[Simulation of bioequivalence study on the base of dissolution curves]

A computer method based on the in vitro dissolution of drug preparations has been elaborated for the estimation of bioequivalence. The method generates a "dissolutaion surface" from the parameters of time (X-axis), from pH (Y-axis) and from the dissolved amount (A) in % of the drug. This dissolution surface allows the determination of the general dissolution curve of the test and reference preparations. By supposing that the absorption rate constant is known from the literature, the change of the amount of dissolved drug as the function of time can be determined. On the base of this function the maximum amount of the dissolved drug in the gastrointestinal tract and the AUC can be calculated. and the test/reference ratio can be determined. In the case of linear pharmacokinetics these ratios are identical to the ratios of parameters that can be calculated in the circulation. By generating parameters between the allowed biological limits the dissolved drug-time curves of "volunteers" in the necessary number are created with the randomly generated "residence times" and their confidence intervals can be determined, i.e., on the base of dissolution curves bioequivalence can be estimated.