(198f) Impact of Polymers and Surfactants on Solid-State Crystallization at the Amorphous Pharmaceutical-Water Interface
AIChE Annual Meeting
Monday, November 11, 2019 - 5:13pm to 5:33pm
Amorphous pharmaceutical formulations are an increasingly common strategy for dissolution and bioavailability enhancement of poorly soluble drug compounds. Stabilization against crystallization during storage as well as during dosing is usually achieved by dispersing amorphous drug in a polymeric matrix and has been well studied. However, during dissolution it is possible to generate drug-rich amorphous interfaces that are not intimately mixed with polymer. Solid-state crystallization at this amorphous drug-water interface is not well understood, nor is the role played by excipients in influencing this crystallization phenomenon. The work presented herein utilizes experimental and modeling tools to characterize and model solid-state crystallization at the amorphous-water interface as well as the impact on crystallization from polymer and surfactant species in solution. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) measurements on the evolving interface reveal non-classical and highly anisotropic crystallization. Interpretive 2D lattice Monte Carlo simulations exhibit semi-quantitative agreement with experiments and elucidate the impact of the surface energy of the underlying amorphous material on the morphology of the crystalline phase. AFM and SEM data also demonstrate crystallization inhibition with polymer additives, with concentration-dependent crystal morphology. In contrast, surfactants promoted crystallization. Preliminary experiments explore these findings by connecting qualitative crystallization observations to the underpinning transport phenomena facilitating surface rearrangement. These results provide fundamental insight for ultimately mitigating this undesirable phase change.