Objective To meet the requirements for high-quality development of food-medicine homology products, taking Xiaoer Xiaoshi Granules (XXG, 小儿消食颗粒) as an example, this study established an intelligent-driven granulation process optimization and quality consistency evaluation method for food-medicine homology granules based on the quality by design (QbD) concept. Methods Firstly, the analytic hierarchy process (AHP) was used to assigned weights to critical quality attributes (CQAs) of XXG, with subsequent risk assessment identifying granulation critical influencing factors. Secondly, following single-factor screening of critical influencing factors, the optimal combination of granulation parameters was selected by comparing the Box-Behnken design-response surface methodology (BBD-RSM) and the genetic algorithm-backpropagation neural network (GA-BPNN). Finally, leveraging the medicine-food homology properties of XXG, a quality consistency assessment was performed targeting both chemical attributes (total flavonoid content) and taste quality attribute based on electronic tongue. Results The excipient properties, ethanol volume fraction of wetting agent, ethanol amount, and excipient-to-drug ratio were determined as critical influencing factors, the optimal granulation parameters for XXG were determined as follows: an excipient system of maltodextrin to mannitol at a 2∶1 ratio, an ethanol concentration of 84%, an ethanol amount of 0.18 mL/g, and an excipient-to-drug ratio of 1.5∶1, yielding a comprehensive score of 103.88. Regarding bioactive constituents, the RSD of total flavonoid content across three batches was as low as 1.95%. For instrumental sensory evaluation, the e-tongue response values demonstrated batch-to-batch consistency with RSDs below 3% across all seven sensors. Conclusion The optimized granulation parameter set demonstrated stability and feasibility, and this process optimization approach can offer valuable insights for developing medicine-food homology products and advancing intelligent manufacturing in traditional Chinese medicine.

medicine-food homology products  /  granulation process  /  quality by design  /  genetic algorithm-backpropagation neural network  /  consistency evaluation  /  Xiaoer Xiaoshi Granules  /  analytic hierarchy process  /  critical quality attributes  /  Box-Behnken design-response surface methodology  /  total flavonoids  /  electronic tongue  /  smart manufacturing