摘要
生物黏附制剂是以天然或合成高分子材料为制剂载体,口服给药后可延长在肠道内滞留时间,具有释药速率可控、促进药物黏膜吸收等优点。本文基于软材的物性参数和黏附性能,提出一种有别于常规筛选最优处方的黏附处方筛选方法,并以该法为指导,采用挤出滚圆法制备黄芪总皂苷生物黏附微丸;基于小动物活体成像技术和建立的猪胃黏蛋白模型,对黏附微丸进行体内和体外黏附性能评价。通过对软材的物性参数与黏附微丸的成型性和黏附性的研究,确定了5种物性参数:硬度(Ha)、黏附性(Ad)、弹性(Sp)、内聚性(Co)和咀嚼性(Ch),作为筛选最优处方的考察指标;基于主成分分析统计学方法,建立综合评价模型对拟定的黏附处方进行综合排名,得出最优的处方:微晶纤维素:(壳聚糖∶卡波姆940=2∶1),其中黏附材料用量占辅料用量20%,药辅比为1∶4。所有动物实验获得上海中医药大学伦理学委员会批准。体内和体外黏附性能评价结果表明,与黄芪总皂苷普通微丸相比,生物黏附微丸具有明显肠道滞留优势,证实了基于软材物性参数建立的黏附处方筛选方法是科学、可靠的。
Bioadhesive preparation can be attached to specific sites to control drug release rate,increase drug concentration and increase efficacy,which is based on natural or synthetic polymer material.In this paper,based on the physical properties of wet mass,a method for screening adhesion formulation was proposed,which was different from conventional way of screening optimal formulation,and astragalosides loaded bioadhesive pellets were prepared by extrusion-spheronization method(extrusion speed 30 r·min-1,spheronization speed 808 r·min-1,spheronization time 7.5 min)based on this formulation screening method,small living animal imaging technology and mucin from porcine stomach model were used to evaluate the in vivo and in vitro adhesiveness behaviour of the pellets.According to the relationship between the physical properties of wet mass and the formability and adhesiveness of bioadhesive pellets,five key physical properties hardness(Ha),adhesiveness(Ad),springiness(Sp),cohesiveness(Co),chewiness(Ch)were selected as the index of screening optimal formulation,therefore a comprehensive evaluation model was established,which based on principal component analysis,to did digital ranking for these proposed adhesion formulation,the optimal formulation was determined:microcrystalline cellulose:(chitosan∶Carbomer 940=2∶1),the adhesive material dosage accounted for 20%of the excipient dosage,and the ratio of drugs to excipients was 1:4.All animal experiments have been approved by Ethics Committee of Shanghai University of Traditional Chinese Medicine.The in vivo and in vitro adhesive evaluation results showed the pellets had a clear advantage in intestinal adhesion over normal pellets,its also proved the scientificity and reliability of the method of screening bioadhesive formulation.
作者
李磊
沈岚
王晓柠
林晓
洪燕龙
冯怡
LI Lei;SHEN Lan;WANG Xiao-ning;LIN Xiao;HONG Yan-long;FENG Yi(School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine of Ministry of Education,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;E-institute of Chinese Traditional Internal Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Innovation Center of Traditional Chinese Medicine Health Service,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《药学学报》
CAS
CSCD
北大核心
2019年第11期2093-2099,共7页
Acta Pharmaceutica Sinica
基金
上海市中医药事业发展三年行动计划(ZY3-CCCX-3-5001)
关键词
黄芪总皂苷
生物黏附微丸
软材
物性参数
猪胃黏蛋白
黏附性
astragalosides
bioadhesive pellet
wet mass
physical property
mucin from porcine stomach
adhesiveness
