Department of Chemical and Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem Quay 3, H-1111 Budapest, Hungary.
Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös Street 6, H-6720 Szeged, Hungary.
Carbohydr Polym. 2023 Jun 15;310:120717. doi: 10.1016/j.carbpol.2023.120717. Epub 2023 Feb 17.
Nepafenac is a highly effective NSAID used for treating postoperative ocular inflammation and pain after cataract surgery and its advantage over conventional topical NSAIDs has been proved many times. However, Nevanac® is a suspension eye drop, which clearly lacks patient compliance causing irritation, blurred vision, foreign body sensation along with problematic dosage due to its sticky, inhomogeneous consistence. In this study, nepafenac containing eye drops were prepared using hydroxypropyl-β-cyclodextrin to ensure complete dissolution of nepafenac, sodium hyaluronate to provide mucoadhesion and adequate viscosity and a preservative-free officinal formula, Oculogutta Carbomerae containing carbomer (just like Nevanac®), therefore providing a similar base for the new formulations. According to an experimental design, 11 formulations were tested in vitro including two reference formulations by measuring their viscosity, mucoadhesion, drug release and corneal permeability. Finally, two formulations were found promising and investigated further on porcine eyes ex vivo and corneal distribution of nepafenac was determined by RAMAN mapping. The results showed that one formulation possessed better bioavailability ex vivo than Nevanac® 0.1 % suspension, while the other formulation containing only 60 % of the original dose were ex vivo equivalent with Nevanac® opening the way to nepafenac-containing eye drops with better patient compliance in the future.
奈帕芬那酯是一种高效的 NSAID，用于治疗白内障手术后的眼部炎症和疼痛，其优势已经多次得到证实。然而，Nevanac®是一种混悬滴眼液，由于其粘性和不均匀的一致性，显然缺乏患者的依从性，导致刺激、视力模糊、异物感以及由于剂量问题而带来的不便。在这项研究中，使用羟丙基-β-环糊精来制备含有奈帕芬那酯的滴眼液，以确保奈帕芬那酯的完全溶解，使用透明质酸钠提供粘弹性和足够的粘度，并采用无防腐剂的处方制剂 Oculogutta Carbomerae，其中含有卡波姆（与 Nevanac®相似），因此为新配方提供了类似的基础。根据实验设计，对 11 种制剂进行了体外测试，包括两种参考制剂，通过测量其粘度、粘弹性、药物释放和角膜通透性。最后，发现两种制剂具有较好的应用前景，并进一步在猪眼进行了离体研究，通过拉曼图谱确定了奈帕芬那酯在角膜中的分布。结果表明，一种制剂的体外生物利用度优于 Nevanac® 0.1%混悬液，而另一种制剂仅含有 60%的原始剂量，与 Nevanac®等效，为未来含有奈帕芬那酯的滴眼液提供了更好的患者依从性的可能性。
