Polymer Templated Structural Evolution of a Poorly Water-Soluble Active Pharmaceutical Ingredient from Nanoparticles to Hierarchical Crystals

摘要

The hydrate form of a poorly water-soluble active pharmaceutical ingredient (API), spironolactone (SP), was produced using antisolvent precipitation in the presence/absence of polymer templates and stirring. Different crystal habits were observed depending on the polymer added. Superstructures consisting of primary constituent units were obtained in the presence of hydroxypropyl methylcellulose (HPMC), while tubular crystals with highly fused surfaces were observed in the presence of polyvinylpyrrolidone (PVP). In contrast, tubular and dendritic crystals were obtained in the absence of polymer. The structural evolution of the particle formation process was monitored by scanning electron microscopy (SEM), which reveals the growth mechanisms leading to different crystal habits. Superstructures are attributed to self-assembly growth, while tubular and dendritic crystals are formed under diffusion limited growth. The results suggest a potential way to produce crystals with the desired crystal habit by appropriate selection of polymer additive and precipitation conditions.