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The bioavailability of diclofenac from enteric coated products in healthy volunteers with normal and artificially decreased gastric acidity
Author(s) -
Van Gelderen Marjet E. M.,
Olling Martin,
Barends Dirk M.,
Meulenbelt Jan,
Salomons Peter,
Rauws Adalbert G.
Publication year - 1994
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510150905
Subject(s) - bioavailability , bioequivalence , diclofenac , cmax , pharmacology , friability , medicine , stomach , in vivo , first pass effect , microbiology and biotechnology , biology
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.