The fundamental requirement of the pharmaceutical industry is the production of high-quality, safe, and effective medications. Traditionally, batch manufacturing has been the predominant method in this field. However, due to the increasing need for improved time and cost efficiency, as well as fast adaptability to market demands, continuous manufacturing has recently gained importance. It is supported by regulatory guidelines and extensive research from the last decade, and further development is expected. In this master's thesis, we focused on continuous wet granulation because the granulation process is often a necessary and critical step in the production of solid pharmaceutical dosage forms. We compared granules of the same composition produced in a continuous twin-screw granulator with those produced in a batch fluidized bed and high shear granulator. By varying key process parameters, we evaluated their impact on critical granule properties, which in turn directly affected the subsequent tableting process and the overall quality of the resulting tablets.
We confirmed that the selected method of granulation affected the properties of the produced granules. Using the twin-screw granulator, we produced granules of various shapes, from elongated and flat to spherical and completely irregular. The size distribution was wide and bimodal, especially at extreme values of the powder flow rate and screw speed, which were outside the optimal range. The granules exhibited moderate flowability and compressibility, with low friability of the tablets produced. In contrast, using a fluidized bed granulator, we were able to produce granules that had a similar size distribution, low bulk density, poor flowability, and high compressibility. Due to the dissolution and the resulting uniform distribution of the binder in the granule structure, they exhibited significantly improved compactibility compared to the other samples, and resulted in tablets that exhibited minimal friability. In contrast, granules from high shear granulation were densely compacted, possessed a spherical morphology, and exhibited a smooth surface. They displayed the lowest compressibility. In addition, the resulting tablet cores did not meet the requirements of the pharmacopoeial friability test for uncoated tablets, as they were visibly chipped at the end of the test, and in some cases, fractures were also evident.
We were not able to draw any significant conclusions from the results of tartrazine content in compressed tablets, as they were satisfactory and comparable for all samples produced.
In conclusion, we have shown that, with further optimization, continuous twin-screw granulation is a potential alternative to conventional batch processes, with the properties of the granules produced representing a reasonable compromise between compressibility and flowability.
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