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QbD-Guided Traditional Chinese Medicine Manufacturing Process: Development and Optimization of Fluid-Bed Granulation and Drying Processes for Xiaochaihu Capsules

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Abstract

Traditional methods of producing Xiaochaihu (XCH) capsules, a traditional Chinese medicine, are time-consuming, costly, and labor-intensive, which is not conductive to modernizing TCM. To address the challenges, new fluid-bed granulation and drying processes with water as the binder were developed and optimized guided by the principles of Quality by Design (QbD) in this study. Ishikawa diagram was applied to conduct a preliminary risk assessment, followed by 6-factor definitive screening design (DSD) serving as a QbD statistical tool to develop and optimize the new processes. Multiple potential factors and interactions were studied with a small number of experiments using the DSD. This study identified critical process parameters (CPPs), established quadratic regression models to reveal CPP-critical quality attributes (CQAs) connections within the DSD framework, and defined a dependable design space. Processes conducted by parameter combinations in the design space produced qualified granules with production yield and raw material utilization higher than 90% and moisture content lower than 4%. Furthermore, quantitative analysis of baicalin of all the granules ensured qualified contents of active pharmaceutical ingredient. The newly developed processes for XCH capsules, with advantages of shorter time, environmental friendliness, and decreased cost, exemplify the effective application of QbD and design of experiments (DoE) methodologies in the modernization of TCM manufacturing processes.

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Funding

This work was financially supported by the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine [ZYYCXTD-D-202002].

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Authors and Affiliations

  1. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Kaixuan Teng, Hao Fu, Xingchu Gong & Haibin Qu

  2. Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310018, China

    Kaixuan Teng, Hao Fu, Xingchu Gong & Haibin Qu

  3. Zhejiang Pralife Pharmaceutical Co., Ltd., Taizhou, 318000, China

    Gelin Wu, Ping Gong, Yongjian Xie & Peng Zhou

Authors
  1. Kaixuan Teng
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Contributions

KT: methodology, validation, investigation, and writing—original draft; HF: acquisition of data for the work; GW: project administration; PG: methodology; YX: methodology; PZ: resources; XG: methodology, data curation; HQ: the conception or design of the work, writing—reviewing and editing—supervision, and funding acquisition. All authors read and approved the final manuscript.

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Correspondence to Haibin Qu.

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Teng, K., Fu, H., Wu, G. et al. QbD-Guided Traditional Chinese Medicine Manufacturing Process: Development and Optimization of Fluid-Bed Granulation and Drying Processes for Xiaochaihu Capsules. AAPS PharmSciTech 24, 210 (2023). https://doi.org/10.1208/s12249-023-02663-z

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