Regarding the potential severe toxicity associated with systemic administration of
methotrexate (MTX), a topical formulation might be of greater utility for the treatment of
psoriasis and other hyperproliferative skin disorders. One of the presumed reasons for the lack of clinical activity of topical
methotrexate in
psoriasis is insufficient percutaneous penetration necessary to inhibit epidermal
DNA synthesis. The present study was undertaken to prepare a formulation to enhance skin penetration of MTX. For this mean, topical gel formulations were prepared and evaluated for MTX percutaneous absorption using rat skin and standard Franz diffusion cells. For enhancing percutaneous absorption, three
surfactants (anionic, cationic and nonionic) were incorporated into formulations with different concentrations. Finally
salicylic acid as a keratolytic material was added for more enhancement effect. The results showed that SLS (
sodium lauryl sulphate) and alkyl benzyl dimethyl
chloride did not show significant enhancement effect on the penetration of MTX.
Transcutol was able to enhance transdermal absorption of MTX and the higher enhancement ratio was obtained with 2% (w/w) concentration of
transcutol. Addition of
salicylic acid increased this ratio. Prepared formulation containing
transcutol 2% (w/w) and
salicylic acid 6% (w/w) showed higher enhancement property and could be used clinically for local treatment of
psoriasis.