Development of Lacosamide-loaded In-Situ Gels through Experimental Design for Evaluation of Ocular Irritation In Vitro and In Vivo.

Autor:	Çoban Ö; Republic of Turkey Ministry of Health, Turkish Medicines and Medical Devices Agency, Ankara, Türkiye. Electronic address: o.coban88@gmail.com., Pınar SG; Faculty of Pharmacy, Department of Pharmaceutical Technology, Suleyman Demirel University, Isparta, Türkiye., Polat HK; Republic of Turkey Ministry of Health, Turkish Medicines and Medical Devices Agency, Ankara, Türkiye., Gedik G; Faculty of Pharmacy, Department of Pharmaceutical Technology, Trakya University, Edirne, Türkiye., Karakuyu NF; Faculty of Pharmacy, Department of Pharmacology, Suleyman Demirel University, Isparta, Türkiye., Pezik E; Faculty of Pharmacy, Department of Pharmaceutical Technology, Erzincan Binali Yıldırım University, Erzincan, Türkiye., Ünal S; Faculty of Pharmacy, Department of Pharmaceutical Technology, Erciyes University, Kayseri, Türkiye., Mokhtare B; Faculty of Veterinary Medicine, Department of Pathology, Dicle University, Diyarbakır, Türkiye., Akşit A; Undergraduate student, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Türkiye.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2024 Dec 18. Date of Electronic Publication: 2024 Dec 18.
DOI:	10.1016/j.xphs.2024.11.027
Abstrakt:	Lacosamide (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. Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Aleyna Aksit reports financial support was provided by The Scientific and Technological Research Council of Türkiye. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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