Formulating Buffered Dissolution Media for Sparingly Soluble Weak Acid and Weak Base Drug Compounds Based on Microenvironmental pHo Considerations

Abstract

The theoretical framework for dissolution of weak acid and weak base drug compounds in buffered media is well established. Therefore, this article is intended to provide a review of this framework and apply it to formulate buffered dissolution media based on ionic equilibrium conditions within the diffusion layer at the solid–liquid interface. The pHo in the microenvironment is identified as a singularly important parameter that reflects ionic interactions between dissolving drug and buffer at the solid–liquid interface. This article is focused on (1) formulating buffered dissolution media based on ionic equilibrium conditions at the solid–liquid interface, (2) identifying key physicochemical parameters for both drug and buffer that are relevant to buffer formulation, and (3) providing experimental and calculation-based methods to estimate the pHo at the solid–liquid interface. A shift in emphasis from relying solely on bulk buffer pH properties forms a basis for formulating buffered dissolution media and also provides insight into the physicochemical factors that affect the dissolution rate of the drug compound.