Impact of route of particle engineering on dissolution performance of posaconazole

Abstract

Even when they have similar particle size, micron sized drug crystals prepared via different process routes may still exhibit considerable variability in pharmaceutical properties, due to the anisotropy of molecular crystals. This study aims to evaluate the dissolution performance of micronized posaconazole obtained through both milling and precipitation, with and without polymer coating. To overcome the problem of pressure-induced amorphization of posaconazole, powder dissolution was performed instead of intrinsic dissolution, which requires compressing powder into pellets. However, direct powder dissolution was challenged by the poor dispersibility of micronized posaconazole powders because of their extremely poor wettability. To solve this problem, we pretreated powders by dispersing them in an aqueous solution with a surfactant. Despite posaconazole forming a hydrate after pretreatment, differences in measured powder dissolution rates are meaningful in predicting impact of routes of API engineering on biopharmaceutical performance since hydration of posaconazole also occurs in vivo. This case study presents a systematic approach in addressing challenges when characterizing dissolution performance of drug powders.