Characterization, Solubility, and Hygroscopicity of BMS-817399

Characteristics of BMS-817399 that could influence the potential utility of the compound as an active pharmaceutical ingredient (API) have been explored. The compound exists as a monohydrate (Form 1) but is physically unstable as its crystal structure changes with variations in relative humidity and temperature. Thus, identifying a form that remains physically stable under fluctuating conditions of relative humidity was the objective of this work. Solubilities of Form 1 in ethanol, isopropanol, acetone, and acetonitrile were obtained using a Crystal16 apparatus, but recrystallization only occurred when the solvent was acetonitrile. X-ray diffraction (XRD) of solids obtained from recrystallization in the Crystal16 apparatus and from larger-scale experiments confirmed the existence of a new form (Form 2) of the compound. Solubilities of Form 2 were subsequently determined by using the Crystal16 apparatus. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed Form 1 as a monohydrate and showed that Form 2 is anhydrous. Dynamic vapor sorption was used to show that the water content of Form 1 varied with the relative humidity. Form 2 also became hygroscopic at elevated relative humidity, but XRD measurements confirmed that it exhibited physical stability.