Lenalidomide acesulfamate: Crystal structure, solid state characterization and dissolution performance

Lenalidomide (LEN) is a first line drug in the treatment of multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma. While, this compound holds poor water solubility, leading to unsatisfied bioavailability. To improve the solubility of LEN, a molecular salt with an artificial sweetener, acesulfame (AH), was obtained in this study. The LEN-AH salt was fully characterized by single-crystal and powder X-ray diffraction (XRD), C-13 solid state nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), as well as dynamic vapour sorption (DVS). The crystal structure of LEN-AH clearly reveals the intermolecular proton transfer from NH group of AH to NH2 of LEN. The ionization state of LEN-AH was further confirmed by its feature C-13 chemical shifts. The maximum solubility value of LEN was significantly enhanced after salt formation. And the supersaturation state of LEN solution can be maintained at a higher level with the presence of 0.1% PVP-K30.(C) 2018 Elsevier B.V. All rights reserved.