Aim: The study was designed to enhance the solubility and dissolution rate of glibenclamide (GLB) and evaluation of its glucose lowering efficacy in diabetic rats.

Methods: Solid dispersions of GLB were prepared by solvent evaporation technique using mixture of PEG-8000, sodium citrate, HPMC as additives in different ratios and subsequently, in-vitro dissolution studies were performed. The characterization of solid dispersions was done by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometer (PXRD), Fourier Transform Infrared (FTIR) Spectroscopy and Scanning Electron Microscope (SEM). Diabetes was induced into rats by giving fructose (10%) in drinking water for six weeks.

Results: Among the twelve formulations, the GCHP-4 (composed of GLB: HPMC: Na-citrate: PEG-8000 1:1:1:1) demonstrated maximum percent of yield (87.76%) and encapsulation efficiency (95.68%). The maximum dissolution of the drug obtained from GCHP-4 (3.34 µg/ml), which was 5.2-fold higher than that of pure GLB (0.64 µg/ml) at 120 min. The mechanism of increased solubility of GLB from solid dispersions resulted due to the conversion of its crystalline nature into amorphous form and there was no interaction between drug and carriers which was confirmed by DSC and FT-IR respectively. Therefore, the hypoglycemic effect of optimized formulation GCHP-4 (designated as GSD) was evaluated in fructose-fed diabetic rats. After 24 hrs of single dose administration of GSD (GSD-L 0.5mg/kg, GSD-H 5mg/kg), pure GLB (5mg/kg) and/or vehicle, optimized GSD-H resulted in significant reduction of glucose level between 8-10 hr (p<0.05). Although, the fasting glucose levels were decreased with GSD-L and pure GLB, the effect was not significant. Diabetic rats pre-treated with GSD and GLB exhibited a significant improvement in glucose tolerance levels (p<0.05).

Conclusion: The results indicated that the solubility and dissolution rate of GLB was improved which may contribute to the enhancement of bioavailability and in-vivo glucose lowering efficacy of GLB when loaded in GSD.

KEY WORDS: Glibenclamide; Hydrophilic carrier; Solid dispersion; Solvent evaporation; In-vitro Dissolution; Physicochemical characterization.