Study of tolbutamide-hydroxypropyl-gamma-cyclodextrin interaction in solution and solid state

Tolbutamide-hydroxypropyl-gamma-cyclodextrin (TBM-HPGCD) interaction has been investigated in an aqueous environment and in the solid state. The solubility of TBM was increased in accord with the amount of HPGCD added to the aqueous medium forming a soluble inclusion compound. The phase solubility diagram obtained was of A(L) type. Physical mixtures and kneaded systems of the drug and cyclodextrin derivative were prepared in 1:1 and 1:2 drug/cyclodextrin mol/mol ratio. All solid binary systems were characterised by hot-stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetry (TG) and X-ray powder diffractometry (XRD). An inclusion complex was formed in both of the kneaded systems. In the 1:2 kneaded system, the entire drug was included in the cyclodextrin cavity, while, in the 1:1 kneaded system only a part of the drug formed an inclusion complex with the cyclodextrin. A significant improvement in the dissolution of the drug was obtained from the kneaded systems in comparison with that of the pure TBM and physical mixtures. However, there was no significant difference between the dissolution profiles of the two kneaded systems. The study suggests that an inclusion complex was obtained both in aqueous solution and in solid state.