Development of lacosamide-loaded in-situ gels through experimental design for evaluation of ocular irritation in vitro and in vivo

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dc.contributor.authorÇoban, Özlem
dc.contributor.authorPınar, Sıla Gülbağ
dc.contributor.authorPolat, Heybet Kerem
dc.contributor.authorGedik, Gülşah
dc.contributor.authorKarakuyu, Nasıf Fatih
dc.contributor.authorPezik, Esra
dc.contributor.authorÜnal, Sedat
dc.date.accessioned2025-02-22T14:10:55Z
dc.date.available2025-02-22T14:10:55Z
dc.date.issued2025
dc.departmentDicle Üniversitesien_US
dc.description.abstractLacosamide (LCM) selectively increases the slow inactivation of voltage-gated sodium channels (VGSCs) and is a N-methyl D-aspartate acid (NMDA) receptor glycine site antagonist. Therefore, it can be used in dryness-related hyperexcitability of corneal cold receptor nerve terminals. Ocular in-situ gels remain in liquid form until they reach the target site, where they undergo a sol-gel transformation in response to specific stimuli. They can show mucoadhesive properties related to the polymer used and increase the residence time of the drug in the mucosa. In the presented study, ocular in-situ gel formulation of LCM, which has potential for use in ocular diseases and consists of hyaluronic acid and poloxamer 407 as polymers, was developed using cold method. The effect of formulation components on target product properties (pH, gelation temperature and viscosity) was evaluated by design of experiments (DoE) design. The optimized LCM-loaded in-situ gel had a pH value of 6.90 ± 0.01, showed pseudo-plastic flow with a viscosity of 562 ± 58 cP at 25 °C, gelled at 33 ± 0.47 °C, and released drugs via the Peppas-Sahlin mechanism. Ocular safety was confirmed via in vitro tests using two different cell lines (L929 and Arpe-19), along with in vivo Draize tests, histological examinations, and Hen's Egg Chario-Allontioc-Membrane (HET-CAM) analysis. In vitro studies confirmed the optimized LCM-loaded in-situ gel's suitability for ocular use, demonstrating long-acting effects through controlled release. In addition, ocular irritation and histological studies have supported that it will not show any toxic effect on the eye tissue. © 2024 American Pharmacists Associationen_US
dc.identifier.doi10.1016/j.xphs.2024.11.027
dc.identifier.issn0022-3549
dc.identifier.pmid39706567en_US
dc.identifier.scopus2-s2.0-85214294958en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.xphs.2024.11.027
dc.identifier.urihttps://hdl.handle.net/11468/29876
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofJournal of Pharmaceutical Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmzKA_Scopus_20250222
dc.subjectDissolution modelsen_US
dc.subjectFactorial designen_US
dc.subjectFormulationen_US
dc.subjectHydrogelsen_US
dc.subjectOphthalmic drug deliveryen_US
dc.subjectPolymeric drug delivery systemsen_US
dc.subjectQuality by design (QBD)en_US
dc.subjectThermal gelsen_US
dc.subjectToxicologyen_US
dc.subjectViscosityen_US
dc.titleDevelopment of lacosamide-loaded in-situ gels through experimental design for evaluation of ocular irritation in vitro and in vivoen_US
dc.typeArticleen_US

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