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) d iclofenac products was compared in 16 healthy volunteers. Only one gen eric product was fully bioequivalent with the reference product Voltar en with regard to AUC, C-max, and t(lag). Two products showed signific ant differences in t(lag). In a second experiment with eight volunteer s the influence of increased gastric pH (ranitidine treatment) on the two mutually most differing products was studied. They showed equivale nce in AUC, but not in C-max. Analysis of t(lag) suggests that the pro duct with the low t(lag) disintegrates within the non-acid stomach whe reas the product with the long t(lag) passes the non-acid stomach inta ct. Several in vitro dissolution tests were conducted. The European Ph armacopeia test did not detect any differences between the products. A t pH 5, both with and without mechanical stress, only the product with the shortest t(lag) released diclofenac. The in vivo results were bes t predicted by the in vitro dissolution tests performed at several fix ed pH values with mechanical stress.