- 12:50 PM

Screening for Cocrystallization Tendency: The Role of Intermolecular Interactions

Guangwen He, Pui Shan Chow, and Reginald B. H. Tan. Institute of Chemical & Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore, Singapore

Much work has been focused on exploring the crystal engineering and design strategies that facilitate supramolecular synthesis of new crystalline phases (cocrystals) of APIs and cocrystal formers. However, few attempts have been made to understanding the equilibrium phase behavior and phase transition kinetics of the cocrystallizing solutions. Such lack of understanding of essential knowledge about the solution physical chemistry often leads to difficulty in screening for potential molecular pairs for API and cocrystal former that form cocrystals effectively. Early trials on designing and making cocrystals are mostly limited to Edisonian approaches or high throughput surveys.

Given these limitations and the increasing interest in making cocrystals in the pharmaceutical industry, the proposed work here focuses on characterization of intermolecular interactions between API and cocrystal former in solution cocrystallization. The self diffusivities of various model systems in solution are measured using pulsed gradient spin-echo nuclear magnetic resonance (PGSE NMR). The pair contribution of the self diffusivity is used to probe the intermolecular interactions for various solutions. The relative magnitude of the pair contributions of homomeric and heteromeric interactions is then used as a novel screening method in determining whether the formation of cocrystals is feasible.