Abstract
Roller compaction is widely used in pharmaceutical manufacturing to improve powder flowability and enable robust tablet production. Although often treated as producing a homogeneous granule population, ribbons may undergo splitting during compaction, generating structurally distinct granules that affect downstream tableting. This study investigates the impact of ribbon splitting on tablet critical quality attributes (CQAs) for 10% and 20% acetaminophen (APAP) formulations. Reduced-order models (ROMs) proposed by Bachawala et al. [1] were applied to predict tablet density, elastic recovery, tensile strength, and tablet weight under split and non-split conditions. Although ribbon splitting alters the granule size distribution (GSD) and ribbon density, tablet CQAs such as tensile strength, elastic recovery, and tablet density are accurately predicted by the existing ROM framework, provided that GSD and ribbon density are known. In contrast, tablet weight predictions deteriorate when split and non-split data are combined, reflecting the sensitivity of die filling to granule packing changes induced by splitting. Separating the datasets improves weight prediction for non-split granules, while split granules remain challenging to model. A multitask Gaussian Process regression model is further used to analyze splitting as a process disturbance, highlighting the need for extended or data-driven approaches to accurately predict tablet weight under split conditions.