School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Kent ME4 4TB, United Kingdom.
School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Kent ME4 4TB, United Kingdom.
Int J Pharm. 2019 Jul 20;566:111-125. doi: 10.1016/j.ijpharm.2019.05.059. Epub 2019 May 23.
Thin and erodible polymeric films were developed as potential ocular drug delivery systems to increase drug retention on the eye with the aim of improving bioavailability and achieving controlled drug release. Two biocompatible film forming polymers, hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC), which are currently used as thickening agents in eye drops were employed. Two different films were prepared (i) as single polymer and (ii) as composite formulations by solvent casting method, incorporating glycerol (GLY) as plasticizer and timolol maleate (TM) as model glaucoma drug. After preliminary optimization of transparency and ease of handling, the formulations were further characterized for their physicochemical properties. No indication of significant drug-polymer or polymer-polymer (in composite films) interaction was observed from FTIR results while evaluation by IR mapping revealed uniform distribution of drug throughout the films. Amorphization of TM in the film matrix was confirmed by both DSC and XRD. Swelling studies illustrated remarkable swelling capacity of HA in comparison with HPMC which directly affected the drug release profiles, making HA a suitable polymer for controlled ocular drug delivery. Tensile and mucoadhesion properties confirmed higher elasticity and adhesiveness of HA while HPMC produced stronger films. The effect of sterilization by UV radiation on mechanical properties was also evaluated and showed no significant difference between the sterilized and non-sterilized films. The SEM results confirmed smoothness and homogeneity of film surfaces for all the formulations studied. The in vitro drug dissolution studies showed more extended release profiles of formulations containing HA. Cytotoxicity study (cell viability) using MTT assay on HeLa cells, confirmed that the single polymer and composite films are generally safe for ocular administration. The present work shows excellent film forming ability of HA and HPMC which can be used as single polymer or combined in composite formulations as potential topical ocular drug delivery platform to enhance drug retention on the ocular surface and therefore potential improved bioavailability.
研制了薄而可蚀的聚合物薄膜，作为潜在的眼部药物传递系统，以增加药物在眼部的滞留时间，从而提高生物利用度并实现药物的控制释放。选用两种生物相容性成膜聚合物，透明质酸 (HA) 和羟丙基甲基纤维素 (HPMC)，它们目前被用作滴眼液中的增稠剂。采用溶剂浇铸法制备了两种不同的薄膜：(i) 单一聚合物，(ii) 复合配方，其中包含甘油 (GLY) 作为增塑剂和马来酸噻吗洛尔 (TM) 作为模型青光眼药物。在初步优化透明度和易于处理后，进一步对配方的物理化学性质进行了表征。FTIR 结果表明，没有明显的药物-聚合物或聚合物-聚合物（在复合膜中）相互作用的迹象，而 IR 映射评估表明药物均匀分布在整个膜中。DSC 和 XRD 均证实 TM 在膜基质中发生无定形化。溶胀研究表明，HA 的溶胀能力明显高于 HPMC，这直接影响药物释放曲线，使 HA 成为适合控制眼部药物传递的聚合物。拉伸和黏膜粘附性能证实了 HA 具有更高的弹性和粘附性，而 HPMC 则产生更强的膜。还评估了 UV 辐射灭菌对机械性能的影响，结果表明，灭菌和非灭菌膜之间没有显著差异。SEM 结果证实了所有研究配方的膜表面的光滑度和均一性。体外药物溶解研究表明，含有 HA 的制剂具有更延长的释放曲线。使用 MTT 测定法对 HeLa 细胞进行的细胞毒性研究（细胞活力）证实，单一聚合物和复合膜通常可安全用于眼部给药。本工作表明 HA 和 HPMC 具有出色的成膜能力，可作为单一聚合物或组合在复合配方中用作潜在的局部眼部药物传递平台，以增强药物在眼部表面的滞留，从而潜在提高生物利用度。
