ZHANG Liyan, SONG Jinchun. Preparation of N-acetylcysteine injection based on quality by design[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(6): 552-558. doi: 10.3969/j.issn.1006-0111.2019.06.016
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ZHANG Liyan, SONG Jinchun. Preparation of N-acetylcysteine injection based on quality by design[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(6): 552-558. doi: 10.3969/j.issn.1006-0111.2019.06.016
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Preparation of N-acetylcysteine injection based on quality by design
- Received Date: 2019-03-03
- Rev Recd Date:
2019-04-28
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Abstract
Objective To optimize the formulation and preparation technology of N-acetylcysteine(NAC) injection based on the concept of quality by design(QbD). Methods Using QbD as the guidance,the critical quality attributes affecting the quality of the injection were determined through literature and the critical process parameters were determined by fishbone diagram and failure mode and effects analysis.Minitab was applied to design experiments and analyze results and design space was established. Results The evaluation indexes were the pH changes before and after sterilization and the concent of NAC.The addition of sodium calcium edetate,preparation temperature and sterilization condition were determined as the critical quality attributes by fishbone diagram and FMEA.The results of variance analysis showed that the P value of the established mathematical models of the process parameters and evaluation indexes were less than 0.05,which indicated that the models had good prediction ability.The optimal parameters were the addition amount of calcium edetate was 0.049 192%,the preparation temperature was 60℃,and the sterilization condition was 116℃,40 min. Conclusion The prescription was reasonable,the process was stable and the established design space based on the concept of QbD improved the durability of the process and ensured uniform and controllability of the quality of the injection.
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