WO2007099433A2 - Forme posologique a liberation controlee de pantoprazole ou d'un de ses sels - Google Patents

Forme posologique a liberation controlee de pantoprazole ou d'un de ses sels Download PDF

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Publication number
WO2007099433A2
WO2007099433A2 PCT/IB2007/000470 IB2007000470W WO2007099433A2 WO 2007099433 A2 WO2007099433 A2 WO 2007099433A2 IB 2007000470 W IB2007000470 W IB 2007000470W WO 2007099433 A2 WO2007099433 A2 WO 2007099433A2
Authority
WO
WIPO (PCT)
Prior art keywords
dosage form
delayed release
release dosage
binder
pantoprazole
Prior art date
Application number
PCT/IB2007/000470
Other languages
English (en)
Other versions
WO2007099433A3 (fr
Inventor
Chandrashekhar Shriram Kandi
Shery Jacob
Girish Kumar Jain
Original Assignee
Wockhardt Ltd
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 Wockhardt Ltd filed Critical Wockhardt Ltd
Publication of WO2007099433A2 publication Critical patent/WO2007099433A2/fr
Publication of WO2007099433A3 publication Critical patent/WO2007099433A3/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
    • A61K9/48—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
    • 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 stable oral dosage form of pantoprazole or salt thereof and processes for their preparation.
  • the invention provides delayed release dosage form comprising of a core containing pantoprazole or salt thereof in admixture with binder, filler and, optionally, other pharmaceutically acceptable excipient and an inorganic base, an inert water-soluble intermediate layer surrounding the core and an outer enteric coat, wherein the binder is hydroxypropyl cellulose LH-11 and/or pre-gelatinized starch.
  • Pantoprazole is a compound that inhibits gastric acid secretion. Chemically, pantoprazole is 5 - (difluoromethoxy) - 2 - [ [(3,4 - dimethoxy - 2 - pyridinyl) methyl] sulfmyl] - IH - benzimidazole. Pantoprazole is indicated for short-term treatment of erosive esophagitis associated with Gastroesophageal Reflux Disease (GERD), maintenance of healing of erosive esophagitis, and pathological hypersecretory conditions Including Zollinger- Ellison Syndrome.
  • GSD Gastroesophageal Reflux Disease
  • U.S. Patent No. 5,997,903 discloses a preparation of pantoprazole in pellet or tablet form for oral administration.
  • the pellet or tablet described in the invention consists of a core in which active compound or its physiologically tolerated salt is in admixture with another tablet auxiliary, an inert water-soluble intermediate layer surrounding the core and an outer layer which is resistant to gastric juice, the binder is polyvinylpyrrolidone and/or hydroxypropylmethyl cellulose and, optionally, the filler is mannitol.
  • the specification of the '903 Patent suggests that the applicants have identified the use of lactose, carboxy methylcellulose and hydroxypropyl cellulose as incompatible with pantoprazole.
  • U.S. patent No. 6,159,499 discloses a composition comprising a core containing an acid-labile benzimidazole active principle, which is not in the form of an alkaline salt and comprises a plurality of nuclei, compressed together, an intermediate layer surrounding the core; and an enteric layer surrounding the intermediate layer.
  • U.S. patent No. 6,068,856 discloses a delayed and controlled release oral pharmaceutical composition comprising pantoprazole, an alkaline pellet or tablet core, at least one intermediate layer controlling release of active ingredient and an outer enteric layer, which is soluble in the small intestine.
  • U.S. Patent No. 6,274,173 discloses oral pharmaceutical composition in pellet or tablet form with delayed and controlled release of active ingredient, comprising an acid-labile irreversible proton pump inhibitor other than pantoprazole, and wherein the composition comprises an alkaline pellet or tablet core, at least one intermediate layer controlling release of active ingredient and an outer enteric layer which is soluble in the small intestine.
  • U.S. Patent No. 6,013,281 provides a process for preparing an oral pharmaceutical formulation comprising forming a core material comprising a proton pump inhibitor and at least one alkaline reacting compound, and applying an enteric coating polymer layer so as to surround the core material thereby forming in situ a separating layer as a water soluble salt product between the alkaline compound and the enteric coating polymer.
  • WO2004066982 discloses stable oral benzimidazole pharmaceutical composition
  • a core comprising a benzimidazole compound, a separating layer surrounding the core and comprising a substantially water-soluble material and an enteric coating surrounding the separating layer without any pharmaceutically acceptable excipients.
  • a stable oral pantoprazole pharmaceutical composition includes a core, a separating layer, and an enteric coating.
  • a delayed release dosage form comprising a core containing pantoprazole or salt thereof in admixture with binder, filler and, optionally, other pharmaceutically acceptable excipient and an inorganic base, wherein the binder is hydroxypropyl cellulose.
