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
  • A61K9/5005—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
  • 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
  • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
• • 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
  • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
  • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
  • A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• • 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
  • A61K9/5052—Proteins, e.g. albumin
• • 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
  • A61K9/48—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 controlled release solid oral compositions of dexlansoprazole or its pharmaceutically acceptable salts and process for preparing the same.
• dexlansoprazole is (+)-2-[(R)- ⁇ [3-methyl-4- (2,2,2trifluoroethoxy)pyridin-2-yl] methyl ⁇ sulfinyl]-iH-benzimidazole.
• Dexlansoprazole is the i?-enantiomer of lansoprazole (a racemic mixture of the R- and S-enantiomers). Its empirical formula is C 16 H 14 F 3 N 3 02S, corresponding to a molecular weight of 369.36 and having the following structural formula:
• Dexlansoprazole is marketed under the trade name of DEXILANT in United States by Takeda in the form of 30 mg and 60 mg delayed release oral capsules, indicated for the healing of erosive esophagitis, maintenance of healed erosive esophagitis and for the treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease.
• U.S. Patent Nos. 6,462,058, 6,664,276, 6,939,971 and 7,285,668 disclose various polymorphic forms of dexlansoprazole and process for their preparation.
• U.S. Patent No. 7,790,755 discloses capsule comprising: (i) a tablet, granule, or fine granule comprising a core particle containing the active ingredient and a pH dependent soluble release-controlled coating layer that releases the active ingredient in a pH range of 6 to 7.5; and (ii) a tablet, granule or fine granule comprising a core particle containing the active ingredient and an enteric coating, such that the active ingredient is released in the pH range of no less than 5 to no more than 6.
• U.S. Patent No. 7,732,474 describes inert core coated with drug which is further coated with one or more optional separating layers and an outer layer comprising an enteric coating, wherein the drug is mixed with a stabilizer comprising microcrystalline cellulose.
• U.S. Patent Application Publication No. 2011/0189271 describes dexlansoprazole composition comprising inert core coated with dexlansoprazole solution containing metal compound, thereby insitu formation of dexlansoprazole salt, which is further coated with enteric layer.
• Inventors of the present invention have developed controlled release pharmaceutical compositions of dexlansoprazole with pH-independent polymer/ material using simplified process that were found to be comparable with marketed DEXILANT ® capsules.
• the present invention relates to controlled release solid oral pharmaceutical composition
• a pH independent polymer/ material comprising dexlansoprazole, a pH independent polymer/ material and at least one pharmaceutically acceptable excipient.
• pharmaceutical capsule composition of dexlansoprazole comprising pellets or spheres or mini tablets or multiunit particulate systems (MUPS) wherein release of the active ingredient is controlled by pH independent polymer/ material selected from ethyl cellulose, starch acetate, protein based zein and combinations thereof.
• MUPS multiunit particulate systems
• composition comprising dexlansoprazole in the form of capsule which comprises: a) a core in the form of i) an active core comprising dexlansoprazole and release control pH independent polymer/ material, wherein the pH independent polymer/ material is present either in the matrix or coated on active core, or ii) an inert core coated with drug layer, followed by a release control coating comprising pH independent polymer/ material and (b) the resulting product is coated with dexlansoprazole followed by a separating layer, and finally (c) coated with enteric polymer.
• Another embodiment of the present invention relates to pharmaceutical composition comprising dexlansoprazole or its pharmaceutically acceptable salts thereof, pH independent polymer/ material or non-gelling polymer or hydrophobic polymer and one or more pharmaceutically acceptable excipients.
• the present invention provides delayed and controlled release solid oral compositions comprising dexlansoprazole or a pharmaceutically acceptable salt thereof.
• composition according to the present invention is used for healing of erosive esophagitis, maintenance of healed erosive esophagitis and for the treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease.
• the term “dexlansoprazole” includes dexlansoprazole in the form of free base or its pharmaceutically acceptable salt, amorphous dexlansoprazole, crystalline dexlansoprazole or any isomer or derivative, hydrate or solvate, prodrug or combinations thereof.
• terms such as “active” or “active ingredient” or “drug” or “drug substance” or “pharmacologically active agent” or “active substance” may be used interchangeably and synonymously for dexlansoprazole or its pharmaceutically acceptable salts thereof.
