A New Reasonable Interpretation of Azilsartan Form II: a Hydrate

ABSTRACT In this study, a new reasonable interpretation of azilsartan form II was suggested which had been reported as a 1,4-dioxane solvate in the literature. Multiple evidence has indicated that azilsartan form II obtained in this study was not a 1,4-dioxane solvate. Results of single crystal diffraction showed that the chemical formula of azilsartan form II was C25H20N4O5•1.25H2O. The apparent solubility and intrinsic dissolution rate of azilsartan form II were greater than that of form I in pH 6.8 phosphate buffer solution at 37 °C. Results of dynamic vapour sorption indicated that azilsartan form I was hardly hygroscopic. Results of accelerated stability test showed that azilsartan form I and II remained stable after 6 months of storage. Differential scanning calorimetry results showed that azilsartan form II had a lower melting point than form I. A cleaner and more efficient preparation method for azilsartan form II was provided. Azilsartan form II could be prepared through the liquid-assisted grinding method by using a very small amount of tetrahydrofuran (η = 0.2 μL mg−1) or acetone (η = 0.3 μL mg−1). Azilsartan form II presents an alternative solid form for pharmaceutical preparation.