In the dissertation, the impact of size, construction, and key settings of the fluidised bed coater on the coating thickness uniformity was studied. We conducted a study on the performance of the coating equipment by using dye in the coating and verified our findings on a prolonged-release formulation. Beneficial effect of the coater modifications with swirl generator to the classic Wurster chamber was confirmed. We were the first to prove that preferential coating does not necessarily mean a thicker coating on larger particles, but can produce similar results on smaller particles if a specific coater design is used. The key is that by setting the gap size between the distribution plate and the draft tube) one can control the outcome of preferntial coating.
In second part, dynamic image in-line analysis was used to define coating end-point as an alternative to the existing method. We compared the robustness of both methods by maintaining constant process conditions or by deliberately varying them. It was confirmed that by adequate control of critical attributes of input materials (water content) and process conditions dynamic image analysis can robustly determine the coating end-point. In addition, we demonstrated the key impact of in-process water on the coating density and, consequently, the drug release profile.
In the last part, we conducted a study on the encapsulation of two-component pellet mixtures and verified how differences in pellet properties are reflected in the final dosage form, hard capsule. It was established that the difference in pellet size is a necessary condition for mixture segregation and that segregation does not occur in the case of a unimodal pellet size distributions. The study revealed that differences imposed on differently sized particle by preferential coating do not pose a risk for differences in the release of the drug during the encapsulation phase, even if the extreme fractions have incomparable drug release profiles.
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