Quality by Design Chapter uri icon

abstract

  • Summary In-depth process understanding and process knowledge are essential for the quality by design (QbD) design space establishment under the FDA's PAT framework and ICH Q8(R2) guideline. Pharmaceutical coprecipitation process is not well understood. In this work, an integrated PAT approach was developed for real-time monitoring of a dynamic pharmaceutical coprecipitation process of gradually introducing water to the ternary system of naproxen?Eudragit L100?alcohol at room temperature. Process trajectory was constructed based on principal component analysis (PCA) of the real-time process NIR spectra and validated by real-time process turbidity profile. The process trajectory clearly reveals that various singular points can be identified. More importantly, it was found that those singular points are corresponding to various distinguishable process events and process signatures, such as incubation, nucleation, and crystal growth. Challenges and opportunities associated with PCA-based process trajectory method for process monitoring and process design space development during pharmaceutical PAT and QbD implementation were discussed.

author list (cited authors)

  • Wu, H., & Khan, M. A.

editor list (cited editors)

  • Reklaitis, G. V., Seymour, C., & Garcia-Munoz, S.

Book Title

  • Comprehensive Quality by Design for Pharmaceutical Product Development and Manufacture

publication date

  • January 1, 2017 11:11 AM