The single dose pharmacokinetic characteristics of four aspirin formulations in humans were compared with their in vitro dissolution properties. The pharmacokinetic parameters were determined by measuring salicylate concentrations in the plasma. Dissolution was measured by using the USP XX single time point dissolution test. The four aspirin products were a commercial tablet, a commercial capsule, a capsule filled with a commercial granulation, and a slow dissolving capsule formulation that failed the USP dissolution specification. It was found that there was a poor correlation between the in vitro dissolution results and the in vivo computed pharmacokinetic parameter statistics. In vivo testing in humans showed that all of the formulations were bioequivalent in terms of half-life and AUC, and the capsule that failed to pass the dissolution specification was bioequivalent to two of the three products that did pass the specification with respect to the maximum plasma concentration. None of the products could be demonstrated to be bioequivalent with regard to the time to maximum plasma concentration. However, none of the in vivo differences between the four aspirin formulations were judged to be clinically significant. Therefore, while there was a poor relationship between the in vitro USP XX dissolution test results and the bioequivalence test results, from a practical viewpoint the dissolution test is a satisfactory manufacturing quality control test, since it can detect differences in in vitro dissolution prior to their having a significant clinical impact.
