Latanoprost-loaded cyclodextrin microaggregate suspension eye drops for enhanced bioavailability and stability

Abstract

ObjectiveThe 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. MethodsOphthalmic 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. ResultsLAT/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 AUC0–6 h, Cmax, 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 AUC0–24 h, Cmax, 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. ConclusionCyclodextrin microaggregate suspension eye drops represent a potential strategy for enhanced bioavailability and stability of LAT.