妇科痛经分散片的制备工艺研究及质量评价
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摘要
目的确定妇科痛经分散片的处方和制备工艺,并建立其质量标准。方法经过系列单因素筛选,初步确定填充剂、崩解剂等辅料的种类和用量范围,在此基础上通过D-最优混料设计筛选确定,进一步再通过单因素筛选确定助流剂、矫味剂用量,确定妇科痛经分散片处方,并检测其崩解时限、硬度、脆碎度、片重差异、毒性成分3种双酯型乌头生物碱的含量及指标性成分6-姜辣素的含量。结果妇科痛经分散片的最佳处方为药粉35.00%,微晶纤维素(MCC)17.90%,山梨醇6.75%,交联聚维酮(PVPP)19.70%,低取代羟丙基纤维(L-HPC)17.40%,阿斯巴甜0.75%、柠檬酸1.00%,微粉硅胶1.00%,硬脂酸镁0.50%;平均崩解时限(50.83±1.47)s,平均硬度(6.44±0.27) kg/cm~2,平均脆碎度1.95%,片重差异1.09%,未检测到新乌头碱、乌头碱和次乌头碱3种剧毒双酯型生物碱,6-姜辣素质量分数(0.617 0±0.007 9) mg/g~。结论制备的妇科痛经分散片剂外观光洁,崩解时限、硬度、脆碎度、片重差异以及3种双酯型乌头生物碱的含量均符合2015年版《中国药典》要求,指标性成分6-姜辣素含量均匀。
Objective To determine the formula and preparation technology of Fuke Tongjing(Gynecologic Dysmenorrheal) Dispersible Tablet, and establish quality standard. Methods After a series of single-factor screening, the types and dosage ranges of fillers, disintegrators and other excipients were preliminarily determined and on this basis, they were screened and determined through D-optimal mixture design. Then the formula of Fuke Tongjing Dispersible Tablet was ensured through single-factor screening for determining dosages of glidants and corrigent. The disintegration time, hardness, friability, tablet weight difference, content of toxic components(3 kinds of diester aconitine alkaloids) and content of 6-gingerol(index component) were detected. Results The optimal formula of Fuke Tongjing Dispersible Tablet was as follows: 35.00% of powder, 17.90% of microcrystalline cellulose(MCC), 6.75% of sorbitol, 19.70% of crospovidone(PVPP), 17.40% of low-substituted hydroxypropyl fiber(L-HPC), 0.75% of aspartame, 1.00%of citric acid, 1.00% of aerosil and 0.50% of magnesium stearate. The average disintegration time was(50.83±1.47) s, average hardness was(6.44±0.27) kg/cm, average friability was 1.95%, and difference in tablet weight was 1.09%. There were no toxic diester aconitine alkaloids including new aconitine, aconitine and hypaconitine detected. The mass fraction of 6-gingerol was(0.617±0.007 9) mg/g. Conclusion The appearance of prepared Fuke Tongjing Dispersible Tablet is smooth, and disintegration time, hardness, friability, tablet weight difference and content of 3 kinds of diester aconitine alkaloids are all accord with requirement of Pharmacopoeia of the People's Republic of China(2015). The content of 6-gingerol is uniform.
Objective To determine the formula and preparation technology of Fuke Tongjing(Gynecologic Dysmenorrheal) Dispersible Tablet, and establish quality standard. Methods After a series of single-factor screening, the types and dosage ranges of fillers, disintegrators and other excipients were preliminarily determined and on this basis, they were screened and determined through D-optimal mixture design. Then the formula of Fuke Tongjing Dispersible Tablet was ensured through single-factor screening for determining dosages of glidants and corrigent. The disintegration time, hardness, friability, tablet weight difference, content of toxic components(3 kinds of diester aconitine alkaloids) and content of 6-gingerol(index component) were detected. Results The optimal formula of Fuke Tongjing Dispersible Tablet was as follows: 35.00% of powder, 17.90% of microcrystalline cellulose(MCC), 6.75% of sorbitol, 19.70% of crospovidone(PVPP), 17.40% of low-substituted hydroxypropyl fiber(L-HPC), 0.75% of aspartame, 1.00%of citric acid, 1.00% of aerosil and 0.50% of magnesium stearate. The average disintegration time was(50.83±1.47) s, average hardness was(6.44±0.27) kg/cm, average friability was 1.95%, and difference in tablet weight was 1.09%. There were no toxic diester aconitine alkaloids including new aconitine, aconitine and hypaconitine detected. The mass fraction of 6-gingerol was(0.617±0.007 9) mg/g. Conclusion The appearance of prepared Fuke Tongjing Dispersible Tablet is smooth, and disintegration time, hardness, friability, tablet weight difference and content of 3 kinds of diester aconitine alkaloids are all accord with requirement of Pharmacopoeia of the People's Republic of China(2015). The content of 6-gingerol is uniform.
