Download Absorption and Drug Development: Solubility, Permeability by Alex Avdeef PDF

By Alex Avdeef

ISBN-10: 0471423653

ISBN-13: 9780471423652

Of the masses of hundreds of thousands of compounds synthesized every year, such a lot have nearly no probability of changing into medicines. This challenge exists simply because such a lot molecules lack the drug-like homes essential to allow them to be potent in vivo. to deal with this factor, Alex Avdeef's Absorption and Drug improvement exhibits the reader find out how to research a compound's pharmaceutical houses, emphasizing oral absorption. This booklet explains the several physicochemical tools presently used to investigate drug applicants and the way to interpret those tools. additionally incorporated are physicochemical information for over two hundred advertisement medicinal drugs. With over six hundred references and a hundred drawings, this e-book is a wonderful source for the sensible pharmaceutical chemist and people looking a greater figuring out of physicochemical measurements.

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Extra resources for Absorption and Drug Development: Solubility, Permeability and Charge State

Example text

Tam and others [131–135,137,138,140–143,228,229] developed a very effective generalized method for the determination of ionization constants and molar absorptivity curves of individual species, using diode-array UV spectrophotometry, 32 CHARGE STATE coupled to an automated pH titrator. Species selection was effected by target factor analysis (TFA), and EFA methods were used. Multiprotic compounds with overlapping pKa values were investigated. Binary mixtures of ionizable compounds were considered [141].

CE methods may also be useful since very small sample quantities are required, and detection methods are generally quite sensitive. If the compound is virtually insoluble (<1 mM), then a pH-metric mixed-solvent approach can be tried [112]. 008 mM (6 ng/mL) [pION]. The most frequently explored solvent systems are based on water–alcohol mixtures [119,164,166,181–210]. DMSO–water [211–215], dioxane–water [216–220], and other systems [221,222] have been explored. Where possible, methanol is the solvent of choice, because its general effect on pKa values has been studied so extensively.

Six sparingly soluble nonsteroidal antiinflammatory weak acids (diclofenac, flurbiprofen, naproxen, ibuprofen, butibufen, fenbufen) were used successfully to illustrate the new technique. 7 pKa MICROCONSTANTS In certain types of multiprotic molecules it is possible that chemically different species of the same stoichiometric composition are formed [142,230–244]. The pH-metric titration technique cannot distinguish between such tautomeric species. In such cases the determined pKa is a composite constant, a macroconstant.

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