DETERMINATION OF DESIGN SPACE OF THE EXTRACTION STAGE AS AN ELEMENT OF MANUFACTURING PROCESS DEVELOPMENT OF ACTIVE PHARMACEUTICAL INGREDIENT OF HERBAL ORIGIN
DOI:
https://doi.org/10.11603/2312-0967.2025.1.15166Abstract
The aim of the work is to determine critical quality attributes (CQA) and design space (DS) of the extraction stage of herbal raw material in order to establish the optimal conditions of the technological process for API manufacturing.
Materials and Methods. The initial data for developing design space were the research findings on the influence of key parameters of Peppermint leaf extraction process (Mentha Piperitae folium) on the efficiency of flavonoids extraction and yield of extractable matter. According to the research design, the extraction of Peppermint raw material was carried out by filtration extraction in a laboratory extractor to a total DER 1:10. As extraction solvents 93%, 70%, 40% ethanol (vol.) and purified water were used. The critical quality attributes were the content of dry residue ωn in the samples and the yield of the sum of flavonoids Ln from the extracted material. The determination of the design space was implemented by overlapping the spaces of dry residue and flavonoid yield on each other.
Results and Discussion. Using the “enhanced” approach to the manufacturing process development, the obtained experimental data were analyzed, the nature of the extraction process of dry residue and analytical marker were studied, critical quality attributes (CQA) were determined, and their acceptance criteria were established. The concentration of extraction solvent and DER were determined as process parameters. According to the established acceptance criteria for CQA, the points (process parameters) were calculated to develop the design space (DS). Within the design space the critical quality attributes corresponded with the acceptance criteria.
Conclusions. The dry residue content ωn in the extract samples and the yield of the sum of flavonoids Ln from extracted raw material were determined as the critical quality attributes (CQA) with the acceptance criteria ωn ≥1% and Ln ≥80% Lmax respectively. It was established that the optimal conditions of the extraction of Peppermint leaf raw materials within the design space (DS) are the extraction of raw materials with 26%–66% ethanol within DER ratio 1:5.7–9.2. The results obtained will be used in the further development of APIs, in particular, when determining the quality target product profile and establishing specifications.
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