Objective This study investigated the effects of critical process parameters (CPPs, e.g., extraction temperature, time, and solid-liquid ratio) on the physical properties and the content of 12 effective components in both alcoholic and aqueous extracts of Guizhi Fuling Capsules (GFC, 桂枝茯苓胶囊). The correlations between physical properties and effective components were analyzed to provide a basis for process optimization and quality control. Methods A single-factor experimental design was adopted. Different process parameters such as extraction temperature (set control temperature of electric heating jacket), extraction time and solid-liquid ratio were set to prepare the corresponding alcohol extract and water extract, and the particle size, polydispersion index (PDI), ζ potential, conductivity, pH value, total solid content and refractive indexof each intermediate were determined. The contents of 12 effective components (gallic acid, 4-hydroxybenzoic acid, oxypaeoniflorin, ethyl gallate, benzoic acid, 1,2,3,4,6-O-pentagalloylglucose, cinnamaldehyde, amygdalin, albiflorin, paeoniflorin, cinnamic acid, paeonol) were quantified by UPLC. Correlations among CPPs, physical parameters, and effective components were analyzed via the chemometric analysis, including orthogonal partial least squares-discriminant analysis (OPLS-DA), Pearson correlation, grey relational analysis, and linear regression model analysis. Results The CPPs exert certain influences on the physical parameters and effective components of GFC alcoholic extracts and aqueous extracts. Specifically, for the alcoholic extraction process, when the temperature of the electric heating mantle is controlled at ≤ 200 ℃, with an extraction duration of 1.5 h and a solid-liquid ratio ranging from 1:6 to 1:8; and for the aqueous extraction process, when the electric heating mantle temperature is maintained at 200—250 ℃, extraction time is set to 1.5—2.0 h and the solid-liquid ratio is 1:6—1:8, the contents of most bioactive substances are relatively high. Furthermore, the chemometric analysis results indicated that ζ potential, conductivity, and total solids correlated well with the content of amygdalin in alcoholic extracts under different solid-liquid ratios (well-fitted, R² > 0.7). And in aqueous extracts under different temperatures, particle size and conductivity showed some correlation with cinnamic acid content, but with poor fitting. Conclusion Critical process parameters significantly influence the correlation between physical properties and effective components by modulating the solution microenvironment and dissolution behavior. Conductivity, ζ potential and total solid content can serve as important bases for the study of the “quantity-quality” transfer law in the process of traditional Chinese medicine manufacturing.

physical properties  /  process quality control  /  Guizhi Fuling Capsules  /  polydispersity index  /  gallic acid  /  4-hydroxybenzoic acid  /  oxypaeoniflorin  /  ethyl gallate  /  benzoic acid  /  1,2,3,4,6-O-pentagalloylglucose  /  cinnamaldehyde  /  amygdalin  /  albiflorin  /  paeoniflorin  /  cinnamic acid  /  paeonol  /  orthogonal partial least squares-discriminant analysis  /  Pearson correlation analysis  /  grey relational analysis  /  linear regression model analysis