US 11,918,590 B2
Stable extended release pharmaceutical composition of clozapine
Rikin Patel, Ahmedabad (IN); Kavan Pandya, Ahmedabad (IN); Piyush Kansagra, Ahmedabad (IN); Satyavan Dhavale, Ahmedabad (IN); and Ashish Sehgal, Ahmedabad (IN)
Assigned to Intas Pharmaceuticals Ltd., Ahmedabad (IN)
Filed by Intas Pharmaceuticals Ltd., Ahmedabad (IN)
Filed on Apr. 8, 2022, as Appl. No. 17/716,694.
Claims priority of application No. 202121058299 (IN), filed on Dec. 15, 2021.
Prior Publication US 2023/0181595 A1, Jun. 15, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/5513 (2006.01); A61K 9/20 (2006.01); A61K 9/48 (2006.01)
CPC A61K 31/5513 (2013.01) [A61K 9/20 (2013.01); A61K 9/48 (2013.01)] 8 Claims
 
1. A stable extended release pharmaceutical composition of Clozapine with one or more pharmaceutically acceptable excipients, comprising: a) granules, pellets, beads or spheroids comprising Clozapine with pharmaceutically acceptable excipients, b) a first seal coat layer comprising a hydrophilic polymer, c) an acidic coating comprising an acidic substance, d) a second seal coat layer comprising a hydrophilic polymer, (e) an extended release coating with a water insoluble polymer and a water soluble polymer, and (f) a third seal coat layer comprising a hydrophilic polymer,
wherein, the amount of the seal coating in the composition is from 2-20%; the amount of the acidic coating in the composition is from 20-40%; the amount of extended release coating in the composition is from 2-20%;
wherein, the hydrophilic polymer comprises hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methylcellulose, carboxymethylcellulose, polyethylene glycol, polyethylene oxides, or polyalcohols; the water insoluble polymer comprises Chitosan, polyurethanes, ethyl cellulose, cellulose acetate or waxes; and the water soluble polymer comprises hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methylcellulose, carboxymethylcellulose, polyethylene glycol, polyethylene oxides, or polyalcohols;
wherein the total impurities in the said pharmaceutical composition is not more than 2% w/w of Clozapine and wherein an assay of the quantity of Clozapine in the said pharmaceutical composition is from 95% to 105% upon storage at 40±2° C. and 75±5% relative humidity (RH) for 6 months, relative to the quantity of Clozapine in the pharmaceutical composition prior to storage; and
wherein the said composition comprises Clozapine having an effective particle size (D90) of less than about 10 micron that provides solubility of Clozapine of at least 20 mg/ml in 0.1N hydrochloric acid.