Djayet Celia, Bremond-Gignac Dominique, Touchard Justine, Secretan Philippe-Henri, Vidal Fabrice, Robert Matthieu P, Daruich Alejandra, Cisternino Salvatore, Schlatter Joël
Assistance Publique-Hôpitaux de Paris, AP-HP, Hôpital Universitaire Necker-Enfants Malades, Service de Pharmacie, Université de Paris, 75015 Paris, France.
Assistance Publique-Hôpitaux de Paris, AP-HP, Hôpital Universitaire Necker-Enfants Malades, Service d'ophtalmologie, CRMR OPHTARA, Université de Paris, 75015 Paris, France.
Pharmaceutics. 2020 Dec 22;13(1):7. doi: 10.3390/pharmaceutics13010007.
Congenital aniridia is a rare and severe panocular disease characterized by a complete or partial iris defect clinically detectable at birth. The most common form of aniridia occurring in around 90% of cases is caused by PAX6 haploinsufficiency. The phenotype includes ptosis, nystagmus, corneal limbal insufficiency, glaucoma, cataract, optic nerve, and foveal hypoplasia. Ataluren eye drops aim to restore ocular surface PAX6 haploinsufficiency in aniridia-related keratopathy (ARK). However, there are currently no available forms of the ophthalmic solution. The objective of this study was to assess the physicochemical and microbiological stability of ataluren 1% eye drop in preservative-free low-density polyethylene (LDPE) bottle with an innovative insert that maintains sterility after opening. Because ataluren is a strongly lipophilic compound, the formulation is complex and involves a strategy based on co-solvents in an aqueous phase or an oily formulation capable of totally dissolving the active ingredient. The visual aspect, ataluren quantification by a stability-indicating chromatographic method, and microbiological sterility were analyzed. The oily formulation in castor oil and DMSO (10%) better protects ataluren hydrolysis and oxidative degradation and permits its complete solubilization. Throughout the 60 days period, the oily solution in the LDPE bottle remained clear without any precipitation or color modification, and no drug loss and no microbial development were detected. The demonstrated physical and microbiological stability of ataluren 1% eye drop formulation at 22-25 °C might facilitate clinical research in aniridia.
先天性无虹膜是一种罕见且严重的全眼球疾病，其特征为出生时临床可检测到的完全或部分虹膜缺损。无虹膜最常见的形式（约90%的病例）由PAX6单倍体不足引起。其表型包括上睑下垂、眼球震颤、角膜缘功能不全、青光眼、白内障、视神经和黄斑发育不全。阿他芦胺滴眼液旨在恢复无虹膜相关角膜病变（ARK）中眼表的PAX6单倍体不足。然而，目前尚无该眼药水的可用剂型。本研究的目的是评估1%阿他芦胺滴眼液在不含防腐剂的低密度聚乙烯（LDPE）瓶中的物理化学和微生物稳定性，该瓶带有一种创新的插入物，打开后可保持无菌状态。由于阿他芦胺是一种强亲脂性化合物，其制剂复杂，涉及基于水相共溶剂或能够完全溶解活性成分的油性制剂的策略。分析了其外观、通过稳定性指示色谱法对阿他芦胺的定量以及微生物无菌性。蓖麻油和二甲基亚砜（10%）中的油性制剂能更好地保护阿他芦胺水解和氧化降解，并使其完全溶解。在整个60天期间，LDPE瓶中的油性溶液保持澄清，无任何沉淀或颜色变化，未检测到药物损失和微生物生长。1%阿他芦胺滴眼液制剂在22 - 25°C下所显示的物理和微生物稳定性可能有助于先天性无虹膜的临床研究。
