Combination of Phospholipid Complex and Submicron Emulsion Techniques for Improving Oral Bioavailability and Therapeutic Efficacy of Water-Insoluble Drug

Water-insoluble drugs cannot be absorbed effectively through the gastrointestinal tract due to insufficient solubility and often face the problems of low bioavailability and poor therapeutic efficacy. To overcome these biopharmaceutical challenges, lipid-based formulations were suggested and have been researched in recent years. In this study, we used atorvastatin as a model drug to prepare a phospholipid complex prodrug system to upgrade its lipophilicity and further developed a drug loaded submicron emulsion to improve its in vivo bioavailability. The mean particle size and zeta potential of submicron emulsion were 122.7 nm and −22.7 mV. Intestinal absorption of atorvastatin from submicron emulsion was significantly improved compared with free drug, and the absorption rate constant (<i>K</i><sub>a</sub>) and apparent permeability coefficients (<i>P</i><sub>app</sub>) increase 2.88-fold and 2.45-fold, respectively. After oral administration, the atorvastatin plasma concentration of the emulsion group was much higher than that of free drug and the area under the curve (AUC) reached to 4.033 mg/L·h (2.58-fold). In vivo pharmacodynamics results revealed that atorvastatin submicron emulsion showed excellent antihyperlipidemia efficacy by reducing the total cholesterol, triglyceride, and low density lipoprotein cholesterol (LDL-cholesterol) levels and simultaneously increasing the high density lipoprotein cholesterol (HDL-cholesterol) level in comparison with Lipitor. In conclusion, drug–phospholipid complex loaded submicron emulsion was a promising oral delivery system for improving in vivo absorption behavior and therapeutic efficacy for water-insoluble drugs.