基于质量源于设计理念优化参蒲盆炎颗粒喷雾干燥工艺
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摘要
目的基于"质量源于设计"(quality by design,Qb D)理念,采用设计空间法优化参蒲盆炎颗粒喷雾干燥工艺。方法首先将集粉率、水分含量及芍药苷、绿原酸、虎杖苷、丹酚酸B含量6个指标作为关键质量属性(critical quality attribute,CQA),采用Plackett-Burman(P-B)设计实验,通过加权标准偏回归系数筛选出进风温度、进样速率、药液密度为3个关键工艺参数(critical process parameter,CPP);再采用Box-Behnken设计实验,通过逐步回归法建立CQA和CPP间的数学模型。结果方差分析显示模型P值均小于0.05,失拟值均大于0.05,可以较好地描述CQA和CPP之间的关系。最后通过MonteCarlo仿真法计算获得基于概率的设计空间并验证。结论在工艺参数设计空间内操作能够保证参蒲盆炎颗粒喷雾干燥工艺品质稳定,有助于提高批次间质量均一性,为产业化提供数据支撑。
Design space approach was applied to optimize the spray drying process of Shenpu Penyan Granule(SPG) based on the concept of quality by design(QbD). The yield, moisture content, the content of paeoniflorin, chlorogenic acid, polydatin and salvianolic acid B were defined as the process critical quality attributes(CQAs). Based on the Plackett-Burman design, three critical process parameters(CPPs) including inlet temperature, specific gravity, and feeding speed were identified by using the weighted standardized partial regression coefficient method. And stepwise regression method was then used to establish the mathematical model between CQAs and CPPs in the Box-Behnken design. The variance analysis results showed that the P values of the five models were less than 0.05 and the mismatch values were all greater than 0.05, indicating that the model could describe the relationship between CQAs and CPPs. Probability based design space was obtained and verified using Monte-Carlo simulation method. According to the verification results, the robustness of first ethanol precipitation process of SPG can be guaranteed by operating within the design space parameters, which helps to improve the quality uniformity between batches of phenol extracts and provides data support for industrialization production.
Design space approach was applied to optimize the spray drying process of Shenpu Penyan Granule(SPG) based on the concept of quality by design(QbD). The yield, moisture content, the content of paeoniflorin, chlorogenic acid, polydatin and salvianolic acid B were defined as the process critical quality attributes(CQAs). Based on the Plackett-Burman design, three critical process parameters(CPPs) including inlet temperature, specific gravity, and feeding speed were identified by using the weighted standardized partial regression coefficient method. And stepwise regression method was then used to establish the mathematical model between CQAs and CPPs in the Box-Behnken design. The variance analysis results showed that the P values of the five models were less than 0.05 and the mismatch values were all greater than 0.05, indicating that the model could describe the relationship between CQAs and CPPs. Probability based design space was obtained and verified using Monte-Carlo simulation method. According to the verification results, the robustness of first ethanol precipitation process of SPG can be guaranteed by operating within the design space parameters, which helps to improve the quality uniformity between batches of phenol extracts and provides data support for industrialization production.
引文
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[3]武景路,张丽丽,孟金硕,等.正交试验优化金银花提取物的真空带式干燥工艺的研究[J].现代药物与临床,2015,30(2):141-144.
[4]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.
[5]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.
[6]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.
[7]张俊鸿,何雁,许燕,等.基于质量源于设计理念的风咳颗粒喷雾干燥工艺研究[J].中草药,2017,48(5):2061-2071.
[8]张建,张欣,毕宇安,等.设计空间法研究龙血竭酚类提取物的精制工艺[J].中国中药杂志,2017,42(18):3546-3552.
[9]韩天燕,付亭亭,费文玲,等.基于质量源于设计理念的仙曲片薄膜包衣工艺研究[J].中草药,2018,49(11):2564-2570.
[10]张小飞,邢传峰,果秋婷.基于质量源于设计(Qb D)理念优化穿心莲内酯固体脂质纳米粒[J].中草药,2015,46(2):194-200.
[11]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.
[12]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.
[13]Gong X C,Chen H L,Pan J Y,et al.Optimization of Panax notoginseng extraction process using a design space approach[J].Sep Purif Technol,2015,141:197-206.
[14]Gong X C,Li Y,Guo Z T,et al.Control the effects caused by noise parameter fluctuations to improve pharmaceutical process robustness:A case study of design space development for an ethanol precipitation process[J].Sep Purif Technol,2014,132:126-137.
[15]Gong X C,Chen H L,Chen T,et al.Unit operation optimization for the manufacturing of botanical injections using a design space approach:A case study of water precipitation[J].PLoS One,2014,9(8):e104493.
[16]孙仙玲,秦建平,王宪平,等.HPLC测定FK IV号颗粒中芍药苷、绿原酸、虎杖苷及丹酚酸B的含量[J].世界科学技术-中医药现代化,2016,18(1):125-129.