A semi-empirical model for estimation of flaw size in internally defective tablets

Capping is a mechanical defect in tablets, which is attributed to multiple factors including intrinsic material properties and tableting conditions. A suitable non-destructive approach using acoustically derived elastic modulus has showed distinctive features between a defective tablet and a defect-free tablet. In this work, a semi-empirical model was developed to estimate flaw size in an internally defective tablet from the relationship among elastic modulus, tablet density, and time of flight (acoustic wave to traverse through the tablet). The model was found fundamentally consistent where the derived flaw size showed clear dependence on powder mechanical properties of seven diverse formulations studied. Furthermore, the flaw size was reasonably correlated with the internal tablet microstructure illustrated by X-ray micro-tomography findings, both qualitatively and quantitatively. This model could thus be efficiently implemented for risk-based evaluation of internal defects in visibly intact tablets to ensure robustness of drug products.