Terbinafine Research Articles

Antifungal activity of azoles, allylamines, and 8-hidroxiquinolines, alone and in combination, against Malassezia pachydermatis in vitro and in vivo

Malassezia pachydermatis is often reported as the causative agent of dermatitis in dogs. This study aims to evaluate the in vitro and in vivo antifungal activity of azoles and terbinafine (TRB), alone and in combination with the 8-hydroxyquinoline derivatives (8-HQs) clioquinol (CQL), 8-hydroxyquinoline-5-(n-4-chlorophenyl)sulfonamide (PH151), and 8-hydroxyquinoline-5-(n-4-methoxyphenyl)sulfonamide (PH153), against 16 M. pachydermatis isolates. Susceptibility to the drugs was evaluated by in vitro broth microdilution and time-kill assays. The Toll-deficient Drosophila melanogaster fly model was used to assess the efficacy of drugs in vivo. In vitro tests showed that ketoconazole (KTZ) was the most active drug, followed by TRB and CQL. The combinations itraconazole (ITZ)+CQL and ITZ+PH151 resulted in the highest percentages of synergism and none of the combinations resulted in antagonism. TRB showed the highest survival rates after seven days of treatment of the flies, followed by CQL and ITZ, whereas the evaluation of fungal burden of dead flies showed a greater fungicidal effect of azoles when compared to the other drugs. Here we showed for the first time that CQL is effective against M. pachydermatis and potentially interesting for the treatment of malasseziosis.

Development and in vitro characterization of the proliposome gel of terbinafine hydrochloride

The study was conducted to prepare the Proliposome Gel of Terbinafine Hydrochloride to improve the drug loading and to sustain the drug release of terbinafine hydrochloride. Proliposome gel of terbinafine hydrochloride were prepared by modified coacervation phase separation method by varying the concentrations of PC to cholesterol. The prepared proliposome gel was evaluated for its pH, viscosity, drug loading, and In vitro drug release studies. The appearance, particle size and drug entrapment of each produced formulation was also evaluated. All proliposome gel formulation made were consistent, homogenous, and white creamy gel.

Invasive fungal infections and oomycoses in cats 2. Antifungal therapy.

Invasive fungal infections (IFIs) and oomycoses (hereafter termed invasive fungal-like infections [IFLIs]) are characterised by penetration of tissues by fungal elements. The environment is the most common reservoir of infection. IFIs and IFLIs can be frustrating to treat because long treatment times are usually required and, even after attaining clinical cure, there may be a risk of relapse. Owner compliance with medication administration and recheck examinations can also decline over time. In addition, some antifungal drugs are expensive, have variable interpatient pharmacokinetic properties, can only be administered parenterally and/or have common adverse effects (AEs). Despite these limitations, treatment can be very rewarding, especially when an otherwise progressive and fatal disease is cured. In the second of a two-part article series, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties, and AEs of antifungal drugs are reviewed, and the treatment and prognosis of specific IFIs/IFLIs - dermatophytic pseudomycetoma, cryptococcosis, sino-orbital aspergillosis, coccidioidomycosis, histoplasmosis, sporotrichosis, phaeohyphomycosis, mucormycosis and oomycosis - are discussed. Part 1 reviewed the diagnostic approach to IFIs and IFLIs. Information on antifungal drugs is drawn from pharmacokinetic studies in cats. Where such studies have not been performed, data from 'preclinical' animals (non-human studies) and human studies are reviewed. The review also draws on the wider published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology. AMB (amphotericin B); FC (flucytosine); FCZ (fluconazole); ISA (isavuconazole); ITZ (itraconazole); KCZ (ketoconazole); PCZ (posaconazole); TRB (terbinafine); VCZ (voriconazole).

