Drug candidates ionization constant

Morgan, M. E. Liu, K. Anderson, B. D., Microscale titrimetric and spectrophotometric methods for determination of ionization constants and partition coefficients of new drug candidates, J. Pharm. Sci. 87, 238-245 (1998). 

Knowledge ofthe aqueous ionization constant,pof an ionizable drug candidate is very important because it can be used to predict solubility, lipophilicity, and permeability at different pH therefore, it... 

Many potential candidate drugs are weak acids or bases, therefore, one of the most pertinent determinations carried out prior to development is the pKa or ionization constant. Strong acids, e.g., HC1, are ionized at all pH values, whereas the ionization of weak acids is dependent on pH. It is useful to know the extent to which the molecule is ionized at a certain pH, since properties such as solubility, stability, drug absorption and activity are affected by this parameter. The basic theory of the ionization constant is covered by most physical chemistry textbooks, and a most useful text is that by Albert and Sargeant (1984). Fundamental to our appreciation of the determination of this parameter, however, is the Bronstead and Lowry theory of acids and bases. This states that an acid is a substance that can donate a hydrogen ion, and a base is one that can accept a proton. 

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