• effective amount or “therapeutically effective amount” used interchangeably, are defined to mean the amount or quantity of the active drug (e.g. dexlansoprazole) which is sufficient to elicit an appreciable biological response when administered to a patient.
• excipients as used herein means a component of a pharmaceutical product that is not an active ingredient such as, for example, fillers, diluents, carriers and the like.
• the excipients that are useful in preparing a pharmaceutical composition are generally safe and nontoxic.
• intermediate layer or “sub coating” or “separating layer” used here in synonymously refers to a layer formed between drug and an enteric layer/ control release layer.
• controlled-release in accordance with the present invention is intended to composition that releases the drug from its dosage form over a period of about 6 hours.
• yed-release refers to composition that resists drug release in gastric fluid and disintegrates in intestinal fluid.
• composition, or formulation refers to solid oral dosage form such as a capsule or tablet comprising dexlansoprazole.
• compositions of the present invention can be made into solid dosage forms such as tablets, capsules, multiunit particulate systems (MUPS), granules, solid dispersions, pellets, spheres, beads, particles, mini-tablets and the like.
• MUPS multiunit particulate systems
• the present invention relates to controlled release pharmaceutical composition
• pH independent polymer/ material is selected from ethyl cellulose, starch acetate, protein based zein and combinations thereof.
• excipients of the present invention comprise diluents, basic inorganic salts, binders, disintegrants, glidants, lubricants and combinations thereof.
• Suitable diluents include mannitol, microcrystalline cellulose, sorbitol, talc, lactose, sugar, starches, modified starches, inorganic salts, calcium sulfate, xylitol, lactitol, starch, pregelatinized starch, kaolin, sucrose, dextrates, dextrin, maltodextrin, dextrose, calcium carbonate, calcium sulfate, dibasic calcium phosphate, tribasic calcium phosphate, magnesium carbonate, magnesium oxide and the like and combinations thereof.
• Suitable basic inorganic salts include carbonates/ bicarbonates/ phosphates/ hydroxides/ oxides of calcium, sodium, magnesium and the like and combinations thereof.
• magnesium carbonate and sodium bicarbonate were used alone or in combination.
• Suitable binders include hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, guar gum, xanthan gum, lactose, starches such as corn starch, potato starch, modified starches, sugars, pectin, wax binders, microcrystalline cellulose, methylcellulose, carboxymethylcellulose, copolyvidone, sodium alginate, acacia, alginic acid, tragacanth, carboxymethylcellulose sodium, ethyl cellulose, gelatin, liquid glucose, povidone and pregelatinized starch and the like and combinations thereof.
• Suitable disintegrants include crospovidone, polacrillin potassium, croscarmellose sodium, sodium starch glycolate, microcrystalline cellulose, polyvinylpyrrolidone, carboxymethyl cellulose calcium, starches such as corn starch, potato starch, pre-gelatinized and modified starches, clays, bentonite and the like and combinations thereof.
• Suitable glidants include colloidal silica, calcium silicate, magnesium silicate, silicon hydrogel, cornstarch, talc and the like and combinations thereof.
• Suitable lubricants include talc, magnesium stearate, calcium stearate, sodium stearyl fumarate, zinc stearate, stearic acid, fumaric acid, palmitic acid, carnauba wax, hydrogenated vegetable oils, mineral oil, polyethylene glycols and the like and combinations thereof.
• Useful additives for coating include, but are not limited to, plasticizers, antiadherents, opacifiers, solvents, and optionally colorants, lubricants, pigments, antifoam agents, and polishing agents.
• plasticizer as used herein is intended to mean a compound used in solid dosage forms to provide the desired plasticity to the coating.
• Suitable plasticizers include triethyl citrate, polyethylene glycol, propylene glycol, acetyl triethyl citrate, acetyltributyl citrate, benzyl benzoate, chlorbutanol, dextrin, glycerin, glycerin monostearate, mannitol, lanolin alcohol, 2- pyrrolidine, sorbitol, triacetin, diacetylated monoglyceride, , tri butyl citrate, triethanolamine and the like and combinations thereof.
