(517l) Solid-State Analysis of An Active Pharmaceutical Ingredient Crystalline Phase Obtained through Desolvation

Polymorph control is an essential drug discovery activity as polymorphism can alter physical properties that affect drug performance. Identification and development of an anhydrous crystalline form is often preferred to a solvate due to the difficulty in maintaining a constant solvate level during storage as well as limitations on residual solvents specified in ICH guidelines. Direct recrystallization of anhydrous APIs is ideal, but often, desolvation is necessary to generate the desired anhydrous crystalline form. This solid-state desolvation often results in a weaker crystalline lattice due to voids created by removed solvent molecules.

This presentation will discuss the physicochemical characterization of an anhydrous crystalline of API, obtained through desolvation. This API forms numerous solvates, including heptane, acetonitrile, tetrahydrofuran, and acetone solvates. Direct crystallization of anhydrate was proven unsuccessful. All solvates yield same anhydrous upon desolvation, regardless of the starting solvate. Some differences were observed in the SSNMR and XRPD spectra of the solids from different batches. Techniques such as solid-state nuclear magnetic resonance (SS-NMR), X-ray powder diffraction (XRPD), thermogravimetic analysis (TG), differential scanning calorimetry (DSC), and vapor sorption were used to help understand the origin of these differences Findings were correlated to a crystal lattice instability.