Preparation of Topical Itraconazole with Enhanced Skin/Nail Permeability and In Vivo Antifungal Efficacy against Superficial Mycosis

Abstract

In this study, a stable and highly skin-permeable topical delivery system for itraconazole (ITZ) was designed to provide effective treatment against superficial mycosis. Herein, ITZ was incorporated into a solution composed of ethanol, benzyl alcohol, hydrochloric acid, Transcutol P, and cyclomethicone as a delivery vehicle, solubilizer, protonating agent, permeation enhancer, and spreading agent, respectively. At 72 h, the optimal topical ITZ formulation (ITZ–TF#11) exhibited 135% enhanced skin permeability, which led to increases in drug deposition in the stratum corneum, epidermis, and dermis of 479%, 739%, and 2024%, respectively, compared with the deposition of 1% ITZ in ethanol (control). Moreover, on day 7, ITZ–TF#11 demonstrated 2.09- and 2.30-fold enhanced nail flux and drug deposition, compared with the control. At a dose of 40 mg/kg/day, ITZ–TF#11 showed 323% greater lesion recovery, a 165% lower mean erythema severity score, and a 37% lower mean logarithm of viable fungal cells in skin in the treated area, compared with mice that received oral ITZ at the same dose. Overall, the findings imply that ITZ–TF#11 is a superior alternative to oral ITZ for treatment of superficial mycosis.

Preparation of topical bimatoprost with enhanced skin infiltration and in vivo hair regrowth efficacy in androgenic alopecia

“…BIM–TF#5), the permeability of BIM up to 10 h was significantly increased, by 92.3%, compared to that of BIM–TF#4, resulting in 7.61-, 3.07-, and 1.71-fold greater flux than BIM in ethanol, BIM–TF#1, and BIM–TF#4, respectively ( Figure 1(C) ). However, no further penetration-enhancing effect was achieved by increasing the concentrations of Transcutol P or cyclomethicone, which may be due to a decrease in drug partition into the skin caused by the water absorption properties of Transcutol P, resulting in changes in drug solubility and thermodynamic activity (Björklund et al., 2016 ; Subedi et al., 2021 ).…”

Formulation and Development of Adapalene Topical Nanohydrogel Using Different Surfactants and Cosurfactants for Antiacne Activity: In Vitro and Ex Vivo Evaluation

“…Then, mobile phase is composed of acetonitrile, tetrahydrofuran, trifluoroacetic acid, and water (43 : 36 : 0.02 : 21v/v) in addition to injection volume and flow that rate were 20 μL and 1 mL/min, respectively [16]. Moreover, in this study, the calibration curve of ADP was prepared by injecting different concentrations of ADP (16,18,20,22, and 24 μg/mL) in HPLC according to the method described above. Finally, the coefficient correlation (R 2 ), slope, and intercept were calculated.…”

“…Then, NH solution containing 1 g was poured on the SC part in the donor section. The stirring was done at 600 rpm in the acceptor region and heated to ensure the maintenance of the surface at 32 ± 0:5 °C until the completion of the experiment [22]. Then, 300 μL of sample solution was withdrawn from the diffusion cell of the receiver compartment at different durations including 1, 3, 6, 9, 12, and 24 hours, and the volume was adjusted by adding the same volume of freshly prepared PBS (pH 7.4).…”

Assessment of antifungal efficacy of itraconazole loaded aspasomal cream: comparative clinical study

“…Accordingly, formulating ITZ in appropriate topical nano-sized delivery systems is imperatively demanded. Referring to recent literature, some studies designed dermally oriented ITZ loaded nanocarriers (Passos et al., 2020 ; Kumar & Goindi, 2021 ; Qumber et al., 2021 ; Subedi et al., 2021 ). Despite their encouraging results, none of these works support clinically their findings.…”