硝苯地平纳米晶体的制备及其在大鼠体内的药动学评价  

Preparation of nifedipine nanocrystals and its in vivo pharmacokinetics evaluation in rats

作　　者：李秋艳 谢鹏 LI Qiuyan;XIE Peng(Department of Pharmacy,Tangshan Vocational and Technical College Affiliated Hospital,Tangshan 063000,Hebei Province,China)

机构地区：[1]唐山职业技术学院附属医院药剂科,河北唐山063000

出　　处：《中国药师》2024年第4期570-579,共10页China Pharmacist

摘　　要：目的 制备硝苯地平纳米晶体(NDP-NCs)并评价其在大鼠体内的药动学。方法 采用介质研磨法制备NDP-NCs,并通过单因素试验确定NDP-NCs的处方组成及制备工艺;采用扫描电镜观察NDP-NCs及其固体颗粒的微观结构,比较NDP-NCs在喷雾干燥前后的粒径分布及Zeta电位,考察NDP-NCs颗粒的稳定性;比较NDP原料药与NDP-NCs颗粒的溶出速率∶,评价NDP混悬液和NDP-NCs颗粒经大鼠口服给药后的体∶内药动学。结果 以羟丙基纤维素(HPC-SL)和十二烷基硫酸钠(SDS)作为稳定剂,药物与稳定剂用量之比为5为1规则颗粒状分布,NDP-NCs颗粒呈多孔球状;NDP-NCs在喷雾干燥前后的平均粒径、多分散系数基本无变化;NDP-NCs颗粒在加速试验的条件下放置6个月稳定性良好;NDP-NCs颗粒在不同pH介质溶液中的溶解度明显提高;NDP-NCs颗粒的溶出速度明显增加,在15 min内药物可溶出90%以上;将NDP制备成纳米晶体后其口服生物利用度显著提高。结论 本研究将硝苯地平制备成纳米晶体,处方设计合理,制备工艺可行,可显著提高硝苯地平的口服生物利用度。Objective To prepare nifedipine nanocrystals(NDP-NCs)and evaluate their in vivo pharmacokinetics in rats.Methods The NDP-NCs was prepared by medium grinding method,and the formulation and preparation technology of NDP-NCs were determined by single factor experiment.The microstructure of NDP-NCs and its solid powder was observed under scanning electron microscope.The particle size distribution and Zeta potential of NDP-NCs before and after spray drying were compared.The stability of the spray drying granules of NDP-NCS was investigated.The dissolution rates of the NDP raw material and NDP-NCs granules were compared.The in vivo pharmacokinetics of NDP suspension and NDP-NCs granules were evaluated after oral administration in rats.Results Using hydroxypropyl cellulose(HPC-SL)and sodium dodecyl sulfate(SDS)as stabilizers,the ratio of drug to stabilizer was 5∶1,the size of grinding medium was 0.2 mm,the ratio of grinding medium to liquid volume was 1∶1,the grinding speed was 2000 r/min,and the grinding time was 3 h.The NDP NCs showed an irregular granular distribution,and the NDP-NCs granules were porous and spherical.The average particle size and polydispersity index had no change before and after spray drying.The NDP-NCs granules had good stability after 6 months under the condition of accelerated testing.The solubility of NDP-NCs in different pH media was obviously improved.The dissolution rate of NDP-NCs granules increased significantly,and the drug could dissolve more than 90%within 15 min.The oral bioavailability of NDP was significantly improved after it was prepared into nanocrystals.Conclusion In this study,the nifedipine is prepared into nanocrystals with reasonable formulation design and feasible preparation technology,which can significantly improve the oral bioavailability of nifedipine.

关 键 词：硝苯地平 纳米晶体 介质研磨法 喷雾干燥 药动学 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]