  • An inert water-soluble intermediate layer surrounds the core and further an enteric coat surrounds the separating layer.
  • the pharmaceutically acceptable excipients comprise one or more of diluents, lubricants, disintegrants, glidants and the like.
  • the delayed release dosage form should not release any pantoprazole in first two hours, when measured in a USP Type II apparatus at 75 rpm and using 0.1N hydrochloric acid at 37 ⁇ 2 0 C. Further, the delayed release dosage form may have dissolution of about 100 % in next one hour when measured in a USP Type II apparatus at 100 rpm and replacing 0.1N hydrochloric acid with pH 6.8 phosphate buffer at 37 ⁇ 2 0 C.
  • a delayed release dosage form comprising of a core containing pantoprazole or salt thereof in admixture with pre- gelatinized starch as binder, filler and, optionally, other pharmaceutically acceptable excipient and an inorganic base, an inert water-soluble intermediate layer surrounding the core and an outer enteric coat surrounding the inert intermediate layer.
  • the delayed release dosage form should not release any pantoprazole in first two hours, when measured in a USP Type II apparatus at 75 rpm and using 0.1N hydrochloric acid at 37 ⁇ 2 0 C. Further, the delayed release dosage form may have dissolution of about 100 % in next one hour when measured in a USP Type II apparatus at 100 rpm and replacing 0. IN hydrochloric acid with pH 6.8 phosphate buffer at 37 ⁇ 2 0 C.
  • pantoprazole or salt thereof in yet another aspect of the present invention, there is provided a process for the preparation of a delayed release dosage form of pantoprazole or salt thereof.
  • the process includes incorporating pantoprazole or salt thereof along with filler, binder and optionally, other pharmaceutically acceptable excipient and an inorganic base in a pellet or tablet core, applying thereto an inert water-soluble intermediate layer surrounding the core, subsequently applying an outer enteric coat.
  • the one or more pharmaceutically acceptable excipients may be selected from one or more diluents, disintegrants, binders and lubricants.
  • the delayed release dosage form containing pantoprazole or salt thereof includes solid oral dosage forms such as tablets, capsules, granules and pellets.
  • hydroxypropyl cellulose LH-11 and/or pre-gelatinized starch when used as a binder provides excellent binding in the preparation of pantoprazole delayed release dosage form. Moreover, it was also observed that hydroxypropyl cellulose LH-Il and/or pre-gelatinized starch is compatible with pantoprazole or salt thereof and other pharmaceutically acceptable excipient used in the dosage form.
  • a first aspect of the present invention provides a delayed release dosage form, which comprises of a core containing pantoprazole or salt thereof in admixture with binder, filler and, optionally, other pharmaceutically acceptable excipient and an inorganic base, an inert water-soluble intermediate layer surrounding the core and an outer enteric coat, wherein the binder is hydroxypropyl cellulose LH- 11.
  • a second aspect of the present invention provides a delayed release dosage form comprising of a core containing pantoprazole or salt thereof wherein the said process comprises of, (a) incorporating active ingredient or salt thereof along with filler, binder and optionally, other pharmaceutically acceptable excipient and an inorganic base in a pellet or tablet core, (b) applying thereto an inert water-soluble intermediate layer surrounding the core, and (c) subsequently applying an outer enteric coat, wherein, the binder is hydroxypropyl cellulose LH-11.
  • a third aspect of the present invention provides a delayed release dosage form comprising of a core containing pantoprazole or salt thereof in admixture with pre- gelatinized starch as binder, filler and, optionally, other pharmaceutically acceptable excipient and an inorganic base, an inert water-soluble intermediate layer surrounding the core and an outer enteric coat.
  • a fourth aspect of the present invention provides a process for preparation of delayed release dosage form comprising of a core containing pantoprazole or salt thereof wherein the said process comprises of, incorporating pantoprazole or salt thereof along with filler, binder and optionally, other pharmaceutically acceptable excipient and an inorganic base in a pellet or tablet core, applying thereto an inert water-soluble intermediate layer surrounding the core, subsequently applying an outer enteric coat, wherein, the binder is pre-gelatinized starch.
  • Embodiments of the delayed release dosage form include one or more of the following features.
  • Pantoprazole can be present in the form of pantoprazole sodium sesquihydrate.
  • the intermediate layer also can be called as seal coat and is formed from an inert water- soluble film former.
  • the pharmaceutically acceptable seal coat forming polymers can be selected from a group comprising of one or more of suitable cellulose ethers such as hydroxypropyl methylcellulose, hydroxypropyl cellulose and other suitable cellulose ethers.
  • the film former has been applied from a solution.
  • the intermediate layer is surrounded by outer enteric coat.
