Granulation development in batch-to-batch and continuous processes from a quality by design perspective

Abstract The process of quality by design (QbD) is of great importance in drug development. This review describes the design of experiments (DoE) method, which is an important component of QbD. DoE is predominantly divided into a screening phase and an optimization phase. The screening phase uses experimental designs, such as factorial design and fractional factorial design, and the optimization phase uses response surface methodology, central composite design, and Box-Behnken design. The description and features of the above mentioned experimental design are briefly explained, in addition to the uses of DoE in current granulation technology for the preparation of final dosage forms such as tablets, capsules, and granules. There are many methods of granulation, which can be divided into batch processes and continuous processes according to the continuity of the process. The criteria and characteristics for mixing these processes and the advantages and disadvantages for applications in the pharmaceutical industry are examined. Through the application of DOE to each granulation process, we examined how the material attributes, process parameters, and quality attributes differed in case studies.