Physicochemical, crystallographic, thermal, and spectroscopic behavior of crystalline and X-ray amorphous ciclesonide

Single crystal structure experiments revealed that the orthorhombic needles of Ciclesonide crystallized in P2(1)2(1)2(1) space group with four independent molecules in the unit cell. Amorphous Ciclesonide was prepared by lyophilization and characterized in comparison with crystalline material by differential scanning calorimetry (DSC), Fourier transformed (FT)-Raman spectroscopy, powder X-ray diffraction, dissolution, and saturation solubility experiments. Significant differences in the dissolution, thermal, and spectrometric behavior were observed for both solid-state phases. DSC- and FT-Raman methods for the determination of amorphous content in crystalline Ciclesonide samples were established. Isothermal and dynamical recrystallization studies on amorphous Ciclesonide were conducted using dispersive hot-stage Raman microscopy. The recrystallization was observed to be a two-step process with an induction period (most likely nuclei formation) followed by the actual recrystallization (crystal growth). The recrystallization rate constants and Avrami exponents (n = 2) were determined from the isothermal experiments at various temperatures using Johnson-Mehl-Avrami theory. Isothermal activation energies were obtained from Arrhenius plots using the temperature dependence of (a) the rate constants (160.4 kJ/mol) and (b) the induction time (140.9 kJ/mol) of the isothermal hot-stage experiments.