Drug release in vitro--an aid in clinical trials?

The topic of this article is biopharmacy. Using delayed release tablets with the active ingredient theophylline as a practical example, it was demonstrated that prior to clinical trials, galenical preparations can be characterized according to drug release in vitro and, that profiles of in vitro drug release can be compared with each other (LEVY-plot). Drug release from the retard tablets was examined following the Cube Root Law which describes the dependency of release rate on surface and agitation. Comparing profiles of in vitro release to a hypothetical or even known profile of in vivo release, produce results that are open to interpretation (LEVY-plot). A postulated correlation between the nonanalogous parameters, relative bioavailability and the mean in vitro dissolution time was confirmed. Due to established in vitro/in vivo correlations, we can in our case, predict the hypothetical in vivo release profiles for tablets showing more or less retarded release profiles in vitro and the relative bioavailability can be estimated. In addition, prediction of blood level is possible. In vitro/in vivo correlations can also provide information about residence times of the delayed release tablets in components of the gastrointestinal tract (stomach, small bowel and large bowel). Thus, using these methods, delayed release tablets (with the active ingredient theophylline) can be optimized for their use in clinical trials.