摘要
目的探讨盐酸西那卡塞纳米结晶(CINA-NCs)的制备,并进行体外溶出度研究。方法采用沉淀-超声法制备CINA-NCs。基于单因素法和响应面法(Box-Behnken)设计对制备工艺和处方进行优化,以粒径和多分散指数(PDI)为指标,获得制备的最佳工艺条件。采用冷冻干燥法制备纳米结晶粉体,并用扫描电镜(SEM)、差示扫描量热仪(DSC)和X射线粉末衍射仪(XRPD)对制剂进行表征。最后,通过体外溶出度的研究,评价CINA-NCs胶囊的溶解度和溶出度。结果最优工艺是:CINA浓度108 mg/mL,聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物Soluplus浓度2.7 mg/mL,水相与有机相的比例40∶1,超声时间30 min。最佳工艺条件下制备的CINA纳米结晶的粒径和PDI分别为(244±2)nm和0.168±0.001。对冻干后的纳米结晶进行表征,表明在制备过程中晶体未发生变化。用30%(w/v)微晶纤维素(MCC),8%(w/v)交联羧甲基纤维素钠(CCNa)和2%(w/v)滑石粉制备的CINA-NCs胶囊在pH 1.2盐酸缓冲液、pH 4.5醋酸缓冲液、pH 6.8磷酸盐缓冲液和水四种介质中的体外溶出度均高于市售片剂Sensipar和原料药。结论纳米晶体技术制备的西那卡塞纳米结晶可以提高西那卡塞的溶解度,可改善西那卡塞口服给药的药效。
Objective In order to improve the solubility and bioavailability of cinacarbose hydrochloride,the preparation and the dissolution in vitro of cinacarbose hydrochloride nanocrystals(CINA-NCs)were studied.Methods Based on single factor method and Box-Behnken design,with the particle size and polydispersity index(PDI)as indexes,the optimal production process was achieved.Results The optimal production process was that the concentration of CINA was 108 mg/mL.The concentration of Soluplus was 2.7 mg/mL.The ratio of aqueous phase to organic phase was 40∶1.The time of ultrasonic was 30 min.It was investigated that the particle size and PDI of the NC prepared on the basis of the optimal formulation were(244±2)nm and 0.168±0.001,respectively.Nanocrystals were solidified and characterized.There was no crystalline change during preparation and lyophilization.CINA-NC capsules prepared with 30%(w/v)MCC,8%(w/v)CCNa and 2%(w/v)talcum powder by orthogonal experimental design presented a enhanced in vitro dissolution rate in four medium which were pH 1.2 hydrochloric acid buffer,pH 4.5 acetic acid buffer,pH 6.8 phosphate buffer saline and water.Conclusion The solubility of CINA can be improved by nano crystallization of CINA.
作者
张庆明
徐云燕
夏超
ZHANG Qing-ming;XU Yun-yan;XIA Chao(Department of Pharmacy,General Hospital of Eastern Theater Command,PLA,Nanjing 210002,Jiangsu,China;Jiangsu Provincial Institute of Materia Medica,Nanjing 210009,Jiangsu,China)
出处
《东南国防医药》
2021年第4期372-377,共6页
Military Medical Journal of Southeast China
关键词
盐酸西那卡塞
纳米晶体
响应面法
溶出度研究
cinacalcet hydrochloride
nanocrystals
box-behnken design
dissolution
