雷洛昔芬（RLX）广泛用于治疗骨质疏松症和预防乳腺癌。然而，由于其水溶性差、系统前代谢高、肠道葡萄糖醛酸化和 P-糖蛋白 (P-gp) 流出，其口服生物利用度低（< 2%）且不一致。因此，目前的工作是以质量源于设计（QbD）驱动开发RLX的磷脂嵌入的纳米结构脂质载体（NLC）来增强其淋巴吸收，增加口服生物利用度，并可能减少药物剂量。使用固体脂质（单硬脂酸甘油酯）、液体脂质（维生素 E）和表面活性剂（吐温 80）进行因素筛选和失效模式效应分析 (FMEA) 研究来描绘高风险因素。采用 Box-Behnken 设计进行响应面优化研究。采用数学和图形方法开始选择具有各种关键质量属性 (CQA) 的优化 NLC，平均粒径为 186 nm、zeta 电位为 - 23.6 mV、包封率为 80.09%、12 小时累积药物释放83.87%。在优化的 NLC 上进行的 DSC 和 FTIR 研究表明药物成功地被捕获到脂质基质中。体外药物释放研究证明了菲克扩散机制。大鼠体内药代动力学研究表明 AUC0-72 h（4.48 倍）和 Cmax（5.11 倍）显着改善，明确表明 RLX-NLC 的口服生物利用度与市售片剂相比明显优越（p< 0.001）公式。随后，在匹配时间点的体外药物溶解百分比和体内药物吸收百分比之间也成功尝试了“A”级体外/体内相关性（IVIVC）。体外细胞毒性和细胞摄取研究也证实了负载香豆素 6 的 NLC 通过微流体通道更高的功效并成功定位到 MG-63 细胞中。© 2023。控释协会。

Raloxifene (RLX) is popularly indicated in treatment of osteoporosis and prevention of breast cancer. Owing to its poor aqueous solubility, high pre-systemic metabolism, intestinal glucuronidation, and P-glycoprotein (P-gp) efflux, however, it demonstrates low (< 2%) and inconsistent oral bioavailability. The current work, Quality by Design (QbD)-driven development of phospholipid-embedded nanostructured lipidic carriers (NLCs) of RLX, accordingly, was undertaken to potentiate its lymphatic uptake, augment oral bioavailability, and possibly reduce drug dosage. Factor screening and failure mode effect analysis (FMEA) studies were performed to delineate high-risk factors using solid lipid (glyceryl monostearate), liquid lipid (vitamin E), and surfactant (Tween 80). Response surface optimization studies were performed employing the Box-Behnken design. Mathematical and graphical methods were adopted to embark upon the selection of optimized NLCs with various critical quality attributes (CQAs) of mean particle size as 186 nm, zeta potential of - 23.6 mV, entrapment efficiency of 80.09%, and cumulative drug release at 12 h of 83.87%. The DSC and FTIR studies, conducted on optimized NLCs, indicated successful entrapment of drug into the lipid matrix. In vitro drug release studies demonstrated Fickian diffusion mechanism. In vivo pharmacokinetic studies in rats construed significant improvement in AUC0-72 h (4.48-folds) and in Cmax (5.11-folds), unequivocally indicating markedly superior (p < 0.001) oral bioavailability of RLX-NLCs vis-à-vis marketed tablet formulation. Subsequently, level "A" in vitro/in vivo correlation (IVIVC) was also successfully attempted between the percentages of in vitro drug dissolved and of in vivo drug absorbed at the matching time points. In vitro cytotoxicity and cellular uptake studies also corroborated higher efficacy and successful localization of coumarin-6-loaded NLCs into MG-63 cells through microfluidic channels.© 2023. Controlled Release Society.