WO2012111024A1 - Compositions pharmaceutiques de dexlansoprazole - Google Patents

Compositions pharmaceutiques de dexlansoprazole Download PDF

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Publication number
WO2012111024A1
WO2012111024A1 PCT/IN2012/000097 IN2012000097W WO2012111024A1 WO 2012111024 A1 WO2012111024 A1 WO 2012111024A1 IN 2012000097 W IN2012000097 W IN 2012000097W WO 2012111024 A1 WO2012111024 A1 WO 2012111024A1
Authority
WO
WIPO (PCT)
Prior art keywords
dexlansoprazole
capsule
total weight
filled
layer
Prior art date
Application number
PCT/IN2012/000097
Other languages
English (en)
Inventor
Ravula Sayisiva Prasad
Muppalla RAMESH
Polasa SRIKANTH
Original Assignee
Suven Nishtaa Pharma Pvt 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 Suven Nishtaa Pharma Pvt Ltd filed Critical Suven Nishtaa Pharma Pvt Ltd
Publication of WO2012111024A1 publication Critical patent/WO2012111024A1/fr

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Classifications

    • 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
    • A61K9/48—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
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—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 present invention relates to the Pharmaceutical composition of Dexlansoprazole and process for the preparation thereof.
  • Dexlansoprazole is the R-enantiomer of Lansoprazole (a racemic mixture of the R- & S- isomers).
  • Dexlansoprazole is represented by the chemical formula as (+)-2-[(i?)- ⁇ [3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl ⁇ sulfinyl]-7H-benzimidazole, with the structure as follows
  • Dexlansoprazole is available in United States with the trade mark DEXILANT in the dosage form of delayed release capsules sold by Takeda Pharmaceutical America, Inc, for the treatment of symptomatic non-erosive gastro esophageal reflux disease- heart burn associated with gastro esophageal reflux disease (GERD) and erosive esophagitis.
  • the inactive excipients of DEXILANT include sugar spheres, magnesium carbonate, sucrose, low substituted hydroxy propyl cellulose, titanium dioxide, hydroxy propyl cellulose, hypromellose 2910, talc, methacrylic acid copolymer, polyethylene glycol 8000, Triethyl citrate, polysorbate 80, and colloidal silicon dioxide.
  • the capsule shell is made of hypromellose, carrageenan and potassium chloride. Based on the capsule shell color, blue contains FD&C Blue No.2 and Aluminum lake, grey contains ferric oxide and Aluminum lake and both contains titanium dioxide.
  • US Patents 6,462,058 and 6,664,256 disclose crystalline forms of Dexlansoprazole or a salt thereof.
  • US Patent 7,790,755 discloses a capsule comprising two kinds of tablet, granule or fine granule as (i) a granule, tablet or pellet in which a release of the active ingredient is controlled and the said pellet comprising the Dexlansoprazole as the active ingredient and a pH dependently soluble release- controlled coating layer which comprises one kind of polymeric substances soluble in the pH range of 6.0 to 7.5 and composition of (ii) a pellet, granule or a tablet comprising a core particle containing the active ingredient and enteric coat such that the active ingredient is released in the pH range of no less than 5.0 to no more than 6.0.
  • This patent further disclose the capsule comprising the two types of pellets in which or granules having dual delayed release of Dexlansoprazole wherein the first portion of the pellets are coated with the extended release coating layer and the second portion of the pellets are coated with the delayed release coating layer.
  • a Pharmaceutical capsule comprising the tablet, Pellets or granules comprising (i) a core ii) the first drug layer comprising 30-90% of Dexlansoprazole of the total weight of the Dexlansoprazole filled into the capsules iii) a first sub coating layer iv) an extended release layer comprising the pH dependently soluble polymer or the combinations thereof, said polymeric substance is soluble in the pH range of 6.0 to 7.5.
