A systematic review of various pKa determination techniques

Int J Pharm. 2023 Mar 25:635:122783. doi: 10.1016/j.ijpharm.2023.122783. Epub 2023 Feb 27.

Abstract

The pKa 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 pKa 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.

Keywords: Partition coefficient; Surface tension; Titration; pK(a) determination; pK(a) values.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Conductometry*
  • Fluorometry
  • Hydrogen-Ion Concentration
  • Solubility