Capsules, as the final pharmaceutical product, are formed through several process steps. Wet granulation is used to combine small particles into granules, which are then transformed into pellets through extrusion and spheronization, and subsequently dried. In pharmaceutical production, scale up is often encountered. The entire process of scaling up the batch size is not straightforward, so it is crucial to have a good understanding of the specific technological process.
The purpose of this master's thesis was to produce capsules of two different strengths as the final pharmaceutical product at twice the scaled-up batch size, while maintaining appropriate and comparable quality to the product at a smaller batch size. The production process of this pharmaceutical product involved the following steps: wet granulation using a high-shear granulator, extrusion and spheronization, drying of pellets in a fluidized bed dryer, final sieving, blending pellets with other excipients, and encapsulation. The proposed process parameters for the scaled-up were calculated using three different approaches, depending on the similarity (kinematic, dynamic, compromise solution) that we wanted to maintain. The samples were evaluated using various methods, including measuring loss on drying, bulk and tapped density, pellet size and size distribution. In the final pharmaceutical form, we evaluated capsule filling weight, content uniformity, dose uniformity and dissolution, comparing the results with data from previous batches manufactured in the last 18 months. Due to limitations in using equipment for larger batches, there were significant differences between the theoretically proposed and practically used process parameters in the wet granulation phase. In the drying process, we used the theoretically proposed airflow, but had to adjust it during pellet drying. Through the analyses, we demonstrated that the capsules met the appropriate quality standards. The intermediate product from small and large batches showed comparable values of bulk and tapped density and a similar Carr's index. The results of pellet size distribution showed comparable values of volume distribution and a relatively narrow distribution. The filling weight of capsules, content uniformity, dose uniformity, and dissolution values for the large batches fell within the upper and lower specification limits and did not significantly deviate from the averages of previous small batches. The results confirmed the successful completion of the batch scaling process and the production of a high-quality pharmaceutical product.
|
