title: Towards determining appropriate hydrodynamic conditions for in vitro in vivo correlations using computational fluid dynamics.
abstract: One of the earliest level A in vitro dissolution in vivo absorption correlations (IVIVCs) was established by Levy and co-workers in 1965 using a beaker dissolution apparatus Levy et al., 1965. In the current work, the computational fluid dynamics (CFD) package, Fluent((R)), was used to simulate the hydrodynamics within the Levy beaker apparatus and compare them to those within the paddle and basket apparatuses. In vitro velocity values relevant to in vivo dissolution, presented as apparent gastrointestinal fluid velocity (AGV) values, were calculated. The AGV values were estimated from IVIVCs of immediate release (IR) dosage forms in each apparatus and CFD simulations. The simulations from the Levy apparatus revealed complex hydrodynamics in the region of the stirrer blades, and radial inflow at the centre of the beaker base. The calculated AGV values ranged from 0.001 to 0.026ms(-1). In vitro fluid velocities should reflect in vivo dissolution rates affected by natural convection and gastrointestinal motility, in addition to local fluid velocity. The maximum CFD generated velocity at the base of the paddle apparatus at 20rpm was similar to the average maximum AGV value determined, suggesting use of agitation rates which are lower than those commonly used (e.g. 50rpm in the paddle apparatus) may be appropriate when attempting an IVIVC for IR dosage forms.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University of Dublin, Trinity College, Dublin 2, Ireland. ddarcy@tcd.ie
authors.forename: Deirdre M
authors.initials: DM
authors.lastname: D'Arcy
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Healy
authors.forename: Owen I
authors.initials: OI
authors.lastname: Corrigan
mesh_terms: D000042:Absorption; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics; D001826:Body Fluids / Q000502:physiology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D005769:Gastrointestinal Motility; D041981:Gastrointestinal Tract / Q000502:physiology; D007700:Kinetics; D015203:Reproducibility of Results; D012995:Solubility; D014867:Water
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014867:Water; D001241:Aspirin