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 C 25 H 20 N 4 O 5 •1.25H 2 O. 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. • A new reasonable interpretation of azilsartan form II was suggested. • Properties of azilsartan form II was investigated. • A cleaner and more efficient preparation method was provided.