来源差异羟丙甲纤维素关键质量属性的表征及对缓释片体外溶出的分析  

Characterization of the critical quality attributes for hydroxypropyl methylcellulose with different sources and analysis of the release of sustained-release tablets in vitro

作　　者：万书林 孙会敏[2] 白玉菱 谢文影 管天冰 王伯初[3] 戴传云[1] WAN Shu-lin;SUN Hui-min;BAI Yu-ling;XIE Wen-ying;GUAN Tian-bing;WANG Bo-chu;DAI Chuan-yun(Chongqing Key Laboratory of Industrial Fermentation Microorganisms,School of Chemistry and Chemical Engineering,Chongqing University of Science and Technology,Chongqing 401331,China;NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,National Institutes for Food and Drug Control,Beijing 100050,China;Key Laboratory of Biorheological Science and Technology Ministry of Education,College of Bioengineering,Chongqing University,Chongqing 400030,China)

机构地区：[1]重庆科技学院化学化工学院,工业发酵微生物重庆市重点实验室,重庆401331 [2]中国食品药品检定研究院,国家药品监督管理局药用辅料质量研究与评价重点实验室,北京100050 [3]重庆大学生物工程学院,生物流变科学与技术教育部重点实验室,重庆400030

出　　处：《药学学报》2022年第2期484-491,共8页Acta Pharmaceutica Sinica

基　　金：国家科技重大新药创制专项(2017ZX09101-001-006);重庆市技术创新与应用发展专项面上项目(cstc2020jscx-msxmX0048)。

摘　　要：不同来源药用辅料的质量差异影响粉体的成型结构从而导致最终产品的性能。本文考察了两个生产厂家(A厂家和B厂家)不同规格的羟丙甲纤维素(HPMC)在粒径分布、物理形貌、黏度和粉末物理质量属性差异以及对不同溶解度的模型药物氨茶碱、双氯芬酸钠和盐酸二甲双胍缓释片体外溶出的影响。结果表明,A和B厂家的HPMC在粒径大小、物理形貌、黏度以及粉末堆积性、流动性、可压性存在一定的差异,对后续制得片剂的硬度、脆碎度均有影响。A和B厂家的HPMC理化性质差异对不同载药缓释效果的影响不同,对易溶性的氨茶碱和盐酸二甲双胍释放度无明显影响,对难溶性的双氯酚酸钠释放度影响较大,并且B厂家的HPMC载药缓释效果优于A厂家,本研究的结果将为制剂处方选择合适的辅料提供理论参考。The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder,resulting in changes in the properties of the final product.In this study,the critical quality attributes of hydroxypropyl methylcellulose(HPMC)with different specifications from two manufacturers(manufacturer A and manufacturer B)were characterized including particle size,physical morphology,viscosity and powder physical quality attributes.Aminophylline,diclofenac sodium,and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets,and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated.The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties(including particle size,physical morphology,viscosity,dimension,compressibility and powder flow),which could change the hardness and friability of the sustained-release tablets.The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro.It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride,but had a greater impact on the release of poorly soluble diclofenac sodium.Compared with manufacturer A,the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent.The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.

关 键 词：药用辅料 羟丙甲纤维素 来源差异 关键质量属性 固体制剂 药物释放 

分 类 号：R943[医药卫生—药剂学]