Hydrogel Microparticle-Templated Anti-Solvent Crystallization of Small-Molecule Drugs.

Abstract

Conventional formulation strategies for hydrophobic small-molecule drug products frequently include mechanical milling to decrease active pharmaceutical ingredient (API) crystal size and subsequent granulation processes to produce an easily handled powder. A hydrogel-templated anti-solvent crystallization method is presented for the facile fabrication of microparticles containing dispersed nanocrystals of poorly soluble API. Direct crystallization within a porous hydrogel particle template yields core-shell structures in which the hydrogel core containing API nanocrystals is encased by a crystalline API shell. The process of controllable loading (up to 64% w/w) is demonstrated, and tailored dissolution profiles are achieved by simply altering the template particle size. API release is well described by a shrinking core model. Overall, the approach is a simple, scalable and potentially generalizable method that enables novel means of independently controlling both API crystallization and excipient characteristics, offering a "designer" drug particle system.