Comparison of different in vitro tests to assess oral lipid-based formulations using a poorly soluble acidic drug

The aim of the current work was to compare different modern in vitro tests using lipid-based formulations of a weakly acidic BCS II drug. Pure indomethacin and the drug-containing SMEDDS were tested using buffers and biorelevant media in a paddle apparatus, a physiologically motivated flow-through cell and a lipolysis test. The results of these dispersion/precipitation tests showed a generally increased solubility of indomethacin in the SMEDDS compared with the solubility of the pure drug. Only the flow-through test and the dispersion in 0.1 N HCl revealed a superior capacity of one SMEDDS in keeping the drug in solution, whereas the lipolysis test did not show similar formulation discrimination. We conclude that a suitable characterization of SMEDDS comprising an acidic drug should involve a physiologically based flow-through test or a dispersion/precipitation test in acidic environment together with a lipolysis test.