Investigation of flurbiprofen pharmacokinetics in rats following dermal administration of optimized cyclodextrin-based nanogel
European Journal of Pharmaceutical Sciences, cilt.206, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 206
- Basım Tarihi: 2025
- Doi Numarası: 10.1016/j.ejps.2025.107021
- Dergi Adı: European Journal of Pharmaceutical Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Directory of Open Access Journals
- Anahtar Kelimeler: Nanogel, Cyclodextrin, Flurbiprofen, Experimental design, Dermal, pharmacokinetic
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Purpose: The main purpose of this study was to optimize a cyclodextrin-based nanogel of flurbiprofen (FP) for prolonged dermal administration and evaluate its stability, in vitro release, ex vivo skin permeation, and in vivo pharmacokinetic profile. Methods: The nanogels were prepared via emulsification/solvent evaporation process and optimized through design of experiments. Optimal formulation was characterized via particle size (PS), polydispersity index (PDI), zeta potential (ZP), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD), solubility, stability, in vitro release/ex vivo permeation studies and mathematical modeling, and pharmacokinetic studies conducted in rats. Results were compared to HPMC-based gel that was not nano-sized (i.e.FP-HPMC gel). Results: The PS, PDI and ZP values of optimal FP-loaded nanogel were 295.5 nm, 0.361 and -31.9 mV, respectively and it was stable for 12 months. In in vitro release studies, the flux from the optimal FP-loaded nanogel (96.3 µg/hcm2) was three times slower (i.e.more controlled) than that of the FP-HPMC gel (287 µg/hcm2); the permeability coefficient of the nanogel (0.015 cm/h) was slightly less than that of FP-HPMC gel (0.046 cm/h). Rat skin studies showed FP-loaded nanogel provided higher drug retention in the skin, compared to FP-HPMC gel. Mathematical modeling from rat skin permeation showed the Hixson-Crowell model was the best fitting model for FP-loaded nanogel, suggesting surface area of the nanogel is changing during the release process. In rat pharmacokinetic studies, the FB-loaded nanogel exhibited prolonged and flatter plasma profile than the FP-HPMC gel, consistent with the higher drug retention in the skin. Conclusion: The optimized nanogel provided prolonged drug permeation and more sustained pharmacokinetic performance compared to FP-HPMC gel.