Inclusion complexation of tolbutamide with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin

Inclusion complexes of tolbutamide with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin were prepared using different methods: kneading, coprecipitation and freeze-drying. Inclusion complexation in aqueous solution and in solid phase state was studied by the solubility method, X-ray diffractometry, thermal analysis and Raman spectroscopy. The solubility of tolbutamide increased as a function of cyclodextrin concentration, showing B-S and A(L) type diagrams for beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, respectively. The dissolution rate of tolbutamide/cyclodextrin complexes were investigated and compared with those of the physical mixtures and pure drug. The dissolution rate of tolbutamide from the inclusion complexes was much more rapid than tolbutamide alone.