Dissolution template titration method

Another common source of uncertainty in solubility determinations is when the compound is highly ionized (>99%) at the pH considered. This usually happens when the pH is more than 2 units above the pKa for an acid or than 2 log units lower than the pKa for a base. In this case the solubility pH profile is very steep around that pH, which results in a higher uncertainty on the result. This is the case of Diclofenac at pH 6.8, where we observed some differences within our measurements and between our data and literature values. This limitation is, however, valid for both dissolution template titration method and the saturation shake-flask. 

Potentiometric methods for solubility measurement have been reported in the literature [467-471]. A novel approach, called dissolution template titration (DTT), has been introduced [472-474], One publication called it the gold standard [509]. 

Avdeef, A., Berger, C. M. pH-metric solubility. 3. Dissolution titration template method for solubility determination. Eur. J. Pharm. Sci. 2001, 14, 281-291. 

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