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Development and Optimization of Itraconazole-Loaded Solid Lipid Nanoparticles for Topical Administration Using High Shear Homogenization Process by Design of Experiments: In Vitro, Ex Vivo and In Vivo Evaluation

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Abstract

The aim of present study was to develop topical itraconazole (ITZ)-loaded solid lipid nanoparticles for treatment of superficial fungal infections. Formulations were prepared using high shear homogenization process, and optimized by employing a two-step design of experiments (DoE) approach. It comprised a Taguchi experimental design for screening of ‘vital few’ factors, and a central composite experimental design for optimization. Overlay of the response surface maps for percent drug entrapment (PDE), particle size, ITZ skin retention and permeation was performed to obtain the optimized ITZ-loaded SLNs (OPT-SLNs) suspension. The optimized ITZ-loaded SLNs (OPT-SLNs) showed mean particle size of (262.92 ± 8.56 nm) and zeta potential value of 22.36 mV. Excellent drug entrapment (94.21 ± 3.35%) and skin retention of ITZ (43.03 ± 1.86 μg/cm2) was achieved by OPT-SLNs. The hydrogel formulation of OPT-SLNs exhibited good gel consistency and spreadability characteristics. Pharmacodynamic and skin sensitivity studies in standardized rodent models revealed that OPT-SLNs hydrogel was more efficacious than conventional oral and topical antifungal therapies, and also safe for topical administration. Furthermore, the histoptahological evaluation depicted complete recovery of infected rats after 14-day treatment regimen of OPT-SLNs hydrogel. The developed formulation was found to have tremendous potential to enhance ITZ activity through topical administration approach.

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Acknowledgements

The authors thank the University Grants Commission (UGC), New Delhi, for providing financial support for this work. The authors are grateful to Professor O. P. Katare and Professor Bhupinder Singh for valuable discussions related to present work. The authors also acknowledge the help of Dr. Sandeep Kumar and Professor A. K. Jana in performing in vivo studies. The present manuscript carries communication no. NIPER-H/2021/174.

Funding

The study was funded by UGC, New Delhi (Major Research Project no. F34-124–08(SR).

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Authors and Affiliations

  1. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160 014, India

    Neeraj Kumar & Shishu Goindi

  2. Department of Regulatory Affairs, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, Telangana, India

    Neeraj Kumar

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NK determined the research framework, performed the experiments, compiled and interpreted the data and drafted the manuscript. SG interpreted the data and supervised the study.

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Kumar, N., Goindi, S. Development and Optimization of Itraconazole-Loaded Solid Lipid Nanoparticles for Topical Administration Using High Shear Homogenization Process by Design of Experiments: In Vitro, Ex Vivo and In Vivo Evaluation. AAPS PharmSciTech 22, 248 (2021). https://doi.org/10.1208/s12249-021-02118-3

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