[The bioequivalence of two different batches of two nifedipine controlled-release preparations with deficient batch conformity in in vitro liberation studies]

The pharmacokinetics of two batches of two different nifedipine (CAS 21829-25-4) controlled release formulations (product 1 or 2, respectively) were investigated during two randomized double-blind cross-over studies testing two treatments each in two separate treatment periods with a total of 40 (2 x 20) healthy male volunteers. Plasma concentrations of nifedipine were determined up to 48 h after administration of 20 mg nifedipine. In spite of different in vitro release rates a positive bioequivalence was determined for product 1, while no bioequivalence could be proven with the investigated batches of product 2. This is compatible with the different in vivo release rates. Therefore, a different in vitro release of a drug does not necessarily lead to a negative bioequivalence decision. On the other hand, deficient conformity of batches in vitro can go along with missing bioequivalence in vivo. A harmless substitution of formulations containing equal substances requires their therapeutical equivalence. A constantly high pharmaceutical quality is required to avoid therapeutic risks.