Abstract In disintegration and dissolution (D&D) testing, high media viscosity, resembling ingested food, is rarely considered for simulated fed state investigations. However, it can strongly alter tablet breakdown and drug release, depending on the formulation factors. A viscous hydroxypropyl methyl cellulose (HPMC) solution as a D&D medium was used to match a blended FDA-standardized meal in terms of viscosity and pH, mimicking postprandial stomach content. However, compendial disintegration and dissolution apparatuses are not specifically designed to be operated with highly viscous media. Overall, tablet D&D performance is considerably slowed down due to high viscosity but is significantly influenced by the tablet’s composition and physical properties, e.g., porosity. There are excipients that can increase coning already in fasted state media, for instance, insoluble fillers like microcrystalline cellulose or dicalcium phosphate. Under poor hydrodynamic conditions, those substances’ negative effects can even be exacerbated. This leads to artefactual dissolution behavior, which did not align with expectations derived from the tablet’s properties. A novel computerized numerical control (CNC)-based D&D apparatus is developed and applied to avoid these phenomena by moving the samples through the medium instead of fluid agitation around the tablet. The movement pattern is three-dimensional at a specified velocity and can be adjusted to desired conditions. Different test tablet formulations with varying soluble and insoluble fillers were used to demonstrate that the approach using the novel CNC apparatus overcomes the challenges of highly viscous media and clearly distinguishes tablets as expected, according to their composition. Graphical Abstract
Stahl et al. (Tue,) studied this question.