Studies on solubility, bioavailability and hypoglycemic activity of gliclazide p-cyclodextrin complexes

The effect of beta-cyclodextrin ((3-CD) complexation with gliclazide (Gz) on both pharmacokinetic and hypoglycemic parameters of pure drug was evaluated and correlated with its in vitro dissolution. The study involves the preparation of solid inclusion complex of Gz with [3-CD using different techniques. The prepared binary systems showed significant enhancement for in vitro dissolution. The pharmacokinetics of neutralization complex (equivalent to 30 mg of gliclazide) was studied in beagle dogs. Gliclazide plasma levels were measured over a period of 48 h from dosing, using a sensitive HPLC method. Significant changes were observed in the mean values of Gz pharmacokinetic parameters (Cm i K , Tm i K and AUC0.„) between the control and pre-treated groups. The findings of this study suggest that neutralization complex in 1:1 and 1:2 Gz/|3-CD molar ratios was the best in enhancing gliclazide dissolution characteristics and bioavailability. Moreover, the various measures of bioavailability (except AUC) correlated well with both in vitro tests and hypoglycemic activity