基于质量源于设计理念的风咳颗粒喷雾干燥工艺研究
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摘要
目的应用质量源于设计(quality by design,QbD)理念,建立风咳颗粒喷雾干燥工艺的设计空间并验证。方法以风咳颗粒处方提取浓缩液为模型药,采用风险评估和Plackeet-Burmann设计对影响因素进行筛选,运用中心点复合设计(CCD)试验优化关键工艺参数,建立工艺设计空间。最后选取4个实验点,用来检验已建立模型的预测能力。结果风险评估和Plackeet-Burmann设计试验确定了进料速度和雾化压力为关键工艺参数;CCD试验方差分析结果显示回归模型的P值均小于0.01,表明所建模型具有较好的预测性,并确定关键工艺参数进料速度和雾化压力的最佳范围分别为11%～14%和41.3～45.0 mm Hg(1 mm Hg=133.322 Pa),在这范围内的工艺参数均可以满足目标要求。结论基于QbD理念建立风咳颗粒喷雾干燥工艺的设计空间,可以提高喷雾干燥过程的灵活性和稳定性,可为今后中试放大研究提供参考。
Objective To establish and validate the design space of spray drying process of Fengke Granule using the concept of quality by design(QbD). Methods Using Fengke Granule formula to extract the concentrated solution as model drug, the risk assessment and Plackeet-Burmann design on influence factors of screening, to determine the liquid inlet velocity and pressure of atomization is the critical process parameters. Then, the central composite design was used to optimize the key parameters and establish the process design space. Finally, four experimental points were selected to test the predictive power of the model. Results Analysis of variance results showed that regression model P values were less than 0.01, which showed that the model had a good prediction, and the optimal range of key parameters of inlet velocity was determined and pressure of atomization were 11%—14% and 41.3—45.0 mm Hg, the process parameters in this range could meet the target requirements. Conclusion The design space of spray drying process is established based on QbD, which could improve the flexibility and stability of spray drying process, and provide reference for the pilot study in the future.
Objective To establish and validate the design space of spray drying process of Fengke Granule using the concept of quality by design(QbD). Methods Using Fengke Granule formula to extract the concentrated solution as model drug, the risk assessment and Plackeet-Burmann design on influence factors of screening, to determine the liquid inlet velocity and pressure of atomization is the critical process parameters. Then, the central composite design was used to optimize the key parameters and establish the process design space. Finally, four experimental points were selected to test the predictive power of the model. Results Analysis of variance results showed that regression model P values were less than 0.01, which showed that the model had a good prediction, and the optimal range of key parameters of inlet velocity was determined and pressure of atomization were 11%—14% and 41.3—45.0 mm Hg, the process parameters in this range could meet the target requirements. Conclusion The design space of spray drying process is established based on QbD, which could improve the flexibility and stability of spray drying process, and provide reference for the pilot study in the future.
引文
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[16]弓志青,陈相艳,程安玮,等.喷雾干燥杨梅粉玻璃化转变温度和结块特性研究[J].食品科学技术学报,2013,31(2):43-46.
[17]谢茵,何雁,曾金娣,等.4种中药浸膏粉等温吸湿规律与吸湿热分析[J].中国实验方剂学杂志,2015,21(11):1-6.
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[19]戴云徽,韩之俊,朱海荣.故障模式及影响分析(FMEA)研究进展[J].中国质量,2007(10):23-26.
[20]田英娜,赵同双,孙建勋,等.药物口服固体制剂制粒工艺风险的FMEA分析[J].中国药事,2013(1):27-32.
[21]陈昌勇,何腊平,李翠芹,等.Plackett-Burman设计和响应面法优化速冻紫苏籽肉丸的配方[J].食品工业科技,2016(4):259-265.
[22]罗赣,徐冰,孙飞,等.基于Qb D理念的微晶纤维素高速剪切湿法制粒过程实验研究[J].药学学报,2015,50(3):355-359.
[23]冯怡,洪燕龙,鲜洁晨,等.基于Qb D理念的中药新药成型工艺研发模式的探讨[J].中国中药杂志,2014,39(17):3404-3408.
[24]刘爽悦,沈金晶,李文龙,等.3种关键工艺参数辨识方法的比较研究[J].中草药,2016,47(18):3193-3198.
