Unsuitability of pharmacopoeial dissolution conditions for entacapone: Effects of various dissolution parameters on dissolution profile

Abstract

Purpose: Entacapone, a catechol-O-methyltransferase inhibitor, is poorly water soluble
(BCS class IV). The dissolution profile of pure Entacapone is improved in the presence
of an alkaline buffer and after addition of a surfactant by facilitating the drug release
process at the solid/liquid interface. Rationale: According to USP the best dissolution
medium for Entacapone is phosphate buffer 5.8 in type II paddle-type apparatus with
a paddle speed of 50 rpm. Materials and Methods: In this article an effect of various
parameters (buffer, surfactant, and RPM) on the dissolution profile of Entacapone is
studied by applying factorial design 33 (phosphate buffer- 5.3, 5.8, and 6.8; sodium
lauryl sulfate- 0.5%, 1.0%, and 1.5%; rotation speed of paddle- 50, 75, and 100). Pure
Entacapone pellets were formed using a hydraulic press. Conclusion: The release profile
data revealed that the dissolution profile of Entacapone is remarkably improved in the
alkaline medium (6.8), addition of surfactant does not affect the release profile, whereas
increasing RPM of the paddle reduces the dissolution profile; hence it can be stated that
Entacapone dissolution is pH dependent, showing maximum dissolution and pH 6.8
which is contradictory to the conditions specified in USP 2010.