rapport au poids du noyau du comprimé), de mannitol séché par pulvérisation ou en granulés ayant une taille moyenne des particules entre 100 µm et 500 µm, d'un agent alcalifiant, d'un désintégrant et d'un lubrifiant classiquement utilisés dans l'industrie pharmaceutique, (b) un film d'enrobage de séparation hydrosoluble, (c) un film d'enrobage à dégradation entérique insoluble dans les sucs gastriques et (d) éventuellement un film d'enrobage de protection. Lesdits comprimés présentent une stabilité accrue lors du stockage.
PCT/HU2004/000111 2003-11-25 2004-11-24 Comprimes de pantoprazole a enrobage enterique WO2005051348A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HUP0303791 2003-11-25
HU0303791A HU227317B1 (en) 2003-11-25 2003-11-25 Enteric coated tablet containing pantoprazole

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WO2005051348A2 true WO2005051348A2 (fr) 2005-06-09
WO2005051348A3 WO2005051348A3 (fr) 2006-04-27

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1747776A1 (fr) 2005-07-29 2007-01-31 KRKA, tovarna zdravil, d.d., Novo mesto Composition pharmaceutique comprenant du pantoprazole granulaire
WO2007029124A2 (fr) * 2005-05-13 2007-03-15 Combino Pharm, S.L. Formulations contenant de l acide libre de pantoprazole et les sels de ce dernier
WO2012013994A3 (fr) * 2010-07-30 2012-03-22 Hajnal Peter COMPOSITION PHARMACEUTIQUE À LIBÉRATION PROLONGÉE DÉPENDANTE DU pH
CN102429884A (zh) * 2011-12-29 2012-05-02 天津市嵩锐医药科技有限公司 盐酸哌甲酯口腔崩解药物组合物
CN114224861A (zh) * 2022-02-22 2022-03-25 轩竹(北京)医药科技有限公司 一种安纳拉唑钠的肠溶片及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4853230A (en) * 1986-04-30 1989-08-01 Aktiebolaget Hassle Pharmaceutical formulations of acid labile substances for oral use
WO1994002140A1 (fr) * 1992-07-17 1994-02-03 Astra Aktiebolag Composition pharmaceutique contenant un agent antiulcereux
WO1996024338A1 (fr) * 1995-02-09 1996-08-15 Astra Aktiebolag Nouvelle formulation pharmaceutique et procede afferent
US5997903A (en) * 1991-06-17 1999-12-07 Byk Gulden Lomberg Chemische Fabrik Gmbh Oral-administration forms of a medicament containing pantoprazol

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4853230A (en) * 1986-04-30 1989-08-01 Aktiebolaget Hassle Pharmaceutical formulations of acid labile substances for oral use
US5997903A (en) * 1991-06-17 1999-12-07 Byk Gulden Lomberg Chemische Fabrik Gmbh Oral-administration forms of a medicament containing pantoprazol
WO1994002140A1 (fr) * 1992-07-17 1994-02-03 Astra Aktiebolag Composition pharmaceutique contenant un agent antiulcereux
WO1996024338A1 (fr) * 1995-02-09 1996-08-15 Astra Aktiebolag Nouvelle formulation pharmaceutique et procede afferent

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007029124A2 (fr) * 2005-05-13 2007-03-15 Combino Pharm, S.L. Formulations contenant de l acide libre de pantoprazole et les sels de ce dernier
WO2007029124A3 (fr) * 2005-05-13 2007-07-26 Combino Pharm Sl Formulations contenant de l acide libre de pantoprazole et les sels de ce dernier
EP1747776A1 (fr) 2005-07-29 2007-01-31 KRKA, tovarna zdravil, d.d., Novo mesto Composition pharmaceutique comprenant du pantoprazole granulaire
WO2007014928A1 (fr) * 2005-07-29 2007-02-08 Krka, Tovarna Zdravil, D.D., Novo Mesto Préparation pharmaceutique comprenant du pantoprazole granulaire
EA014187B1 (ru) * 2005-07-29 2010-10-29 Крка, Товарна Здравил, Д. Д., Ново Место Таблетка, содержащая гранулированный пантопразол
WO2012013994A3 (fr) * 2010-07-30 2012-03-22 Hajnal Peter COMPOSITION PHARMACEUTIQUE À LIBÉRATION PROLONGÉE DÉPENDANTE DU pH
US9839607B2 (en) 2010-07-30 2017-12-12 Péter Hajnal pH-dependent gradual release pharmaceutical composition
CN102429884A (zh) * 2011-12-29 2012-05-02 天津市嵩锐医药科技有限公司 盐酸哌甲酯口腔崩解药物组合物
CN114224861A (zh) * 2022-02-22 2022-03-25 轩竹(北京)医药科技有限公司 一种安纳拉唑钠的肠溶片及其制备方法

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HU227317B1 (en) 2011-03-28
HUP0303791A3 (en) 2009-03-30
WO2005051348A3 (fr) 2006-04-27
HUP0303791A2 (en) 2007-09-28

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