INFLUENCE OF FORMULATION ON THE IN-VITRO TRANSDERMAL PENETRATION OF FLUTRIMAZOLE

Flutrimazole (1-[(2-fluorophenyl) (4-fluorophenyl)phenylmethyl]-1H-imi dazole, CAS 119006-77-8, UR-4056) is a new wide spectrum local imidazo lic antifungal agent that has already been formulated as a dermal crea m (FDC). A comparative study was carried out of the release of flutrim azole from two emulsions in which the drug has been incorporated diffe rently: one dissolved in the oily phase (E24) and the other dispersed in the aqueous formulation phase (E25). Based on the E25 formulation, two more dermal creams were prepared, E27 with benzyl alcohol and E28 with diazolidinyl urea as preservative agents. A comparative study of transdermal penetration including E27, E28, FDC (reference 1% flutrima zole dermal cream) and 1% flutrimazole hydroalcoholic solution was als o performed. An amount of the sample dosage form containing 10 mg of f lutrimazole was applied to a Franz type cell. The penetration membrane used was cellulose acetate in the release studies and human skin prov ided by a plastic surgery clinic in the transdermal penetration study. The amount released after 7 h was 36.3 +/- 4.9 mu g when flutrimazole was dissolved (E24) and 35.9 +/- 5.3 mu g when flutrimazole was dispe rsed (E25). Although the differences were not significant, the cream w ith dispersed flutrimazole was selected for further penetration studie s due to its better stability observed in previous studies. The amount s of drug penetrated after 44 h were 31.3, 41.5, 38.3 and 186.5 mu g f or E27, E28, FDC dermal creams and topical hydroalcoholic solution, re spectively. The solution showed a statistically significant difference (p < 0.05) from the other formulations, however, no differences were observed between the dermal cream formulations. No differences were ne ither obtained between the different dermal creams when the amount of drug retained in the skin was compared. This allows to assert that the excipients used do not have different influences on transdermal penet ration. In all cases, the mean quantity penetrated in relation to the dose applied was at most 0.5%. These results allow to infer that flutr imazole shows scarce transdermal penetration. Further, the amount of f lutrimazole retained per gram of skin is more than 100 times the MIC p er gram obtained in previous in vitro studies. It may be assumed that the topical application of the new formulations assayed would allow to obtain a good therapeutic response.