It is often stated that in vitro drug dissolution testing may never be able to predict the physiological outcome as the environment, and processes within, may be too complex and variable to be adequately reproduced in vitro. This prevents to achieve adequate and bio-relevant dissolution results. This belief may not reflect the reality and appears to lack any experimental evidence.
The belief appears to be based on dissolution results obtained using mostly paddle and basket apparatuses. Interestingly, it has been shown repeatedly that these apparatuses poorly mimic physiological environment (e.g. see), which is required for dissolution testing. It is, therefore, should be expected that these apparatuses would not provide physiologically relevant results. In addition to a lack of physiological relevancy, it has further been shown that hydrodynamics within dissolution apparatuses (paddle/basket) is such that these apparatuses should provide highly variable and unpredictable results [link]. It is, therefore, safe to assume that it is not the difficulty and complexity of reproducing a physiological environment in vitro but the choice of dissolution apparatuses which appears to have caused the lack of success. Recent studies using the modified spindle (crescent-shaped) which addresses the artifacts of the paddle and basket apparatuses, appear to provide choice of physiologically relevant experiment conditions, thus providing improved and physiologically relevant results [Link]. The use of the crescent-shaped spindle provides a common and product independent testing environment one observes in vivo, where products are also evaluated under common and product independent environment. This is in contrast with the current practices of using paddle and basket apparatuses where practically each and every product is analyzed using its own method, a physiologically non-relevant condition.
It is, therefore, essential that for accurate dissolution results and their interpretation one should conduct drug dissolution tests using apparatuses which can simulate physiologically relevant experimental conditions. As the paddle and basket apparatuses provide a non-physiological testing environment, they will provide non-physiologically relevant results, thus the lack of the faith.
