Monitoring microsphere coating processes using PAT tools in a bench scale fluid bed

Abstract

Among the factors that influence adherence to medication within the pediatric population, taste/irritation has been identified as a critical barrier to patient compliance. With the goal of improving compliance, microspheres (matrix systems within which the drug is dispersed) can be coated with a reverse enteric polymer that will prevent the release of the drug in the oral cavity while maintaining an immediate release once the drug product reaches the stomach, thereby achieving a taste neutral profile. In this work, the in-line performance of three process analytical technology (PAT) tools is evaluated in order to monitor the microsphere coating process. These tools are Raman spectroscopy, near-infrared spectroscopy and focused beam reflectance measurements, together with process data and raw material attributes. The ability of these different sources of information to predict the coating's barrier performance is evaluated by using a combined-data-approach: multiblock partial least squares (MBPLS). Results show that Raman spectroscopy has a superior predictive performance and that it has the potential to monitor the coating process of the microspheres as well as to detect process discrepancies (such as spray rate changes), demonstrating its usefulness for the monitoring of fluid bed coating processes. It was also demonstrated that Raman can be used to clearly differentiate batches with significantly difference in-vitro dissolution performance. This monitoring is considered critical to ensure consistent coating performance for this thin film barrier membrane that is essential to patient compliance.