a School of Natural Product Studies, Department of Pharmaceutical Technology , Jadavpur University , Kolkata , India.
Drug Dev Ind Pharm. 2019 Jun;45(6):946-958. doi: 10.1080/03639045.2019.1583755. Epub 2019 Mar 5.
To prepare and characterize an optimized phospholipid complex of Ursolic acid (UA) to overcome the poor pharmacokinetic properties and to investigate the impact of the complex on hepatoprotective activity and bioavailability in animal model.
UA is a potential phytoconstituent obtained from several plant sources, which has been explored for its diverse pharmacological activities including hepatoprotection. Its major limitation is poor absorption, rapid elimination, and hence low bioavailability after administration.
Response surface methodology was adopted to formulate an optimized (UA) complex. The complex was characterized by differential thermal analysis (DTA), Fourier transform-Infrared Spectroscopy, Powder X ray Diffraction, molecular docking, etc. The physico-chemical profile (solubility, oil/water partition coefficient) and in vitro dissolution profile was estimated. The formulation was then used to study hepatoprotective activity and bioavailability in animal models.
Results showed that the phospholipid complex of UA has enhanced the hepatoprotective potential as compared to pure UA at the same dose level. The complex restored the levels of serum hepatic marker enzymes with respect to untreated group and increased the relative bioavailability of UA in rat plasma by 8.49-fold in comparison with pure compound at the same dose level. It enhanced the elimination half-life (t) from 0.69 ± 1.76 to 8.28 ± 1.98 h.
Complexation of UA with phospholipid markedly enhanced the hepatoprotective potential of UA by improving its bioavailability and pharmacokinetic parameters. Novelty statement The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals. Novelty statement The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals.
制备并表征熊果酸（UA）的优化磷脂复合物，以克服其较差的药代动力学特性，并研究该复合物对动物模型中肝保护活性和生物利用度的影响。
UA 是一种从多种植物来源获得的潜在植物成分，已被探索用于其多种药理活性，包括肝保护作用。其主要限制是吸收不良、快速消除，因此给药后生物利用度低。
采用响应面法（RSM）来制备优化的（UA）复合物。通过差示热分析（DTA）、傅里叶变换-红外光谱、粉末 X 射线衍射、分子对接等方法对复合物进行了表征。评估了物理化学特性（溶解度、油/水分配系数）和体外溶解特性。然后，该制剂用于研究动物模型中的肝保护活性和生物利用度。
结果表明，与相同剂量水平的纯 UA 相比，UA 的磷脂复合物具有增强的肝保护潜力。与未处理组相比，复合物恢复了血清肝标志物酶的水平，并使 UA 在大鼠血浆中的相对生物利用度提高了 8.49 倍，而相同剂量水平的纯化合物则提高了 8.49 倍。它提高了消除半衰期（t）从 0.69±1.76 到 8.28±1.98 h。
通过提高生物利用度和药代动力学参数，将 UA 与磷脂络合可显著增强 UA 的肝保护潜力。
