摘要
目的采用纳米晶结合微丸层积上药技术将难溶性药物非洛地平制备成便于口服的纳米晶微丸,并通过大鼠灌胃给药评价其口服生物利用度。方法采用介质研磨法将非洛地平制备成纳米晶混悬液,并通过流化床层积上药工艺将非洛地平纳米晶负载到蔗糖丸芯表面;考察非洛地平纳米晶在流化床包衣上药前后的粒径分布、多聚分散系数(PDI)和Zeta电位的变化情况,并在扫描电镜下观察非洛地平纳米晶的微观形貌;比较非洛地平纳米晶微丸与非洛地平片的体外药物溶出速率,通过大鼠灌胃给药比较非洛地平纳米晶微丸与非洛地平混悬液的药动学和口服生物利用度。结果制备的非洛地平纳米晶平均粒径为(226.3±10.9)nm,PDI为(0.188±0.005),Zeta电位为(-25.1±0.5)mV,层积上药前、后非洛地平纳米晶的粒径分布未发生显著变化;在扫描电镜下可观察到非洛地平纳米晶呈不规则状分布;非洛地平纳米晶微丸中的药物体外溶出速率显著快于非洛地平片;大鼠体内药动学结果显示,非洛地平纳米晶微丸可显著提高药物的达峰质量浓度,增加药物的口服生物利用度。结论将非洛地平制备成纳米晶微丸,能显著提高药物的溶出速度,增加药物的口服生物利用度。
Objective The poorly water-soluble drug felodipine was prepared into nanocrystalline pellets by using nanocrystal combined with pellets technology,and their oral bioavailability was evaluated in rats.Methods Felodipine was prepared into nanocrystals by media grinding technology.The felodipine nanocrystals were loaded on to sucrose pellets through fluidized bed coating technology.The nanocrystals were observed under scanning electron microscope.The particle size changes of the nanocrystals before and after the fluidized bed coating were investigated.The in vitro dissolution of the nanocrystal pellets and Felodipine Tablets were compared.The pharmacokinetics and oral bioavailability of felodipine nanocrystalline pellets and felodipine suspensions were compared by intragastric administration in rats.Results The particle size distribution of felodipine nanocrystals was(226.3±10.9)nm,the PDI was(0.188±0.005),and the Zeta potential was(-25.1±0.5)mV.An irregular distribution of felodipine nanocrystals could be observed under the scanning electron microscope.The particle size distribution of felodipine nanocrystals did not change significantly before and after the layering of the drug.The in vitro dissolution rate of felodipine nanocrystalline pellets was significantly faster than that of Felodipine Tablets.The pharmacokinetics in rats showed that felodipine nanocrystalline pellets could significantly increase the peak concentration and improve the oral bioavailability.Conclusion The felodipine nanocrystalline pellets could significantly increase the dissolution rate and improve the oral bioavailability.
作者
吴玉萍
李芳平
周盾
WU Yuping;LI Fangping;ZHOU Dun(Department of Traditional Chinese Medicine,the Red Cross Hospital of Wuhan,Wuhan 430015,China;Department of Pharmacy,the Red Cross Hospital of Wuhan,Wuhan 430015,China;Department of Traditional Chinese Medicine,Wuhan First Hospital,Wuhan 430015,China)
出处
《西北药学杂志》
CAS
2022年第3期134-138,共5页
Northwest Pharmaceutical Journal