引文
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[9] 晋兴华,张慧,赵振宇,等. D-最优混料设计优化尼莫地平骨架片的处方[J]. 中国药学杂志,2009,44(7):516-520.Jin XH, Zhang H, Zhao ZY, et al. Optimization the formulations of Nimodipine Matrix Tablet using D-optimal mixture design[J]. Chin Pham J, 2009, 44(7): 516-520.
[10] 陈立. 枸橼酸苯海拉明口腔崩解片制备及其评价[D]. 重庆:西南大学,2013.Chen L. Preparation and evaluation of diphenhydramine citrate orally disintegrating tablets[D]. Chongqing: Southwest University, 2013.
[11] 代玉玲,普俊学,廖荣,等.中药分散片与其他中药口服制剂特点比较[J]. 中国民族民间医药,2017,26(8):63-65.Dai YL, Pu JX, Liao R, et al. Comparison of oral preparations of Chinese medicine dispersible tablets and traditional Chinese medicine[J]. Chinese Journal of Ethnomedicine and Ethnopharmacy, 2017, 26(8): 63-65.
[12] 刘伟,周春丽,赵婧,等. 姜酚的研究进展[J]. 食品研究与开发,2014,35(17):127-131.Liu W, Zhou CL, Zhao J, et al. Research advance in gingerols[J]. Food Research and Development, 2014, 35(17): 127-131.
[2] Latthe PM , Champaneria R, Khan KS. Dysmenorrhea[J]. Clin Evid, 2011, 2: 813.
[3] 苏占辉,刘玉翠,李国军,等. 中药分散片工艺设计及质量标准研究进展[J]. 中国医药导刊, 2009,11(7):1240-1241.Su ZH, LIU YC, LI GJ, et al. Research progress on technics design and quality standard of dispersible tablets of Chinese medicinals[J]. Chinese Journal of Medicinal Guide, 2009, 11(7): 1240-1241.
[4] 国家药典委员会. 中华人民共和国药典:四部[M]2015版. 北京:中国医药科技出版社,2015:403.National Pharmacopoeia Committee. Pharmacopoeia of the People’s Republic of China, Part 4[M]2015 Edition. Beijing: China Medical Science and Technology Press, 2015: 403.
[5] 黄大福. 分散片研究进展[J]. 临床医药文献杂志,2017,47(4):9289-9290.Huang DF. Research progress of dispersible tablets[J]. Journal of Clinical Medical Literature, 2017, 47(4): 9289-9290.
[6] Mura P, Furlanetto S, Cirri M, et al. Optimization of glibenclamide tablet composition through the combined use of differential scanning calorimetry and D-optimal mixture experimental design[J]. J Pharm Biomed Anal, 2005, 37(1): 65-71.
[7] 张丽华,关志宇,陈丽华,等. D-最优混料设计优选新疆一枝蒿滴丸处方[J]. 中国医院药学杂志,2014,34(11):877-880.Zhang LH, Guan ZY, Chen LH, et al. Optimization of the formulations of Artemisia rupestria dropping pill using D-optimal mixture design[J]. Chin Hosp Pharm J, 2014, 34(11): 877-880.
[8] 章烨雯,于竞新,王景雁,等. D-最优混料设计结合多种力学指标优化柴栀凝胶贴膏的基质处方及其体外释放透皮研究[J]. 中国中药杂志,2016,41(6):1046-1053.Zhang YW, Yu JX, Wang JY, et al. Matrix formulation of chaizhi cataplasma optimized by D-optimal mixture design combined with multiple mechanical indicators and its in vitro evaluation[J]. Chin J Chin Mater Med, 2016, 41(6): 1046-1053.
[9] 晋兴华,张慧,赵振宇,等. D-最优混料设计优化尼莫地平骨架片的处方[J]. 中国药学杂志,2009,44(7):516-520.Jin XH, Zhang H, Zhao ZY, et al. Optimization the formulations of Nimodipine Matrix Tablet using D-optimal mixture design[J]. Chin Pham J, 2009, 44(7): 516-520.
[10] 陈立. 枸橼酸苯海拉明口腔崩解片制备及其评价[D]. 重庆:西南大学,2013.Chen L. Preparation and evaluation of diphenhydramine citrate orally disintegrating tablets[D]. Chongqing: Southwest University, 2013.
[11] 代玉玲,普俊学,廖荣,等.中药分散片与其他中药口服制剂特点比较[J]. 中国民族民间医药,2017,26(8):63-65.Dai YL, Pu JX, Liao R, et al. Comparison of oral preparations of Chinese medicine dispersible tablets and traditional Chinese medicine[J]. Chinese Journal of Ethnomedicine and Ethnopharmacy, 2017, 26(8): 63-65.
[12] 刘伟,周春丽,赵婧,等. 姜酚的研究进展[J]. 食品研究与开发,2014,35(17):127-131.Liu W, Zhou CL, Zhao J, et al. Research advance in gingerols[J]. Food Research and Development, 2014, 35(17): 127-131.