Toward Biorelevant Dissolution: Application of a Biphasic Dissolution Model as a Discriminating Tool for HPMC Matrices Containing a Model BCS Class II Drug

Abstract

The potential of a biphasic dissolution system to assist with the analysis of controlled-release (CR), Biopharmaceutics Classification System (BCS) Class II pharmaceutical products has been investigated. Use of a biphasic dissolution medium (aqueous/octanol) provided sink conditions and afforded complete dissolution of nifedipine formulated in a CR matrix tablet while maintaining the dosage form in an aqueous environment. This was not possible in a monophasic (aqueousonly) dissolution medium. Consequently, the biphasic model allowed the discrimination of three formulations containing different HPMC loadings while the monophasic medium did not. The performance of the formulations in conventional dissolution media incorporating the inorganic salt dibasic sodium phosphate, the surfactant sodium dodecyl sulfate (SDS), and ethanol as solubility modifiers was assessed. The addition of the salt and surfactant failed to produce complete discrimination in a predictive manner. The use of a hydroalcoholic medium comprising water and ethanol enabled the statistical discrimination of the three formulations but not as effectively as the biphasic medium.