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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 max (3.4-fold) and AUC 0–12h (2.7-fold) of glipizide from solid S-SNEDDS as compared with the pure drug. Solid S-SNEDDS showed a significant (p

A solid self-nanoemulsifying drug-delivery system (solid SNEDDS) has been explored to improve the solubility and dissolution profile of glipizide. SNEDDS preconcentrate was systematically optimized using a circumscribed central composite design by varying Captex 355 (Oil), Solutol HS15 (Surfactant) and Imwitor 988 (Co-surfactant). The optimized SNEDDS preconcentrate consisted of Captex 355 (30% w/w), Solutol HS15 (45% w/w) and Imwitor 988 (25% w/w). The saturation solubility (SS) of glipizide in optimized SNEDDS preconcentrate was found to be 45.12 ± 1.36 mg/ml, indicating an improvement (1367 times) of glipizide solubility as compared to its aqueous solubility (0.033 ± 0.0021 mg/ml). At 90% SS, glipizide was loaded to the optimized SNEDDS. In-vitro dilution of liquid SNEDDS resulted in a nanoemulsion with a mean droplet size of 29.4 nm. TEM studies of diluted liquid SNEDDS confirmed the uniform shape and size of the globules. The liquid SNEDDS was adsorbed onto calcium carbonate and talc to form solid SNEDDS. PXRD, DSC, and SEM results indicated that, the presence of glipizide as an amorphous and as a molecular dispersion state within solid SNEDDS. Glipizide dissolution improved significantly (p