A holistic strategy for the preparation and quality control of sugar-free Fufang Ciwujia granules: Comprehensive quality evaluation through fingerprint and QAMS.

Fufang Ciwujia granule (FCG), a herbal extract formulation effective for treating insomnia and dream-disturbed sleep, is limited for sugar-restricted populations due to its high sucrose content. Furthermore, its quality control (QC), reliant on a single marker compound, is inadequate for representing the multi-component nature of this traditional Chinese medicine formulation. This study developed a sucrose-free FCG formulation suitable for populations requiring glycemic control, and established a comprehensive QC strategy to ensure its quality equivalence to the original product. The Analytic Hierarchy Process-Entropy Weight (AHP-Entropy) combined with Box-Behnken response surface methodology (RSM) optimized the granulation process, identifying an optimal composite filler system (soluble starch, dextrin, maltodextrin) and 10% ethanol as the wetting agent. Pilot-scale batches demonstrated excellent formability (>96%). A high-performance liquid chromatography (HPLC) fingerprinting method and quantitative analysis of multi-components by a single marker (QAMS) were established. Comparative analysis revealed high fingerprint similarity (>0.98), minimal variation in the content of eight marker components (RSD<4%), and equivalent dissolution profiles (f2>50) between the sucrose-free and sucrose-based granules, which provides a holistic framework, from formulation to comprehensive quality assessment, for developing sucrose-free TCM granules, demonstrating successful preservation of critical quality attributes despite significant excipient reformulation.This study covers the entire workflow from formulation development and quality evaluation to consistency verification. It provides a complete technical framework for the clinical translation of sugar-free FCG and the development of other sugar-free TCM granule formulations.