基于质量源于设计理念的仙曲片薄膜包衣工艺研究
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摘要
目的结合质量源于设计(quality by design,Qb D)理念,对仙曲片的薄膜包衣工艺进行考察,以提高包衣效率和稳定性。方法以"质量源于设计"理念为指导和Design-Expert软件为工具,确定影响仙曲片薄膜包衣目标的关键质量属性为响应值,影响关键质量属性的工艺参数为因素,运用Box-Behnken响应面法优化工艺参数,建立控制空间,通过测定仙曲片的吸湿性,对设计空间进行验证。结果通过95%置信区间对空间进行优化,减小实际误差,得到最佳工艺参数范围:片床温度37~43℃,包衣液浓度9%~11%,包衣增重4%~5%,在既定条件下对仙曲片薄膜包衣后,片剂色泽均匀,片面光滑细腻,吸湿性显著降低。结论以Qb D为根本,采用合理的实验设计理念,通过建立合理的设计空间为仙曲片薄膜包衣过程提供预测模型,提高了包衣过程的可控性和可适用性,保证了稳定的产品质量。
Objective To investigate the film coating process of Xianqu Tablets based on the concept of quality by design(Qb D), and improve the coating efficiency and stability. Methods Using the Qb D as an experimental guidance and the Design-Expert software as a tool, the critical quality attributes affecting Xianqu film coating targets were first determined as the response values, and the process parameters of influencing critical quality attributes were selected as the key factors. Then the Box-Behnken design was used to optimize the process parameters and establish a control space. Finally, the design space were verified by measuring the hygroscopicity of Xianqu Tablets. Results The results showed that the design space was optimized to reduce the actual error by 95% confidence interval, the best range of process parameters were obtained as follow: bed temperature 37—43 ℃, coating solution concentration 9%—11%, coating weight gain 4%—5%. After the Xianqu Tablets were coated under the given conditions, the hygroscopicity of Xianqu Tablets, which had a smooth surface and uniform color, was significantly reduced. Conclusion The desired effects by using a reasonable experimental design concept of Qb D were efficiently achieved, it provides a predictive model for the film coating process of Xianqu Tablets through constructing reasonable design space, which not only enhances the flexibility and applicability of the coating process, but also ensures the stable product quality.
Objective To investigate the film coating process of Xianqu Tablets based on the concept of quality by design(Qb D), and improve the coating efficiency and stability. Methods Using the Qb D as an experimental guidance and the Design-Expert software as a tool, the critical quality attributes affecting Xianqu film coating targets were first determined as the response values, and the process parameters of influencing critical quality attributes were selected as the key factors. Then the Box-Behnken design was used to optimize the process parameters and establish a control space. Finally, the design space were verified by measuring the hygroscopicity of Xianqu Tablets. Results The results showed that the design space was optimized to reduce the actual error by 95% confidence interval, the best range of process parameters were obtained as follow: bed temperature 37—43 ℃, coating solution concentration 9%—11%, coating weight gain 4%—5%. After the Xianqu Tablets were coated under the given conditions, the hygroscopicity of Xianqu Tablets, which had a smooth surface and uniform color, was significantly reduced. Conclusion The desired effects by using a reasonable experimental design concept of Qb D were efficiently achieved, it provides a predictive model for the film coating process of Xianqu Tablets through constructing reasonable design space, which not only enhances the flexibility and applicability of the coating process, but also ensures the stable product quality.
引文
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[3]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.
[4]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(10):2061-2066.
[5]冯怡,洪燕龙,杜若飞,等.Qb D理念的中药新药成型成型工艺研发模式的探讨[J].中国中药杂志,2014,39(17):3404-3407.
[6]Mazumder S,Pavurala N,Manda P,et al.Quality by design approach for studying the impact of formulation and process variables on product quality of oral disintegrating film[J].Int J Pharm,2017,527:151-160.
[7]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.
[8]万丹,张水寒,肖娟,等.Box-Behnken设计-效应面法优选酒黄连炮制工艺[J].药物评价研究,2014,37(4):341-345.
[9]江敏瑜,闫丹,陈娇,等.三七跌打软膏的制备及体外透皮特性研究[J].中草药,2017,48(22):4639-4647.
[10]王璐.基于质量源于设计的中药质量分析方法研究[D].杭州:浙江大学,2016.
[11]中国药典[S].四部.2015.
[12]罗赣,徐冰,崔向龙,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):359-360.
[13]Patwardhan K,Asgarzadeh F,Dassinger T,et al.A quality by design approach to understand formulation and process variability in pharmaceutical melt extrusion processes[J].J Pharm Pharmacol,2015,67(5):673-684.
[14]Kovacs S,Berko E,Csanyi I,et al.Development of nanostructured lipid carriers containing salicyclic acid for dermal use based on the quality by design method[J].Eur J Pharm Sci,2017,99:246-257.
[15]陈叶明.以质量源于设计为基础的盐酸二甲双胍缓释片的研究[D].苏州:苏州大学,2014.
[16]Yu L X,Amidon G,Khan M A,et al.Understanding pharmaceutical quality by design[J].AAPS J,2014,16(4):771-784.
[17]徐冰,史新元,吴志生,等.论中药质量源于设计[J].中国中药杂志,2017,42(6):1016-1021.
[18]李敏.可靠度分析的响应面法研究[D].重庆:重庆大学,2016.