SOLUBILITY OPTIMIZATION OF TERBINAFINE HYDROCHLORIDE SOLID DISPERSION BY BINARY AND TERNARY METHOD

Background: In the process of drug development, the most challenging factor is poor solubility. To formulate an oral dosage form, poor solubility and bioavailability are the main challenges. Objective: The objective of this research was to increase the solubility of terbinafine hydrochloride (TBF) by formulating binary and ternary solid dispersion (SD) by different techniques. Terbinafine hydrochloride is a BCS class II drug having low solubility, poor absorption and low bioavailability. Methodology: Physical mixture (PMSD), solvent evaporation (SESD), and kneading method (KMSD) were used to improve the solubility of TBF and prepare PMSD, SESD, KMSD and ternary solid dispersion (TSD) using PVPK30 and sodium lauryl sulphate (SLS) as hydrophilic polymer and surfactant. Nine formulations were designed to formulate binary SD by varying the ratios of TBF, PVPK30 and SLS (1:1, 1:3 and 1:5). Three formulations were prepared to form TSD with varying percentage of TBF with best formulation from binary SD (5%, 10% and 15%). Entire formulations were test for solubility studies, and a formulation that exhibit maximum increased solubility was selected to prepare binary and ternary SD of TBF. Every developed formulation was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) to observe chemical interactions, crystallinity and morphological changes, respectively. Results: The results show that binary SD and TSD has increased solubility in comparison with a pure drug. Although, TSD prepared using kneading method displayed the highest drug solubility (14.48 times) as compared to pure drug. Conclusion: The research determined that the solubility of TBF increased due to increased wettability, hydrophilicity of the carrier and reduced crystallinity.

Ruthenium nanoparticles encrusted with nitrogen & sulphur magnetic quantum dots as an efficient electrochemical sensor for simultaneous determination of itraconazole and terbinafine; a dual regimen for black fungus: Magnetic solid phase micro-extraction for urine and plasma analysis

After COVID-19 pandemic, Mucormycosis (black fungus) spreads as one of its related complications, due to the decrease in immunity system after administration of COVID-19 treatment drugs. A combination therapy of Itraconazole (ITR) and Terbinafine (TEB) was proved to be effective for treatment of black fungus. A novel electrochemical sensor was designed for estimation of ITR & TEB simultaneously by square wave voltammetric (SWV) technique. The sensor was fabricated using N&S-codoped magnetic quantum dots (N,S-MQDs) and ruthenium nanoparticles (Ru NPs). The fabricated sensor was characterized by cyclic voltammetry (CV), scanning electron microscope (SEM), powder X ray diffraction (pXRD), Fourier transform-Infrared (FT-IR), Raman spectroscopy and electrochemical impedance spectroscopy (EIS). Full optimization study for various experimental and instrumental parameters, in addition to method validation following International conference on Harmonization (ICH) guidelines was achieved. A good linearity in the range of 0.5–30 μg mL−1 with limit of detection (LOD) 0.24 and 0.19 μg mL−1 for ITR and TEB, respectively were obtained. The sensor was applied for analysis of ITR and TEB simultaneously in human plasma and urine samples without any interferences by applying dispersive magnetic solid phase micro-extraction (dMSPE) technique, where excellent recovery results exceeding 95 % were achieved.

The Exploitation of pH-Responsive Eudragit-Coated Mesoporous Silica Nanostructures in the Repurposing of Terbinafine Hydrochloride for Targeted Colon Cancer Inhibition: Design Optimization, In Vitro Characterization, and Cytotoxicity Assessment.

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.

Formulation and Evaluation of Terbinafine Hydro-chloride Loaded Microsponges Gel

Background: Microsponges are porous, polymeric microspheres employed for sustained topical treatment. They may modify the release pattern, lessen adverse effects, and improve stability. Terbinafine HCL is a fungicidal allylamine derivative with a wide range of antifungal activity. It is used to treat various skin disorders like ringworm, athlete’s foot, and jock itch. Objective: The aim of the current study focuses on the development of terbinafine HCL microsponges that will release the drug in a sustained pattern to prevent side effects and then put those microsponges into a gel. Method: The quasi-emulsion solvent diffusion method was employed to develop Microsponges by using various drug: polymer ratios. Result: The results of the FTIR spectra showed that there was an absence of interaction between Terbinafine HCL and the excipients. Based on the evaluation parameter, it was found that batch MS3 showed the highest entrapment efficiency of 86.32%. Polymer EC showed better results. Microsponges and Microsponges gel showed sustained release of drug till 8 and 10 hours, respectively. The gels were shown to be stable throughout a wide temperature range, according to the stability studies. Conclusion: It was concluded that the Microsponges release the drug in a stained manner. The production process for microsponge technology has the potential to improve patient compliance with terbinafine hydrochloride microsponge gel.

