Alternative and generalized approach to in vitro-in vivo correlation

Evaluation of in vitro-in vivo correlation (IVIVC) plays important role in securing therapeutic effect if a dosage form undergoes technological modifications. Similarity (closeness) of dissolution profiles of the original and modified dosage forms has been traditionally considered to be sufficient for similar in vivo responses. This may be true if the IVIVC model (dependence between the dissolution and corresponding absorption profiles) is given by a linear straight line with the unit slope. The paper presents an alternative and generalized approach to IVIVC evaluation. Influences of pre-systemic processes (disintegration, dissolution, absorption) on the system response (concentration time profile C(t), bioavailability BD and other) are analyzed and evaluated. Both the magnitude and sign of IVIVC are then derived from the magnitudes and signs of these influences. The underlining idea is that pre-systemic processes do not correlate with the system response, (e.g., plasmatic concentration) if small modifications of the former do not induce significant changes of the later. If this is so, the therapeutic effects of the modified and original dosage forms may be considered equal or at least similar. In this way the problem of IVIVC is not only exactly mathematically founded but modifications of pre-systemic processes are directly projected to the system output-- the time profile of plasmatic concentration. Moreover, the approach is applicable to virtually any dosage form. Its feasibility was validated in vivo.