title: A Novel Disintegration Tester for Solid Dosage Forms Enabling Adjustable Hydrodynamics.
abstract: A modified in vitro disintegration test device was designed that enables the investigation of the influence of hydrodynamic conditions on disintegration of solid oral dosage forms. The device represents an improved derivative of the compendial PhEur/USP disintegration test device. By the application of a computerized numerical control, a variety of physiologically relevant moving velocities and profiles can be applied. With the help of computational fluid dynamics, the hydrodynamic and mechanical forces present in the probe chamber were characterized for a variety of device moving speeds. Furthermore, a proof of concept study aimed at the investigation of the influence of hydrodynamic conditions on disintegration times of immediate release tablets. The experiments demonstrated the relevance of hydrodynamics for tablet disintegration, especially in media simulating the fasted state. Disintegration times increased with decreasing moving velocity. A correlation between experimentally determined disintegration times and computational fluid dynamics predicted shear stress on tablet surface was established. In conclusion, the modified disintegration test device is a valuable tool for biorelevant in vitro disintegration testing of solid oral dosage forms.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kindgen
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Rach
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nawroth
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, Staudingerweg 5, 55128 Mainz, Germany. Electronic address: langguth@uni-mainz.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
mesh_terms: D000284:Administration, Oral; D001826:Body Fluids / Q000737:chemistry; D003198:Computer Simulation; D057446:Hydrodynamics; D008962:Models, Theoretical; D033081:Shear Strength; D012984:Software; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D013997:Time Factors
chemical_list: D013607:Tablets
keywords: computational fluid dynamics; disintegration testing; hydrodynamics; in vitro models; liberation; tablets