In vitro Azole Susceptibility Testing of Japanese Isolates of Itraconazole-Resistant Dermatophytes.

We conducted antifungal susceptibility testing on itraconazole (ITCZ)-resistant isolates of Trichophyton interdigitale and Trichophyton rubrum collected from Japanese patients in 2021 and 2022. The aim of the present study was to determine the most effective drug against ITCZ-resistant strains of dermatophytes. In all isolates, the minimum inhibitory concentrations (MICs) were > 32 mg/l for ITCZ, < 0.03 to 0.5 mg/l for ravuconazole (RVCZ), and < 0.03 mg/l for efinaconazole (EFCZ), luliconazole (LUCZ), and terbinafine (TRBF). Thus, in tinea unguium cases with ITCZ-resistant strains, treatment should be switched to TRBF or other azoles with a stronger antifungal efficacy, such as EFCZ, LUCZ, or RVCZ, and treatment must continue until the infectious organisms are completely eliminated.

Topical Delivery of Terbinafine HCL Using Nanogels: A New Approach to Superficial Fungal Infection Treatment.

This study investigated pH-responsive Terbinafine HCL (TBH)-loaded nanogels as a new approach to treating superficial fungal infections. Acrylic acid (AA) is a synthetic monomer that was crosslinked with a natural polymer (gelatin) using a free radical polymerization technique to fabricate gelatin-g-poly-(acrylic acid) nanogels. Ammonium persulphate (APS) and N, N'-methylene bisacrylamide (MBA) were used as the initiator and crosslinker, respectively. Developed gelatin-g-poly-(acrylic acid) nanogels were evaluated for the swelling study (pH 1.2, 5, 7.4), DEE, particle size, FTIR, thermal stability (TGA, DSC), XRD, SEM, DEE, and in vitro drug release study to obtain optimized nanogels. Optimized nanogels were incorporated into 1% HPMC gel and then evaluated in comparison with Lamisil cream 1% for TBH stratum corneum retention, skin irritation, and in vitro and in vivo antifungal activity studies. Optimized nanogels (AAG 7) demonstrated a 255 nm particle size, 82.37% DEE, pH-dependent swelling, 92.15% of drug release (pH) 7.4 within 12 h, and a larger zone of inhibition compared to Lamisil cream. HPMC-loaded nanogels significantly improved the TBH skin retention percentage, as revealed by an ex vivo skin retention study, indicating the usefulness of nanogels for topical use. In vivo studies conducted on animal models infected with a fungal infection have further confirmed the effectiveness of nanogels compared with the Lamisil cream. Hence, Gelatin-g-poly-(acrylic acid) nanogels carrying poorly soluble TBH can be a promising approach for treating superficial fungal infections.

Ternary cyclodextrin systems of terbinafine hydrochloride inclusion complexes: Solventless preparation, solid-state, and in vitro characterization

