Drug candidates have a tendency to exhibit low water solubility, which may create issues when 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 compound. The 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.
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