Characterization, Dissolution and Diffusion Properties of Tolbutamide-β-Cyclodextrin Complex System

Abstract

The solubility of tolbutamide was increased about 2.5 fold due to complex formation with (β -cyclodextrin (β -CD). Phase solubility studies showed that at high β -CD concentrations an insoluble microcrystalline complex was formed which had a stoichiometry of 1:2 (tolbutamide: β -CD); this was confirmed by chemical analysis. The endothermic peak for tolbutamide completely disappeared in differential scanning calorimetry studies and x-ray diffraction spectra indicated that the prepared complex was less crystalline than the parent drug. More evidence of the complex formation was obtained from infra-red studies. The dissolution of tolbutamide in pH 1.2 buffer was significantly enhanced by complexation with β-CD. after 20 minutes the % of drug released was 12 and 93 for the drug alone and the complex samples respectively. Increased solubility, decreased crys-tallinity, and improved wettability are responsible for the observed enhancement in dissolution rate. Diffusion studies across dimethyl poly-siloxane revealed that the drug apparent permeability constant was concentration dependent and decreased in the presence of β-CD.