Multi-particulate pharmaceutical composition of quetiapine

Abstract

The present invention discloses an extended release multi-particulate sprinkle composition comprising a plurality of discrete units, each discrete unit comprising quetiapine or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

1 . An extended release multi-particulate sprinkle dosage form comprising a plurality of discrete units, wherein each unit comprises:
 a) a drug core comprising quetiapine or a pharmaceutically acceptable salt thereof;   b) at least two coatings on the drug core wherein one of the at least two coatings comprises a pH sensitive polymer; and   wherein the release of the drug is controlled by a combination of said at least two coatings.   
     
     
         2 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein out of the two coatings surrounding the core, at least one coating is an extended release coating and the other coating is a delayed release coating. 
     
     
         3 . The extended release multi-particulate sprinkle dosage form according to  claim 2 , wherein the extended release coating comprises a pH neutral polymer in an amount of about 50% to about 80% based on the weight of the enteric coating. 
     
     
         4 . The extended release multi-particulate sprinkle dosage form according to  claim 2 , wherein the delayed release coating comprises a pH sensitive polymer in an amount of about 55% to about 95% based on the weight of the delayed-release coating. 
     
     
         5 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein out of the two coatings surrounding the core, at least one coating comprises a pH neutral polymer or a pH sensitive polymer. 
     
     
         6 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the two coatings may optionally comprise a combination of a pH sensitive and pH neutral polymer. 
     
     
         7 . The extended release multi-particulate sprinkle dosage form according to  claim 1  wherein the drug core is devoid of any release controlling polymer. 
     
     
         8 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the coating may further comprise an optional non-function coating. 
     
     
         9 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the dosage form is a sustained or controlled release dosage form. 
     
     
         10 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the dosage form is a delayed or modified release dosage form. 
     
     
         11 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein said composition further comprises pharmaceutically acceptable excipients selected from a diluent, a binder, a disintegrant, a pore-former, a lubricant, a glidant, a surfactant, a sweetener, an anti-tacking agent, an opacifier, an anti-foaming agent, a coloring agent, a flavoring agent, or a mixture thereof. 
     
     
         12 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the drug release from the multiparticulate dosage form is controlled with a combination of at least one pH neutral polymer in a pH neutral coating and at least one pH sensitive polymer in a pH sensitive coating. 
     
     
         13 . The extended release multi-particulate sprinkle dosage form according  claim 1 , wherein the dosage form is in the form of a sachet, pouch or capsule. 
     
     
         14 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein at least one of the discrete units is a form selected from a pellet, a bead, a particle, a granule or a mini-tablet. 
     
     
         15 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the pH neutral polymer is a water-insoluble polymer. 
     
     
         16 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the dosage form further comprises a pore former, wherein the ratio of the pH neutral polymer and the pore former is 80:20 to 95:5. 
     
     
         17 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein D50 of at least one of said discrete units is in a range of about 0.7 to 1.3 mm or particle size of the discrete units is less than about 1.6 mm. 
     
     
         18 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein said dosage form when administered orally as a single dose with high fat meals results in not more than a 35% change in Cmax or AUC when compared to a similar dosing under fasting condition. 
     
     
         19 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the administration of the sprinkle dosage form under fasting conditions provides a Cmax in range of about 180 ng/mL to about 450 ng/mL and/or a mean AUC0-inf in the range of 4000 hr·ng/mL to 4800 hr·ng/mL. 
     
     
         20 . The extended release multi-particulate sprinkle dosage form according to  claim 1 , wherein the administration of the sprinkle dosage form under fed conditions provides a Cmax in range of about 250 ng/mL to about 650 ng/mL and/or a mean AUC0-inf in the range of 4300 hr·ng/mL to 6300 hr·ng/mL. 
     
     
         21 . The extended release multi-particulate sprinkle dosage according to  claim 1 , wherein said multi-particulate sprinkle dosage form releases not more than 30% of quetiapine when measured in a United States Pharmacopeia (USP) type I dissolution apparatus, 200 rpm, at a temperature of 37° C.±0.5° C. in 1000 mL of pH 6.60 phosphate buffer follow on media (after 2 hours dissolution in 0.1 NHCl) after 1st hour of buffer stage. 
     
     
         22 . An extended release multi-particulate sprinkle dosage form comprising a plurality of discrete units, wherein said multi-particulate sprinkle dosage form releases about 40% to about 70% of quetiapine when measured in a United States Pharmacopeia (USP) type I dissolution apparatus, 200 rpm, at a temperature of 37° C.±0.5° C. in 1000 mL of pH 6.60 phosphate buffer follow on media (after 2 hours dissolution in 0.1 NHCl) after 6th hour of buffer stage. 
     
     
         23 . An extended release multi-particulate sprinkle dosage form comprising a plurality of discrete units, wherein said multi-particulate sprinkle dosage form comprise coated discrete units having a particle size in the range of 0.5 mm-1.6 mm, wherein the discrete units when exposed to water for 60 minutes in a syringe, and then passed through a 12 French nasogastric tube into a dissolution medium of 0.1N HCl, releases not more than 0.5% of quetiapine N-oxide impurity after 2 hours, when placed in 1000 mL of 0.1N HCl at 100 rpm in USP apparatus I. 
     
     
         24 . The extended release multi-particulate sprinkle dosage form according to  claim 1  wherein, a higher amount of quetiapine in a dose range of 50-400 mg can be administered as a sprinkle dosage form for nasogastric administration, wherein the dosage form can be administered to a patient suffering from a psychiatric disorder selected from schizophrenia, bipolar disorder, mania, depression where patients are unconscious or having swallowing difficulty. 
     
     
         25 . A method for treating a patient suffering from a psychotic disorders selected from schizophrenia, bipolar disorder, mania, or depression, or as an adjunctive therapy with an antidepressant, by administering a therapeutically effective amount of a multi-particulate quetiapine sprinkle dosage form according to  claim 1 . 
     
     
         26 . An extended release multi-particulate sprinkle dosage form prepared by a process comprising:
 mixing quetiapine or its pharmaceutically acceptable salt with suitable excipients and at least two coatings on a drug core wherein one of the at least two coatings comprises a pH sensitive polymer; and   wherein the release of the drug is controlled by a combination of the at least two coatings.   
     
     
         27 . The method of  claim 26 , wherein said process comprises:
 i. mixing quetiapine or a pharmaceutical acceptable salt thereof with suitable pharmaceutical acceptable excipients in a dry mix followed by granulation using a suitable technique;   ii. extruding the resultant from step i above followed by spheronization;   iii. drying the resulting drug containing spheroids;   iv. sifting the resultant from step iii above;   v. coating the drug containing core with suitable coatings; and   vi. lubricating the coated core followed by filling into a suitable sachet or pouch or capsule.   
     
     
         28 . The method of  claim 26 ,
 wherein said excipient is selected from a diluent, a binder, a disintegrant, a pore-former, a plasticizer, a lubricant, a glidant, a surfactant, a sweetener, an anti-tacking agent, an opacifier, an anti-foaming agent, a coloring agent, a flavoring agent or a mixture thereof.