Objective This study applied the quality by design (QbD) principle to identify key attributes and elucidate their transfer relationships along the “spray-dried powder-ribbon-granule” manufacturing chain of Shanzha (Crataegi Fructus) formula granules. Methods A fractional factorial design was implemented to investigate seven major factors affecting the properties of the spray-dried powder, ribbons, and granules. The relevant properties of these intermediates were measured. Modeling and attribute identification were performed using analysis of variance, multiple linear regression, and orthogonal partial least squares-discriminant analysis (OPLS-DA). Results Excipient amount, inlet air temperature, and roller pressure were identified as critical process parameters. A key attribute transfer relationship was established, centered on glass transition temperature (T_g) and median particle size (D₅₀), and associated with supporting attributes including moisture content (H₁), bulk density (ρ_b1), tapped density (ρ_t1) of the spray-dried powder, ribbon yield, and granule yield. Among these, T_g served as a representative key indicator with both discriminative and transfer functions. Conclusion This research clarifies the identification and transfer relationships of key attributes in the dry granulation process of Crataegi Fructus formula granules, providing a basis for developing effective quality control strategies and supporting the high-quality development of the formula granules industry.

Crataegi Fructus formula granules  /  key attributes  /  discrimination  /  transfer  /  glass transition temperature