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Background: Nanostructured lipid carriers (NLCs) are emerging as the second generation of lipid nanoparticles to solve the shortcomings of the first generation (structured lipid carriers). Terbinafine hydrochloride is used to treat various fungal skin diseases. Objectives: The study’s main objective was to study the drug release and permeation between NLC and NLC-based gel formulation to select the better one. Methods: A central composite face-cantered (α=1) design with two components (the amount of liquid lipid and the homogenization speed) and 13 runs were used through Design-Expert® software (version 7.1.5). Terbinafine hydrochloride-loaded NLC (TH_NLC) was produced by using the hot-homogenization technique. Fourier transform infrared study was done to determine drug excipients’ compatibility. Dynamic light scattering (DLS) was employed to determine particle size. Utilizing scanning electron microscopy (SEM), the morphology and shape of the TH_NLC formulation were examined. The hydrogel was filled with the optimized products chosen by point prediction in design expert software. These products were assessed by their pH, spreadability, viscosity, homogeneity, extrudability, and drug content. The in vitro drug release study and the ex vivo permeation investigation for the optimized TH_NLCopt and TH_NLCopt gel formulation were carried out using Franz diffusion cells Results: The formulation contains nanoscale particles, as evidenced by the size range of the particles (17.57 to 329.4 nm). Entrapment efficiency was 60.95% and 98% for TH_NLCopt TH_NLCopt gel, respectively. Within 7 hours, 96.35% and 83.37% of the drug were released from optimized NLC and NLC-based gel, respectively. The amount of drug that had penetrated the skin in 7 hours ranged from 54.19% to 31.16%, with a retention range of 22.46% to 61.87%. Conclusion: The topical delivery of the TH_NLC-based gel system is quite promising.

In this article, formulation studies for terbinafine hydrochloride nanoemulsions, prepared by high-energy ultrasonication technique, are described. Pseudo-ternary phase diagram was constructed in order to find out the optimal ratios of oil and surfactant/co-solvent mixture for nanoemulsion production. Clove and olive oils were selected as oil phase. Based on the droplet size evaluation, maximum nanoemulsion region were determined for formulation development. Further characterization included polydispersity index (PDI), zeta potential, Fourier transform infrared (FT-IR) spectroscopy, morphology, pH, viscosity, refractive index, ex vivo skin permeation, skin irritation, and histopathological examination. Droplet sizes of optimized formulations were in colloidal range. PDI values below 0.35 indicated considerably homogeneous nanoemulsions. Zeta potential values were from 13.2 to 18.1 mV indicating good stability, which was also confirmed by dispersion stability studies. Ex vivo permeation studies revealed almost total skin permeation of terbinafine hydrochloride from the nanoemulsions (96–98%) in 6 hours whereas commercial product reached only 57% permeation at the same time. Maximum drug amounts were seen in epidermis and dermis layers. Skin irritation and histopathological examination demonstrated dermatologically safe formulations. In conclusion, olive oil and clove oil-based nanoemulsion systems have potential to serve as promising carriers for topical terbinafine hydrochloride delivery.

Targeted drug delivery is achieving great success in cancer therapy due to its potential to deliver drugs directly to the action site. Terbinafine hydrochloride (TER) is a broad-spectrum anti-fungal drug that has been found to have some potential anti-tumor effects in the treatment of colon cancer. We aimed here to design and develop pH-sensitive Eudragit (Eud)-coated mesoporous silica nanostructures (MSNs) to control drug release in response to changes in pH. The diffusion-supported loading (DiSupLo) technique was applied for loading TER into the MSNs. The formulation was optimized by a D-optimal design, which permits the concurrent assessment of the influence of drug/MSN%, coat concentration, and MSN type on the drug entrapment efficiency (EE) and its release performance. The optimal formula displayed a high EE of 96.49%, minimizing the release in pH 1.2 to 16.15% and maximizing the release in pH 7.4 to 78.09%. The cytotoxicity of the optimal formula on the colon cancer cells HT-29 was higher than it was with TER alone by 2.8-fold. Apoptosis in cancer cells exposed to the optimum formula was boosted as compared to what it was with the plain TER by 1.2-fold and it was more efficient in arresting cells during the G0/G1 and S stages of the cell cycle. Accordingly, the repurposing of TER utilizing Eud/MSNs is a promising technique for targeted colon cancer therapy.

Topical antifungals may be considered to treat onychomycosis with minimal risk of systemic side effects. In this study, we assess the safety, tolerability, systemic exposure, and pharmacokinetic characteristics of topical terbinafine hydrochloride 10% solution (MOB015B) in adults with moderate-to-severe onychomycosis. Clinically and mycologically confirmed patients with toenail onychomycosis ( N = 20) were enrolled in this single-center, open-label study . Each patient had ≥50% involvement of both great toenails and at least four additional toenails affected. MOB015B was applied once daily to all toenails for 28 days. Blood was drawn on days 1, 14, and 28. Plasma concentrations of MOB015B after the first dose were quantifiable in all subjects by 24 h. Steady-state levels in plasma were reached by day 28. The mean systemic exposure on day 28 of 0.72 ng/mL for maximum plasma concentration (C max ) was approximately 2,000 times lower than the mean plasma level of 1.39 µg/mL seen after oral administration of 250 mg terbinafine for 28 days. Adverse events (five patients), such as headache ( n = 3), seasonal allergy ( n = 1), and neck pain ( n = 1), were considered unrelated to MOB015B; no application site reactions or study discontinuations due to an adverse event were observed. MOB015B applied to all affected toenails under maximal usage conditions for 28 days demonstrated very low levels of terbinafine in plasma (C max <1 ng/mL after 28 days), consistent with a favorable safety and tolerability profile., Clinical Trials: This study is registered with ClinicalTrials.gov as NCT03244280., Competing Interests: A.T. is an employee of Moberg Pharma, who funded the study and manufactures the product. J.C.D. and A.K.G. have no conflicts of interest to declare.

