Telange Darshan R, Patil Arun T, Pethe Anil M, Fegade Harshal, Anand Sridhar, Dave Vivek S
Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, Maharashtra, India.
SPP School of Pharmacy & Technology Management, Pharmaceutics Division, SVKM's NMIMS University, Mumbai, Maharashtra, India.
Eur J Pharm Sci. 2017 Oct 15;108:36-49. doi: 10.1016/j.ejps.2016.12.009. Epub 2016 Dec 8.
The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility.
芹菜素 - 磷脂植物药制剂（APLC）的研发旨在提高芹菜素的水溶性、溶出度、体内生物利用度及抗氧化活性。APLC的合成以全因子设计策略为指导，纳入特定的制剂和工艺变量以生产优化产品。对设计优化后的制剂进行了水溶性、体外溶出度、药代动力学及抗氧化活性测定。通过评估其对大鼠模型中四氯化碳诱导的肝功能标记酶升高的影响来进行药理评价。通过研究其对肝脏抗氧化标记酶的影响来评估抗氧化活性。使用设计优化的制剂和工艺变量水平对所建立的模型进行验证。物理化学表征证实了植物药制剂的形成。与纯芹菜素相比，优化后的制剂显示芹菜素的水溶性提高了36倍以上。该制剂在溶出度研究中还表现出芹菜素释放速率和程度显著更高。药代动力学分析表明，与纯芹菜素相比，所制备制剂中芹菜素的口服生物利用度显著提高。肝功能测试表明，所制备的植物药制剂能显著改善所有四氯化碳诱导升高的大鼠肝功能标记酶的恢复情况。所制备的制剂还通过显著提高谷胱甘肽、超氧化物歧化酶、过氧化氢酶水平及降低脂质过氧化物水平表现出抗氧化潜力。该研究表明，基于磷脂的植物药制剂是一种有前景且可行的策略，可用于改善芹菜素及类似低水溶性植物成分的递送。
