Solid Dispersion of an Anti-Diabetic Drug with Block Co-Polymer for Enhancement of Aqueous Solubility, Dissolution and Bioavailability

Abstract

The present research work deals with pre-formulation and formulation studies for development of solid dispersions with enhanced oral bioavailability. Gliclazide (GLC), an oral hypoglycemic agent, is characterized by low solubility in gastric fluid, low dissolution rate and inter-individual variability in bioavailability. The objective of this study was therefore to design optimized solid dispersions (SD) of GLC with a hydrophilic carrier viz., poloxamer 407 (PXM) by lyophillisation method in an attempt to enhance the aqueous solubility and therapeutic efficacy of the drug. Phase solubility study with increasing PXM concentrations (0.5 to 10% w/v) was done to study the influence of polymer concentration on solubility of GLC. SD’s of GLC and PXM in 1:1, 1:3 and 1:5w/w ratios were prepared by physical mixing and lyophillisation (freeze drying) method, followed by dissolution studies. A comparative in vivo study between optimized SD and GLC was conducted on twelve healthy New Zealand rabbits. The dissolution rate of GLC from the lyophilized dispersions was greatly enhanced as compared to those from physical mixtures and pure drug. The in-vivo studies indicated that the pharmacokinetic parameters following oral administration of the optimized SD and pure GLC were significantly different (P < 0.05). The peak serum concentration (Cmax) for the lyophilized SD and GLC were found to be 3.01±0.42 µg/mL and 2.27 ± 0.39 µg/mL respectively, whereas the time required to reach the peak serum concentration (Tmax) for the optimized SD was significantly shorter (2.16±0.41h) compared to that for GLC (4.33±0.52h). The relative bioavailability of the SD under in-vivo test was found to be 158.52%. These results demonstrate that the use of a suitable hydrophilic carrier like PXM to formulate SDs by the lyophillisation technique can rapidly accelerate the solubility and in vitro dissolution of a lipophilic drug like GLC. The suggested method provides good signs of improvement in the rate of absorption as well as bioavailability of gliclazide following oral administration and can be explored for other hydrophobic drug moities.