Food Effect and Formulation: How Soluble Fillers Affect the Disintegration and Dissolution of Tablets in Viscous Simulated Fed State Media

The food-induced viscosity of the media can alter tablet disintegration and eventually the release of the drug. The extent of this retardation depends on tablet formulation factors such as the solubility of excipients. Objectives: This research aimed to study the effect of filler solubility on the disintegration and dissolution performances of tablets in different testing conditions. Methods: Tablet formulations containing acetaminophen as a model compound, mixtures of different ratios of fillers, and other excipients were directly compressed using uniform manufacturing parameters. The formulations were investigated under simulated viscosity of fasted and fed state conditions inspired by a Liquid Penetration Ratio (LPR) theoretical framework. The disintegration and dissolution tests were performed in both compendial and novel testing apparatuses. Results: Soluble fillers in the tablets affected the disintegration and dissolution in simulated fed state media but only marginally under fasted conditions. The testing devices showed partially contrasting results based on the hydrodynamics of the testing media. The novel CNC (computed numerical control) apparatus offered 3D-motion and effectively exposed tablets to the viscous testing media, in contrast to the compendial paddle apparatus. Conclusions: This study explored the impact of filler solubility on tablet disintegration and dissolution performances. As envisaged by the LPR framework, higher filler solubility has positive effects on tablet disintegration and dissolution performance in viscous conditions. Additionally, soluble filler proportion is also inversely correlated with disintegration time. Further investigation of the formulation parameters as well as the testing conditions would provide additional insights into the food effects on the tablets.