(164c) Additive Mediated Crystallization for API Physical Property Control

A central goal of the drug substance development process is to generate API's with acceptable physical properties that facilitate downstream processing, enable drug product formulation and achieve sufficient bioavailability. Controlling these physical properties has historically involved modification of crystallization processing parameters including solvent system, supersaturation relief (anti-solvent addition rate, cooling rate), seeding, sonication, mixing hydrodynamics, etc. Recent literature examples highlight an additional means to exact control of physical properties, wherein quantities of additives present during crystallization have demonstrated influence on: ? particle size ? particle morphology ? crystal form ? API flow and compactability Tailor made additives or impurities have been demonstrated to have influence on crystallizations. However, work presented here focuses on the use of pharmaceutically acceptable polymers and surfactants in order to circumvent concerns with adulterating a pure processing step. The routes by which various additives influence crystallizations were explored using multiple development compounds in an array of solvent systems. Select examples from bench scale experiments will be presented. The underlying mechanisms will be speculated upon, including how these could be interpreted to best select and use the additives.