Alshammari Farhan, Alshammari Bushra, Alshamari Asma Khalaf, Sarkar Kaushik, Thakur Raghu Raj Singh
Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Hail 81442, Saudi Arabia.
Medical and Diagnostic Research Center, University of Ha'il, Hail 55473, Saudi Arabia.
Pharmaceutics. 2025 Aug 17;17(8):1066. doi: 10.3390/pharmaceutics17081066.
Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study aimed to develop a sustained-release ocular insert containing bromfenac sodium (BS)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) with an initial 3% (/) free BS fraction incorporated into a poly(vinyl alcohol) (PVA) matrix designed to achieve a dual-phase release profile for improved postoperative therapy. PLGA-based MPs were fabricated using a double emulsion solvent evaporation technique and incorporated into PVA films to produce ocular inserts with varying MP content. Formulations were characterized for morphology, particle size, zeta potential, drug loading, entrapment efficiency, mucoadhesion, drug distribution, and in vitro release. Data were analyzed by an ANOVA and -tests with < 0.05 as significance. MPs were smooth, spherical, and well-dispersed in the PVA inserts. Particle sizes ranged from 3.7 to 5.6 µm, with drug loading 7-8% and entrapment efficiencies 47-52%. Multiphoton imaging confirmed uniform drug distribution. In vitro release showed a dual-phase profile with an initial burst followed by sustained release for up to 4 days, with only negligible further release through Day 6 in one formulation (M1-7525). The developed BS-loaded PLGA MP/PVA insert demonstrated a dual-phase release profile relevant to postoperative ocular inflammation. Its biodegradable, single-application design holds promise for enhancing compliance and therapeutic outcomes in ophthalmic care.
术后眼部炎症是眼科手术常见的并发症，通常使用皮质类固醇或非甾体抗炎药（NSAIDs）眼药水进行治疗。然而，眼部生物利用度差以及因频繁给药导致患者依从性差限制了传统眼药水的治疗效果。本研究旨在开发一种含有载有溴芬酸钠（BS）的聚乳酸-羟基乙酸共聚物（PLGA）微粒（MPs）的缓释眼部植入物，初始游离BS含量为3%，并将其掺入聚乙烯醇（PVA）基质中，以实现双相释放曲线，从而改善术后治疗效果。基于PLGA的MPs采用双乳液溶剂蒸发技术制备，并掺入PVA薄膜中以生产具有不同MP含量的眼部植入物。对制剂的形态、粒径、zeta电位、载药量、包封率、粘膜粘附性、药物分布和体外释放进行了表征。数据采用方差分析和t检验进行分析，以P < 0.05为显著性水平。MPs光滑、呈球形且在PVA植入物中分散良好。粒径范围为3.7至5.6 µm，载药量为7 - 8%，包封率为47 - 52%。多光子成像证实药物分布均匀。体外释放显示出双相曲线，初始有一个突释阶段，随后是长达4天的持续释放，在一种制剂（M1 - 7525）中，到第6天仅有可忽略不计的进一步释放。所开发的载有BS的PLGA MP/PVA植入物显示出与术后眼部炎症相关的双相释放曲线。其可生物降解的单剂量应用设计有望提高眼科护理中的依从性和治疗效果。