  • the capsule according to the above mentioned ( 1 ) wherein the first drug layer comprises the 30-90% of Dexlansoprazole of the total weight of the Dexlansoprazole filled into the capsules. 4. The capsule according to the above mentioned (3) wherein the first drug layer composition is 5- 15% of the total weight of the pellets or granules filled into the capsule. 5. The capsule according to the above mentioned (1 ) wherein the first sub coating layer composition is 5-10% of the total weight of the pellets or granules filled into the capsule. 6. The capsule according to the above mentioned ( 1 ) wherein the extended release layer is 5-10% of the total weight of the granules filled into the capsules. 7.
  • the capsule according to the above mentioned (1) wherein the extended release layer comprises the pH dependent soluble release polymer.
  • the pH dependent release soluble polymer is selected from the group consisting of hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate, carboxymethyl ethyl cellulose, methyl methacrylate-methacrylic acid copolymer, methacrylic acid-ethyl acrylate copolymer, methyl methacrylate- ethyl acrylate copolymer, hydroxy propyl acetate succinate and polyvinyl acetate phthalate. 9.
  • the capsule according to the above mentioned ( 1 ) wherein the second drug layer comprises 10-70% of the Dexlansoprazole of the total weight of the Dexlansoprazole filled into the capsules.
  • the capsule according to the above mentioned ( 1 ) wherein the second drug layer is 4-6% of the total weight of the granules filled into the capsules.
  • the capsule according to the above mentioned ( 1 ) comprises the basic inorganic salt as a stabilizer.
  • the present invention relates to a pharmaceutical capsule comprising the tablet, Pellet or granules comprising (i) a core ii) the first drug layer comprising 30-90% of Dexlansoprazole of the total weight of the Dexlansoprazole filled into the capsules iii) a first sub coating layer iv) an extended release layer comprising the pH dependently soluble polymer or the combinations thereof, said polymeric substance is soluble in the pH range of 6.0 to 7.5.
  • a second sub coating on the extended release layer vi) the second drug layer comprising 10-70% of the Dexlansoprazole of the total weight of the Dexlansoprazole filled into the capsules vii) a third sub coating layer onto the second drug layer viii) an enteric coating layer comprising the enteric coating polymer such that the 10-70% of the active ingredient is released in the pH range of no less than 5.0 to no more than 6.0.
  • the core particles used for the drug layering is the inactive carrier such as NON- PARIEL (NONPARIEL- 101 (particle diameter- 850 ⁇ m-710 ⁇ m, 710-500 ⁇ m and 500-355 ⁇ m), NONPARIEL- 103 (particle diameter- 850 ⁇ m-710 ⁇ m, 710-500 ⁇ m and 500-355 ⁇ m), NONPARIEL-105 (particle diameter- 850 ⁇ m-710 ⁇ m, 710-500 ⁇ m and 300-180 ⁇ m); and Celphere ( CP-507 (Particle diameter-500-710 ⁇ m ) and CP-305 (Particle diameter 300-500 ⁇ m) ) .
  • a core particle can be produced by granulating excipient such as lactose, white sugar, mannitol, corn starch and crystalline cellulose and Dexlansoprazole, using binders such as hydroxy propyl methyl cellulose, hydroxy propyl cellulose, methyl cellulose, a poly
  • the core particles composition is 5-15% of the total weight of the granules filled into the capsule.
  • the first drug layer comprises 30-90%) of total amount of the Dexlansoprazole filled into the capsule formulation.
  • the drug layering material is obtained by appropriately compounding the Dexlansoprazole Active ingredient with the polymeric substances such as low substituted hydroxy propyl cellulose, hydroxy propyl cellulose, hydroxy propyl methyl cellulose, poly vinyl pyrrolidinone, poly vinyl alcohol, methyl cellulose.
  • the first drug layer composition is 10- 15%) of the total weight of the granules filled into the capsule.
  • the coating material for the first sub coating layer include those obtained by appropriately compounding polymeric materials such as low substituted hydroxy propyl cellulose, hydroxy propyl methyl cellulose, poly vinyl pyrrolidone, poly vinyl alcohol, methyl cellulose.
  • the excipients such as titanium dioxide and talc may be suitably added to the Sub coating layer.
  • the first sub coating layer composition is 1 - 10% of the total weight of the granules filled into the capsule.
