Study of In Vitro Drug Release and Percutaneous Absorption of Fluconazole from Topical Dosage Forms

Abstract

Abstract. The present study aimed to evaluate different dosage forms, emulsions, emulgels, lipogels, and thickened microemulsion-based hydrogel, as fluconazole topical delivery systems with the purpose of determining a formulation with the capacity to deliver the whole active compound and maintain it within the skin so as to be considered a useful formulation either for topical mycosis treatment or as adjuvant in a combined therapy for Cutaneous Leishmaniasis. Propylene glycol and diethyleneglycol monoethyl ether were used for each dosage form as solvent for the drug and also as penetration enhancers. In vitro drug release after application of a clinically relevant dose of each formulation was evaluated and then microemulsions and lipogels were selected for the in vitro penetration and permeation study. Membranes of mixed cellulose esters and full-thickness pig ear skin were used for the in vitro studies. Candida albicans was used to test antifungal activity. A microemulsion containing diethyleneglycol monoethyl ether was found to be the optimum formulation as it was able to deliver the whole contained dose and enhance its skin penetration. Also this microemulsion showed the best performance in the antifungal activity test compared with the one containing propylene glycol. These results are according to previous reports of the advantages of microemulsions for topical administration and they are very promising for further clinical evaluation.

Development and Evaluation of New Microemulsion-Based Hydrogel Formulations for Topical Delivery of Fluconazole

“…Additionally, it is important to point out that there are few previous published studies regarding the in vitro fluconazole permeation through pig ear skin from topical dosage forms (45).…”

“…In order to overcome this inconvenience, topical treatment of dermatomycosis using a drug delivery system, which localises the fluconazole at the level of the skin has been recommended. Over the last years, different dosage forms including lipogels, amphiphilogels, hydrogels, emulsions, microemulsions, emulgels, microemulsion gels and liposomal gels have been investigated as vehicles for topical delivery of fluconazole (39)(40)(41)(42)(43)(44)(45)(46)(47).…”

“…formulations 5, 7 and 8) have been shown to be a suitable/appropriate dosage form for fluconazole dermal penetration in comparison with conventional hydrogel, their antifungal effect was not enhanced most probably because of the influence of the excipients used in formulation. It was reported that in vitro antifungal activity of fluconazole in microemulsions was reduced by the presence of propyleneglycol in the formulation (45). However, it is necessary to remark that propyleneglycol is frequently used in the formulation of topical products containing azole derivatives (e.g.…”

Design Development and Evaluation of Topical Microemulsion

“…Increasing magnification, Bright field imaging modes were used find the type and size [30][31] of the microemulsion. In order to perform the TEM an observation, the microemulsion was diluted with distilled water (1/100).…”

“…Franz diffusion apparatus having an effective diffusion [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] area of 3.14 cm 2 receptor volume was 20 ml were employed for the permeation study. The optimized skin was placed at 25 o C for 30 minutes before conducting the experiment.…”