盐酸雷洛昔芬固体脂质纳米粒的制备与体内药动学研究  

Preparation and in vivo pharmacokinetics of raloxifene hydrochloride solid lipid nanoparticles

作　　者：张琪 龚麟凤 ZHANG Qi;GONG Linfeng(Department of Pharmacy,the Red Cross Hospital of Wuhan,Wuhan 430015,China)

机构地区：[1]武汉市红十字会医院药剂科,武汉430015

出　　处：《西北药学杂志》2022年第1期82-86,共5页Northwest Pharmaceutical Journal

摘　　要：目的制备盐酸雷洛昔芬固体脂质纳米粒(raloxifene hydrochloride solid lipid nanoparticles,RLX-SLNs),并研究其在大鼠体内的药动学。方法采用热熔乳化-高压均质法制备RLX-SLNs,通过测定包封率、粒径分布、Zeta电位、微观形态并用差示扫描量热法(differential scanning calorimetry,DSC)对其进行表征;考察了RLX-SLNs的体外释药特性和稀释稳定性;比较了RLX混悬剂与RLX-SLNs经大鼠口服给药后的体内药动学。结果制备的RLX-SLNs外观呈乳白色溶液状,包封率为97.8%±1.6%,粒径为(194.5±8.5)nm,多聚分散指数(polydispersity index,PDI)为0.183±0.08,Zeta电位为(-34.3±1.5)mV;在透射电镜下观察到RLX-SLNs呈球状分布,无聚集;DSC测定结果显示RLX-SLNs中的药物吸热峰消失;RLX-SLNs在4种释放介质中均表现为双相释药特征;大鼠口服RLX-SLNs后,其药物达峰质量浓度和口服生物利用度均显著高于RLX混悬剂。结论将盐酸雷洛昔芬制备成固体脂质纳米粒,制备工艺可控,生物利用度显著提高,为盐酸雷洛昔芬的二次开发奠定了实验基础。Objective To prepare raloxifene hydrochloride solid lipid nanoparticles(RLX-SLNs)and study its pharmacokinetics in rats.Methods The RLX-SLNs were prepared by hot melt emulsification-high pressure homogenization method,and were characterized by encapsulation efficiency,particle size distribution,Zeta potential,microscopic morphology and differential scanning calorimetry(DSC).The in vitro dissolution characteristics and dilution stability of RLX-SLNs were investigated.The in vivo pharmacokinetics of RLX suspensions and RLX-SLNs after oral administration in rats were compared.Results The RLX-SLNs were milky white solution,the encapsulation efficiency was 97.8%±1.6%,the particle size was(194.5±8.5)nm,the polydispersity index(PDI)was(0.183±0.08),and the Zeta potential was(-34.3±1.5)mV.Under the transmission electron microscope,the RLX-SLNs were spherical distribution without aggregation.DSC measurement showed that the endothermic peak of RLX disappeared in RLX-SLNs.The in vitro drug release showed that the RLX-SLNs exhibited biphasic release characteristics.After oral administration of RLX-SLNs in rats,the peak plasma concentration and oral bioavailability were significantly higher than RLX suspensions.Conclusion In this study,raloxifene hydrochloride was prepared into solid lipid nanoparticles,which could significantly improve the oral bioavailability.It was of great significance for the secondary development of raloxifene hydrochloride.

关 键 词：盐酸雷洛昔芬 固体脂质纳米粒 药动学 热熔乳化-高压均质法 生物利用度 

分 类 号：R969[医药卫生—药理学]