Department of Drug Discovery and Development, Auburn University, Auburn, Alabama, 36849, USA.
Vetsuisse Faculty, University of Bern, Länggassstrasse 128, CH-3012, Bern, Switzerland.
AAPS PharmSciTech. 2018 Aug;19(6):2554-2563. doi: 10.1208/s12249-018-1094-0. Epub 2018 Jun 13.
Nepafenac is a nonsteroidal anti-inflammatory drug (NSAID), currently only available as 0.1% ophthalmic suspension (Nevanac®). This study utilized hydroxypropyl-β-cyclodextrin (HPBCD) to increase the water solubility and trans-corneal permeation of nepafenac. The nepafenac-HPBCD complexation in the liquid and solid states were confirmed by phase solubility, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) analyses. Nepafenac 0.1% ophthalmic solution was formulated using HPBCD (same pH and osmolality as that of Nevanac®) and pig eye trans-corneal permeation was studied versus Nevanac®. Furthermore, nepafenac content in cornea, sclera, iris, lens, aqueous humor, choroid, ciliary body, retina, and vitreous humor was studied in a continuous isolated pig eye perfusion model in comparison to the suspension and Nevanac®. Permeation studies using porcine corneas revealed that the solution formulation had a permeation rate 18 times higher than Nevanac®. Furthermore, the solution had 11 times higher corneal retention than Nevanac®. Drug distribution studies using porcine eyes revealed that the solution formulation enables detectable levels in various ocular tissues while the drug was undetectable by Nevanac®. The ocular solution formulation had a significantly higher drug concentration in the cornea compared to the suspension or Nevanac®.
奈帕芬那是一种非甾体类抗炎药（NSAID），目前仅以 0.1%的眼用混悬剂（Nevanac®）形式存在。本研究利用羟丙基-β-环糊精（HPBCD）来提高奈帕芬那的水溶性和经角膜渗透。通过相溶解度、差示扫描量热法（DSC）、X 射线衍射（XRD）、傅里叶变换红外光谱（FT-IR）和核磁共振波谱（NMR）分析，证实了奈帕芬那-HPBCD 复合物在液态和固态下的形成。使用 HPBCD（与 Nevanac®相同的 pH 值和渗透压）配制了 0.1%的奈帕芬那眼用溶液，并对其在猪眼上的经角膜渗透进行了研究，与 Nevanac®进行了比较。此外，还在连续的离体猪眼灌注模型中研究了奈帕芬那在角膜、巩膜、虹膜、晶状体、房水、脉络膜、睫状体、视网膜和玻璃体中的含量，与混悬剂和 Nevanac®进行了比较。利用猪角膜进行的渗透研究表明，该溶液制剂的渗透速率比 Nevanac®高 18 倍。此外，该溶液制剂在角膜中的滞留时间比 Nevanac®长 11 倍。利用猪眼进行的药物分布研究表明，该溶液制剂可使各种眼部组织中检测到药物，而 Nevanac®则检测不到药物。与混悬剂或 Nevanac®相比，该溶液制剂在角膜中的药物浓度显著更高。
