Development of a Process Analytical Technology (PAT) for in-line monitoring of film thickness and mass of coating materials during a pan coating operation.

Abstract

The aim of this study was to perform in-line Near Infrared (NIR) measurements inside a pan coater to monitor a coating operation in real-time, by predicting the increases in mass of coating materials and coating thickness. A polymer combination of ethylcellulose/poly(vinyl-alcohol)-poly(ethylene-glycol) graft copolymer was used as functional aqueous coating. Coated tablets were sampled at regular intervals during the coating operation, then subjected to either simple and fast weighing (n=50) or accurate and non-destructive Terahertz Pulsed Imaging (TPI) measurements (n=3). Off-line NIR spectra analysis revealed that the coating operation could efficiently be controlled by focusing on two distinct NIR regions, related to absorption bands of ethylcellulose. Principal component analysis of in-line NIR spectra gave a clear classification of the collected coated tablets. Real-time quantitative monitoring of the coating operation was successfully performed from partial least square calibration models built using either TPI or weighing as reference method. Coating thicknesses as well as mass of coating materials used as primary values provided accurate NIR predictions. A comparison study demonstrated that both reference methods led to reliable and accurate real-time monitoring of the coating operation. This work demonstrated that in-line NIR measurements associated with multivariate analyses can be implemented to monitor in real-time a pan coating operation in order to fulfil the expectations of ICH Q8 guideline on pharmaceutical development, especially in terms of PAT control strategy and reduced end-product testing.