Cyclodextrins (CD) are used extensively in the pharmaceutical industry to improve the water solubility and bioavailability of drugs. Preparing ternary systems by applying a third component can enhance these beneficial effects. The complexation methods of these ternary systems are the same as those of two-component complexes. These methods are solvent (co-evaporation, co-precipitation, etc.) or solventless “green” techniques (co-grinding, microwave irradiation, etc.). Using solvent-free methods is considered to be an economically and environmentally desirable technology.This study aimed to prepare ternary systems by the co-grinding method and evaluate the effect of a third component by comparing it to products obtained by solvent methods, binary systems, and marketed products. For that, we used terbinafine hydrochloride as a model drug, sulfobutyl-ether-beta-cyclodextrin as a complexation agent and 5 or 15 w/w% of polyvinylpyrrolidone K-90 (PVP) or hydroxypropyl methylcellulose (HPMC) as auxiliary components.Physicochemical evaluation (X-Ray Diffractometry, Differential Scanning Calorimetry, Thermogravimetry) showed that new solid phases were formed, while Scanning Electron Microscopy was performed to study morphological aspects of the products. Fourier transform infrared spectroscopic measurements suggested different intermolecular interactions depending on the type of polymer. In vitro dissolution studies showed beneficial effects of CD and further improvement with the applied polymers. Products showed less cell toxicity with one exception.Both polymers enhanced the physicochemical and in vitro properties, suggesting a greater bioavailability of the model drug. However, the percentage of polymers applied did not appear to be an influencing factor for these properties.

Thermo-Responsive Sol-Gel-Based Nano-Carriers Containing Terbinafine HCl: Formulation, In Vitro and Ex Vivo Characterization, and Antifungal Activity.

The current research aims to create a sol-gel-based nanocarrier containing terbinafine formulated for transdermal delivery of the drug into the skin. Sol-gel-based nanocarriers were prepared via the cold method using poloxamer-188, poloxamer-407, and distilled water. The prepared formulation was examined for pH, gelation temperature, Fourier transform infrared spectrophotometer (FTIR) analysis, thermal stability analysis, X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size analysis, zeta potential, and anti-microbial activity. The in-vitro drug release study of F1 was found to be 94%, which showed greater drug release as compared to F2 and F3. The pH of the formulation was found to be within the range applicable to the skin. The gelation temperature was detected at 28 °C. The SEM images of formulations have spotted various particles well-segregated from each other. Analysis of formulations showed a mean globule size diameter of 428 nm, zeta potential values of 0.04 mV, refractive index (1.329), and viscosity (5.94 cP). FTIR analysis confirmed various functional groups' presence in the prepared formulation. Thermal analysis has confirmed the stability of the drug within the prepared formulation. The growth of inhibition was found to be 79.2% in 60 min, which revealed that the prepared formulation has shown good permeation from the membrane. Hence, the sol-gel-based nanocarrier formulation of terbinafine was successfully developed and evaluated.

Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes.

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150nm with a narrow size distribution, the zeta potential was around + 6mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

Genomic Analysis of Antifungal Drug Resistance Induced in Trichophyton rubrum After Prolonged Culture with Terbinafine.

In this study, we induced terbinafine (TRF) resistance in a T. rubrum strain in vitro for 18months then compared the genomes of the TRF-resistant (N42-3) and TRF-susceptible wild-type (N42WT) strains to identify mutations. In the SQLE gene, N42WT had no mutation while N42-3 had a F397L mutation. We sequenced approximately 22.53Mb of the genomes of the N43WT and N42-3 strains. Other than the F397L mutation in SQLE, there were three other genetic mutations in three different genes that were found in N42-3, but not in N43WT; however, these three mutations were not detected in other TRF-resistant T. rubrum strains. From this genome sequencing analysis, the only variation that was confirmed to be associated with drug resistance in the genome of the TRF-resistant T. rubrum was a hotspot mutation in SQLE.

Long Amplification PCR (LA-PCR) Detection of Azole Resistant Trichophyton indotineae.

Trichphyton indotineae, a species newly designated in 2020 independent of T. interdigitale, comprises highly terbinafine (TRF)-resistant dermatophytosis that is epidemic in North India and spreding to worldwide. Some clinical isolates of T. indotineae have been resistance both TRF and azoles that might be caused the treatment failure. To detect the azole resistance strains, we developed a long amplification PCR (LA-PCR) detection method for the tandem repeat of the CYP51B (encoding sterol 14a-demethylase gene) in T. indotineae. Contrasting the drug susceptibility test results with the LA-PCR results confirmed a trend toward low susceptibility to azole antifungal agents in strains with amplifications of 9.5kbp or greater (3 or more copies of CYP51B). Our results suggest that the method could be detected rapidly of low-susceptibility strains to azole antifungal agents.

