FaSSIF-V3, but not compendial media, appropriately detects differences in the peak and extent of exposure between reference and test formulations of ibuprofen

BackgroundThe predictive capacity of in vitro dissolution tests using 50 mM phosphate buffer at pH 6.8 to anticipate in vivo bioequivalence outcomes for highly permeable and poorly soluble weak acids has been questioned. In previous work, it was shown that using a lower buffer capacity could correctly distinguish the in vivo behavior of products containing ibuprofen free acid and those containing its salts.AimTo assess whether adjustments in the composition of the medium, including matching the phosphate buffer concentration to the reported pH0 of dissolving ibuprofen free acid in bicarbonate buffer, as well as in the stirring rate, could detect differences in the extent and peak of exposure between reference and test formulations.ResultsUsing the recently revised fasted state simulated intestinal fluid (FaSSIF-V3) with reduced phosphate buffer concentration (5 mM), it was possible to predict in vivo differences in peak and extent of exposure between test and reference formulations of ibuprofen.ConclusionFor ibuprofen products, a modified Biopharmaceutics Classification System (BCS) based biowaiver dissolution test may be a way forward to approve generic products without having to perform pharmacokinetic studies. More studies with other BCS Class 2 weakly acidic compounds would be necessary to assess whether this approach could be applied more generally.

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