ENHANCEMENT OF DISSOLUTION RATE AND HYPOGLYCEMIC ACTIVITY OF GLIBENCLAMIDE WITH BETA-CYCLODEXTRIN

Glibenclamide formed an inclusion complex with beta-cyclodextrin in so lution and in the solid state. Phase solubility studies revealed a thr ee-fold increase in the solubility of glibenclamide in the presence of beta-cyclodextrin. The formation of an inclusion complex with beta-cy clodextrin in the solid state was confirmed by infrared spectroscopy, X-ray diffractometry and differential scanning calorimetry. The in vit ro dissolution rates of glibenclamide/beta-cyclodextrin inclusion comp lex and a kneaded mixture were respectively eight and seven times high er at 20 min than the pure drug. Oral administration of the inclusion complex and the kneaded mixture to diabetic mts at 1 mg glibenclamide equivalent/kg dose level significantly lowered blood glucose levels at 4 h (p < 0.02) and at 6 and 8 h (p < 0.05), as compared with the same dose level of pure glibenclamide. In contrast, at 0.7 mg glibenclamid e equivalent/kg dose level, the inclusion complex and kneaded mixture produced a similar hypoglycemic effect as that of 1 mg/kg of pure glib enclamide.