Development of Innovative Electrospun Nepafenac-Loaded Nanofibers-based Ophthalmic Inserts

Safaa Omer; Nándor Nagy; Emőke Szőcs; Szabina Kádár; Gergely Völgyi; Balázs Pinke; László Mészáros; Gábor Katona; Anna Vincze; Péter Dormán; Zoltán Zs Nagy; György T Balogh; Adrienn Kazsoki; Romána Zelkó

doi:10.1016/j.ijpharm.2023.123554

Development of Innovative Electrospun Nepafenac-Loaded Nanofibers-based Ophthalmic Inserts

Int J Pharm. 2023 Oct 28:123554. doi: 10.1016/j.ijpharm.2023.123554. Online ahead of print.

Authors

Affiliations

¹ University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Street 7-9, H-1092 Budapest, Hungary.
² Department of Anatomy, Histology and Embryology Semmelweis University, Tűzoltó Street 58, H-1094 Budapest, Hungary.
³ Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem Rkp. 3, H-1111, Budapest, Hungary; Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre Street 9, H-1092 Budapest, Hungary.
⁴ Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre Street 9, H-1092 Budapest, Hungary.
⁵ Department of Polymer Engineering, Faculty of Mechanical Engineering, Budapest University of Technology and Economics, Műegyetem Rkp. 3, H-1111 Budapest, Hungary.
⁶ Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
⁷ Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem Rkp. 3, H-1111 Budapest, Hungary.
⁸ Department of Ophthalmology, Semmelweis University, Ma ́ria Street 39, 1085 Budapest, Hungary.
⁹ University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Street 7-9, H-1092 Budapest, Hungary. Electronic address: [email protected].
¹⁰ University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Street 7-9, H-1092 Budapest, Hungary. Electronic address: [email protected].

PMID: 39492434
DOI: 10.1016/j.ijpharm.2023.123554

Abstract

Electrospun nanofibers can be utilized to develop patient-centric ophthalmic formulations with reasonable bioavailability at the targeted site. The current study aimed to develop 0.1% w/w of nepafenac-loaded electrospun nanofibrous webs as potential candidates for ocular delivery of nepafenac with improved solubility and stability. Nine different formulations were prepared by electrospinning and investigated for morphology, physicochemical properties, drug release, cytocompatibility, and in vitro and ex vivo permeability. The scanning electron microscopy images showed fibrous samples. Fourier transform infrared spectroscopy and X-ray diffraction confirmed the polymer cross-linking and the formation of amorphous solid dispersion. All formulations showed complete and fast release of nepafenac (≤ 60 minutes), and the release followed first-order kinetics (β values for all formulations were <1). The formulations (F3, F6, and F9) showed considerable in vitro and ex vivo permeability. The Raman studies revealed comparable corneal distributions of F3 and the commercial Nevanac® suspension at 60 min (p value = 0.6433). The fibrous composition remains stable under stress conditions (40 ± 2 °C, 75 ± 5% relative humidity). The formulation composition showed good cytocompatibility with hen eggs tested on the chorioallantoic membrane of chick embryos. The developed nanofiber webs could be a promising candidate for nepafenac-loaded ophthalmic inserts. Chemical compounds studied in this article Nepafenac (PubChem CID151075); Polyvinyl alcohol (PubChem CID 11199); Poloxamer 407 (PubChem CID 24751); Chloroform (PubChem CID 6212); Methanol (PubChem CID 887); L-α-phosphatidylcholine (PubChem CID 10425706); Ethylenediaminetetraacetic acid (PubChem CID 6049).

Keywords: Nepafenac-loaded formulations; accelerated stability test; cytocompatibility study; electrospun nanofiber-based ocular insert; ex vivo permeability study; in vitro dissolution study; morphological and solid-state characterization.