title: Computational Fluid Dynamics Simulation of Hydrodynamics and Stresses in the PhEur/USP Disintegration Tester Under Fed and Fasted Fluid Characteristics.
abstract: Disintegration of oral solid dosage forms is a prerequisite for drug dissolution and absorption and is to a large extent dependent on the pressures and hydrodynamic conditions in the solution that the dosage form is exposed to. In this work, the hydrodynamics in the PhEur/USP disintegration tester were investigated using computational fluid dynamics (CFD). Particle image velocimetry was used to validate the CFD predictions. The CFD simulations were performed with different Newtonian and non-Newtonian fluids, representing fasted and fed states. The results indicate that the current design and operating conditions of the disintegration test device, given by the pharmacopoeias, are not reproducing the in vivo situation. This holds true for the hydrodynamics in the disintegration tester that generates Reynolds numbers dissimilar to the reported in vivo situation. Also, when using homogenized US FDA meal, representing the fed state, too high viscosities and relative pressures are generated. The forces acting on the dosage form are too small for all fluids compared to the in vivo situation. The lack of peristaltic contractions, which generate hydrodynamics and shear stress in vivo, might be the major drawback of the compendial device resulting in the observed differences between predicted and in vivo measured hydrodynamics.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University Mainz, Mainz, 55128, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kindgen
authors.affiliation: Boehringer Ingelheim Pharma GmbH and Company KG, Ingelheim, 55216, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Wachtel
authors.affiliation: Pharmaceutical Development, AstraZeneca R&D, Mölndal, 43183, Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Abrahamsson
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University Mainz, Mainz, 55128, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
mesh_terms: D001826:Body Fluids / Q000737:chemistry; D003198:Computer Simulation; D004304:Dosage Forms; D005215:Fasting; D057446:Hydrodynamics; D008962:Models, Theoretical; D011312:Pressure; D012212:Rheology / Q000379:methods; D033081:Shear Strength; D012995:Solubility; D013607:Tablets / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D014783:Viscosity
chemical_list: D004304:Dosage Forms; D013607:Tablets
keywords: LADME; biopharmaceutics; computational fluid dynamics; disintegration testing; food effects; hydrodynamics; in vitro models; mathematical model; oral drug delivery; solid dosage form