Coating film thickness of pharmaceutical pellets measured by near infrared spectroscopy

Coated pellets typically used for filling pharmaceutical capsules and pressing tablets are increasingly replacing powder especially because of the better compression and flow characteristics and superior drug release rate management. However, the highly complex multivariable coating process needs to be well-controlled in order to ensure high product yield and prevent failures in the coating process resulting in discarded batches and potentially significant loss of revenue. This requires reliable in-process measurement of the coating film thickness. Near infrared (NIR) spectroscopy was found to be the most suitable tool for studying the properties of pellets. However, the existing methods are based on complex calibration requiring reference data on the coating film thickness of several production or even custom batches which are typically assessed by a microscope. Such approach is highly time consuming and impractical. Therefore, we propose an alternative method for analysis of NIR spectra, which produces useful results even without calibration. The proposed method also requires no prior knowledge on the coating process or previous batches of uncoated or coated pellets. The method was tested on samples taken from the coating process of two different batches of pharmaceutical pellets. The correlation coefficient between the average coating film thickness estimated from the NIR spectra and the average coating film thickness measured by the reference method was 0.99, which can be considered an excellent result. Therefore, the method was found feasible for laboratory or in-process approximation of the average coating film thickness of pharmaceutical pellets.