The solid-state characterization of fusidic acid

Abstract

Purpose The aim of this work was to characterize the solid-state properties of fusidic acid (FA). Methods Solid forms of FA were prepared by solvent-mediated polymorphic transformation of commercial FA (Form III) in acetonitrile (ACN), and methanol:H 2O (50:50), or generated by solvent recrystallization from dichloromethane (DCM). Polymorphs were characterized using, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), polarizing hot stage microscopy (HSM), and intrinsic dissolution rate (IDR). Results Slurrying commercial FA (Form III) in methanol:H 2O (50:50), yielded a metastable form (Form IV). This metastable form converts to Form I or back to Form III in ACN and H 2O, respectively, and Form II upon recrystallization from DCM. IDR of Form IV was 0.092 mg/min/cm 2, and was statistically different ( p < 0.05) from the IDR of Forms I, II, and III, with IDR of 0.053, 0.043, and 0.045 mg/min/cm 2, respectively. The amorphous FA had an IDR of 0.125 mg/min/cm 2, and was significantly higher ( p < 0.05) than any other solid form. There were no statistical differences in the IDR of Form I, II, or III. Conclusions This work provides evidence for the existence of two previously unreported polymorphic forms of FA (Forms II and IV) and an amorphate.