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BACKGROUND The proposed study was aimed to formulate and evaluate the Glipizide-Phospholipid Nano-complex. Since Glipizide is a poorly soluble drug, its complexation with phospholipids is an ideal approach to improving solubility. METHOD To improve the oral potency of Glipizide, its phospholipid complex was prepared by employing the solvent evaporation method. The formulations were characterized using DSC, FT-IR, PXRD, SEM, TEM, and hot stage microscopy (HSM). Solubility tests of the Glipizide-Phospholipid Nano-complex revealed a significant increase in aqueous solubility compared to Glipizide's physical combination. The oral bioavailability of the Glipizide-Phospholipid Nano-complex was measured by using HPLC in Wistar rats' plasma. FTIR and PXRD results revealed no significant interaction between the drug and the phospholipid in the formulation. SEM and TEM studies confirmed the morphology of the formulation assuring the conversion of crystalline form into an amorphous structure. RESULTS The Glipizide-Phospholipid Nano-complex had a greater peak plasma concentration (5.2 vs 3.8 g/mL), a larger AUC (26.31 vs 19.55 μgh/L), and a longer T1/2 (2.1 vs 4.1 h) than free Glipizide, indicating that it improved drug dissolution rate. CONCLUSION The outcomes suggested that a phospholipid complexation is a potential approach to increasing water-insoluble drugs' oral bioavailability.n.