Tablet capping predictions of model materials using multivariate approach.

The present study demonstrated the prediction of predominant root causes of capping behavior as a function of the powder rheological and the mechanical behavior of Acetaminophen (APAP) and Ibuprofen (IBU). The authors analyzed powder rheological properties for powder blend permeability, pressure drop, and cohesion. The measured deformation properties were compact porosity, internal air pressure, Brinell hardness, and tensile strength. The data were evaluated qualitatively and quantitatively using multivariate techniques, such as principal component analysis (PCA) and principal component regression (PCR) models, respectively, to identify the effect of powder air entrapment efficiency and mechanical behavior on the tablet capping score. The PCA model indicated that pressure drop, cohesion, API amount, and compression pressure correlated positively, whereas permeability, porosity, internal air pressure, Brinell hardness, and tensile strength correlated negatively to the capping potential. APAP and IBU also showed two independent mechanisms as a function of their amount on the capping score at all compression pressures. APAP and IBU followed an exponential and linear relationship, respectively. Furthermore, the dominant powder rheological and deformation behavior affecting the capping score of each material was identified and quantified using two separate PCR models. These models showed that APAP capping was predominantly dependent on its powder properties, while that of IBU was predominantly based on its deformation properties. In conclusion, APAP and IBU compacts capping had respective air induced and deformation induced capping behavior. The proposed approach can aid in understanding the underlying mechanisms of capping and developing an effective, optimized strategy to ensure tablet quality.