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Luliconazole Nail Lacquer for the Treatment of Onychomycosis: Formulation, Characterization and In Vitro and Ex Vivo Evaluation

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Abstract

Onychomycosis is the most common fungal infection of the nail affecting the skin under the fingertips and the toes. Currently, available therapy for onychomycosis includes oral and topical therapies, either alone or in combination. Oral antifungal medication has been associated with poor drug bioavailability and potential gastrointestinal and systemic side effects. The objective of this study was to prepare and evaluate the luliconazole nail lacquer (LCZ-NL) for the effective treatment of onychomycosis. In the current work, LCZ-NL was formulated in combination with penetration enhancers to overcome poor penetration. A 32 full factorial formulation design of experiment (DOE) was applied for optimization of batches with consideration of dependent (drying time, viscosity, and rate of drug diffusion) and independent (solvent ratio and film former ratio) variables. The optimized formulation was selected based on drying time, viscosity, and rate of drug diffusion. The optimized formulation was further evaluated for % non-volatile content assay, smoothness of flow, water resistance, drug content, scanning electron microscope (SEM), atomic force microscope (AFM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), in vitro drug release, ex vivo transungual permeation, antifungal efficacy, and stability study. The optimized LCZ-NL contained 70:30 solvent ratio and 1:1 film former ratio and was found to have ~ 1.79-fold higher rate of drug diffusion in comparison with LULY™. DSC and XRD studies confirmed that luliconazole retains its crystalline property in the prepared formulation. Antifungal study against Trichophyton spp. showed that LCZ-NL has comparatively higher growth inhibition than LULY™. Hence, developed LCZ-NL can be a promising topical drug delivery system for treating onychomycosis.

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Abbreviations

NL:

Nail lacquers

LCZ:

Luliconazole

LCZ-NL:

Luliconazole NL

AFM:

Atomic force microscope

SEM:

Scanning electron microscope

XRD:

X-ray diffraction

DSC:

Differential scanning calorimetry

T. rubrum :

Trichophyton rubrum

T. mentagrophytes :

Trichophyton mentagrophytes

USFDA:

United States Food and Drug Administration

HPC-EF:

Hydroxypropyl cellulose EF

HEF:

Hydration enhancement factor

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Acknowledgements

The authors are grateful to the Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi–221005, India, for providing the infrastructure for successful execution of the current project.

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India

    Deepa Dehari, Abhishesh Kumar Mehata, Vishnu Priya, Dharmnath Parbat, Anand Kumar Srivastava, Sanjay Singh & Ashish Kumar Agrawal

  2. Department of Microbiology, Institute of Medical Sciences (BHU), Varanasi, 221005, India

    Deepak Kumar

  3. Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, 226025, India

    Sanjay Singh

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  1. Deepa Dehari
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Contributions

Deepa Dehari: conceptualization, experimentation literature survey, original draft writing. Abhishesh Kumar Mehata: compilation of data and editing. Vishnu Priya: review and editing. Dharmnath Parbat: literature survey and editing. Deepak Kumar: helped in antimicrobial studies. Anand Kumar Srivastava: Project administration. Ashish Kumar Agrawal: Conceptualization, project administration, overall modification, and correction.

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Correspondence to Anand Kumar Srivastava or Ashish Kumar Agrawal.

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Dehari, D., Mehata, A.K., Priya, V. et al. Luliconazole Nail Lacquer for the Treatment of Onychomycosis: Formulation, Characterization and In Vitro and Ex Vivo Evaluation. AAPS PharmSciTech 23, 175 (2022). https://doi.org/10.1208/s12249-022-02324-7

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