  • the pH dependent soluble polymer is preferably a substance which is dissolved at the higher pH (preferably a pH of 6.0 or above and 7.5 or below, and more preferably a pH of 6.5 or above and below 7.2).
  • the Dexlansoprazole polymers such as hydroxy propyl methyl cellulose phthalate, Cellulose acetate phthalate, carboxy methyl ethyl cellulose, methyl- methacrylate methacrylic acid copolymer (Eudragit L 100 (methacrylic acid copolymer L), or Eudragit S 100 (methacrylic acid copolymer S) ) methacrylic acid- ethyl acrylate polymer (Eudragit L I 00-55 (dried methacrylic acid copolymer LD) or Eudragit L30D-55 (methacrylic acid copolymer LD), methacrylic acid-methyl acrylate-methyl methacrylate copolymer (Eudragit L I 00-55
  • the extended release layer composition is 5- 10% of the total weight of the pellets or granules filled into the capsule.
  • the second sub coating on the extended release layer can be obtained by compounding polymeric materials such as low substituted hydroxy propyl cellulose, hydroxy propyl methyl cellulose, poly vinyl pyrrol idinone, poly vinyl alcohol, methyl cellulose.
  • the excipients such as titanium dioxide and talc may be suitably added to the Seal coating layer.
  • the second sub coating composition is 4-8% of the total weight of the pellets or granules filled into the capsule.
  • the second drug coating layer encompassing the second sub coat comprises 10-70% of total amount of the Dexlansoprazole filled into the capsule formul3 ⁇ 4tion.
  • the drug layering material is obtained by appropriately compounding the Dexlansoprazole Active ingredient with the polymeric substances such as low substituted hydroxy propyl cellulose, hydroxy propyl cellulose, hydroxy propyl methyl cellulose, poly vinyl pyrrolidinone, poly vinyl alcohol, methyl cellulose.
  • the second drug layer composition is 2-6% of the total weight of the granules filled into the capsule.
  • the coating for the second sub coating layer include those obtained by appropriately compounding polymeric materials such as low substituted hydroxy propyl cellulose, hydroxy propyl methyl cellulose, poly vinyl pyrrolidinone, poly vinyl alcohol, methyl cellulose.
  • the excipients such as titanium dioxide and talc may be suitably added to the Sub coating layer.
  • the third sub coating layer composition is 12- 10% of the total weight of the granules filled into the capsule.
  • the enteric coating layer comprises the methacrylic acid-ethyl acrylate polymer (Eudragit L I 00-55 (dried methacrylic acid copolymer LD) or Eudragit L30D-55 (methacrylic acid copolymer LD) that releases the 10-70% of the Dexlansoprazole in the pH range of no less than 5.0 to no more than 6.0.
  • the enteric coating layer composition is 20-25% of the total weight of the granules fi lled into the capsule.
  • Table- 1 provides the composition of batches of present invention.
  • Drug Loading-I To the purified water hydroxy propyl cellulose, magnesium carbonate and about 75% of total weight of the Dexlansoprazole to be filled into each capsule are added and homogenized. The coating solution prepared as above is coated onto the seal coated pellets using fluid bed processer.
  • Sub coat-I Hypromellose and talc are added to the solvent purified water and stirred till a homogenous suspension is formed. Suspension obtained is coated onto the drug loaded pellets using the fluid bed processer.
  • Extended release coating Extended release polymer Eudragit S 100, Triethyl citrate and talc are added to the purified water under stirring. Enteric coating suspension formed as above is coated onto the sub coated pellets.
  • Drug Loading- II To the purified water hydroxy propyl cellulose, magnesium carbonate and 25% of the total weight of the Dexlansoprazole filled into capsules are added and homogenized. The drug coating solution prepared as above is coated onto the sub coated-II pellets obtained in step no.5. 7. Sub Coating II: Hypromellose and talc are added to purified water and stirred a homogenous suspension is obtained. Suspension obtained as above is coated onto the drug loaded II pellets obtained in the step no. 6 using the fluidized bed processor. 8. Enteric coating: Purified water is divided into portions.

