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John Comer
Christine Prosser Paula Garcia John Comer Shenaz Nunhuck Darren Edwards Toni Llinās


The interrelationships between solubility, lipophilicity and pKa for ionisable molecules

John Comer, Sirius Analytical Instruments Ltd

Knowledge of lipophilicity and solubility is important at various stages of drug discovery, selection and pre-formulation. This talk will describe how solubility and lipophilicity are influenced by the ionisation properties of the compound. Examples will be used to show the relationships between intrinsic compound properties and pH-dependent compound properties. Also, some new instrumental techniques for studying these properties for ionisable drug molecules will be discussed.

Noting the correlation between PAMPA permeability and logP dodecane-water values, we have developed a new way to measure logP dodecane-water on Sirius GLpKa. The method involves acid base titration with UV detection, and requires less than 0.4mg of sample per assay. The results compare well with pH-metric values.

We have also introduced CheqSol (patent applied for), a new pH-UV method for measuring equilibrium solubility. CheqSol gets a result in 20 minutes for many samples, and confirms it several times in a one-hour assay. It has been validated by comparison with shake-flask for about 25 acidic and basic drugs. CheqSol also measures kinetic solubility in the same experiment. Kinetic solubility is higher than equilibrium solubility for samples that form supersaturated solutions, but identical for samples that do not supersaturate.

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Last modified: 28 April 2008