Box-Behnken设计
色谱法
Zeta电位
多佐酰胺
阳离子聚合
材料科学
响应面法
超声
化学
纳米技术
眼压
眼科
高分子化学
医学
纳米颗粒
噻吗洛尔
作者
Ahmed Alaa Kassem,Abeer Salama,Amira Mohamed Mohsen
标识
DOI:10.1016/j.jddst.2021.103047
摘要
The present study was designed to develop dorzolamide HCl (DRZ) loaded cationic nanoemulsions (CNEs) for enhanced ocular delivery. CNEs were prepared employing high-speed homogenization followed by ultrasonication. A three-factor, three-level Box-Behnken design was utilized for formulation optimization. The oil content (%), surfactant content (%) and cationic agent content (%) were selected as independent variables, whereas droplet size (DS), zeta potential (ZP) and polydispersity index (PDI) as dependent variables. The design suggested an optimized DRZ loaded CNE formulation (F-Opt) consisting of isopropyl myristate (8.36%), Tween 80 (3%) and Cetyl trimethyl ammonium bromide (1%). F-Opt exhibited DS, ZP, PDI and DRZ content values of 336.3 nm, 32.5 mV, 0.209 and 99.13%, respectively. It showed spherical morphology under transmission electron microscopy with acceptable pH value, optimum viscosity, refractive index, surface tension and osmolality of 4.84, 1.31 cP, 1.332, 42.5 mN/m and 158 mOsm/kg, respectively. The in vitro drug release profile from F-Opt revealed a sustained release pattern compared to plain DRZ solution governed by a non-Fickian diffusion mechanism. F-Opt displayed pronounced in vitro mucoadhesive properties in comparison with plain DRZ and marketed DRZ eye drops. The results depicted that F-Opt was robust to dilution, thermodynamically stable and remained stable for one month after storage at ambient (25 °C) and refrigeration (4 °C) temperatures. Furthermore, the optimized formulation showed an enhanced and extended lowering effect of intraocular pressure (IOP) using male albino New Zealand rabbits compared to plain DRZ and marketed DRZ eye drops. Ocular Draize irritancy assessment revealed that F-Opt was safe and non-irritant for ocular application. Hence, F-Opt showed the potential for successful ocular delivery with proved safety and enhanced therapeutic efficacy for management of elevated IOP.
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