Quality by Design Guided Development of Polymeric Nanospheres of Terbinafine Hydrochloride for Topical Treatment of Onychomycosis Using a Nano-Gel Formulation

Vinam Puri; Anna Froelich; Parinbhai Shah; Shernelle Pringle; Kevin Chen; Bozena Michniak-Kohn

doi:10.3390/pharmaceutics14102170

Quality by Design Guided Development of Polymeric Nanospheres of Terbinafine Hydrochloride for Topical Treatment of Onychomycosis Using a Nano-Gel Formulation

Pharmaceutics. 2022 Oct 12;14(10):2170. doi: 10.3390/pharmaceutics14102170.

Authors

Vinam Puri^{1

2}, Anna Froelich³, Parinbhai Shah^{1

2}, Shernelle Pringle⁴, Kevin Chen^{1

2}, Bozena Michniak-Kohn^{1

2}

Affiliations

¹ Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA.
² Center for Dermal Research, Life Science Building, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
³ Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.
⁴ Department of Biomedical Sciences, School of Graduate Studies, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA.

Abstract

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.

Keywords: antifungal nanospheres; design of experiments; onychomycosis; quality by design; terbinafine; topical formulation; ungual drug delivery.

Grants and funding

Part of the studies as well as the Graduate Assistantship for Vinam Puri were funded by the Center for Dermal Research CDR at Rutgers, The State University of New Jersey. Anna Froelich was funded by the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no. 778051 and the Ministry of Science and Higher Education of Poland fund for supporting internationally co-financed projects in 2018–2022 (agreement no. 3899/H2020/2018/2).