Virtual Crystal Design: Prediction of the Solvent Effect on Crystal Growth
Controlling the shape of crystals is one of the key goals of crystal design and engineering in the pharmaceutical development phase, which aims to bring to market active pharmaceutical ingredients (APIs) coming from drug discovery. The solid-state properties of the API, such as crystal structure, solubility, and morphology are assessed during the pre-formulation and formulation stages of development to ascertain its ideal form. Identifying fit-for-purpose morphology is particularly important as many physical properties relevant to pharmaceutical development depend on the morphology of the API crystals, e.g. powder flow, stickiness, compressibility, filtration rate, and dissolution rate. This study presents a predictive first principles-based approach to quantify the solvent effect on crystal growth. The Conductor-Like Screening Model for Real Solvents, COSMO-RS in its COSMOtherm implementation, is used to determine the activity coefficient of the crystal growth faces of a selection of APIs as constructed by Materials Studio. The ability of the presented workflow to predict the effects of solvent on crystal growth and morphology is assessed with the use of hierarchical clustering tools to classify the solvents according to their interaction strength. In addition, the COSMO-RS approach allows for a physical interpretation of the predictions in terms of surface polarity. 2022 BIOVIA Conference
