Volume 33; Critical Compilation of pKa Values for Pharmaceutical Substances

Richard John Prankerd

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There are numerous compliations of pKa values in the physical chemistry literature, including several for pharmaceutically relevant organic weak acids and bases [1-8].These are complemented by further compliations of pharmaceutically relevant physicochemical data such as partition coefficients, solubilities, and reaction rate constants[6]. At the same time, other pharmaceutically interesting phenomena have not yet received the attention they deserve, such as the detailed substrate specificity and kinetics of endogenous enzyme systems (e.g., esterases and phosphates), which are relevant to the rational design of prodrugs and the predictability of their bioconversion to active drug[13]. Along with solubilties, partition coefficients, and reaction rates, pKa values are the most importnat physicochemical properties of drugs and the excipients used to formulate them into useful medicines. The determination of pKa values is typically discussed either first or second (after solubility) in preformulation text-books. The extent of ionization (overall state of charge) for a dissolved drug is a function of its intrinsic pKa value(s) and the pH value of the solution [14]. The extent of ionization for a drug can control its solubility, dissolution rate, reaction kinetics, complexation with drug carriers (e.g., cyclodextrins), absorption across biological membranes, distribution of the site of action, renal elimination, metabolsim, protein binding, or receptor interactions. Clearly, research in many aspects of the drug sciences requires knowledge and use of drug pKa values. When an investogator chooses to make use of tabulated or complied physicochemical constants, reliably assessed data is required to account best for physicochemical or biopharmaceutical results that are dependent on the relationship between pH and pKa.
Original languageEnglish
Place of PublicationUSA
Number of pages726
ISBN (Print)978-0-12-260833-9
Publication statusPublished - 2007

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