Lupin, Inc.

Piramal Enterprises Limited

Chirag Anilkumar Shah

Milind Moreshwar Gharpure

Sajeev Chandran

Ashish Ashokrao Deshmukh

Ashutosh Jagtap

Changdev Raut

Navnath Patil

Navnath Shinde

Dhileepkumar Krishnmurthy

Dhananjay Sadashiv Bakhle

Snehal Ameet Gadve

Neha Sharma

A timed release pharmaceutical composition comprising donepezil is provided, wherein the composition exhibits the in vitro dissolution profile when tested in a Paddle dissolution apparatus at 50 rpm in 900 ml 6.8 buffer at 37&#xb0; C., less than about 20% w/w of donepezil is released in 3 to 6 hrs, and more than 90% w/w of donepezil is released after 12 hrs.

Pharmaceutical compositions of donepezil having specific in vitro dissolution profile or pharmacokinetics parameters

The present invention provides an improved process for the preparation of 8-chloro-1-phenyl-1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione (hereafter referred to as the compound (IV)), which is useful as a key intermediate for the synthesis of Clobazam (referred to as the compound (I)) 7-chloro-1-methyl-5-phenyl-1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione. The process of the present invention further involves transformation of the compound (IV) into Clobazam (I), comprising (a) reacting the compound (II) (as described herein) with monoalkyl malonate in the presence of a coupling agent to obtain the compound (III) (as described herein); followed by the cyclization using a base; (b) reacting the compound-IV (as described herein) obtained from step (a) with methylating agent. The process of the present invention involves formation of novel intermediates methyl 3-((4-chloro-2-(phenylamino)phenyl)amino)-3-oxopropanoate (IIIa) and 3-((4-chloro-2-(phenylamino)phenyl)amino)-3-oxopropanoic acid (V).

Process for the preparation of clobazam and its intermediate

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Maharashtra, India

Chirag Anilkumar Shah