Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
Department of Pharmaceutics, College of Pharmacy, Aljouf University, Sakaka, Aljouf, KSA
Curr Drug Deliv. 2017;14(7):1005-1015. doi: 10.2174/1567201813666161230141717.
The objective of this study was to formulate and optimize Candesartan Cilexetil (CC) loaded nanostructured lipid carriers (NLCs) for enhanced oral bioavailability.
Glycerol monostearate (GMS), Oleic acid, Tween 80 and Span 40 were selected as a solid lipid, liquid lipid, surfactant and co- surfactant, respectively. The CC-NLCs were prepared by hot emulsion probe sonication technique and optimized using experimental design approach. The formulated CC-NLCs were evaluated for various physicochemical parameters and further optimized formulation (CC-NLC-Opt) was assessed for in vivo pharmacokinetic and pharmacodynamic activity.
The optimized formulation (CC-NLC-Opt) showed particle size (183.5±5.89nm), PDI (0.228±0.13), zeta potential (-28.2±0.99mV), and entrapment efficiency (88.9±3.69%). The comparative in vitro release study revealed that CC-NLC-Opt showed significantly better (p<0.05) release and enhanced permeation as compared to CC-suspension. The in vivo pharmacokinetic study gave many folds increase in oral bioavailability than CC suspension, which was further confirmed by antihypertensive activity in a murine model.
Thus, the results of ex vivo permeation, pharmacokinetic study and pharmacodynamics study suggest the potential of CC-NLCs for improved oral delivery.
本研究的目的是制备和优化坎地沙坦西酯（CC）负载的纳米结构脂质载体（NLC），以提高口服生物利用度。
甘油单硬脂酸酯（GMS）、油酸、吐温 80 和司盘 40 分别被选为固体脂质、液体脂质、表面活性剂和助表面活性剂。CC-NLC 是通过热乳化探头超声技术制备的，并采用实验设计方法进行优化。对所制备的 CC-NLC 进行了各种理化参数的评价，并对进一步优化的配方（CC-NLC-Opt）进行了体内药代动力学和药效学活性评估。
优化的配方（CC-NLC-Opt）显示出粒径（183.5±5.89nm）、PDI（0.228±0.13）、zeta 电位（-28.2±0.99mV）和包封效率（88.9±3.69%）。比较体外释放研究表明，CC-NLC-Opt 显示出明显更好的（p<0.05）释放和增强的渗透作用，与 CC 混悬剂相比。体内药代动力学研究表明，CC-NLC-Opt 的口服生物利用度比 CC 混悬剂增加了数倍，这在小鼠模型中的降压活性进一步得到了证实。
因此，体外渗透、药代动力学研究和药效学研究的结果表明，CC-NLC 具有改善口服递送的潜力。
