Anhydrates and hemihydrate of tasimelteon: Synthesis, structure, and pharmacokinetic study

[Display omitted] •New crystalline forms of tasimelteon are reported first time.•Hemihydrate crystal form is more soluble than hydrate crystal form under water (pH = 7.0) and pH 1.2 buffer condition.•The bioavailability of hydrate crystal form oral administration was better than that of hemihydrate crystal form. Two new crystal forms of tasimelteon TSM-I and TSM-II were reported here. Crystallization of crude in methanol or mixture solvent results in anhydrate crystal form (TSM-I) and hemihydrate crystal form (TSM-II) respectively. To the best of our knowledge, it is the first report about crystalline form of tasimelteon. The two crystal forms were exhaustively characterized by Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, Raman Spectra, Differential Scanning Calorimetry, Thermogravimetric Analysis, Solid State NMR Spectroscopy and Powder X-ray diffraction and Single Crystal X-ray Diffraction. Furthermore, the pharmacokinetic behavior of TSM-I and TSM-II in rats were measured. We found that though TSM-II is considerably more soluble than TSM-I under water (pH = 7.0) and pH 1.2 buffer conditions, the bioavailability of TSM-Ivia oral administration was better compared to that of TSM-II.