Thermodynamics of distribution of salicylates in semi-solid ointment bases.

The distribution behavior of salicylic acid and its various esters (methyl, ethyl, phenyl, and glycol) between different semisolid vehicles (PEG, Carbopol 940, Plastibase) and non-miscible second phases has been examined over a range of temperature. The derived thermodynamics data can be used to discuss drug-vehicle interactions and changes in the thermodynamic activity of the solute. Salicylic acid interacts little, if at all, with inert materials such as Plastibase (mineral oil thickened with polyethylene) but together with its esters shows strong interaction with PEG. An increased interaction with increase in molecular weight (ethylene oxide content) of PEG is demonstrated. The salicylate esters have a lower affinity for Carbopol gels than for PEG because of entropy effects. Glycol salicylate in Carbopol gels demonstrates anomalous behavior. The relevance of the data to studies on drug release, and in particular the evaluation of rheological factors, is discussed.