(252c) Design of LLPS Based Spherulitic Crystallization to Address Tableting Challenges

Control and manipulation of bulk physical properties of an API is an important aspect of the pharmaceutical development because of their influence on formulation development. This is especially true for the significant number of active pharmaceutical materials that exhibit acicular morphology and low bulk density as these API's have the troublesome tendency of "sticking" and "picking" during tablet manufacture. A need therefore exists in pharmaceutical industry to manipulate crystal properties in order to avoid negative implications of sticking to the surfaces of punches. Towards that end, we are developing novel crystallization techniques that employ spherical crystallization through liquid-liquid phase separation (LLPS). In this work, we explore various solution parameters that influence the nucleation and growth processes of spherical crystals. We present the results of our experiments with actual pharmaceutical compounds and identify a few key variables that dictate the size distribution and surface properties of the resulting crystals. Our work demonstrates the beneficial effects of the often-avoided spherulitic crystallization and highlights the need to understand the underlying mechanisms of this process.