[25]冯怡,张继全,王优杰,等.关于中药复方新药工艺研究的思考[J].中国医药工业杂志,2016,47(9):1125-1129.
[2]徐冰,史新元,乔延江,等.中药制剂生产工艺设计空间的建立[J].中国中药杂志,2013,38(6):924-929.
[3]徐丽敏,刘燕琳.“质量源于设计”理念探讨[J].科学中国人,2014(2):8-9.
[4]徐芳芳,毕宇安,王振中,等.过程分析技术在中药注射剂生产过程中的应用研究进展[J].中草药,2016,47(14):2563-2567.
[5]杨胤,冯怡,徐德生,等.干燥工艺与中药提取物物理性质的相关性研究[J].中国药学杂志,2008,43(17):1295-1299.
[6]蔡薇,韩静,李智.喷雾干燥技术在中药领域中的应用及进展[J].沈阳药科大学学报,2006,23(9):613-616.
[7]周扬,刘力,徐德生,等.纳米喷雾干燥技术用于生地黄低聚糖微粉的制备工艺研究[J].中草药,2016,47(1):65-71.
[8]雷红.利用喷雾干燥技术调控产品颗粒性质性能—颗粒成型机理研究[D].苏州:苏州大学,2016.
[9]Lebrun P,Krier F,Mantanus J,et al.Design space approach in the optimization of the spray-drying process[J].Eur J Pharm Biopharm,2012,29(9):226-234.
[10]Louren?o V,Lochmann D,Reich G,et al.A quality by design study applied to an industrial pharmaceutical fluid bed granulation[J].Eur J Pharm Biopharm,2012,2(6):438-447.
[11]Teckoe J,Mascaro T,Farrell T P,et al.Process optimization of a novel immediate release film coating system using Qb D principles[J].AAPS Pharm Sci Tech,2013,14(2):531-540.
[12]Gong X C,Chen H,Pan J Y,et al.Optimization of Panax notoginseng extraction process using a design space approach[J].Sep Purif Technol,2015,12(2):197-206.
[13]张俊鸿,曲敬来,李俊,等.基于药效优化风咳颗粒提取工艺[J].江西中医药,2016,47(7):65-69.
[14]田彦芳,万海同,朱紫烨,等.基于熵权法的多目标筛选甘草黄酮类成分纯化工艺[J].中草药,2016,47(7):1118-1125.
[15]吴伟,崔光华,陆彬.实验设计中多指标的优化:星点设计和总评“归一值”的应用[J].中国药学杂志,2000,35(8):530-533.
[16]弓志青,陈相艳,程安玮,等.喷雾干燥杨梅粉玻璃化转变温度和结块特性研究[J].食品科学技术学报,2013,31(2):43-46.
[17]谢茵,何雁,曾金娣,等.4种中药浸膏粉等温吸湿规律与吸湿热分析[J].中国实验方剂学杂志,2015,21(11):1-6.
[18]韩志伟.浅析喷雾干燥生产中影响产品质量的若干因素[J].中小企业管理与科技,2015(6):252.
[19]戴云徽,韩之俊,朱海荣.故障模式及影响分析(FMEA)研究进展[J].中国质量,2007(10):23-26.
[20]田英娜,赵同双,孙建勋,等.药物口服固体制剂制粒工艺风险的FMEA分析[J].中国药事,2013(1):27-32.
[21]陈昌勇,何腊平,李翠芹,等.Plackett-Burman设计和响应面法优化速冻紫苏籽肉丸的配方[J].食品工业科技,2016(4):259-265.
[22]罗赣,徐冰,孙飞,等.基于Qb D理念的微晶纤维素高速剪切湿法制粒过程实验研究[J].药学学报,2015,50(3):355-359.
[23]冯怡,洪燕龙,鲜洁晨,等.基于Qb D理念的中药新药成型工艺研发模式的探讨[J].中国中药杂志,2014,39(17):3404-3408.
[24]刘爽悦,沈金晶,李文龙,等.3种关键工艺参数辨识方法的比较研究[J].中草药,2016,47(18):3193-3198.
[25]冯怡,张继全,王优杰,等.关于中药复方新药工艺研究的思考[J].中国医药工业杂志,2016,47(9):1125-1129.