Merck

Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation.

AAPS PharmSciTech (2018-06-28)
Haley Shelley, Makenzie Grant, Forrest T Smith, Eva M Abarca, R Jayachandra Babu
摘要

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®.

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Sigma-Aldrich
Nepafenac, ≥98% (HPLC)
Supelco
Discovery® Glycan SPE Tube, bed wt. 250 mg, volume 3 mL, pk of 54
Supelco
Discovery® Glycan SPE Bulk Packing, pkg of 50 g
Supelco
Discovery® Glycan SPE Tube, bed wt. 500 mg, volume 6 mL, pk of 30
Supelco
Discovery® Glycan SPE Tube, 5 g, volume 60 mL, pk of 16
Supelco
Discovery® Glycan SPE Tube, bed wt. 1 g, volume 12 mL, pk of 20