Optimization of a semi-batch tablet coating process for a continuous manufacturing line by design of experiments.

The aim of the study was to optimize a tablet coating process for a continuous manufacturing line. High throughputs should be achieved while inter-tablet coating variability should be as small as possible. Drug-free cores were coated with a colored suspension. All processes were monitored in-line with Raman spectroscopy. A statistical design of experiment was performed to find optimum process parameters. Tablet loading, spray rate and drum rotation speed were studied. Image analysis was performed using a computer scanner. Tablet hue and saturation were evaluated to obtain information about the inter-tablet color variabilities and the numbers of outliers. Low variabilities could be achieved using low spray rates and high rotation speeds and they were independent from the tablet batch sizes in the studied factor space. For the prediction of the coating thickness, univariate analysis was compared to PLS-regression. Calibration models were built based on the three center points of the statistical design of experiment resulting in RMSEC of 1.07% of sprayed suspension with R2 of 0.9989 and Q2 of 0.9987. Model prediction was possible independent from loading, spray rate and drum rotation speed. The experiment with lowest color variability was conducted with a desired throughput rate of 25 kg/h and with a RMSEP of 2.5%.