Theoretical physicochemical analysis based on ionization, pK a, and partitioning predicted the same trend and confirmed the experimental results. ![]() ![]() The opposite trend was evident for metoprolol. ![]() Similarly, segmental-dependent in-vivo intestinal permeability was revealed as the intestinal region becomes progressively distal, and the pH gradually increases, the permeability of furosemide significantly decreased. Log D of furosemide at the three pH values 6.5, 7.0, and 7.5 (representing the conditions throughout the SI) showed a downward trend. Furosemide was found to be a low-solubility compound. Metoprolol was used as the low/high permeability class boundary. In addition, advanced in-silico simulations (GastroPlus ®) were used to elucidate furosemide regional-dependent absorption pattern. Furosemide solubility, physicochemical properties, and intestinal permeability were thoroughly investigated in-vitro and in-vivo throughout the SI. In this work, we investigated the solubility/permeability of BCS class IV drug, furosemide, considering the complexity of the entire small intestine (SI). While solubility is often predictable, intestinal permeability is rather complicated and highly dependent on many biochemical/physiological parameters. Biopharmaceutical classification system (BCS) class IV drugs (low-solubility low-permeability) are generally poor drug candidates, yet, ~5% of oral drugs on the market belong to this class.
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