基于移动窗F检验法的中药配方颗粒混合均匀度近红外分析研究Near infrared analysis of blending homogeneity of Chinese medicine formula particles based on moving window F test method
杨婵;徐冰;张志强;王馨;史新元;付静;乔延江;
YANG Chan;XU Bing;ZHANG Zhi-qiang;WANG Xin;SHI Xin-yuan;FU Jing;QIAO Yan-jiang;Research Center of Traditional Chinese Medicine Information Engineering,Beijing University of Chinese Medicine;Beijing Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine;Beijing Tcmages Pharmaceutical Co.,LTD;
摘要(Abstract):
混合均匀度是保证中药配方颗粒产品批内质量一致性的关键。该文以乌梅配方颗粒中乌梅提取物粉末-糊精体系(糊精比例10%)为研究对象,在其混合过程中设计多个取样位点,将采集的粉末样品进行近红外(near infrared,NIR)漫反射光谱分析,并结合移动窗F检验(moving window F test,MW-F test)法对混合过程均匀度进行判断。同时采用HPLC对混合过程中枸橼酸的含量变化进行分析,以验证MW-F test法的有效性。结果显示乌梅配方颗粒混合过程在200~300 r达到混匀状态,300~400 r出现脱混现象,400 r后又趋于稳定,移动窗F检验分析结果与HPLC分析结果基本一致。移动窗F检验算法通过F界值设定均匀度判别阈值,避免了常规移动窗标准偏差法中阈值设定的随机性和模糊性,可推广应用于其他中药粉末混合过程的在线监控。
Blending uniformity is essential to ensure the homogeneity of Chinese medicine formula particles within each batch. This study was based on the blending process of ebony spray dried powder and dextrin( the proportion of dextrin was 10%),in which the analysis of near infrared( NIR) diffuse reflectance spectra was collected from six different sampling points in combination with moving window F test method in order to assess the blending uniformity of the blending process. The method was validated by the changes of citric acid content determined by the HPLC. The results of moving window F test method showed that the ebony spray dried powder and dextrin was homogeneous during 200-300 r and was segregated during 300-400 r. An advantage of this method is that the threshold value is defined statistically,not empirically and thus does not suffer from threshold ambiguities in common with the moving block standard deviatiun( MBSD). And this method could be employed to monitor other blending process of Chinese medicine powders on line.
关键词(KeyWords):
中药配方颗粒;混合均匀度;近红外;移动窗F检验法;过程分析技术
Chinese medicine formula particles;blending homogeneity;near infrared;moving window F test method;process analytical technology
基金项目(Foundation): 国家自然科学基金项目(81403112);; 北京市自然科学基金项目(7154217);; 中药生产过程控制与质量评价北京市重点实验室2015年度科技创新基地培育与发展专项(Z151100001615065);; 北京中医药大学自主选题项目(2016-JYB-XS110)
作者(Author):
杨婵;徐冰;张志强;王馨;史新元;付静;乔延江;
YANG Chan;XU Bing;ZHANG Zhi-qiang;WANG Xin;SHI Xin-yuan;FU Jing;QIAO Yan-jiang;Research Center of Traditional Chinese Medicine Information Engineering,Beijing University of Chinese Medicine;Beijing Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine;Beijing Tcmages Pharmaceutical Co.,LTD;
Email:
DOI:
参考文献(References):
- [1]周嘉林,徐以亮,李松,等.黄芩配方颗粒的制备方法:中国,CN101167801[P].2008-04-30.
- [2]Vanarase A U,AlcalàM,Rozo J I J,et al.Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy[J].Chem Eng Sci,2010,65(21):5728.
- [3]Lin Y,Li W,Xu J,et al.Development of a NIR-based blend uniformity method for a drug product containing multiple structurally similar actives by using the quality by design principles[J].Int J Pharm,2015,488(1):120.
- [4]Scheielhofer O,Balak N,Wahl P R,et al.Monitoring blending of pharmaceutical powders with multipoint NIR spectroscopy[J].AAPS Pharm Sci Tech,2013,14(1):234.
- [5]薛忠,徐冰,张志强,等.药物粉末混合过程在线监控技术研究进展[J].中国药学杂志,2016,51(2):91.
- [6]Scheibelhofer O,Balak N,Koller D M,et al.Spatially resolved monitoring of powder mixing processes via multiple NIR-probes[J].Powder Technol,2013,243:161.
- [7]Storme-Paris I,Clarot I,Esposito S,et al.Near infrared spectroscopy homogeneity evaluation of complex powder blends in a small-scale pharmaceutical preformulation process,a real-life application[J].Eur J Pharm Biopha,2009,72(1):189.
- [8]Li W,Qu H.Characterization of herbal powder blends homogeneity using near-infrared spectroscopy[J].J Innov Opt Heal Sci,2014,7(6):1450004.
- [9]Sekulic S S,Wakeman J,Doherty P,et al.Automated system for the on-line monitoring of powder blending processes using near-infrared spectroscopy:partⅡ.Qualitative approaches to blend evaluation[J].J Pharm Biomed,1998,17(8):1285.
- [10]Hausman D S,Cambron R T,Sakr A.Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity[J].Int J Pharm,2005,298(1):80.
- [11]Adam S,Suzzi D,Radeke C,et al.An integrated Quality by Design(Qb D)approach towards design space definition of a blending unit operation by discrete element method(DEM)simulation[J].Eur J Pharm Sci,2011,42(1):106.
- [12]Food and Drug Administration.Powder blends and finished dosage units-stratified in-process dosage unit sampling and assessment[EB/OL].[2011-03-01].http://www.fda.gov/OHRMS/DOCKETS/98fr/03d-0493-gd[000].pdf.
- [13]Besseling R,Damen M,Tran T,et al.An efficient,maintenance free and approved method for spectroscopic control and monitoring of blend uniformity:the moving F-test[J].J Pharmaceut Biomed,2015,114:471.
- [14]Devos O,Ruckebusch C,Durand A,et al.Support vector machines(SVM)in near infrared(NIR)spectroscopy:focus on parameters optimization and model interpretation[J].Chemometr Intell Lab,2009,96(1):27.
- [15]Blanco M,BaóR G,Bertran E.Monitoring powder blending in pharmaceutical processes by use of near infrared spectroscopy[J].Talanta,2002,56(1):203.
- 中药配方颗粒
- 混合均匀度
- 近红外
- 移动窗F检验法
- 过程分析技术
Chinese medicine formula particles - blending homogeneity
- near infrared
- moving window F test method
- process analytical technology
- 杨婵
- 徐冰
- 张志强
- 王馨
- 史新元
- 付静
- 乔延江
YANG Chan- XU Bing
- ZHANG Zhi-qiang
- WANG Xin
- SHI Xin-yuan
- FU Jing
- QIAO Yan-jiang
- Research Center of Traditional Chinese Medicine Information Engineering
- Beijing University of Chinese Medicine
- Beijing Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine
- Beijing Tcmages Pharmaceutical Co.
- LTD
- 杨婵
- 徐冰
- 张志强
- 王馨
- 史新元
- 付静
- 乔延江
YANG Chan- XU Bing
- ZHANG Zhi-qiang
- WANG Xin
- SHI Xin-yuan
- FU Jing
- QIAO Yan-jiang
- Research Center of Traditional Chinese Medicine Information Engineering
- Beijing University of Chinese Medicine
- Beijing Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine
- Beijing Tcmages Pharmaceutical Co.
- LTD