FORMULATION FACTORS AFFECTING RELEASE OF DRUG FROM TOPICAL VEHICLES .2. 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 an d into the skin is the thermodynamic activity of the drug within its f ormulation. This study addresses certain thermodynamic dependencies of topical delivery in a model system. Prototypical water-in-oil (W/O) a nd oil-in-water (O/W) emulsions and their component phases are used as the test vehicles, polydimethylsiloxane is the membrane, and three ho mologous 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 activ ity in the external phase in contact with the membrane. The emulsifier s (surfactants) impact strongly on partitioning and permeation as a re sult of the extra solubilizing capacity contributed by the surfactant micelles. The lower flux in the aqueous phase of the O/W emulsion is t he result of micellar solubilization, and this solubilization increase d with increasing ester chain length. Solubilization is also an influe nce in nonaqueous phases, but permeant hydrophobicity is without speci fic influence; therefore, transport becomes less dependent upon the st ructure of the compound.