Effects of Grinding in Pharmaceutical Tablet Production

Continuous Heterogeneous Crystallization on Excipient Surfaces

“…The downstream process of the drug product manufacturing starts from the crystallization step of the API (drug substance upstream) and often includes many intermediate steps of milling, mixing (with required excipients) and blending, granulation, drying, sieving, and tablet pressing − (Figure a). Many risks, challenges, technical hurdles, and considerations are associated with each of the aforementioned steps. − The precise final dosage, content uniformity, composition, mechanical properties, and critical quality attribute of every single tablet, which are highly regulated, ,− highly depend on the performance of the involved stages, for instance, component segregation, which can be caused by differences in particle size, density, or shape, and segregation in blending, hoppers, transfer lines, or feeders, and results in heterogeneity in tablet compositions. − Significant academic research and industrial development have been invested to overcome drug product line challenges and enable consistent manufacturing of high-quality tablets. − These challenges, and subsequent effects, are more problematic in the continuous manufacturing arena, , where the continuous flow of material, continuous workload of the drug product line, residence time distribution, and validation of “batches” of the final product enter into the design of already complicated processes. ,,,, …”