  • the pharmaceutically acceptable enteric coating forming polymers can be selected from methacrylic acid/methyl methacrylate copolymers such as Eudragit L or cellulose derivatives such as carboxymethyl cellulose, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate and other suitable polymers.
  • Embodiments of the delayed release dosage form include one or more of the following features.
  • the one or more pharmaceutically acceptable excipients may be selected from binder, filler, lubricant, alkalizing agent, disintegrant, glidant and the like.
  • the binder is hydroxypropyl cellulose LH-11 and/or pre-gelatinized starch.
  • Suitable fillers include one or more of sugars, such as dextrose, glucose, lactose; sugar alcohols such as sorbitol, xylitol, and mannitol; starches like maize starch, pregelatinized starch and the like.
  • the lubricants may be one or more of magnesium stearate, calcium stearate, polyethylene glycol, hydrogenated vegetable oils, stearic acid, sodium stearyl fumarate and sodium benzoate.
  • the glidants may be one or more of colloidal silicon dioxide and talc.
  • Suitable disintegrants may include one or more of sodium starch glycolate, croscarmellose sodium and other suitable disintegrants.
  • the delayed release dosage form containing pantoprazole or salt thereof includes solid oral dosage forms such as tablets, capsules, granules and pellets.
  • Table 2 provides the dissolution data for the pantoprazole DR tablets prepared as per the Formula given in Table 1.
  • USP Type II Apparatus rpm 75
  • 0.1N hydrochloric acid in 750 ml was used as a medium (2 hrs)
  • 1000ml of 6.8 pH phosphate buffer (1 hr).
  • Example 1 Pantoprazole, mannitol, starch 1500 and aerosil were sifted through ASTM mesh # 40 and mixed thoroughly using suitable blender. Sodium carbonate was dissolved in purified water, and used as a granulating fluid for carrying out granulation of above mix. Wet dough was passed through ASTM mesh #12 and the wet granules were dried at 60° C to achieve an LOD of 2.0-3 .0%. Dried granules are sized through ASTM mesh # 30 to get uniform size granules. The granules thus obtained were mixed with aerosil, starch 1500, talc, sodium starch glycolate and calcium stearate, which were passed ASTM mesh # 60.
  • the granules were further lubricated with ingredient sodium carbonate anhydrous and compressed into tablets. Tablets were coated with 10% w/w aqueous solution of Opadry, this forms seal coat around the core. Further 30%w/w aqueous solution of Eudragit L 30-D55 along with sodium hydroxide, tri ethyl citrate and talc was used to give enteric coat to the seal coated tablets.
  • Example 2 Pantoprazole, mannitol, hydroxypropyl cellulose LH-I l and aerosil were sifted through ASTM mesh # 40 and mixed thoroughly using suitable blender. Sodium carbonate was dissolved in purified water, and used as a granulating fluid for carrying out granulation of above mix. Wet dough was passed through ASTM mesh #12 and the wet granules were dried at 60° C to achieve an LOD of 2.0-3 .0%. Dried granules are sized through ASTM mesh # 30 to get uniform size granules. The granules thus obtained were mixed with aerosil, talc, sodium starch glycolate and magnesium stearate which were passed through ASTM mesh # 60.
  • the granules were further lubricated with ingredient sodium carbonate anhydrous and compressed into tablets. Tablets were coated with 10% w/w aqueous solution of Opadry, this forms seal coat around the core. Further 30%w/w aqueous solution of Eudragit L 30-D55 along with sodium hydroxide, tri ethyl citrate and talc was used to give enteric coat to the seal coated tablets.
  • composition of the batches is provided in Table 3.
  • Table 4 provides the dissolution data for the pantoprazole DR tablets prepared as per the Formula given in Table 3.
  • USP Type II Apparatus rpm 75
  • 0.1N hydrochloric acid in 750 ml was used as a medium (2 hrs)
  • 1000ml of 6.8 pH phosphate buffer (1 hr).
  • Table 3 discusses the examples of Pantoprazole delayed release tablets (40 mg) prepared by using pre-gelatinized starch as a binder Table 3
  • Procedure-Pantoprazole, mannitol, starch 1500 and aerosil were sifted through ASTM mesh # 40 and mixed thoroughly using suitable blender. Sodium carbonate was dissolved in purified water, and used as a granulating fluid for carrying out granulation of above mix.
  • Wet dough was passed through ASTM mesh #12 and the wet granules were dried, at 60° C to achieve an LOD of 2.0-3 .0%. Dried granules are sized through ASTM mesh # 30 to get uniform size granules.
  • the granules thus obtained were mixed with aerosil, starch 1500, talc, sodium starch glycolate and calcium stearate which were passed ASTM mesh # 60.
  • the granules were further lubricated with ingredient sodium carbonate anhydrous and compressed into tablets. Tablets were coated with 10% w/w aqueous solution of Opadry, this forms seal coat around the core. Further 30%w/w aqueous solution of Eudragit L 30-D55 along with sodium hydroxide, tri ethyl citrate and talc was used to give enteric coat to the seal coated tablets.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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Abstract

