COMPARISON OF TOLBUTAMIDE BETA-CYCLODEXTRIN INCLUSION-COMPOUNDS AND SOLID DISPERSIONS - PHYSICOCHEMICAL CHARACTERISTICS AND DISSOLUTION STUDIES

Tolbutamide was found to form an inclusion complex with β-cyclodextrin. An equilibrium phase solubility diagram was obtained for the tolbutamide-β-cyclodextrin system in water. The solubility of tolbutamide increased on addition of β-cyclodextrin, displaying a Bs-type phase diagram. A stability constant of 2.101 × 103 M-2 was calculated. The insoluble complex obtained thereby had a stoichiometry of 1:2 (tolbutamide: β-cyclodextrin). Comparison of the complex was carried out with PEG 6000 solid dispersions, prepared by either the comelting or coprecipitation method, using X-ray diffraction, infrared spectrophotometry and differential thermal analysis. Dissolution profiles in a pH 2 medium, of tolbutamide, comelt, coprecipitate and inclusion complex demonstrated a faster dissolution rate of the inclusion complex compared to solid dispersions and tolbutamide alone. After 20 min the amount of drug released was around 19% for the powdered free drug, 33% for the coprecipitate, 38% for the comelt and 100% for the inclusion complex. © 1990.