pKa determination

ALAN TALEVI; CAROLINA L. BELLERA

The ADME Encyclopedia. A Comprehensive Guide on Biopharmacy and Pharmacokinetics

Springer Nature

Año: 2022; p. 1013 - 1018

The acid dissociation constant (Ka) (also known as ionization constant, as acidic dissociation constant, or sometimes as acidity constant) is among the most relevant physicochemical parameters from a (bio)pharmaceutical perspective.The different chemical species (neutral or ionized, either anionic or cationic) often have vastlydifferent ADME properties. Ionized species tend to be more water soluble, while the neutral speciesare more lipophilic and thus present higher permeability across biological membranes (thereader is referred to the entry ▶ ?pH Partition Theory? for further discussion). Therefore, theionization state exerts considerable influence on absorption, distribution, and excretion rate andextent (lipophilic species are not only better absorbed and more rapidly distributed, but alsothey are more easily reabsorbed during biliary or urinary excretion). Whereas these are the mostinvoked reasons to explain the pharmaceutical relevance of ionization equilibria, there are someothers [1]. Pharmaceutical waste has emerged as a new major public and environmental health concern [2]: active pharmaceutical ingredients and their derivatives are continually introduced in theenvironment as a result of manufacturing processes, excreta, and disposal of unused or expireddrug products. Much of this waste ends up in soils and waters, where they accumulate and jeopardize terrestrial or aquatic life. Knowledge of dissociation constants is important from an environmental perspective, to estimate the occurrence, fate, and effects of pharmaceutical ingredients. At last, ionization state is important from an analytical perspective, as for weak acid or bases the pH may influence compound volatility, UV absorption, or chromatography retention times