Host-guest interactions between dapsone and β-cyclodextrin (Part II): thermal analysis, spectroscopic characterization, and solubility studies

The complex of dapsone with beta-cyclodextrin was prepared by the co-precipitation/freeze-drying method. The physical-chemical characteristics of the complex were investigated by different methods and compared with those of the physical mixture and of the isolated compounds. The methods used were infrared spectroscopy, X-ray diffractometry and differential scanning calorimetry. The stability constant was calculated from phase solubility diagram (Higuchi-Connors) and fluorescence spectroscopy. The stoichiometry of the complex was confirmed by Job's plot. Fluorescence measurements at different temperatures provided the thermodynamic parameters of the complexation. The infrared spectrum showed the disappearance of the SO2 asymmetric stretching band of the drug at 1275 cm(-1) after complexation. The amorphization of the samples, as revealed by the X-ray diffraction patterns, was an indirect proof of the inclusion complex. The thermal analysis showed that the curves of the physical mixture are combination of the curves of both constituents (dapsone and beta-cyclodextrin) while the absence of the melting peak of the drug in the DSC curve of the complex suggests the inclusion of the drug molecule in the host cavity as a 1:1 complex as indicated by Job's plot. There was a linear increase in its solubility with the increase of the cyclodextrin concentration and the complex was classified as an A(L)-type. The value of the stability constant was 3,998 L mol(-1) calculated by the Higuchi-Connors diagram and around 18,100 L mol(-1) from the fluorescence method indicating a strong interaction between the host and the guest. Complex formation was a spontaneous and enthalpy directed process.