Influence of isosorbide dinitrate concentration on its skin permeability from adhesive matrix devices

Adhesive matrix devices containing a model drug, isosorbide dinitrate (ISDN), were prepared with three different types of pressure sensitive adhesives (PSAs). ISDN permeation through excised hairless rat skin from the different devices was measured in vitro. For each PSA type, the steady state permeation rate of ISDN increased proportionally with an increase of ISDN concentration in the PSA and reached a maximum level at a certain concentration. Although the concentrations reaching the maximum skin permeation level varied among PSA types, the maximum rate for each PSA type was largely similar to that for ISDN aqueous suspension. The release rate of ISDN from devices was too fast to influence the skin permeation rate for all devices. In the PSA of devices showing maximum skin permeability, ISDN crystalline was observed by polarizing microscopy and differential scanning calorimetry. These results suggest that the skin permeation of ISDN from adhesive matrix devices was controlled by the thermodynamic activity of the drug in the PSAs.