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Unit operation optimization for the manufacturing of botanical injections using a design space approach: a case study of water precipitation.

Gong X, Chen H, Chen T, Qu H - PLoS ONE (2014)

Bottom Line: Saponin recoveries decreased as DMCC increased.Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria.Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

ABSTRACT
Quality by design (QbD) concept is a paradigm for the improvement of botanical injection quality control. In this work, water precipitation process for the manufacturing of Xueshuantong injection, a botanical injection made from Notoginseng Radix et Rhizoma, was optimized using a design space approach as a sample. Saponin recovery and total saponin purity (TSP) in supernatant were identified as the critical quality attributes (CQAs) of water precipitation using a risk assessment for all the processes of Xueshuantong injection. An Ishikawa diagram and experiments of fractional factorial design were applied to determine critical process parameters (CPPs). Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.86 for all the models. High TSP in supernatant can be obtained when DMCC is low and SS is high. Saponin recoveries decreased as DMCC increased. Incomplete collection of supernatant was the main reason for the loss of saponins. Design space was calculated using a Monte-Carlo simulation method with acceptable probability of 0.90. Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria. Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.

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Design space obtained using Monte-Carlo simulations.
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pone-0104493-g007: Design space obtained using Monte-Carlo simulations.

Mentions: The calculated design space are shown in Figure 7. It can be concluded that the design space is an irregular polygon. Recommended normal operation region to attain CQA criteria are located in DMCC of 0.38–0.41 g/g, AWA of 3.7–4.9 g/g, and SS of 280–350 rpm with a probability more than 0.919. Verification experiments were carried out. The prediction results and experimental results of process CQAs are listed in Table 4. The recoveries of notoginsenoside R1, ginsenoside Rg1, and ginsenoside Re of Experiment V1 are lower than their criteria. While all the experimental values of Experiment V2 were in the ranges listed in Table 6. These results indicate that criteria of CQAs can be attained by operating CPPs within design space.


Unit operation optimization for the manufacturing of botanical injections using a design space approach: a case study of water precipitation.

Gong X, Chen H, Chen T, Qu H - PLoS ONE (2014)

Design space obtained using Monte-Carlo simulations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125280&req=5

pone-0104493-g007: Design space obtained using Monte-Carlo simulations.
Mentions: The calculated design space are shown in Figure 7. It can be concluded that the design space is an irregular polygon. Recommended normal operation region to attain CQA criteria are located in DMCC of 0.38–0.41 g/g, AWA of 3.7–4.9 g/g, and SS of 280–350 rpm with a probability more than 0.919. Verification experiments were carried out. The prediction results and experimental results of process CQAs are listed in Table 4. The recoveries of notoginsenoside R1, ginsenoside Rg1, and ginsenoside Re of Experiment V1 are lower than their criteria. While all the experimental values of Experiment V2 were in the ranges listed in Table 6. These results indicate that criteria of CQAs can be attained by operating CPPs within design space.

Bottom Line: Saponin recoveries decreased as DMCC increased.Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria.Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

ABSTRACT
Quality by design (QbD) concept is a paradigm for the improvement of botanical injection quality control. In this work, water precipitation process for the manufacturing of Xueshuantong injection, a botanical injection made from Notoginseng Radix et Rhizoma, was optimized using a design space approach as a sample. Saponin recovery and total saponin purity (TSP) in supernatant were identified as the critical quality attributes (CQAs) of water precipitation using a risk assessment for all the processes of Xueshuantong injection. An Ishikawa diagram and experiments of fractional factorial design were applied to determine critical process parameters (CPPs). Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.86 for all the models. High TSP in supernatant can be obtained when DMCC is low and SS is high. Saponin recoveries decreased as DMCC increased. Incomplete collection of supernatant was the main reason for the loss of saponins. Design space was calculated using a Monte-Carlo simulation method with acceptable probability of 0.90. Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria. Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.

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