Computer simulations using GastroPlus to justify a biowaiver for etoricoxib solid oral drug products.

PURPOSE: The purpose of this study was to compare the dissolution behaviour of etoricoxib in different dissolution media and to establish in vitro/in vivo correlation (IVIVC) using computer simulations.

METHODS: Drug solubility was measured in different media. The dissolution behaviour of etoricoxib was studied in the USP Apparatus 2 using different dissolution media. A dissolution transfer model was used to investigate if the drug stays in solution when the pH of the medium changes. Drug permeability assessment was performed using the caco-2 cell culture technique. The in vitro data were used as input functions in GastroPlus to simulate the in vivo profiles of the drug.

RESULTS: Solubility of etoricoxib was highest at low pH, and there was no significant difference in the solubility observed between blank buffers and biorelevant media of similar pH. The drug remained solubilised when transferred into simulated intestinal fluids. Using the in vitro data as input function in Gastro Plus, an IVIVC was established. Further simulations confirmed that the drug absorption occurs similar to the absorption of an oral solution.

CONCLUSIONS: Due to the solubility behaviour within the physiological pH gradient of the gastrointestinal tract, etoricoxib can be classified as an intermediate class 1/2 drug rather than BCS class 2. In vitro results combined with in silico simulations using GastroPlus support scientifically that a biowaiver for immediate release etoricoxib solid oral dosage forms is justified.