摘要
通过纳米晶技术将难溶性药物姜黄素制备成方便给药的口服纳米晶固体制剂,以提高姜黄素的溶解度及溶出速率,进而提高生物利用度。采用介质研磨法制备姜黄素纳米晶混悬液,得到两种稳定的姜黄素纳米晶混悬液处方,稳定剂分别为聚乙烯吡咯烷酮(PVP K30)/十二烷基硫酸钠(SDS)(1∶1),以及吐温80;通过流化床底喷包衣工艺将姜黄素纳米晶负载于丸芯上得到载药微丸,灌装后得到纳米晶胶囊。纳米晶再分散稳定性实验和扫描电镜(SEM)实验结果表明,以PVP K30/SDS为稳定剂时载药微丸形态均一且再分散前后纳米晶粒径均在200 nm左右,为最优处方。体外溶出研究表明,粒径为200 nm时显著提高了溶出速率和溶出度;X射线粉末衍射(XRPD)和差示扫描量热(DSC)分析结果表明,纳米晶制备过程中少部分晶型转变为无定型;大鼠体内药代动力学研究显示,姜黄素制成纳米晶后生物利用度达到原料药的9.3倍。本研究开发的姜黄素纳米晶胶囊可显著提高药物的体外溶出速率和溶出度、体内吸收速度和生物利用度,在改善药物难溶性方面具有重要意义。
The poorly water-soluble drug curcumin was prepared into oral nanocrystalline solid preparation by nanocrystal technology to improve the solubility,dissolution rate,and bioavailability.Curcumin nanocrystals were prepared by media grinding technology,and two types of stable curcumin nanocrystal suspension formula⁃tions were developed.The stabilizers in the two formulations were polyvinylpyrrolidone(PVP K30)/sodium lauryl sulfate(SDS)(1∶1)and Tween 80,respectively.The prepared curcumin nanocrystal suspension was loaded onto microcrystalline cellulose pellets through fluidized bed coating technology,and the nanocrystalline capsules were obtained after filling.The results of nanocrystal redispersion stability and scanning electron microscope(SEM)showed that the morphology of drug-loaded pellets was uniform when PVP K30 and SDS were used as stabilizers,and the diameter of nanocrystals before and after redispersion was about 200 nm,which was determined as the optimal formulation.In vitro dissolution study showed that curcumin nanocrystals at the size of 200 nm exhibited significantly promoted dissolution.The results of X-ray powder diffraction(XRPD)and differential scanning calo⁃rimetry(DSC)showed that the curcumin crystalline partly turned amorphous during the preparation of nanocrys⁃tals.Pharmacokinetic studies in rats showed that the bioavailability of curcumin nanocrystals was 9.3 times high⁃er than that of the bulk drug.The curcumin nanocrystalline capsules developed in this research can significantly improve the dissolution rate and bioavailability,which is of great significance in improving the poor solubility of drugs,and is expected to become a new dosage form for clinical treatment.
作者
彭一凡
王增明
王荣荣
杜祎萌
高翔
郑爱萍
张慧
PENG Yifan;WANG Zengming;WANG Rongrong;DU Yimeng;GAO Xiang;ZHENG Aiping;ZHANG Hui(China Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850;School of Pharmacy,North China University of Science and Technology,Tangshan 063210,China)
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2021年第2期211-218,共8页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.81573357,No.82073793)。
关键词
姜黄素
纳米晶
稳定性
介质研磨
底喷包衣
curcumin
nanocrystalline
stability
media grinding
bottom spray coating
