Polymorphs of DP-VPA Solid Solutions and Their Physicochemical Properties

Abstract

Different solid forms possess various physicochemical properties, which can significantly affect the stability, bioavailability, and manufacturability of the final product. DP-VPA, a complex of 1-stearoyl-2-valproyl-sn-glycero-3-phosphatidylcholine (DP-VPA-C18) and 1-palmitoyl-2-valproyl-sn-glycero-3-phosphatidylcholine (DP-VPA-C16), is currently under development as an antiepileptic drug. DP-VPA-C16 and DP-VPA-C18 crystallize together in solid solution forms. The solid forms of DP-VPA solid solution were studied herein. Powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), dynamic vapor sorption (DVS) and optical microscopy were used to characterize the different crystalline forms, known as polymorphs. The physicochemical properties, including hygroscopicity, thermodynamic behavior, and relative stability, of each form were investigated. DVS analysis showed that DP-VPA solid solution reduced the hygroscopicity of DP-VPA-C16. The relative humidity stability study revealed that Forms A and B are relatively stable, while Forms A-1, B-1, C and D are highly unstable under natural humidity. Further analysis revealed that Form A transforms into Form B through milling. Given the physicochemical properties of the available physical forms, Form B may be the optimal form for the formulation and development of antiepileptic drugs.