Paper Information

Journal:   PHARMACEUTICAL SCIENCES   WINTER 2008 , Volume - , Number 4; Page(s) 31 To 45.
 
Paper:  FORMULATION OF METHOTREXATE TOPICAL FORM ULATION (GEL) AND EVALUATION OF ITS IN VITRO TRANSDERMAL ABSORPTION
 
Author(s):  JAVADZADEH Y.*, SIAHI M.R., RAJABI ZOHREH, KEYVAN I., SAFDARI REZVAN, ASNA ASHARI O.
 
* SCHOOL OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES
 
Abstract: 

Objectives: Psoriasis is a chronic, recurrent disease that affects between 1% and 6% of the population. Methotrexate (MTX) is an effective systemic chemotherapeutic agent for the treatment of psoriasis and possibly cutaneous lymphoma (CTCL).However the risk of hepatic fibrosis and other systemic toxicity, such as bone marrow suppression, has precluded its use in all but the most severe cases of these diseases. In considering the potential severe toxicity associated with systemic administration of 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 optimize penetration of MTX in vitro.
Methods: For this mean, several gel formulations were prepared and investigated in the case of stability and physical characteristics. Among them three formulations were selected for percutaneous absorption studies using rat skin and standard Franz diffusion cells. Assay of drug was done using HPLC method. For enhancing percutaneous absorption, three penetration enhancers were added to the bases formulation with different concentrations. Among the evaluated formulations, the best one from view point of having better penetration profile was selected and the effect of various enhancers on penetration profile investigated. For this mean 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.
Results: The results showed that SLS (sodium louryl sulphate) and alkyl benzyl dimethyl chloride had not any significant enhancement property on penetration of MTX. Lower ability of these surfactants on drug penetration through the skin probably aroused from drug enhancer complexation and formation of micells with low penetration ability containing the drug molecules. Transcutol P was able to enhance transdermal absorption of MTX and the higher enhancement ratio was obtained with 2% (w/w) concentration of transcutol P. Adding of salicylic acid increased this ratio. Better penetration profile was shown with increasing of salicylic acid concentration.
Conclusion: prepared formulation containing transcutol p 2% (w/w) and salicylic acid 6% (w/w) had higher enhancement property and could be used clinically for local treatment of psoriasis.

 
Keyword(s): METHOTREXATE, PERCUTANEOUS ABSORPTION, PSORIASIS, ENHANCER, FORMULATION
 
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