The robustness of the pellet coating process with and without the use of an in-process coating thickness analyzer (PATVIS APA) was investigated. Pellets containing model drug were coated with a prolonged release film coating, using different process conditions. In the first set of experiments film coating was performed as process repetitions with unintentional variation of process parameters, and in the second set, controlled changes (inlet air humidity, gap between distribution plate and Wurster partition, starting pellet load) were made. Within the first set of experiments, the coating process endpoint was determined either via gravimetric consumption of coating dispersion or by means of in-line coating thickness monitoring. The release profiles of the pellets were analyzed and the density of coating calculated. Both methods of the process endpoint determination can be relatively robust in batch processing, if key factors influencing drug release profile are under control. PATVIS APA was shown to be a useful tool to better understand the coating process and can be helpful if coating process interruptions are encountered. Water content was shown to be the key factor influencing the drug profile, presumably by influencing the structure and thickness of the coating applied.

The focus of the current work is to study and demonstrate the impact of the design, the scale, and settings of fluid-bed coating equipment on the differences in pellet coating thickness, which in case of prolonged-release pellets dictates the drug release. In the first set of coating experiments, the pellet cores were coated with the Tartrazine dye with the aim of estimating the coating equipment performance in terms of coating thickness distribution, assessed through color hue. In the second set, drug-layered pellets were film-coated with prolonged-release coating and dissolution profile tests were performed to estimate the thickness and uniformity of the coating thickness among differently sized pellets. In both study parts, film coating was performed at the laboratory and the pilot scale and essentially two types of distribution plate and different height adjustments of the draft tube were compared. The dye coating study proved to be extremely useful, as the results enable process correction and the optimal use of the process equipment in combination with the appropriate process parameters. Preferential film coating of larger drug-containing pellets was confirmed on the laboratory scale, while on the pilot scale, it was possible to achieve preferential coating of smaller pellets using rational alternatives of settings, which is desirable in terms of particle size-independent drug release profile of such prolonged-release dosage forms.