USP 4 Dissolution Apparatus (Flow Through Cell)
- Whereas it is widely known that the hydrodynamic environment can affect the dissolution rate, hydrodynamic characteristics of dissolution conditions are not routinely monitored as part of dissolution testing.
- The physics of fluid flow are governed by the principles of conservation of mass, momentum, and energy.
- These can be represented mathematically by the Navier- Stokes partial differential equations, or by their integral formulations.
- The process of numerically solving these equations in space and/or time is called computational fluid dynamics (CFD).
- In terms of particulate systems in the FTC apparatus, Shadowgraph imaging has proven useful for exploring particle behavior within the FTC apparatus in terms of particle velocities, sizes, and particle agglomeration tendencies.
- MRI has been used to visualize and quantify flow in the FTC apparatus, both with and without a cylindrical disk “tablet”
- Qualitative and quantitative velocimetric techniques are frequently used in combination with computational fluid dynamics (CFD) simulations to characterize and simulate hydrodynamics and mass transfer in pulsing flow.
- low velocity pulsing flow running counter to gravity inhibited dissolution rate compared to that in a free convection system.
- It is difficult to directly compare hydrodynamics between apparatuses in terms of the anticipated effects on dissolution, as dosage form location and behavior (i.e., motion and disintegration) during a dissolution test can also vary between apparatuses.
- Additionally, the dosage form itself, through its geometry and solubility characteristics can affect the hydrodynamic environment in which it is located.
- In addition to inhibitory effect of flow regimen on dissolution, the solubility of dissolving solute was observed to be a further confounding factor.
- The higher solubility of lactose results in a denser saturated solution at the dissolving surface.
- Simulations of the hydrodynamics in the presence of this denser solution at the surface suggested a notable gravity induced downward flow from this denser solution, and a marked difference in the hydrodynamics in FTC as compared to a saturated solution of (less soluble) benzoic acid.
- Thus, the interaction between the upward pulsing flow and the downward flow due to both flow reversal and natural convection from solute solutions will be dependent on the flow rate and density of the solute solution.
- The effect of downward flow arising from gravity induced natural convection had a significant effect for the more soluble compound, LM(Lactose Monohydrate), on local fluid velocities, whereas flow reversal induced by the forced convection environment was a significant feature impacting on the hydrodynamics in the slightly soluble BA (Benzoic acid) species transfer simulation.
- In contrast to other dissolution apparatuses, the FTC apparatus uses a piston pump that generates a sinusoidal or semi-sinusoidal flow profile. This results in a pulsing flow resulting in variation in the fluid velocity with time and, thus, an inconstant Reynold’s number.
- larger Ø22.6 mm cell has lower average linear fluid velocities than the smaller cell at equivalent flow rates due to an increased cross-sectional area.
- flow field appears asymmetric and non-uniform in the proximity of the ruby bead in the simulation with no glass beads.
- when the ruby bead is included and the lower conical section of the column is packed with the glass beads, no notable difference is predicted between open and packed column configurations for the shear stress distribution.
- The tablet position in the flow-through cell containing glass beads does not seem to be important for both erodible and coated matrix tablets.
- When glass beads are not used in the cells, the tablet position affects drug release from both erodible and coated matrix tablets in different ways.
- wall shear stresses on the tablet surface varied markedly during the acceleration and deceleration phases of the pump discharge, at time points when the inflow velocity would be the same.
- The horizontally oriented tablet experienced increased axial and radial fluid velocities due to the reduced cross-sectional area available for flow.
- Radial velocity distributions differed over the course of the pulse, depending on tablet orientation, with greater variation around the vertically oriented tablet.
- Horizontally oriented non-disintegrating tablets exhibited higher dissolution rates than vertically oriented tablets.
Knowledge of the operating hydrodynamics provides insights into the choice of test conditions, which will enable the use of the dissolution test in a robust way.