盐酸雷洛昔芬纳米晶体的制备及口服生物利用度研究  

Preparation and Oral Bioavailability of Raloxifene Hydrochloride Nanocrystals

作　　者：高洋洋[1] 陈丽[1] 丁瑞 Gao Yangyang;Chen Li;Ding Rui(Department of Pharmacy,Third People’s Hospital of Dalian,Liaoning Dalian 116033,China)

机构地区：[1]大连市第三人民医院药剂部,辽宁大连116033

出　　处：《中国药师》2021年第11期2033-2037,共5页China Pharmacist

摘　　要：目的:制备盐酸雷洛昔芬纳米晶体(RLX-NCs),并考察其口服生物利用度。方法:以泊洛沙姆188和十二烷基硫酸钠作为稳定剂,采用高压均质法制备RLX-NCs,并经喷雾干燥固化成固体粉末;比较RLX-NCs在固化前、后的粒径分布及Zeta电位的变化情况,在扫描电镜下观察RLX-NCs及其固体粉末的微观结构,测定RLX-NCs在不同pH介质溶液中的溶解度,考察RLX-NCs的体外溶出情况,评价RLX混悬液和RLX-NCs经大鼠口服给药后的体内药动学以及生物利用度。结果:RLX-NCs在喷雾干燥前后的平均粒径、PDI和Zeta电位值基本无变化;在扫描电镜下可观察到RLX-NCs呈不规则颗粒状分布,喷雾干燥后呈多孔球状;RLX-NCs在不同pH介质溶液中的溶解度明显提高;RLX-NCs的溶出速度明显加快,在10 min内药物可完全溶出;将RLX制备成纳米晶体后其口服生物利用度显著提高。结论:本研究将盐酸雷洛昔芬制备成纳米晶体,处方设计合理,易于放大生产,可显著提高盐酸雷洛昔芬的口服生物利用度。Objective: To prepare raloxifene hydrochloride nanocrystals(RLX-NCs) and to investigate its oral bioavailability. Methods: Using poloxamer 188 and sodium lauryl sulfate as the stabilizers, RLX-NCs were prepared by high-pressure homogenization, and spray-dried into solid powder. The particle size distribution and zeta potential changes of RLX-NCs before and after solidification were compared. The microstructure of RLX-NCs and solid powder were observed under a scanning electron microscope. The solubility of RLX-NCs in different pH media was measured. The in vitro dissolution characteristics of RLX-NCs were investigated. The in vivo pharmacokinetics and bioavailability of RLX suspension and RLX-NCs after oral administration in rats were studied. Results: The average particle size, PDI and zeta potential of RLX-NCs had basically no change before and after solidification. It was observed that RLX-NCs were distributed in irregular granular form, and RLX-NCs were spray-dried into porous powder form. The dissolution rate of RLX-NCs was significantly increased, and the drug could be completely dissolved within 10 minutes. After RLX was prepared into nanocrystals, the oral bioavailability was significantly improved. Conclusion: In this study, RLX was prepared into nanocrystals. The formulation design is reasonable, and the production process is easy to scale up. It can significantly improve the oral bioavailability of RLX.

关 键 词：盐酸雷洛昔芬 纳米晶体 高压均质法 渗透性 口服生物利用度 

分 类 号：R944.9[医药卫生—药剂学]