Near infrared (NIR) and Raman spectroscopic analyzers applied through an immersion Lighthouse Probe (LHP) were used for simultaneous in-line monitoring of a fluid bed pellet coating process. Multivariate curve resolution analysis of data, collected from four pilot-scale batches, has shown that the two techniques deliver complementary information about the process and their combination may be synergistic. This data analysis enabled a much better understanding of some of the process observations and also gave some interesting insights into the best way to use the techniques themselves.PLS regression analysis of the product moisture and the quantity of coating material sprayed was performed using NIR and Raman data blocks both separately and in combination. The performance of method combination compared to individual techniques is analyzed and discussed.

A new method for the prediction of the drug release profiles during a running pellet coating process from in-line near infrared (NIR) measurements has been developed. The NIR spectra were acquired during a manufacturing process through an immersion probe. These spectra reflect the coating thickness that is inherently connected with the drug release. Pellets sampled at nine process time points from thirteen designed laboratory-scale coating batches were subjected to the dissolution testing. In the case of the pH-sensitive Acryl-EZE coating the drug release kinetics for the acidic medium has a sigmoid form with a pronounced induction period that tends to grow along with the coating thickness. In this work the autocatalytic model adopted from the chemical kinetics has been successfully applied to describe the drug release. A generalized interpretation of the kinetic constants in terms of the process and product parameters has been suggested. A combination of the kinetic model with the multivariate Partial Least Squares (PLS) regression enabled prediction of the release profiles from the process NIR data. The method can be used to monitor the final pellet quality in the course of a coating process.