Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat, India.
J Adv Res. 2016 May;7(3):423-34. doi: 10.1016/j.jare.2016.03.002. Epub 2016 Mar 5.
The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 3(2) factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and -12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX.
本工作旨在利用纳米结构脂质载体 (NLCs) 的潜力，提高盐酸雷洛昔芬 (RLX) 的口服生物利用度。RLX 负载的 NLC 是通过溶剂扩散法制备的，分别使用甘油单硬脂酸酯和 Capmul MCM C8 作为固体脂质和液体脂质。采用完全 3(2) 因子设计来研究两个独立参数（即固体脂质与液体脂质的比例和稳定剂浓度）对制备的 NLC 包封效率的影响。统计评估证实，当制剂中液体脂质含量从 5%w/w 增加到 15%w/w 时，包封效率显著提高。在优化的 NLC-8 制剂中进行的固态特性研究（DSC 和 XRD）表明 RLX 从结晶态转变为无定形态。优化的制剂表现出 32.50 ± 5.12nm 的平均粒径和-12.8 ± 3.2mV 的 zeta 电位，赋予 NLC 分散体良好的稳定性。体外释放研究表明，初始 8 小时内有突释，随后持续释放至 36 小时。TEM 研究证实了光滑表面离散的球形纳米尺寸颗粒。得出最终结论，进行了体内药代动力学研究，结果表明与普通药物混悬剂相比，优化的 NLC 制剂使生物利用度提高了 3.75 倍。这些结果表明 NLCs 具有显著提高难溶性 RLX 口服生物利用度的潜力。
