A novel approach to unified compaction curve model for improved tabletability prediction of virtual roller compacted...

Loss of tensile strength in roller compacted granules compared to the pregranulation blend is a critical concern when selecting the roller compaction process for drug product manufacturing. While this loss in compactibility is attributed to granule size enlargement and granule hardening by earlier studies, the phenomenon of unified compaction curve (UCC) model to explain this decrease in compactibility has long been overlooked despite of its mechanistic interpretation. The present study offers a profound improvement of the UCC model structure where a proper workflow in predicting granule tabletability was first established from the compaction characteristics of the pregranulation blend only. Following this workflow, the original model though revealed varying extent of overestimation for realistic multicomponent formulations. This shortcoming was addressed by introducing the modified UCC model where different tabletability slopes for pregranulation blend and granules were critically considered that consistently performed better than the UCC model. A correction factor was finally introduced to directly predict granule tabletability of virtual formulations from the compression characteristics of the pregranulation blend. The study demonstrates an integrated digital design-based predictive platform to screen virtual formulations through a minimum 25-fold reduction in batch size compared to typical conventional operations.