Segregation of Formulated Powders in Direct Compression Process and Evaluations by Small Bench-Scale Testers

[Display omitted] •Segregation of formulated powders in a direct compression process,•Assess powder segregation in a process using bench-scale testers,•Validation of segregation index measured from bench-scale testers with process rig,•Segregation on bench-scale tester is highly correlated to the segregation in process,•A prediction model was established based on segregation harshness factors,•Measured segregation index on bench-scale testers linearly correlated to process rig, Powder segregation can cause severe issues in processes of pharmaceutical drugs for control of content uniformity if the powder is likely to be free or easy flowing. Assessing segregation intensity of formulated powders in a process is challenging at the formulation stage because of the limited availability of samples. An advanced segregation evaluation using small bench-scale testers can be useful for formulation decisions and suggestions of operation conditions in the process, which has not been practically investigated before. In this study, eight formulations (two co-processed excipients blended with one active pharmaceutical ingredient at different ratios) were used for the segregation study on two types of bench-scale testers (air-induced and surface rolling segregation tester), and a pilot simulation process rig as a comparative study. The results show that segregation measured on the bench-scale testers can give a good indication of the segregation intensity of a blend if the segregation intensity is not more than 20%. The comparison also shows that both the bench-scale testers have a good correlation to the process rig, respectively, which means either segregation tester can be used independently for the evaluation. A linear regression model was explored for prediction of segregation in the process.