Kneaded pioglitazone poloxamer solid dispersions for enhancement of In Vitro dissolution and In Vivo bioavailability

Abstract

Pioglitazone (PG) an oral hypoglycemic agent is characterized by low solubility in gastric fluid, low dissolution rate and inter-individual variability in bioavaibility .The objective of this study was therefore to design optimized solid dispersion (SD) of PG with hydrophilic carriers eg Poloxamer 188 by kneading method in an attempt to enhance to the aqueous solubility and therapeutic efficacy of drug phase solubility study with increasing PXM (1:1-1:8) was done to study the influence of polymer concentration on solubility of PG.SD’of PG and PXM in 1:1 to 1:8 w/w ratio were prepared by physically mixing and kneading method followed by dissolution studies .A comparative in-vivo study between optimized SD and PG was conducted on six healthy New-Zealandrabbits. The dissolution rate of PG from the kneaded dispersion was greatly enhanced as compared to those from physical mixture and pure drug. The in vivo studies indicated that the pharmacokinetic parameter following oral administration of the optimized SD and pure PG were significantly different. The peak serum conc.(Cmax) for the kneaded SD and PG were found to be 596.33+0.84 ng/ml and 528.50+0.71 ng/ml resp. Whereas the time required to reach the peak serum conc.(Tmax) for optimized SD was Significantly shorter 1.5+0.04 hrscompared to that for PG 2.00+0.02hrs.The relative bioavaibility of SD under in-vivo test was found to be 120.98%.Thease results demonstrate that the use of a suitable hydrophilic carrier like PXM to formulate SDs by the kneading technique can rapidly accelerates the solubility and in vitro dissolution of a lipophilic drug like PG the suggested method also provides good signs of important in the rate of absorption as well as bioavaibility of Pioglitazone following oral administration.