Partition coefficient (P) is a widely‐measured property, yet there is considerable variation among published log P values. This paper examines the factors that can affect the measurement of partition coefficient, and makes recommendations as to good practice. Accuracy of partition coefficient determination can be affected by temperature, lack of mutual phase saturation, pH, buffer type and concentration, phase miscibility, solute concentration, solute and solvent purity, solute stability, phase volume ratio, solute adsorption and failure to reach equilibrium conditions. It is recommended that partitioning be carried out at constant temperature using either a stirred flask technique or the filter probe.

Abstract:The Gibbs free energy, enthalpy and entropy of partitioning of 45 simple aromatic compounds (phenols, benzoic acids and acetanilides) from water to octanol and from water to cyclohexane have been determined using the filter-probe method. This involved the measurement of partition coefficients over the temperature range 20-45 o C.The aim of the work was to explore the effects of intramolecular hydrogen bonding and steric factors on the partitioning process. It was found that the intramolecular hydrogen bond is intact in 2-nitrophenol and salicylic acid, and possibly in 2-hydroxybenzaldehyde, in all three solvents, but 2-chlorophenol is intramolecularly hydrogen bonded only in inert solution. The evidence indicates that 2-nitroresorcinol and 2,6-dihydroxybenzoic acid possess only one intramolecular hydrogen bond, although they are theoretically capable of possessing two. There is evidence of steric shielding in 2,6-dimethylphenol, whilst 2,6-dimethylbenzoic acid and ortho-substituted acetanilides show evidence of steric twisting of the carboxyl and acetamido groups respectively out of the plane of the aromatic ring. Unusual steric effects are displayed in the methyl-2-nitrophenols whereby, depending upon the position of the methyl group, the intramolecular hydrogen bond is either weakened or strengthened.

The descriptors in the Abraham solvation equation, especially the solute hydrogen bond acidity descriptor, A, have been compared to values of DH o and DS o for partitioning in the water-cyclohexane and wateroctanol systems obtained by Dearden and Bresnen. It is shown that effects on DH o and DS o due to internal hydrogen bonding parallel very closely effects on A values for substituted phenols and substituted benzoic acids, thus suggesting a common structural origin. Steric effects of ortho-substituted methyl groups in phenols, benzoic acids and acetanilides on DH o and DS o also parallel effects on the Abraham solvation parameters. Some of these steric effects, such as those in 2,6-dimethylacetanilide, can be very large. Both the thermodynamics of partitioning and the Abraham descriptors suggest that in 2,6-dihydroxybenzoic acid there is only one internal hydrogen bond, and that 2-nitroresorcinol behaves as though it had two internal hydrogen bonds.

Observation of clinical pharmacists' activities has identified that a significant proportion of their time could be categorised as 'waste'. There are practical steps that could be implemented in order to ensure their time is used as productively as possible. Given the challenges facing the UK National Health Service, the adoption of 'Lean' techniques provides an opportunity to improve quality and productivity while reducing costs.

Animal models are known not to predict human responses well, in general. However, we have been able to demonstrate that, for a series of non-steroidal anti-inflammatory drugs that are or were in clinical use, the incorporation of two simple physicochemical properties results in excellent correlations between human and rodent potencies for anti-inflammatory, analgesic and anti-pyretic activities. This has the potential to allow the use of historical data to improve drug development.