Solid supersaturatable self-nanoemulsifying drug delivery systems for improved dissolution, absorption and pharmacodynamic effects of glipizide

Abstract

The objective of this study was to prepare a solid supersaturatable self-nanoemulsifying drug delivery system (solid S-SNEDDS) to improve the dissolution, absorption and pharmacodynamic effects of a poorly water-soluble drug: glipizide. The liquid supersaturatable formulation (liquid S-SNEDDS) was prepared by adding a polymeric precipitation inhibitor (HPMC-E5 at 5% w/w) to a liquid SNEDDS. Dilution of the liquid S-SNEDDS generated a nanoemulsion with a mean droplet size of 28.0 nm. The liquid S-SNEDDS was transformed into a free-flowing powder (solid S-SNEDDS) by adsorption onto calcium carbonate and talc. The solid S-SNEDDS generated a higher glipizide concentration in comparison with the solid SNEDDS (without HPMC-E5) during an in-vitro supersaturation test. Moreover, glipizide precipitated in an amorphous form from the solid S-SNEDDS. SEM studies of solid S-SNEDDS indicated the existence of molecularly dissolved glipizide. The solid S-SNEDDS was found to be stable during accelerated stability studies. In-vivo pharmacokinetic studies showed a significant (p < 0.001) increase in Cmax (3.4-fold) and AUC0–12h (2.7-fold) of glipizide from solid S-SNEDDS as compared with the pure drug. Solid S-SNEDDS showed a significant (p < 0.001) decrease in the plasma glucose level by 1.3, 1.3, and 2.9-fold as compared with solid SNEDDS, the commercially available drug product and the pure drug, respectively.