Pharmaceutical application of multivariate modelling techniques: a review on the manufacturing of tablets

The tablet manufacturing process is a complex system, especially in continuous manufacturing (CM). It includes multiple unit operations, such as mixing, granulation, and tableting. In tablet manufacturing, critical quality attributes are influenced by multiple factorial relationships between material properties, process variables, and interactions. Moreover, the variation in raw material attributes and manufacturing processes is an inherent characteristic and seriously affects the quality of pharmaceutical products. To deepen our understanding of the tablet manufacturing process, multivariable modeling techniques can replace univariate analysis to investigate tablet manufacturing. In this review, the roles of the most prominent multivariate modeling techniques in the tablet manufacturing process are discussed. The review mainly focuses on applying multivariate modeling techniques to process understanding, optimization, process monitoring, and process control within multiple unit operations. To minimize the errors in the process of modeling, good modeling practice (GMoP) was introduced into the pharmaceutical process. Furthermore, current progress in the continuous manufacturing of tablets and the role of multivariate modeling techniques in continuous manufacturing are introduced. In this review, information is provided to both researchers and manufacturers to improve tablet quality.