Background: Twin-screw wet granulation (TSWG) is a promising continuous manufacturing technology, featuring high operational flexibility, short residence time and consistent quality. The process development of TSWG relies on the synergy of material characterization, screw configuration, and process parameter optimization. Objective: In order to fully combine various design variables, and to accelerate the process development of TSWG, a material–process–equipment integrated design (MPEID) methodology is first applied to the TSWG process of Guizhi Fuling capsule, a botanical drug product. Methods: First, an equivalent formulation was designed to save trial costs. Second, 3D printing technology was used to customize both conveying and kneading elements with the lead, with the kneading discs stagger angle (SA) and the thickness (thick) as screw element variables. The position of fabricated kneading elements was varied to generate different screw configurations. Then, the critical screw parameters (CSPs) and critical process parameters (CPPs) were identified by a two-step design of experiment (DOE) toward optimizing granule quality. Results: As a result, the SA and thick were identified as CSPs, and the liquid-to-solid ratio was the CPP. Under the optimal TSWG process conditions, the twin-screw granulator could be operated under low torque (i.e., average torque = 1.48 ± 0.06 Nm). The dried granules exhibited superior flowability, as well as highly consistent particle size distribution with industrial batches. After capsule filling, the dissolution test results showed the prepared Guizhi Fuling capsules reached 93.7% cumulative dissolution at 15 min, which approached that of commercial capsules (i.e., 93.0%). Conclusions: This study demonstrated the feasibility of proposed MPEID methodology, supporting the efficient and cost-effective process development of TSWG.

Flavor profile and water dissolvability serve as core evaluation benchmarks for the quality of food and medicinal plant-derived instant granules. Currently, studies integrating flavor and dissolvability analysis to comprehensively characterize the overall performance of such granules remain scarce, and the existing literature lacks systematic comparative research on commercial products across multiple sources and batches. This study investigated 90 batches of four categories of plant extract instant granules and established a dynamic-static joint evaluation system coupled with multiple indicators and the Analytic Hierarchy Process (AHP). The three primary indicators were dissolving extent, dissolving rate, and taste, with equal weights assigned to each; the secondary indicators were classified and integrated based on the results of Principal Component Analysis (PCA) and correlation matrix. Quantitative analysis revealed that the comprehensive evaluation scores of all 90 batches of samples fluctuated between 0.5406 and 0.9503, and obvious disparities existed among different granule varieties. This multi-index evaluation framework effectively avoids the subjective bias inherent in conventional evaluation approaches, and lays a solid scientific foundation for quality supervision, formula optimization research and development, as well as market popularization of plant-based instant granules.