Physicochemical characterisation of difluprednate and 6α9α-difluoroprednisolone : determination of solubility, pKa and LogP

Abstract

Steroids are used in the treatment of diverse pathological conditions for their anti-inflammatory and immunosuppressive effects, with the mode of action being affected by their physicochemical characteristics. To date, difluprednate (DFBA) has been characterised using computational methods which rely on the selected computational model and disregard external factors. The aim of the study was to determine the solubility, pKa and LogP of DFBA and its metabolite, 6α9α-difluoroprednisolone (DFP) using experimental methods. Methods using UV–Visible spectroscopy and High-Performance Liquid Chromatography (HPLC) were developed to determine the solubility and the pKa, LogD and LogP of the selected steroids. The steroids are soluble in acetonitrile and methanol, and are insoluble in water. DFBA achieved a solubility of 5.76 mg/mL and 0.81 mg/mL in acetonitrile and methanol, while DFP achieved solubility of 2.29 mg/mL and 0.16 mg/mL, respectively. DFBA had an average LogP value of 3.2, and DFP had an average LogP of 1.5. The pKa values for DFBA were 1.5 and 7.2 and for DFP, were 5.9 and 10.8. The characterisation of the physicochemical properties of DFBA and DFP can help support efficient formulation development.