[Design space approach to optimize first ethanol precipitation process of Dangshen]

Area of Science:

• Pharmaceutical Technology
• Natural Product Chemistry
• Process Engineering

Background:

• Codonopsis Radix (Dangshen) is a valuable medicinal herb.
• Ethanol precipitation is a key step in Dangshen extract processing.
• Optimizing this process is crucial for maximizing therapeutic compound recovery and minimizing impurities.

Purpose of the Study:

• To enhance the robustness of the first ethanol precipitation process for Codonopsis Radix.
• To identify critical process parameters (CPPs) and critical quality attributes (CQAs).
• To establish a design space for reliable Dangshen extract production.

Main Methods:

• Application of the design space approach.
• Plackett-Burman design to identify CPPs (DMCE, E/C ratio, CEA).
• Box-Behnken design to model CPP-CQA relationships.
• Monte-Carlo simulation for design space verification.

Main Results:

• Identified Dry Matter Content of Concentrated Extract (DMCE), Ethanol to Concentrated Extract ratio (E/C ratio), and Ethanol Concentration (CEA) as CPPs.
• Established quantitative models linking CPPs to CQAs (flavonoid recovery, dry matter removal, pigment removal).
• Defined a verified probability-based design space ensuring process robustness.

Conclusions:

• The design space approach successfully enhanced the robustness of the Dangshen first ethanol precipitation.
• Operating within the recommended parameters (DMCE: 45.0%-48.0%, E/C ratio: 2.48-2.80 g/g, CEA: 92.0%-92.7%) guarantees process reliability.
• This optimization leads to improved quality and consistency of Dangshen extracts.