Zhou Xiangying, Li Xiaolin, Xu Jiangmin, Cheng Yanju, Cao Feng
Department of Pharmaceutical, School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China.
Department of Biologics R&D Center, Chia Tai Tianqing Pharmaceutical Group Co. Ltd., No. 1099 Fuying Road, Jiangning District, Nanjing 211122, China.
Eur J Pharm Sci. 2021 May 1;160:105758. doi: 10.1016/j.ejps.2021.105758. Epub 2021 Feb 12.
The bioavailability of conventional eye drops is very low due to different physiological barriers. Commercial latanoprost (LAT) eye drops (Xalatan®) need to be refrigerated and protected from light. The purpose of this study was to develop novel LAT eye drops to improve ocular bioavailability and stability.
Ophthalmic suspension containing LAT/γ-cyclodextrin (γCD) aggregates was designed and the preparation process was sufficiently studied. The prepared formulations were evaluated for pH, viscosity, osmolality, particle size, entrapment efficiency and in vitro release study. In vitro permeability study using Human Corneal Epithelial Cells and in vivo studies on rabbits were also performed.
LAT/γCD aggregates were formed and confirmed by scanning electron microscopy. LAT/γCD eye drops showed obvious sustained release profiles and were more stable than Xalatan®. In vitro corneal permeation study indicated LAT/γCD eye drops had no significant cytotoxicity and had higher cell permeability. In vivo precorneal retention study showed AUC , C, and mean residence time (MRT) of LAT/γCD eye drops were 3.98, 2.12, and 2.07 times higher than those of Xalatan®, respectively. In vivo ocular distribution study revealed that AUC , C, and MRT for latanoprost acid in aqueous humor exhibited 2.60-fold, 1.36-fold, and 1.99-fold increase in LAT/γCD eye drops group than those of Xalatan® group, respectively.
Cyclodextrin microaggregate suspension eye drops represent a potential strategy for enhanced bioavailability and stability of LAT.
由于存在不同的生理屏障，传统眼药水的生物利用度非常低。市售的拉坦前列素（LAT）眼药水（适利达®）需要冷藏并避光保存。本研究的目的是开发新型LAT眼药水，以提高眼部生物利用度和稳定性。
设计了含有LAT/γ-环糊精（γCD）聚集体的眼用混悬剂，并对其制备工艺进行了充分研究。对制备的制剂进行pH值、粘度、渗透压、粒径、包封率和体外释放研究。还进行了使用人角膜上皮细胞的体外渗透研究以及对兔子的体内研究。
通过扫描电子显微镜证实形成了LAT/γCD聚集体。LAT/γCD眼药水显示出明显的缓释特性，并且比适利达®更稳定。体外角膜渗透研究表明，LAT/γCD眼药水没有明显的细胞毒性，并且具有更高的细胞渗透性。体内角膜前滞留研究表明，LAT/γCD眼药水的AUC、C和平均驻留时间（MRT）分别比适利达®高3.98倍、2.12倍和2.07倍。体内眼部分布研究显示，LAT/γCD眼药水组房水中拉坦前列素酸的AUC、C和MRT分别比适利达®组增加了2.60倍、1.36倍和1.99倍。
环糊精微聚集体混悬剂眼药水是提高LAT生物利用度和稳定性的一种潜在策略。
