Sensitivity of Different In Vitro Performance Tests and Their In Vivo Relevance for Calcipotriol/Betamethasone Ointment.

PURPOSE

We compared results of in vitro performance testing with results of therapeutic equivalence study for calcipotriol/betamethasone ointment, to evaluate their sensitivity and in vivo relevance.

METHODS

Different in vitro methods were used to evaluate drug release and permeation from the test and reference ointment. Moreover, 444 psoriasis patients were randomized in the therapeutic equivalence study and the parameters of efficacy and safety were compared with in vitro results.

RESULTS

In vitro release and permeation rate of calcipotriol and betamethasone from the test formulation was higher than from the reference product for all methods used (p ≤ 0.05 for calcipotriol and p < 0.01 for betamethasone). Observed batch-to-batch variability of reference product confirmed high sensitivity and discriminatory power of in vitro methods. Higher release and permeation rate of calcipotriol and betamethasone from test product was reflected in the efficacy assessment (mean response difference 4.78 mPASI percentage points), but the observed difference was within the equivalence margins. Systemic exposure to calcipotriol and betamethasone was similar in both treatment groups.

CONCLUSION

The results of in vitro experiments rank orderly correlated with the results of clinical study. In vitro methods are more sensitive and highly discriminatory when compared to in vivo performance.