A systematic review of various pK_a determination techniques

The pK_a values of functional groups is crucial in determining the pharmacokinetic properties of a drug, affecting its absorption and thus bioavailability. This physicochemical property is also vital for the designing of drug excipients and vehicles. There are currently 13 known methods of determining a pK_a value, namely: potentiometric titration, spectrometry, fluorometry, NMR, HPLC, conductometry, electrophoresis, voltammetry, solubility, partition coefficient, calorimetry, computational, and surface tension. Some of these techniques are more widely utilized and well-established compared to others, with each having their inherent advantages and disadvantages. This review discusses each of the aforementioned techniques with emphasis on their pros and cons.