Targeted probiotic tabletting: A hybrid active learning and finite element modelling approach for process optimisation.

Tablets are an efficient dosage form for delivering probiotics. Prior studies have identified compression pressure, compression speed, and precompression pressure as critical process parameters determining probiotic survival during tabletting. However, due to the labour-intensive and time-consuming nature of experimental investigations, most previous studies focused on evaluating the impact of individual parameters in isolation. Consequently, the rapid and systematic identification of optimal process parameters to maximise probiotic survival remains a significant and unresolved challenge in pharmaceutical formulation research. To address this gap, an integrated approach combining active learning (AL) based Gaussian process regression (GPR) with finite element (FE) modelling was developed to systematically explore the compaction parameter space and identify optimal process conditions. All data utilised in AL were generated using an FE model that was specifically developed to predict viability of probiotics during tabletting. Remarkably, the integrated approach achieved high prediction performance after only 78 iterations, demonstrating a coefficient of determination (R