The purpose of the thesis was to compare the robustness of the pellet coating process with and without in-process coating thickness evaluation. Pellets were coated with film coating under various conditions to achieve prolonged release. The experiments were conducted in two parts. In the first part we evaluated robustness of film coating processes, executed under the same process conditions. We controlled the first set of coating processes with the PATVIS APA in-process analyser by stopping the process when target thickness of the film coating was achieved. In the second set of experiments coating was finished, when the target mass of the suspension was sprayed onto pellets. We used the dissolution test to determine the release kinetics of active substance from pellets and analysed resulting dissolution profiles with the goal of verifying comparability of individual batches of pellets. To numerically evaluate similarity of the dissolution profiles, we calculated difference and similarity factors for all possible batch pairs. In the first part of the thesis, we showed that both methods of the process control are relatively robust. Following the results of first part, we wanted to understand why drug release profiles were divided into two distinct groups. We found that the groups coincide with different sizes of the neutral pellet cores we used for coating. We calculated the mass of coating suspension necessary to achieve the same rate of release from differently sized particles. We found out that we already sprayed appropriate amount of coating suspension to selected groups. Based on the correlation of process variables and properties of pellets with the fraction of released substance after 6 hours, we determined that observed profile changes happened due to a change in the moisture content of the pellets during the coating process. In the second part of the thesis, we tested the robustness of film coating processes under deliberate variations of process conditions. By intentionally changing the conditions, we wanted to influence the efficiency of the process. By raising the humidity of the inlet air, we have increased the yield of the process. The release profiles of pellets coated with and without an in-process thickness evaluation were comparable with each other, but not with the profiles of previous samples. We then reduced the gap between the distribution plate and Wurster partition. Separately, we coated a smaller mass of neutral pellet cores, while reducing the gap between the distribution plate and the Wurster partition. The planned reduction in the coating yield was only partially achieved. The pellet release profiles with and without in-process coating thickness evaluation were also comparable in this group. Based on all the collected results, we concluded that film coating processes with and without in-process control exhibit comparable robustness.
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