This thesis investigates the thermomechanical behaviour of powder compaction, with a particular focus on its impact on the probiotic survival mechanisms. The study integrates numerical modelling, machine learning (ML), and optimisation to systematically analyse the relationships between critical process parameters (CPPs) and critical quality attributes (CQAs), including probiotic viability and tablet porosity.

The numerical analysis consists of three parts. First, a compaction model based on the Drucker Prager Cap (DPC) model and the finite element (FE) method was developed to analyse stress-strain evolution within the powder bed during compaction. Second, the FE model was coupled with the energy balance equation to explore thermomechanical behaviour of powders. Third, a thermal tolerance model was incorporated into the framework to enable quantitative prediction of viability of probiotics. In parallel, comprehensive experimental validation was performed to explore mechanical and thermal response and determine the probiotic viability. The experimental findings confirmed the accuracy of the numerical analyses. Building upon these results, this study further integrates ML methods, specifically Gaussian process regression (GPR) and active learning (AL), to establish an efficient predictive tool capable of rapidly evaluating the responses over the process parameter space, improving predictive accuracy, and reducing experimental demand. In addition, multi-objective optimisation (MOO) was conducted using the Non-dominated Sorting Genetic Algorithm II (NSGA-II), where the survival rates of multiple probiotic strains and tablet porosity were simultaneously considered. This approach identified optimal processing conditions and established a design space for balancing probiotic viability and tablet porosity.

Overall, this thesis combines numerical simulation, experimental validation, and data-driven methods to optimise the probiotic tablet quality, providing a scientific basis and practical guidance for the development and industrial production of robust probiotic solid dosage forms.