Optimizing fluconazole-embedded transfersomal gel for enhanced antifungal activity and compatibility studies

Abstract

Fungal infections are of major concern all over the globe, and fluconazole is the most prevalently used drug to treat it. The goal of this research work was to formulate a fluconazole-embedded transfersomal gel for the treatment of fungal infections. A compatibility study between fluconazole and soya lecithin was performed by differential scanning calorimetry (DSC). Transfersomes were formulated by a thin-film hydration technique using soya lecithin and Span 80. A central composite design was adopted to prepare different formulations. Soya lecithin and Span 80 were chosen as independent variables, and the effect of these variables was studied on in vitro drug diffusion. Formulations were evaluated for entrapment efficiency and in vitro drug diffusion. The results of in vitro drug diffusion were analyzed using the analysis of variance (ANOVA) test. Optimized formulation was prepared based on the overlay plot and evaluated by scanning electron microscopy, DSC, vesicle size, polydispersity index (PDI), zeta potential, and in vitro drug diffusion studies. An optimized formulation was loaded into xanthan gum gel base and evaluated for pH, viscosity, in vitro and ex vivo drug diffusion, and antifungal activity. DSC studies revealed compatibility between fluconazole and soya lecithin. Entrapment efficiency and in vitro drug diffusion of various formulations ranged between 89.92% ± 0.20% to 97.28% ± 0.42% and 64% ± 1.56% to 85% ± 2.05%, respectively. A positive correlation was observed between in vitro drug diffusion and Span 80; conversely, a negative correlation was noted with soya lecithin. Entrapment efficiency, particle size, zeta potential, PDI, and drug diffusion of optimized formulation were 95.0% ± 2.2%, 397 ± 2 nm, -38 ± 5 mV, 0.43%, and 81 % ± 2%, respectively. SEM images showed well-distributed spherical-shaped transfersomes. In vitro, ex vivo drug diffusion and antifungal studies were conclusive of better diffusion and enhanced antifungal potential fluconazole in transfersomal formulation.

Keywords: ex-vivo studies; fluconazole; topical application; transfersomal gel; transfersomes.

FIGURE 1

DSC thermogram of (A) fluconazole showed sharp melting at 139.6°C. (B) Soya lecithin indicated sharp melting at 172.1°C and 247.4°C. (C) Physical mixture revealing melting of the drug at 138°C, suggestive of intactness of the drug in the presence of soya lecithin.

FIGURE 2

Drug entrapment efficiency of various formulations of transfersomes representing good entrapment of fluconazole in vesicles.

FIGURE 3

In vitro diffusion of fluconazole from various transfersomal formulations for 7 h depicting the impact of soya lecithin and Span 80 on diffusion of fluconazole.

FIGURE 4

(A) Contour plot, (B) 3D surface plot, (C) and overlay plot, indicative of factors affecting drug diffusion and the optimum concentration of soya lecithin and Span 80 for desired drug diffusion.

FIGURE 5

Characterization of optimized transfersomes: a scanning electron microscopy study on uniform distribution and spherical morphology for effective vesicular drug delivery.

FIGURE 6

(A) Particle size and PDI suggestive of mono-dispersed microscopic particles. (B) Zeta potential of optimized formulation −38 ± 5 mV revealing stable and dispersed particles.

FIGURE 7

DSC thermogram of the optimized formulation indicating the peak at 102.89°C, suggestive of reduction in the melting point of the drug, owing to solubilization in the lipid phase and surfactant.

FIGURE 8

In vitro diffusion of transfersomes loaded for the optimized formulation showed drug release up to 7 h.

FIGURE 9

Evaluation parameters for the transfersomal gel. (A) In vitro drug diffusion from gel formulations for 7 h. (B) Ex vivo drug diffusion from gel formulations for 7 h. (C) Texture analysis profile of the transfersomal gel. (D) Texture analysis profile of the marketed gel showed better spreadability of the transfersomal gel. (E) Zone of inhibition for the transfersomal gel was 30 ± 0.9 mm. (F) Zone of inhibition for the marketed gel was 20 ± 1.2 mm, indicating more antimicrobial potential of the transfersomal gel.