“…This apparent discrepancy in reduced permeability in FeB and FeSSIF, which is unexpected for a class III drug, may possibly be explained by the pH differences between the fasted and fed state media. Maleic acid, which is a component in both FaSSIF and FeSSIF, has pKa values of 1.9 for the first deprotonation and 6.1 for the second deprotonation (Prabhakaran et al, 2008). The pKa value of 6.1 gives a variation of the -1 and -2 charge states of maleic acid between fed and fasted states, which might have high impact on salt formation between maleic acid and the basic nadolol (Roche, 2007).…”