2006 Volume 21 Issue 5 Pages 537-544
Permeation of meloxicam (MEL) through excised hairless mouse skin under the influence of various additives was investigated with respect to mechanisms of action. Of a total of 23 additives, such as alcohols, fatty acids, esters, terpenes, amines and surfactants. 12 were found to enhance the skin permeation of MEL, and these could be classified into three groups that are influencing diffusion in the skin, partition to the skin and solubility of the drug. Combination of additives enhancing diffusion and partition resulted in approximately 6-fold increase in permeation as compared to the water control case, whereas diisopropanolamine enhancing solubility combined with 1-menthol enhancing diffusion or glycerin monocaprylate enhancing partition caused 500-fold elevation. Therefore, to achieve high enhancement with combinations having differing mechanisms of action, use of an additive enhancing solubility with either of the other two types may have advantages.
With tape type patches containing diisopropanolamine to increase solubility of MEL with 1-menthol to increase diffusion in the skin or glycerin monocaprylate to increase partition to the skin, permeation was well enhanced, but this was not the case with poultice type patches. With these latter, improvement was obtained on substitution of polyoxyethylene oleylamine (5E.O.), a hydrophobic solvent, for the hydrophilic diisopropanolamine.
These results suggest that combinations of enhancers and confirmation of the miscibility of additives enhancing solubility with the base is important for achieving high permeation of drugs from transdermal patches.
