Drug candidates show a tendency to exhibit low water solubility; as a result, present with issues measuring pKa by a traditional aqueous methods. Solid State Pharma is capable of measuring compounds with low water solubility by using an organic co-solvent. Titrations are completed in a variety of water:co-solvent ratios to collect pKas of the substance; pKa can be then be extrapolated by a Yasuda-Shedlovsky plot.
UV-metric and pH-metric acquisition methods can used in conjunction with co-solvent methods to overcome compound solubility issues. Log P and log D are simultaneously measured through a series of titrations typically using 1-octonal as a partitioning solvent.