Evaluation of synergistic adsorption approach for terbinafine removal by cotton shell powder immobilized zerovalent copper: Adsorption kinetics and DFT simulation

Cotton shell powder (CS), nano zerovalent copper (nZVC) and cotton shell powder immobilized zerovalent copper (ZVC@CS) were evaluated for their adsorption efficiencies towards terbinafine hydrochloride (TBH), an antifungal drug. The nZVC and ZVC@CS synthesized via one pot redox precipitation method were characterized by FTIR, XRD, BET, FESEM and TGA analysis. The TGA and AAS analysis confirmed the loading of nearly 10% of nZVC on cotton shell powder in ZVC@CS. The effect of operational parameters (pH, adsorbent dose, initial drug concentration, time, etc.) determining the extent of terbinafine hydrochloride adsorption on ZVC@CS were investigated to ascertain the optimal experimental conditions to achieve maximum adsorption efficiencies. To investigate the adsorption behavior of TBH on ZVC@CS, the experimental data were fitted for five different adsorption models viz. Langmuir, Freundlich, Temkin, Redlich-Peterson and Hill isotherms. The TBH adsorption data was best fit with Hill isotherm model indicating cooperative sorption of TBH molecules on ZVC@CS surface. Among the five kinetic equations namely the pseudo-first-order (PFO), the pseudo-second-order (PSO), Elovich model, the intraparticle diffusion model, and Boyd kinetic model used to estimate the adsorption mechanism, the PFO kinetic model give best fit with a good correlation for the physisorption of TBH on ZVC@CS composite. The mechanism of the adsorption process was observed to be complex, consisting of both surface adsorption and pore diffusion. However, the Boyd plot confirms external mass transport as the rate limiting step for the adsorption of TBH on ZVC@CS. The synergistic adsorption of TBH on ZVC@CS was hypothesized, and the idea was supported by structure optimization results from DFT studies. The ZVC@CS exhibits equilibrium TBH adsorption efficiency (qmax) of 285.3 mg.g−1, significantly higher than adsorbents used in literature for the TBH removal.It is suggested that ZVC@CS may serve as sustainable adsorbents for the removal of cationic contaminants from acidic medium.

Antimicrobial evaluation of the Patchouli (Pogostemon cablin Benth.) leaf essential oil combination with standard antimicrobial compounds

Pogostemon cablin Benth's leaves, which belong to the Lamiaceae family, are used to make patchouli essential oil (PEO). Sesquiterpenes are the main compounds in essential oil. Antibacterial, antifungal, antiviral, antiemetic, and anti-inflammatory activities are just a few of the many pharmacological actions that are well-known. In this investigation, cefuroxime (CEF), moxifloxacin (MOX), clarithromycin (CLA), fluconazole (FLU), and terbinafine (TER) were combined with patchouli (Pogostemon cablin leaf essential oil). Gram-positive Staphylococcus aureus ATCC 6538, Gram-negative Escherichia coli ATCC 8739, and yeasts Candida albicans ATCC 10231, and C. tropicalis ATCC 750 were tested against all combinations. Drug interaction was given as fractional inhibitory concentrations (FIC) after combinations of the essential oils were tested for their minimum inhibitory concentrations (MIC). The checkerboard method was used to assess antimicrobial interactions, Fluconazole, terbinafine, cefuroxime, and clarithromycin combined with essential oil demonstrated an "additive effect" against Candida strains together with E. coli and S. aureus.

Linalool-Incorporated Synergistically Engineered Modified Liposomal Nanocarriers for Enhanced Transungual Delivery of Terbinafine against Onychomycosis.

