Multi-layer tablets (MLT) are increasingly recognized as potent instruments forfixed-dose combination (FDC) therapy. They offer benefits compared to traditionalmonolithic tablets, including enhanced effectiveness of active ingredients, diminishedtoxicity, better patient compliance with treatment plans, and ease of usage, distribution,and dispensing. In this study, comprehensive studies were carried out to develop effectivetools for identifying tablet failures in MLTs containing low-dose evogliptin tartrate (EG)and high-dose metformin HCl (MF), and confirmed the mechanism of internal crack anddelamination of MLT using finite element method (FEM) modelling.In chapter 2, the effects of compression pressure on the surface roughness of the firstlayer, the necessary compaction force to fracture the MLTs, and the interfacial strength.Additionally, it assesses their relationships in MF and EG bilayer and trilayer tablets. Adecrease in the first layer's roughness, detected with an energy dispersive spectrometer(EDS)-equipped scanning electron microscope (SEM), led to lesser inter-penetration atthe interface. This decrease in penetration weakened the interfacial bonding strength,resulting in the delamination of the MF/EG MLTs.In chapter 3, the ejection pressure, dependent on main compression pressure (MAINP), was evaluated, and its relationship with the internal crack formation within the tabletswas investigated using FE-SEM and X-ray microcomputed tomography scans. In thischapter, ejection pressure was demonstrated as a feasible tool for tracking and identifyinginvisible cracks.In chapter 4, the internal cracks and delamination mechanism of MLT during thecompression and ejection process were proposed using FEM simulation. To validate theejection pressure value predicted by the numerical model depending on MAIN-P, resultswere compared with experimental results from ejection pressure tests described in chapter3.In summary, this study conducted a comprehensive evaluation of the impact ofcompression pressure on various factors influencing tablet failure, including delamination.Throughout these studies with the development of identification tools for tablet failureand simulations of failure mechanism, insightful evidence and strategies were providedto ensure consistent quality in MLT manufacturing processes.