Computational fluid dynamics: applications in pharmaceutical technology - Computer-Aided Applications in Pharmaceutical Technology - page 246

stability testing, obtaining marketing approval for new and generic drugs,
testing how the post-approval changes made to formulation or
manufacturing procedure affect drug product performance, development
of an in vitro-in vivo correlation, etc.
The choice of an appropriate dissolution apparatus and experimental
conditions is of great importance, as it can considerably affect the results.
Knowledge of the hydrodynamic conditions specifi c to the selected
dissolution apparatus is important, since small differences in
hydrodynamic conditions can result in misleading conclusions. However,
comprehensive knowledge of hydrodynamics, both in vitro and in vivo ,
is still lacking (Dressman and Krämer, 2005). The results of the studies,
which will be presented in the following text, indicate that CFD can be
successfully applied for simulation, analysis, and gaining insight into the
hydrodynamic conditions present in different dissolution apparatuses.
The USP paddle apparatus is the most widely used dissolution
apparatus with a relatively simple design, but there are still problems
related to the reproducibility of the results and development of an in
vitro-in vivo correlation. This can be partly attributed to the complex
hydrodynamics, which are not well understood and seem to be variable
at different locations within the vessel. It was shown that small differences
in tablet position within the vessel can affect the hydrodynamics, leading
to pronounced differences in dissolution rates (Healy et al., 2002).
Extensive work has been carried out by a research group at the School of
Pharmacy, Trinity College, Dublin, to elucidate hydrodynamics in paddle
dissolution apparatus by using CFD simulations (McCarthy et al., 2003,
2004; D'Arcy et al., 2005). McCarthy et al. (2003) revealed the presence
of a low-velocity domain directly below the center of the rotating paddle.
Interestingly, they found that this domain is surrounded by a high velocity
region, with 3- to 4-fold difference in fl uid velocity within a distance of
approximately 8 to 10 mm. The authors postulated that these pronounced
differences in fl uid velocities within a small area, where the dosage form
is located during the test, might be a reason for variable results. Indeed,
when a cylindrical tablet was placed at the bottom of the vessel, fl uid
fl ow was even more complicated (Figure 7.9). The results of this study
indicate that CFD simulations can provide thorough information on
hydrodynamics throughout the dissolution vessel, in contrast to laser
Doppler measurements, which can provide limited information about
fl uid velocity values at certain positions in the vessel.
In the study that followed, McCarthy et al. (2004) applied CFD to
simulate the infl uence of paddle rotational speed on hydrodynamics in a
dissolution vessel. It was found that the magnitude of both axial and

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