Disintegration-dissolution modeling of bilayer tablets: Predicting plasma profiles and antimicrobial efficacy under postprandial conditions.

This study presents the application of the Disintegration-Dissolution Model (DDM) as a first-principle approach for analyzing and predicting dissolution profiles of complex tablet formulations, such as Augmentin XR, which consists of two layers with distinct disintegration characteristics. The DDM successfully extracted disintegration kinetics from dissolution time profiles and was validated by comparison with independent magnetic moment measurements. Additionally, the study integrates the DDM with a Stomach Absorption Window (DDM-SAW) model to enhance pharmacokinetic predictions for amoxicillin and clavulanic acid under in vivo conditions. Monte Carlo simulations used to assess efficacy of amoxicillin treatment across different dosing scenarios, provide valuable insights into the impact of dosing regimens on therapeutic outcomes. The DDM-SAW model also facilitates dose balance calculations, offering detailed information about the bioavailability of amoxicillin released from individual tablet layers. The results demonstrate that the DDM-SAW model can be a useful tool to enable formulation optimization, improve the understanding of dissolution and absorption processes, and predict pharmacokinetics. The study highlights the potential of model-based analysis in drug development and optimization, especially for complex formulations with multiple components and distinct dissolution behaviors.