EXTENDED RELEASE FORMULATION OF NEVIRAPINE

摘要

Disclosed herein is a pharmaceutical composition in the form of a tablet which; (a) comprises 300 mg or 400 mg of nevirapine in an extended release matrix and which, when administered as a single-dose to a fasting human, wherein the extended release matrix comprises a hydrophilic polymer selected from hydroxypropylmethylcellulose (HPMC, hypromellose), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), xanthan gum, sodium alginate, polyethylene oxide, and crosslinked homopolymers and copolymers of acrylic acid, or a mixture thereof, which exhibits a single-dose fasting Tmax of 10 to 48 hr; which exhibits a Cmax,ss/Cmin,ss which is in the range of 1.1 to 2, measured during multiple-dosing; and which has an in-vitro dissolution profile such that at least 2% w/w and no more than 30% w/w of the nevirapine is released at 2 hours; at least 20% w/w and up to 100% w/w of the nevirapine is released at 8 hours; at least 40% w/w and and up to 100% w/w of the nevirapine is released at 14 hours, when dissolution is measured by the USP Paddle Method at 50 rpm at a volume of 900 mL aqueous buffer containing 6% w/w of sodium lauryl sulfate, having a pH of 6.8 at 37°C wherein a 300mg desirably exhibits (1) a geometric mean Cmax of 1,000 to 2,300 ng/mL; and (2) a geometric mean AUC0-? of 73,400 to 178,100 hr(ng/mL); and which, when administered in multiple doses to a fasting human, exhibits (1) a geometric mean Cmax, ss of 2,300 to 3,700 ng/mL; and (2) a geometric mean AUC0-24, ss of 45,000 to 75,000 hr(ng/mL); or And for a 400mg dose exhibits: (1) a geometric mean Cmax of 1,210 to 2,740 ng/mL; and (2) a geometric mean AUCO-? of 109,000 to 237,000 hr(ng/mL); and which, when administered in multiple doses to a fasting human, exhibits (1) a geometric mean Cmax, ss of 3,100 to 4,900 ng/mL; and (2) a geometric mean AUC0-24, ss of 60,000 to 99,000 hr(ng/mL). Also disclosed in a tablet pharmaceutical dosage form wherein each table comprises: (a) 400 mg of anhydrous nevirapine; (b) 270 mg of Hypromellose 2208; (c) 400 mg of lactose monohydrate; and (d) 10 mg of Magnesium stearate; wherein each tablet is compressed by a force of 10-25 kN.