Fluid bed granulation is currently one of the most widely used methods for producing granules in the pharmaceutical industry. In the scope of the master's thesis, we evaluated the influence of selected process parameters of fluid-bed granulation on the physical properties of the produced granules.
In the first set of experiments on placebo batches, we evaluated the impact of batch size at the same percentage of filling in 3L, 6L, and 12L granulation vessels, different batch sizes and consequently different percentages of filling in the 3L granulation vessel, nozzle position, granulation liquid feeding rate, and polymer concentration in the granulation liquid using placebo trials. We found a significant influence of batch size while maintaining the same percentage of vessel filling and appropriate adjustment of process parameters. The granules produced in the smallest (3L) vessel were the smallest and had the narrowest size distribution, while the granules produced in the largest vessel (12L) were the largest with the widest size distribution. We also found that changing the percentage of vessel filling resulted in larger granules when using a lower percentage of vessel filling. The nozzle position had a significant impact on the granulation efficiency, as a larger portion of powdery ungranulated particles was observed when the nozzle was in a lower position. Increasing the spray rate of granulation liquid resulted in larger granules. Additionally, we observed the influence of polymer concentration in the granulation liquid on the properties of the granules, as larger granules were obtained when using a more concentrated granulation liquid.
Based on placebo samples, we determined the optimal process parameters for granulation to conduct the second set of experiments with a model active pharmaceutical ingredient (API). We used APIs with different particle sizes to evaluate the influence of API particle size on the physical properties of the granules. Tablets were then prepared from the final granules at different compression forces. The tablets were tested for hardness, disintegration, friability, and prolonged friability, and the results were compared to evaluate the impact of API particle size on the tablet properties. We demonstrated that API particle size has a significant effect on the behavior of the initial mixture. The largest granules were obtained when using the smallest API particles, while the smallest granules were obtained when using the largest API particles. Considering the comparable tablet hardness results with the smallest and largest API particles compressed at different compression forces, we concluded that API particle size does not have a substantial impact on tablet hardness. However, the disintegration time of all tablets increased with increasing compression force. The tablets made from granules containing the smallest API particles had the longest disintegration time. Friability and prolonged friability of the tablets were acceptable in all experiments regardless of the API particle size.
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