Isolation Strategies and Transformation Behaviors of Spironolactone Forms

Abstract

Spironolactone (SPI) is one kind of potassium-sparing diuretic, and two polymorphs (form I and form II) along with five solvates (methanol, ethanol, acetonitrile, ethyl acetate, and benzene) of SPI have been reported in the literature. However, no detailed information about the stability, solubility, and transformation behaviors of SPI forms has been reported. In this paper, two new forms of SPI, 1-propanol solvate and 2-propanol solvate, were found and characterized. The thermodynamic stability and solubility of form II and four alcohol solvates of SPI were investigated and determined. It was found that methanol solvate and ethanol solvate of SPI are relatively stable while 1-propanol solvate and 2-propanol solvate of SPI are metastable in corresponding solvents, and 1-propanol solvate and 2-propanol solvate of SPI would transform to form II in corresponding solvents. Furthermore, the transformation processes of 1-propanol solvate and 2-propanol solvate were in situ monitored by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and Raman spectroscopy and some offline tools such as microscopy and powder X-ray diffraction (PXRD). The reasons behind the transformation were explained by the enthalpy data of different solvates