• ingredients such as stabilizers and antiadherants conventionally used for pharmaceutical formulations may also be included in the present formulation.
• pharmaceutical capsule composition of dexlansoprazole comprising pellets or spheres or mini tablets or multiunit particulate systems (MUPS) wherein release of the active ingredient is controlled by pH independent polymer/ material selected from ethyl cellulose, starch acetate, protein based zein and combinations thereof.
• MUPS multiunit particulate systems
• composition comprising dexlansoprazole in the form of capsule which comprises: a) a core in the form of i) an active core comprising dexlansoprazole and release control pH independent polymer/ material, wherein the pH independent polymer/ material is present either in the matrix or coated on active core, or ii) an inert core coated with drug layer, followed by a release control coating comprising pH independent polymer/ material and (b) the resulting product is coated with dexlansoprazole followed by a separating layer, and finally (c) coated with enteric polymer.
• Controlled release compositions of dexlansoprazole may be processed either by layering technology or extrusion and spheronization or wet granulation.
• Inert core may be in the form of sugar spheres, microcrystalline cellulose spheres, lactose spheres, non-pareil seeds, silicon dioxide glass beads or sodium bicarbonate beads.
• Extrusion and spheronization process comprise the steps of: (i) blending dexlansoprazole, one or more excipients and optionally a pH independent polymer/ material (ii) granulating the blended mixture of step no (i) with binder solution to form a wet mass, (iii) extruding the wet mass of step no (ii) followed by spheronization using spherodizer to obtain spheroids/ spherical granules/ spheres, (iv) coating the spheroids of step no (iii) with dexlansoprazole followed by a separating layer, and finally (v) coating the with enteric polymer, (vi) blending the enteric coated spheroids of step no (v) with a lubricant and filling into capsules or alternatively compressing into tablets.
• Mini-tablets of the present invention may be prepared by wet granulation process including: (i) sifting and blending dexlansoprazole with one or more excipients to form a dry mix, (ii) granulating the dry mix of step no. (i) using binder solution to form granules followed by drying, (iii) blending the granules of step no. (ii) with lubricant and finally compressing into mini- tablets, (iv) optionally, subcoating the mini-tablets, (v) coating the mini-tablets of step no. (iii or iv) with pH independent polymer/ material, (vi) coating the resulted product of step no.
• Minitablets of the present invention have a size of 5mm to 7mm in diameter.
• core is in the form of pellets or spheres or granules or mini tablets or multiunit particulate systems (MUPS).
• Enteric coated multiple unit cores/ minitablets of the present invention were further lubricated/ or mixed with one or more pharmaceutically acceptable excipients and finally filled into capsules or alternatively compressed into tablets.
• the present invention further relates to a pharmaceutical composition
• a pharmaceutical composition comprising dexlansoprazole or its pharmaceutically acceptable salts thereof, pH independent polymer/ material or non-gelling polymer or hydrophobic polymer and one or more pharmaceutically acceptable excipients.
• the present invention provides delayed and controlled release solid oral pharmaceutical compositions comprising dexlansoprazole or a pharmaceutically acceptable salt thereof and a pH independent hydrophobic material selected from ethyl cellulose, starch acetate, protein based zein and combinations thereof.
• Delayed release is release delayed for a period of time after administration and can be accomplished, for example, by applying a coating of enteric materials.
• the enteric polymer may be one or more selected from a group consisting of Poly(methyl acrylate, methyl methacrylate, methacrylic acid) 7: 3 :1 (e.g., Eudragit FS 30D), Poly(methacrylic acid, methyl methacrylate) 1 : 1 (e.g., Eudragit L 100), Poly(methacrylic acid, ethyl acrylate) 1 : 1 (e.g., Eudragit ® L 30 D-55), hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, hydroxymethylethyl cellulose phthalate, carboxymethylethyl cellulose and the like.
• a method for healing of erosive esophagitis, maintenance of healed erosive esophagitis, symptomatic non-erosive gastroesophageal reflux disease comprising administering a composition comprising a therapeutically effective amount of dexlansoprazole.
• crospovidone was also dispersed in solution of step 1.
• dexlansoprazole and cremophore were dispersed in dispersion of step 2 and coated over sugar spheres in wurster coater.
