Improved oral bioavailability of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol using nanoemulsion based on phospholipid complex: design, characterization, and in vivo pharmacokinetics in rats

Xiangrong Zhang,1,2,* Yi Zhang,1,* Shuang Guo,3 Feifei Bai,1 Tong Wu,1 Yuqing Zhao1 1Department of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, 2Department of Pharmaceutics, School of Pharmacy, 3Department of Biomedical Science, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of the study was to improve the oral absorption of the compound 25-OCH3-PPD with poor hydrophilicity and lipophilicity. 25-OCH3-PPD-phospholipid complex was prepared by solvent evaporation, then characterized by differential scanning calorimetry, scanning electron microscopy, and infrared absorption spectroscopy. The aqueous solubility and oil–water partition coefficient were compared with the free compound. A nanoemulsion loaded with 25-OCH3-PPD-phospholipid complex was developed by dissolving the complex in water in the presence of hydrophilic surfactant under sonication. After oral administration of the nanoemulsion and the suspension of 25-OCH3-PPD in rats, the concentrations of 25-OCH3-PPD in plasma were determined by high-performance liquid chromatography–tandem mass spectrometry method. The results showed that the solubility of the complex in water and n-octanol was enhanced. The oil–water partition coefficient improved 1.7 times. Peak plasma concentration and area under the curve(0–24 h) of the nanoemulsion of 25-OCH3-PPD-phospholipid complex were higher than that of free compound by 3.9- and 3.5-folds. Keywords: 25-OCH3-PPD, phospholipid complex, solubility, bioavailability, LC–MS/MS