Characterization of the inclusion complex of 16,17α-epoxyprogesterone with randomly methylated β-cyclodextrin in aqueous solution and in the solid state

The inclusion complex between 16,17α-epoxyprogesterone (EP) and randomly methylated β-cyclodextrin (RM-β-CD) was prepared by freeze-drying method and subsequently characterized by means of differential scanning calorimetry, X-ray powder diffractometry, scanning electron microscopy and Fourier transform infrared spectroscopy techniques. The results clearly revealed that EP molecules were included in the cavity of RM-β-CD, thus giving rise to the solubility enhancement of EP in aqueous solution. The effect of RM-β-CD on the aqueous solution of EP was evaluated by the phase solubility diagram. The amount of EP increased linearly with the addition of RM-β-CD according to an AL type plot, indicating the formation of 1:1 stoichiometric inclusion complexes. Thermodynamic study showed the complexation process between EP and RM-β-CD (ΔG = −34.4 kJ mol−1) was driven by both favorable enthalpy (ΔH = −21.4 kJ mol−1) and entropy (ΔS = 43.2 J mol−1 K−1) changes. Dissolution studies showed that such inclusion complex offered a marked improvement in the dissolution rate compared to EP alone and the physical mixture.