• mannitol was dissolved in purified water and the resulted solution was coated over the pellets obtained in step 4 till desired weight gain is achieved.
• hydroxypropyl cellulose and magnesium carbonate light were dissolved in purified water and methanol separately.
• crospovidone was also dispersed in solution of step 6.
• dexlansoprazole and cremophore were dispersed in dispersion of step 7 and coated over step 4 pellets in wurster coater.
• hydroxypropyl methylcellulose was dissolved in purified water and talc was dispersed with stirring or homogenization.
• step 9 solution of step 9 was sprayed on coated pellets of step 9 till desired weight gain is achieved.
• eudragit FS30D/ eudragit L 100 and plasacryl T20 were dispersed in purified water and coated over pellets obtained in step 10 till desired weight gain is achieved.
• step 11 the pellets of step 11 were lubricated with talc and encapsulated in hard gelatin capsules.
• Buffer stage 900 ml of pH 7.0 phosphate buffer with 5 mM of SLS
• Titanium dioxide 1.350
• Hydroxypropyl cellulose was dissolved in purified water, sodium bicarbonate was dissolved in methanol and both the solutions were mixed together.
• crospovidone was also dispersed in solution obtained in step 1.
• dexlansoprazole was dispersed in dispersion of step 2 and coated over sugar spheres in wurster coater.
• hypromellose was dissolved in purified water; talc and titanium dioxide was dispersed with stirring or homogenization.
• step 4 solution of step 4 was sprayed on the drug coated pellets of step 3 till desired weight gain is achieved.
• ethycellulose was dispersed in purified water and coated over the pellets obtained in step 5 till desired weight gain is achieved.
• hydroxypropyl cellulose and sodium bicarbonate were dissolved in purified water and methanol separately.
• dexlansoprazole was dispersed in dispersion of step 8 and coated over pellets obtained in step 6 in wurster coater.
• hypromellose was dissolved in purified water; talc and titanium dioxide was dispersed with stirring or homogenization.
• step 10 solution of step 10 was sprayed on coated pellets of step 9 till desired weight gain is achieved.
• talc and titanium dioxide were dispersed in purified water.
• eudragit, tri ethyl citrate was dispersed in dispersion of step 12 and coated over pellets obtained in step 11 till desired weight gain is achieved.
• pellets were lubricated with talc and encapsulated in hard gelatin capsules.
• Hydroxypropyl cellulose was dissolved in purified water, sodium bicarbonate was dissolved methanol and both the solutions were mixed together.
• step 2 mannitol, crospovidone and dexlansoprazole were mixed together. 3. mixture obtained in step 2 was granulated with solutions obtained in step 1, dried and milled to get desired granules; obtained granules were lubricated with magnesium stearate and compressed to mini tablets of 5.2 mm using suitable punches.
• hypromellose was dissolve in purified water; talc and titanium dioxide were dispersed in it with stirring or homogenization.
• step 4 solution of step 4 was sprayed on mini tablets of step 3 till desired weight gain is achieved.
• ethycellulose was dispersed in purified water and coated over pellets obtained in step 5 till desired weight gain is achieved.
• hydroxypropyl cellulose and sodium bicarbonate were dissolved in purified water and methanol separately.
• crospovidone was also dispersed in solution of step 7 .
• dexlansoprazole was dispersed in dispersion of step 8 and coated over mini tablets obtained in step 6 in wurster coater.
• hypromellose was dissolved in purified water; talc and titanium dioxide were also dispersed in it with stirring or homogenization.
• step 10 solution of step 10 was sprayed on to coated pellets of step 9 till desired weight gain is achieved.
• talc was dispersed in purified water.
• the obtained pellets were lubricated with talc and encapsulated in hard gelatin capsules.
• Hydroxypropyl cellulose was dissolved in purified water, sodium bicarbonate was dissolved in methanol and both the solutions were mixed together.
• step 1 mannitol, microcrystalline cellulose and dexlansoprazole were mixed and granulated with solution obtained in step 1.
• hypromellose was dissolved in purified water; talc and titanium dioxide were also dispersed in it with stirring or homogenization.
• step 5 solution of step 5 was sprayed on pellets of step 4 till desired weight gain is achieved.