This work investigates the synthesis of linalool-containing invasomes for terbinafine (TBF-IN) in order to increase the solubility, bioavailability, and nail permeability of terbinafine (TBF) for transungual administration. TBF-IN was created utilising the thin-film hydration technique, and with the Box-Behnken design (BBD), optimisation was carried out. TBF-INopt were investigated for vesicle size, zeta potential, PDI (Polydispersity index), entrapment efficiency (EE) and in vitro TBF release. In addition, nail permeation analysis, TEM (transmission electron microscopy), and CLSM (confocal scanning laser microscopy) were performed for further evaluation. The TBF-INopt exhibited spherical as well as sealed vesicles with a considerably small size of 146.3 nm, an EE of 74.23 per cent, a PDI of 0.1612, and an in vitro release of 85.32 per cent. The CLSM investigation revealed that the new formulation had better TBF nail penetration than the TBF suspension gel. The antifungal investigation demonstrated that the TBF-IN gel has superior antifungal activity against Trichophyton rubrum and Candida albicans compared to the commercially available terbinafine gel. In addition, an investigation of skin irritation using Wistar albino rats indicates that the TBF-IN formulation is safe for topical treatment. This study confirmed that the invasomal vesicle formulation is an effective vehicle for the transungual delivery of TBF for the treatment of onychomycosis.

Prevalence and Antifungal Susceptibility of Sporothrix species in Guangzhou, Southern China.

Sporotrichosis is a subcutaneous and chronic infection caused by traumatic inoculation of pathogenic sporothrix species, usually infecting the skins and subcutaneous tissues of humans and animals. However, the lack of epidemiological data required further molecular identification to describe the distribution of this fungus in our region. In this study, forty-eight clinical sporothrix isolated from Sun Yat-Sen Memorial Hospital were classified, and the susceptibility of each strain to seven antifungal agents was determined. Forty strains of S. globosa and eight strains of S. shenkshii were identified via colony morphology and PCR sequencing of calmodulin gene. Antifungal susceptibility tests of the mycelial phase in vitro showed terbinafine (TRB) and luliconazole (LULI) were the most effective, followed by itraconazole (ITZ) and amphotericin B (AMB). By contrast, voriconazole (VCZ), 5-flucytosine (5FC) and fluconazole (FCZ) have low efficacy with high MIC. Our results showed a predominantly S. globosa infection trend in southern China. Simultaneously, sporothrix is sensitive to TRB, LULI, ITZ and AMB whereas resistant to FCZ. This study firstly reports antifungal sensitivity test in vitro and epidemiological correlation analysis of sporothrix in southern China, and also the first time to find that sporothrix is sensitive to LULI.

Solubility Determination and Thermodynamic Correlation for Terbinafine Hydrochloride in Several Mono-solvents from 283.15 to 323.15 K

Solubility Determination and Thermodynamic Correlation for Terbinafine Hydrochloride in Several Mono-solvents from 283.15 to 323.15 K

Terbinafine HCl Film-Forming Spray for the Treatment of Topical Fungal Infections

Abstract: Terbinafine HCl is an allylamine used to treat fungal infections. It has substantial side effects that can be mitigated by using a topical semisolid dose form. The objective of this study was to develop a 1% Terbinafine HCl film-forming spray formulation to treat topical fungal infections. The formulation was developed by combining polymers, penetration enhancer, plasticizer, and a suitable solvent system. The central composite design with 3 independent variables and 2 dependent variables is implemented to optimize the formulation. The film-forming spray was put through its tests to assess formulation and container-related parameters such as pH, spray angle, spray pattern, density, volume delivered for one actuation and evaporation time. From the study, it was observed that the concentration of ethyl cellulose and Eudragit RSPO has a greater influence on the viscosity of the spray solution, whereas the eutectic mixture has a greater influence on the drug permeation followed by the polymers. It also tested with various fungi, and it was found that formulation showed better fungicidal activity than the marketed product achieved by triple action. The stability studies have shown that the optimized formulation was stable with temperature of 25 ± 2°C and RH 60 ± 5(six months) on the pH, viscosity and visual appearance of the formulation. The study has concluded that the formulated film-forming spray formulation is highly efficient in treating topical and transdermal fungal infections when compared to the traditional dosage forms. Keywords: Terbinafine HCl, Formulation, Fungal infection, Solid dosage forms, Ethyl cellulose.