The bioavailability of diclofenac from enteric coated products in healthy volunteers with normal and artificially decreased gastric acidity

The relative bioavailability of four monolithic enteric coated (MEC) diclofenac products was compared in 16 healthy volunteers. Only one generic product was fully bioequivalent with the reference product Voltaren with regard to AUC, C(max) and t(lag). Two products showed significant differences in t(lag). In a second experiment with eight volunteers the influence of increased gastric pH (ranitidine treatment) on the two mutually most differing products was studied. They showed equivalence in AUC, but not in C(max). Analysis of t(lag) suggests that the product with the low t(lag) disintegrates within the non-acid stomach, whereas the product with the long t(lag) passes the non-acid stomach intact. Several in vitro dissolution tests were conducted. The European Pharmacopeia test did not detect any differences between the products. At pH 5, both with and without mechanical stress, only the product with the shortest t(lag) released diclofenac. The in vivo results were best predicted by the in vitro dissolution tests performed at several fixed pH values with mechanical stress.