Abstract
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.
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