目的 研究羟丙甲纤维素(HPMC)的关键质量属性对双氯芬酸钠缓释片体外释放行为的影响。方法 对A,B和C 3个厂家的HPMC K15M的外观形貌、粒径、密度、压缩度和比表面积等特性指标进行研究和全面分析评价,采用压力-抗张强度曲线法、川北方程和久野方程将HPMC K15M的压缩数据进行非线性拟合,然后以不同质量属性的HPMC为凝胶骨架,双氯芬酸钠为模型药制备缓释片,测定其体外释放行为,找出影响双氯芬酸钠缓释片体外释放的HPMC的关键质量属性。结果 HPMC的取代型对双氯芬酸钠缓释片的释放度影响显著,黏度、密度和比表面积也有影响,粒径影响较小。结论 HPMC的取代型、黏度、密度和比表面积是与双氯芬酸钠缓释片的体外释放相关的关键质量属性。
Abstract
OBJECTIVE To investigate the effect of the critical quality attributes of hypromellose (HPMC) on the release profile of diclofenac sodium sustained-release tablets in vitro. METHODS The characteristics including appearance, particle size, density, compression and specific surface area of HPMC K15M from three manufacturers (A, B and C) were studied and evaluated comprehensively. The compression data of HPMC K15M were non-linear fitted via the pressure-tensile strength curve method, Kawabe equation and Hasano equation. Sustained-release tablets were prepared by using diclofenac sodium as the active ingredient with different HPMC as gel matrix, and the in vitro release behavior of the tablets was determined in order to identify the critical quality attribute of HPMC that affect the in vitro release profile of diclofenac sodium sustained-release tablets. RESULTS The release rate of diclofenac sodium sustained-release tablets was correlated with the substitution type of HPMC, viscosity, density and specific surface area, but less affected by particle size. CONCLUSION Substitution, viscosity, density and specific surface area of HPMC are the CQAs factors influencing the release profile of diclofenac sodium sustained- release tablets.
关键词
羟丙甲纤维素 /
关键质量属性 /
双氯芬酸钠缓释片 /
释放度
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Key words
HPMC /
critical quality attribute (CQA) /
diclofenac sodium sustained-release tablet /
release rate
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中图分类号：
R944
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参考文献
[1] ZHANG W. Medicinal excipients hypromellose HPMC applications. Chin Pharm J(中国药学杂志),2002,37(2):93.
[2] SHEN L L. Hypromellose in the application of pharmaceutical preparations and research. Chin J Pharm(中国药业),2007,16(12):64-64.
[3] WANG M,WU W C,WANG C M, et al. Different manufacturers hypromellose functional indicators of the study. J Guangdong Coll Pharm(广东药学院学院),2015,31(6):705-708.
[4] HUANG Z Y, MENG C,LI S Z, et al. Comparative study on the relative properties of domestic and imported hypromellose as slow release scaffolds. Drug Eval Res(药物评价研究),2016,39(2):237-241.
[5] JIANG J Z.Particle size distribution width representation method. Filtration and Separation(过滤与分离),2006,16(1):21-23.
[6] LIAO Z,ZHANG N,ZHAO G, et al. Multivariate analysis approach for correlations between material properties and tablet tensile strength of microcrystalline cellulose. Pharmazie,2012,67(9):774-779.
[7] DU Y,FENG Y,XU D S, et al. Advances in research on the properties of drug powder compression and binding. China Mod Appl Pharm(中国现代应用药学),2012,29(1):24-30.
[8] CUI F D,LONG X Y,LV W L, et al. Pharmaceutics(药剂学). 7th ed. Beijing:People′s Medical Publishing House,2011:98.
[9] SUN Y P,LIU H L,LIANG S, et al. The research progress of powder compressibility in tablets. Chin J Pharm:Online Ed(中国药剂学杂志网络版), 2013,11(2):27-34.
[10] CHEN S J,ZHU J B,QI X L.Evaluation of the powder properties of powder direct press tablets commonly used excipients. Chin J Pharm(中国医药工业杂志),2013,44(10):1010-1013.
[11] CUI F D, LONG X Y, LV W L, et al. Pharmaceutics(药剂学). 7th ed. Beijing:People′s Medical Publishing House,2011:100-101.
[12] YANG J R, LI J, ZHU Y. Self-made diclofenac sodium sustained release tablets and its in vitro release consistent with the original drug ritadol sustained-release tablets. Shanghai Pharm(上海医学),2017,38(5):11-14.
[13] ZHANG C Y,LIU J Q, WANG H G. Preparation of diclofenac sodium sustained release tablets and in vitro release. Chin J New Drugs(中国新药杂志),2005,14 (5):391-393.
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脚注
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基金
国家重大新药创制科技专项资助(2015ZX09303001002007)
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