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  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
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Abstract

La présente invention concerne une capsule pharmaceutique comprenant le comprimé, les pastilles ou les granules comprenant i) un cœur, ii) la première couche de médicament comprenant 30-90 % de dexlansoprazole du poids total de dexlansoprazole remplissant les capsules, iii) une première couche de sous-revêtement, iv) une couche de libération prolongée comprenant le polymère à solubilité dépendant du pH ou leurs combinaisons, ladite substance polymère étant soluble dans l'intervalle de pH de 6,0 à 7,5, v) un deuxième sous-revêtement sur la couche de libération prolongée, vi) la deuxième couche de médicament comprenant 10-70 % du dexlansoprazole du poids total de dexlansoprazole remplissant les capsules, vii) une troisième couche de sous-revêtement sur la deuxième couche de médicament, viii) une couche de revêtement entérique comprenant le polymère de revêtement entérique de telle sorte que 10-70 % de l'ingrédient actif sont libérés dans l'intervalle des pH qui ne sont pas inférieurs à 5,0 et pas supérieurs à 6,0.
PCT/IN2012/000097 2011-02-18 2012-02-13 Compositions pharmaceutiques de dexlansoprazole WO2012111024A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN3943CH2010 2011-02-18
IN3943/CHE/2010 2011-02-18

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WO2012111024A1 true WO2012111024A1 (fr) 2012-08-23

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6462058B1 (en) 1999-06-17 2002-10-08 Takeda Chemical Industries, Ltd. Benzimidazole compound crystal
US6664256B1 (en) 2000-07-10 2003-12-16 Kowa Co., Ltd. Phenylpyridazine compounds and medicines containing the same
WO2006049565A1 (fr) * 2004-11-04 2006-05-11 Astrazeneca Ab Nouvelles formulations de comprimes a liberation modifiee pour inhibiteur de la pompe a protons
WO2006076338A2 (fr) * 2005-01-12 2006-07-20 Pozen Inc. Forme dosifiee contre les troubles gastro-intestinaux
WO2007075980A2 (fr) * 2005-12-20 2007-07-05 Teva Pharmaceutical Industries Ltd. Comprimes de lansoprazole se desintegrant oralement
EP1930030A1 (fr) * 2005-09-29 2008-06-11 Eisai R&D Management Co., Ltd. Préparation pour impulsion ayant de meilleures propriétés de désintégration in vivo
US7790755B2 (en) 2002-10-16 2010-09-07 Takeda Pharmaceutical Company Limited Controlled release preparation
WO2010117756A2 (fr) * 2009-03-31 2010-10-14 Dr. Reddy's Laboratories Ltd Formulations pharmaceutiques de benzimidazole substitué
WO2012001705A2 (fr) * 2010-06-29 2012-01-05 Cadila Healthcare Limited Compositions pharmaceutiques de (r)-lansoprazole

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6462058B1 (en) 1999-06-17 2002-10-08 Takeda Chemical Industries, Ltd. Benzimidazole compound crystal
US6664256B1 (en) 2000-07-10 2003-12-16 Kowa Co., Ltd. Phenylpyridazine compounds and medicines containing the same
US7790755B2 (en) 2002-10-16 2010-09-07 Takeda Pharmaceutical Company Limited Controlled release preparation
WO2006049565A1 (fr) * 2004-11-04 2006-05-11 Astrazeneca Ab Nouvelles formulations de comprimes a liberation modifiee pour inhibiteur de la pompe a protons
WO2006076338A2 (fr) * 2005-01-12 2006-07-20 Pozen Inc. Forme dosifiee contre les troubles gastro-intestinaux
EP1930030A1 (fr) * 2005-09-29 2008-06-11 Eisai R&D Management Co., Ltd. Préparation pour impulsion ayant de meilleures propriétés de désintégration in vivo
WO2007075980A2 (fr) * 2005-12-20 2007-07-05 Teva Pharmaceutical Industries Ltd. Comprimes de lansoprazole se desintegrant oralement
WO2010117756A2 (fr) * 2009-03-31 2010-10-14 Dr. Reddy's Laboratories Ltd Formulations pharmaceutiques de benzimidazole substitué
WO2012001705A2 (fr) * 2010-06-29 2012-01-05 Cadila Healthcare Limited Compositions pharmaceutiques de (r)-lansoprazole

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