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 mmHg（1 mmHg=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 mmHg, 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.

江西省科技计划专项（20151BBG70031）；“赣鄱555”工程领军人才培养计划项目