Optimization of Xiaoer Lingyin granule formulation using single-factor and response surface methodology

This study aimed to develop and optimize Xiaoer Lingyin granules (XLGs), a pediatric traditional Chinese medicine formulation for acute pharyngitis, by integrating single-factor experiments, multi-index quality evaluation, and response surface methodology (RSM). Key formulation and process variables, including drug-to-excipient ratio, ethanol concentration, ethanol dosage, drying temperature, and drying time, were systematically evaluated to improve granule formability, flowability, dissolution performance, and palatability. The optimized formulation consisted of a drug-to-excipient ratio of 1 : 1, 65% (v/v) ethanol, 22.5% ethanol dosage, drying at 70 °C for 60 min, 0.2% sucralose, and 0.8% strawberry flavoring. Under these conditions, the granules showed high molding ratios, acceptable flowability, and dissolution ratios of ≥79.76%. The RSM model exhibited good predictive reliability, as confirmed by ANOVA, lack-of-fit analysis, R ²-related statistics, and validation experiments. This study establishes a quantitative formulation optimization framework for pediatric TCM granules by integrating granulation quality, dissolution behavior, and sensory acceptability, providing a practical strategy for improving the standardization and patient compliance of traditional Chinese medicine preparations.