Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt.
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
Drug Deliv. 2022 Dec;29(1):2868-2882. doi: 10.1080/10717544.2022.2115164.
Loratadine (LORA), is a topical antihistamine utilized in the treatment of ocular symptoms of COVID-19. The study aimed to develop a Loratadine Nanostructured Lipid Carriers Ocugel (LORA-NLCs Ocugel), enhance its solubility, trans-corneal penetrability, and bioavailability. full-factorial design was established with 2 trials to investigate the impact of several variables upon NLCs properties. LORA-NLCs were fabricated by using hot melt emulsification combined with high-speed stirring and ultrasonication methods. All obtained formulae were assessed in terms of percent of entrapment efficiency (EE%), size of the particle (PS), zeta potential (ZP), as well as release. Via using Design Expert® software the optimum formula was selected, characterized using FTIR, Raman spectroscopy, and stability studies. Gel-based of optimized LORA-NLCs was prepared using 4% HPMC k100m which was further evaluated in terms of physicochemical properties, Ex-vivo, and In-vivo studies. The optimized LORA-NLCs, comprising Compritol 888 ATO, Labrasol, and Span 60 showed EE% of 95.78 ± 0.67%, PS of 156.11 ± 0.54 nm, ZP of -40.10 ± 0.55 Mv, and Qh6% of 99.67 ± 1.09%, respectively. Additionally, it illustrated a spherical morphology and compatibility of LORA with other excipients. Consequently, gel-based on optimized LORA-NLCs showed pH (7.11 ± 0.52), drug content (98.62%± 1.31%), viscosity 2736 cp, and Q12% (90.49 ± 1.32%). LORA-NLCs and LORA-NLCs Ocugel exhibited higher ex-vivo trans-corneal penetrability compared with the aqueous drug dispersion. Confocal laser scanning showed valuable penetration of fluoro-labeled optimized formula and LORA-NLCs Ocugel through corneal. The optimized formula was subjected to an ocular irritation test (Draize Test) that showed the absence of any signs of inflammation in rabbits, and histological analysis showed no effect or damage to rabbit eyeballs. C and the AUC were higher in LORA-NLCs Ocugel compared with pure Lora dispersion-loaded gel The research findings confirmed that NLCs could enhance solubility, trans-corneal penetrability, and the bioavailability of LORA.
洛雷他定（LORA）是一种局部抗组胺药，用于治疗 COVID-19 的眼部症状。本研究旨在开发一种洛雷他定纳米结构化脂质载体 Ocugel（LORA-NLCs Ocugel），以提高其溶解度、透角膜性和生物利用度。采用两因素试验设计建立了全因子设计，以研究几种变量对 NLCs 性质的影响。通过热熔乳化法结合高速搅拌和超声处理方法制备 LORA-NLCs。根据包封效率（EE%）、粒径（PS）、Zeta 电位（ZP）和释放度评估所有获得的配方。通过使用 Design Expert®软件选择最佳配方，使用傅里叶变换红外光谱（FTIR）、拉曼光谱和稳定性研究对其进行表征。使用 4%HPMC k100m 制备优化后的 LORA-NLCs 的凝胶制剂，并进一步评估其理化性质、离体和体内研究。包含 Compritol 888 ATO、Labrasol 和 Span 60 的优化 LORA-NLCs 的 EE%为 95.78±0.67%，PS 为 156.11±0.54nm，ZP 为-40.10±0.55Mv，Qh6%为 99.67±1.09%。此外，它显示出 LORA 与其他赋形剂的球形形态和相容性。因此，基于优化的 LORA-NLCs 的凝胶制剂显示出 pH 值（7.11±0.52）、药物含量（98.62%±1.31%）、粘度 2736cp 和 Q12%（90.49±1.32%）。与水性药物分散体相比，LORA-NLCs 和 LORA-NLCs Ocugel 显示出更高的体外透角膜性。共焦激光扫描显示，荧光标记的优化配方和 LORA-NLCs Ocugel 可通过角膜有效穿透。优化配方进行了眼刺激性试验（Draize 试验），结果表明兔子没有任何炎症迹象，组织学分析显示兔子眼球没有受到任何影响或损伤。与负载纯 Lora 的凝胶相比，LORA-NLCs Ocugel 的 C 和 AUC 更高。研究结果证实，NLCs 可以提高 LORA 的溶解度、透角膜性和生物利用度。
