Gastric acidity-dependent bioavailability of commercial sustained release preparations of indomethacin, evaluated by gastric acidity-controlled beagle dogs.

The relationship between gastric acidity and the bioavailability of two kinds of sustained-release indomethacin (IM) formulations was investigated in gastric acidity-controlled beagle dogs, and compared with that of rapid-release IM formulations. All test dosage forms were more rapidly dissolved in simulated intestinal fluid than in simulated gastric fluid. Gastric acidity did not affect the bioavailability of IM from the rapid-release formulation. However, the bioavailability of IM from the two kinds of sustained-release formulations were markedly influenced by gastric acidity. The rates of IM bioavailability from both of the sustained-release formulations were faster under low acidity conditions than under high acidity conditions (p less than 0.01). In addition, Tmax and mean residence time (MRT) were approximately the same for the rapid-release and sustained-release formulations under low acidity conditions. These results suggest that the IM sustained-release formulations showed a rapid-release profile under low acidity conditions.