This article presents the findings of a clinical trial that compared the effectiveness of two antifungal creams, ciclopirox olamine and terbinafine hydrochloride, in treating dermatophytosis. The study involved 60 patients with tinea corporis, tinea cruris, or tinea faciei, who were divided into three groups and treated with different creams for 6 weeks. The results showed that both creams were effective in treating the condition, but the combination therapy of both creams had a better response and lower relapse rate. The study acknowledges its limitations, such as a small sample size and short follow-up period, but concludes that the combination therapy is effective with no significant side effects. [Extracted from the article]

Aim/Background: According to estimates, about a billion people in the world have fungal infections of the skin, nails, and hair. Skin disorders are a significant contributor to disability, deformity, and misery among people. In the present study, a versatile vesicular delivery of terbinafine hydrochloride through the dermal route in a biocompatible platform consisting of glycerine, phospholipids, and cholesterol is proposed for the treatment of mycoses. Materials and Methods: The glycerosomes of terbinafine hydrochloride were formulated by thin film hydration technique using central composite design to explore the composition effects on the formation of nanosized stable glycerosomes and drug loading. The optimized formulation was evaluated for deformability, antifungal activity, compatibility by FTIR, surface morphology, in vitro and ex vivo drug diffusion, skin irritation, histopathology, and cytotoxicity studies on HaCaT cell lines. Results: Numerical optimization of the design revealed that the particle size and entrapment efficiency of the drug were remarkably affected by the composition. Surface imaging by TEM revealed the formation of well-defined vesicles with no aggregation. The elasticity of the vesicles was established by determining their deformability index. The in vitro and ex vivo drug release study revealed better permeation of the drug compared to the marketed formulation. The histopathology and cytotoxicity study conceded the suitability of the glycerosomal carrier system for the transdermal delivery of terbinafine hydrochloride. Conclusion: Hence it can be concluded that the glycerosomes of terbinafine hydrochloride possess a potential formulation approach for treating dermal infection. [ABSTRACT FROM AUTHOR]

Superficial fungal diseases of the skin and nails are an increasingly common occurrence globally, requiring effective topical treatment to avoid systemic adverse effects. Polymeric nanoparticles have demonstrated sustained and effective drug delivery in a variety of topical formulations. The aim of this project was to develop polymeric antifungal nanospheres containing terbinafine hydrochloride (TBH) to be loaded into a hydrogel formulation for topical nail drug delivery. A quality by design (QbD) approach was used to achieve optimized particles with the desired quality target product profile (QTPP). Polyvinyl alcohol (PVA) at 2% w/v and a drug to polymer ratio of 1:4, together with a robust set of processes and material attributes, resulted in nanoparticles of 108.7 nm with a polydispersity index (PDI) of 0.63, 57.43% recovery, and other desirable characteristics such as zeta potential (ZP), particle shape, aggregation, etc. The nanospheres were incorporated into a carbomer-based gel, and the delivery of TBH through this formulation was evaluated by means of in vitro drug release testing (IVRT) and ex vivo nail permeation study. The gel containing the TBH nanospheres demonstrated a slower and controlled drug release profile compared with the control gel, in addition to a more efficient delivery into the nail. These antifungal nanospheres can be utilized for topical therapy of a multitude of superficial fungal infections.

Molecular complexation with cyclodextrins (CDs) has long been a known process for modifying the physicochemical properties of problematic active pharmaceutical ingredients with poor water solubility. In current times, the focus has been on the solvent-free co-grinding process, which is an industrially feasible process qualifying as a green technology. In this study, terbinafine hydrochloride (TER), a low solubility antifungal drug was used as a model drug. This study aimed to prepare co-ground products and follow through the preparation process of the co-grinding method in the case of TER and two amorphous CD derivatives: (2-hydroxypropyl)-β-cyclodextrin (HPBCD); heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB). For this evaluation, the following analytical tools and methods were used: phase solubility studies, differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), hot-stage X-ray powder diffractometry (HOT-XRPD), Fourier-transform infrared (FT-IR), Raman spectroscopy, and Scanning Electron Microscopy (SEM). Furthermore, in vitro characterization (dissolution and diffusion studies) was performed in two kinds of dissolution medium without enzymes. In the XRPD and SEM studies, it was found that the co-grinding of the components resulted in amorphous products. FT-IR and Raman spectroscopies confirmed the formation of an inclusion complex through the unsaturated aliphatic chain of TER and CDs. In vitro characterization suggested better dissolution properties for both CDs and decreased diffusion at higher pH levels in the case of HPBCD.