Potential usefulness of solubility index for prediction of the skin permeation rate of 5-ISMN from pressure-sensitive adhesive tape

Skin permeation of 5-ISMN from pressure sensitive adhesive (PSA) tape was e valuated using thermodynamic activity of the drug in PSA. Three acrylic adh esives (Gelva 737, Gelva 1430 and Gelva 1753) were used as PSA. Since the d rug activity in PSA is difficult to determine. however, a solubility index was defined. Several PSA tapes containing different amounts of 5-ISMN were prepared, and heat of fusion at the dissolution of 5-ISMN in each PSA was d etermined by DSC. No exothermic peak was found when the drug concentration was less than the solubility in PSA, whereas the heat of fusion increased p roportionally with amount of solid drug in the PSA when the drug concentrat ion was above the solubility. The bending point in the profile of heat of f usion versus 5-ISMN content in PSA was defined as the solubility index. In vitro skin permeation was determined using excised hairless rat skin from 5 -ISMN-saturated PSA tapes. The obtained skin permeation of the drug decreas ed with increases in the solubility index. These profiles were confirmed by a theoretical approach using the differential equation corresponding to Fi ck's second law of diffusion. These results suggested that the solubility i ndex can be utilized for prediction of the skin permeability of drugs from PSA tape. (C) 2001 Elsevier Science B.V. All rights reserved.