Preparation and Optimization of Itraconazole Transferosomes-Loaded HPMC Hydrogel for Enhancing Its Antifungal Activity: 2^3 Full Factorial Design

Abstract

Itraconazole (ITZ) is a triazole antifungal agent characterized by broad-spectrum activity against fungal infections. The main drawback of ITZ, when applied topically, is the low skin permeability due to the stratum corneum, the outermost layer of the skin, which represents the main barrier for drug penetration. Therefore, this study aimed to prepare itraconazole as transferosomes (ITZ-TFS) to overcome the barrier function of the skin. ITZ-TFSs were prepared by thin lipid film hydration technique using different surfactants, sodium lauryl sulfate (SLS) and sodium deoxycholate (SDC). The prepared ITZ-TFS were evaluated for entrapment efficiency (EE) %, particle size, polydispersity index (PDI), zeta potential, and in vitro drug release to obtain an optimized formula. The surface morphology of the optimized formula of ITZ-TFS was determined by transmission electron microscope (TEM). The optimized formulation was prepared in the form of gel using hydroxyl propyl methyl cellulose (HPMC) gel base. The prepared ITZ-TFS gel was evaluated for homogeneity, drug content, spreadability, pH, and in vitro antifungal activity in comparison with the free ITZ- gel. The prepared ITZ-TFS formulations exhibited high EE% ranging from 89.02 ± 1.65% to 98.17 ± 1.28% with particle size ranging from 132.6 ± 2.15 nm to 384.1 ± 3.46. The PDI for all ITZ-TFSs was less than 0.5 and had a negative zeta potential. The TEM image for the optimized formulation (ITZ-TFS4) showed spherical vesicles with a smooth surface. The prepared gels had good spreadability, pH, and acceptable drug content. ITZ-TFS gel showed higher antifungal activity than free ITZ gel as determined by zone of inhibition. ITZ was successfully prepared in form of TFSs with higher antifungal activity than the free drug.

Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis

“…These vesicles were then downsized using an ultrasonication apparatus (Heilscher UP100H, Teltow, Germany) to create unilamellar vesicles. The formulations were finally stored in a refrigerator at 4 • C until needed [25].…”

Development and Evaluation of Bigels Containing Naproxen Sodium for Topical Administration

“…Other ingredients that can be included in the composition of a hydrogel are glycerol or propylene glycol as humectants, preservative ingredients (nipagin, nipasol) and co-solvents (alcohol). For oleogels, other gelling ingredients can be used, such as Aerosil ® , white or yellow wax, dispersed in different types of oils: sunflower oil, linseed oil, almond oil and coconut oil [21][22][23][24]. In order to develop bigels, a surfactant or a mixture of surfactants should be used.…”

Itraconazole Loaded Biosurfactin Micelles with Enhanced Antifungal Activity: Fabrication, Evaluation and Molecular Simulation

“…ITZ's pharmacokinetic profile, including its dependence on gastric acidity for absorption, can lead to inconsistent drug levels in some patients, potentially impacting treatment outcomes [4]. Various attempts have been made to reduce dose-dependent toxicity of ITZ by forming nanoparticles [5], cyclodextrin complexation [6] and transferosomes [7]. After an extensive study to increase ITZ's bioavailability and enhanced activity at lower doses, a new oral formulation of ITZ-loaded micelles has been created employing biosurfactants, such as surfactin A (SA).…”