Maintaining Supersaturation of Active Pharmaceutical Ingredient Solutions with Biologically Relevant Bile Salts

Abstract

Currently, it is of interest to improve the oral absorption of poorly water-soluble therapeutic agents using supersaturating formulations. Understanding crystallization kinetics of supersaturated drug solutions is central to the design and evaluation of such formulations. Bile salts have drawn increasing attention in this context as they serve important roles in biorelevant dissolution media, in vivo, and have been shown to slow down the crystallization of active pharmaceutical ingredients. The goal of this study was to evaluate the impact of bile salt monomers and micelles on the crystallization of telaprevir, a poorly water-soluble drug, from aqueous solution. To better describe the crystallization driving force in the presence of the bile salts, a side-by-side diffusion cell was used to evaluate telaprevir mass flow rate, and hence solute activity, in the absence and presence of different bile salts. The effectiveness of monomeric and miceller bile salts as crystallization inhibitors was then evaluated...