Formulation factors affecting release of drug from topical vehicles. II. Effect of solubility on in vitro delivery of a series of n-alkyl p-aminobenzoates.

The major influence on the rate of drug transfer out of its vehicle and into the skin is the thermodynamic activity of the drug within its formulation. This study addresses certain thermodynamic dependencies of topical delivery in a model system. Prototypical water-in-oil (W/O) and oil-in-water (O/W) emulsions and their component phases are used as the test vehicles, polydimethylsiloxane is the membrane, and three homologous n-alkyl p-aminobenzenzoate esters are the test permeants. In an emulsion, the interaction of the compound between the water and oil phase can determine the extent of lowering of the thermodynamic activity in the external phase in contact with the membrane. The emulsifiers (surfactants) impact strongly on partitioning and permeation as a result of the extra solubilizing capacity contributed by the surfactant micelles. The lower flux in the aqueous phase of the O/W emulsion is the result of micellar solubilization, and this solubilization increased with increasing ester chain length. Solubilization is also an influence in nonaqueous phases, but permeant hydrophobicity is without specific influence; therefore, transport become less dependent upon the structure of the compound.