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(2)O (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(2)O (50:50), yielded a metastable form (Form IV). This metastable form converts to Form I or back to Form III in ACN and H(2)O, 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 0.045mg/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.