La présente invention concerne une forme posologique orale stable de pantoprazole ou d'un de ses sels et ses procédés de fabrication. L'invention concerne une forme posologique à libération contrôlée comprenant un cœur contenant du pantoprazole ou un de ses sels en mélange avec un liant, une charge et éventuellement d'autres excipients pharmaceutiquement acceptables et une base inorganique, une couche intermédiaire inerte hydrosoluble entourant le cœur et un revêtement entérique externe, le liant étant de l'hydroxypropyl-cellulose LH-11 et/ou de l'amidon prégélatinisé.
PCT/IB2007/000470 2006-02-28 2007-02-28 Forme posologique a liberation controlee de pantoprazole ou d'un de ses sels WO2007099433A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN284/MUM/06 2006-02-28
IN284MU2006 2006-02-28
IN280MU2006 2006-02-28
IN280/MUM/06 2006-02-28

Publications (2)

Publication Number Publication Date
WO2007099433A2 true WO2007099433A2 (fr) 2007-09-07
WO2007099433A3 WO2007099433A3 (fr) 2009-04-23

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3522889A4 (fr) * 2016-10-06 2020-05-27 Jubilant Generics Limited Composition pharmaceutique de pantoprazole à action retardée et son procédé de préparation

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6013281A (en) * 1995-02-09 2000-01-11 Astra Aktiebolag Method of making a pharmaceutical dosage form comprising a proton pump inhibitor
US6489346B1 (en) * 1996-01-04 2002-12-03 The Curators Of The University Of Missouri Substituted benzimidazole dosage forms and method of using same
US6599529B1 (en) * 1997-09-11 2003-07-29 Nycomed Danmark A/S Modified release multiple-units compositions of non-steroid anti-inflammatory drug substances (NSAIDs)

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6013281A (en) * 1995-02-09 2000-01-11 Astra Aktiebolag Method of making a pharmaceutical dosage form comprising a proton pump inhibitor
US6489346B1 (en) * 1996-01-04 2002-12-03 The Curators Of The University Of Missouri Substituted benzimidazole dosage forms and method of using same
US6599529B1 (en) * 1997-09-11 2003-07-29 Nycomed Danmark A/S Modified release multiple-units compositions of non-steroid anti-inflammatory drug substances (NSAIDs)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3522889A4 (fr) * 2016-10-06 2020-05-27 Jubilant Generics Limited Composition pharmaceutique de pantoprazole à action retardée et son procédé de préparation

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WO2007099433A3 (fr) 2009-04-23

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