The food-induced viscosity of the media can alter tablet disintegration and eventually the release of the drug it contains. The extent of this retardation depends on tablet formulation factors, such as the solubility of its excipients. Objectives: This research aimed to study the effect of filler solubility on the disintegration and dissolution of tablets under 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. These formulations were investigated under fasted- and fed-state conditions to determine the influence of viscosity on their disintegration, inspired by the liquid penetration ratio (LPR) theoretical framework. Disintegration and dissolution tests were performed using both compendial and novel testing apparatuses. Results: The soluble fillers in the tablets affected their disintegration and dissolution in the simulated fed-state medium, while fasted-state conditions affected the tablets only marginally. The testing devices showed partially contrasting results, which appeared to be due to the hydrodynamics of the testing media used. The novel CNC (computed numerical control) apparatus offered 3D motion and effectively exposed the tablets to the viscous testing media, unlike the compendial paddle apparatus. Conclusions: This study explored the impact of filler solubility on the disintegration and dissolution of tablets. As the LPR framework revealed, fillers with a higher solubility have positive effects on the disintegration and dissolution of tablets in viscous conditions. Additionally, the proportion of soluble filler used is also inversely correlated with the disintegration time. Further investigation of the formulation parameters, as well as the testing conditions, would provide additional insights into the effects of food on these tablets.

In disintegration and dissolution (D&D) testing, high media viscosity, resembling ingested food, is rarely considered for simulated fed state inves

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.

Background: Postprandial gastric conditions such as changed motility and increased viscosity of gastric content can interact with an ingested dosage form, such as a tablet. This can affect the mechanisms of disintegration and dissolution and result in the altered performance of the tablet. Hereby, the individual characteristics of the tablet play a crucial role, since they determine the interaction potential with hydrodynamic and physico-chemical properties of the gastric environment. Excipient properties such as solubility, swellability, or gelling tendency can have an influence. Further, tablet characteristics such as porosity or pore size can affect its breakdown by regulating water uptake or determining its physical stability. Methods: Four midodrine hydrochloride generic products with known in vivo bioequivalence, but different formulations, were used as references to improve the simulated fed-state disintegration and dissolution testing methods involving highly viscous media. The tablet samples were evaluated towards the aforementioned characteristics, estimating which parameters of the testing method influence their dissolution performance under highly viscous conditions. Hereby, different hydrodynamic and mechanical stresses were simulated by a previously presented computed numerical controlled apparatus, as well as a novel flow-through cell for viscous media. By a mechanistic biopharmaceutics modeling approach, the convoluted dissolution data were compared to in vivo plasma profiles. Results: A sequential motion method yielded similar dissolution profiles as assessed by the similarity factor (f2). Convoluted plasma profiles showed good approximation with the in vivo profiles. Conclusions: The sequential dissolution method was established as a biopredictive tool for simulating the fed state by incorporating physiologically increased postprandial chyme viscosity and hydrodynamic stress.