Detailed accounts of segregation mechanisms and the evolution of pharmaceutical blend segregation analysis: A review

Abstract

Segregation refers to the separation of components in a powder mixture, resulting in potential issues related to concentration inhomogeneity. Any well-mixed blend that undergoes secondary processing is inherently susceptible to segregation which, if unmitigated, will lead to active compound concentration variance and poorer product quality. The consequences range from adverse financial impact to manufacturers with product failures to the detrimental health effects to product users. Hence, the topic of segregation is of paramount importance to the industry, requiring it to be dissected and scrutinized intensively by scientists worldwide. This review provides a well-crafted theoretical framework designed to understand the common segregation mechanisms that manufacturing facilities face, followed by the efforts to gauge the degree of segregation. To minimize segregation in blends, various approaches – mathematical modeling, empirical experiments, and empirical methods with modeling consideration – have been utilized in segregation research and are covered in this review. The past segregation studies from many fields are discussed, with particular emphasis on pharmaceuticals. The review also discusses the evolution and advances in mixing technology and storage systems implemented by the pharmaceutical industry to prevent segregation. In the conclusion, the authors articulated their perspectives on potential mitigation measures, including suggestions for improvements and future studies.