• ethycellulose was dispersed in purified water and coated over pellets obtained in step 6 till desired weight gain is achieved.
• hydroxypropyl cellulose and sodium bicarbonate were dissolved in purified water separately.
• crospovidone was also dispersed in solution of step 8 .
• dexlansoprazole was dispersed in dispersion of step 9 and coated over pellets obtained in step 7 in wurster coater.
• hypromellose was dissolved in purified water; talc and titanium dioxide were also dispersed in it with stirring or homogenization.
• step 11 solution of step 11 was sprayed on coated pellets of step 10 till desired weight gain is achieved.
• talc and titanium dioxide were dispersed in purified water.
• step 13 eudragit, triethyl citrate were dispersed in step 13 dispersion and coated over pellets of step 12 till desired weight gain is achieved.
• the pellets were lubricated with talc and encapsulated in hard gelatin capsules.
• Hydroxypropyl cellulose was dissolved in purified water, sodium bicarbonate was dissolved in methanol and both the solutions were mixed together.
• mannitol, microcrystalline cellulose and dexlansoprazole were mixed together and granulated with solution obtained in step 1.
• hypromellose was dissolved in purified water; talc and titanium dioxide were also dispersed in it with stirring or homogenization.
• step 5 solution of step 5 was sprayed on pellets of step 4 till desired weight gain is achieved.
• starch acetate/ zein was dispersed in dichloromethane and coated over pellets obtained in step 6 till desired weight gain is achieved.
• crospovidone was dispersed in solution of step 8.
• dexlansoprazole was dispersed in dispersion of step 9 and coated over pellets of step 7 in wurster coater.
• hypromellose was dissolved in purified water; talc and titanium dioxide were dispersed in it with stirring or homogenization.
• step 11 solution of step 11 was sprayed on coated pellets of step 10 till desired weight gain is achieved.
• talc and titanium dioxide were dispersed in purified water.
• eudragit, triethyl citrate were dispersed in the dispersion obtained in step 13 and pellets obtained in step 12 till desired weight gain is achieved.
• the pellets were lubricated with talc and encapsulated in hard gelatin capsules.
• xanthan gum, guar gum, microcrystalline cellulose and dexlansoprazole were mixed together and granulated with solution of step 1.
• hypromellose was dissolved in purified water; talc and titanium dioxide were also dispersed in it with stirring or homogenization.
• step 5 solution of step 5 was sprayed on to pellets of step 4 till desired weight gain is achieved.
• zein was dispersed in dichloromethane and coated over pellets obtained in step 6 till desired weight gain is achieved.
• crospovidone was dispersed in solution of step 8.
• dexlansoprazole was dispersed in dispersion of step 9 and coated over pellets obtained in step 7 in wurster coater.
• hypromellose was dissolved in purified water; talc and titanium dioxide were dispersed in it with stirring or homogenization.
• step 11 solution of step 11 was sprayed on to the coated pellets of step 10 till desired weight gain is achieved.
• talc and titanium dioxide were dispersed in purified water.
• eudragit, triethyl citrate were dispersed in dispersion of step 13 and coated over pellets obtained in step 12 till desired weight gain is achieved.
• the pellets were lubricated with talc and encapsulated in hard gelatin capsules.
• Hydroxypropyl cellulose was dissolved in purified water, sodium bicarbonate was dissolved in methanol and both the solutions were mixed together.
• mannitol, microcrystalline cellulose and dexlansoprazole were mixed together and granulated with solutions obtained in step 1 and ethylcellulose aqueous dispersion.
• hydroxypropyl cellulose was dissolved in purified water.
• crospovidone was also dispersed in solution of step 5.
• dexlansoprazole was dispersed in dispersion of step 6 and coated over pellets of step 4 in wurster coater.
• hypromellose was dissolved in purified water; talc and titanium dioxide were also dispersed in it with stirring or homogenization.
• step 8 was sprayed on coated pellets of step 7 till desired weight gain is achieved.
• talc and titanium dioxide were dispersed in purified water.
• eudragit, triethyl citrate were also dispersed in dispersion of step 10 and coated over pellets obtained in step 9 till desired weight gain is achieved.
• pellets were lubricated with talc and encapsulated in hard gelatin capsules.

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