Optimising PAT for Continuous Direct Compression using the Feed Frame Simulator

In fifteen words or less, explain the significance of this contribution (Novel Aspect).: Application of in-line PAT for Continuous Direct Compression to enable real-time quality control of formulations.

Abstract Text:

Monitoring formulation quality during Continuous Direct Compression (CDC) to maintain product specifications is complex. Critical Quality Attributes (CQAs) are controlled by adjusting the Critical Process Parameters (CPPs) as a key component of the overall control strategy. Determining the appropriate CPPs solely through process data is challenging; however, this can be significantly improved by employing an enhanced control strategy that incorporates chemometric modelling through Process Analytical technology (PAT). PAT sensors allow in-line CQA and process monitoring, reducing the time and effort required for both sampling and off-line analysis.

This work delves into optimising PAT for CDC, focusing on integrating spectroscopic techniques into the Feed Frame Simulator (FFSIM). By employing Near-Infrared (NIR) spectroscopy, Raman spectroscopy and NIR-Spatially Resolved Spectroscopy (NIR-SRS), the project aims to enhance the accuracy and efficiency of both the technologies and the resulting models for low-dose formulations, ensuring consistent product quality. The potential improvements for real-time process monitoring and control from the adoption of these advanced technologies offer compelling benefits.

Key components include optimising acquisition parameters such as integration time and number of averages across the technologies, enabling dynamic data collection and model development using Principal Component Analysis (PCA) and Partial Least Squares (PLS) regression. A critical aspect of this study is performing a sensitivity comparison of these technologies for the analysis of given drug formulation blends, based on these optimised parameters. By standardising data analysis methodologies and developing an integrated Real Time Release Testing (RTRT) strategy, the project seeks to address current challenges in PAT applications.

Future developments will continue to refine the simultaneous use of multiple PAT techniques, to further enhance process control. The ultimate goal is to establish a robust, transferable PAT strategy for CDC, facilitating standardised practices across various sites and processes. This will provide valuable insights for the development of new continuous manufacturing control strategies for low-dose formulations.