Defense Date

8-15-2024

Graduation Date

Fall 12-20-2024

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

Carl A. Anderson

Committee Member

James K. Drennen

Committee Member

Ira Buckner

Committee Member

Lauren Petraglia

Committee Member

Patrik Johansson

Keywords

Continuous Manufacturing, Process Analytical Technology, Iterative Optimization Technology, Principal Component Analysis, Process Development

Abstract

The pharmaceutical industry is actively pursuing technologies which improve manufacturing processes with the goal of producing high-quality pharmaceutical products for patients, manifesting in an industry-wide investment in continuous manufacturing (CM). Process analytical technology (PAT) has been recognized for its successful monitoring of critical quality attributes during routine production and is often cited alongside CM due to its ability to make timely, in-line measurements of intermediate materials. Various PAT tools are valuable in process development, particularly as continuous wet granulation processes are developed for use within pharmaceutical manufacturing. This work applied PAT and chemometric modeling during CM process development to enhance process understanding and reduce material consumption during model calibration. A novel strategy for analyzing granule size data was developed, resulting in a multivariate analysis of granule size distributions (GSD) via principal component analysis (PCA). The PCA of GSDs method was developed and demonstrated with a combination of synthetic and experimental data, followed by implementation alongside traditional granule size data analyses during granulation process development studies. Additionally, iterative optimization technology coupled with near-infrared spectroscopy was deployed for predicting active ingredient potency in multiple CM platforms. The reduction in material consumption during model calibration was advantageous for promoting PAT application during early pharmaceutical development. Deploying PAT tools in process development is a practical method for accelerating the adoption of novel equipment designed to accomplish CM, effectively contributing to the advancement of pharmaceutical manufacturing.

Language

English

Additional Citations

Henson, S., et al., Development of iterative optimization technology: Selecting pure component spectra using a small-scale feed frame simulator. Int J Pharm, 2024. 657: p. 124079.

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