Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation

Abstract

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®.

Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes

“…Phase solubility analysis can provide valuable information about changes in drug solubility when it interacts with different concentrations of CDs. Since the changes of physicochemical and biological properties of a drug are dependent on the stability constant of CD complexes, it is essential to determine this parameter accurately [36].…”

Physicochemical properties and mechanism of solubilised neohesperidin system based on inclusion complex of hydroxypropyl‐β‐cyclodextrin

“…The equilibrium constant of phase solubility can reflect the change in solubility when the drug interacts with CDs at different concentrations. Since the change in physicochemical and biological properties of drugs depended on the stability constant of CD complexes, it was necessary to know this parameter accurately (Shelley et al ., 2018). The solubility of β‐CD, DM‐CD, SBE‐CD, γ‐CD, HP‐γ‐CD and HP‐β‐CD complexes of NH also increased linearly with the increase in the addition of CD as shown in Fig.…”

Hispolon Cyclodextrin Complexes and Their Inclusion in Liposomes for Enhanced Delivery in Melanoma Cell Lines

“…In addition, the greater solubilization efficiency of hispolon, as observed in Figure 1, justified the selection of SBEβCD over HPβCD for use in liposome formulations in the current investigation. The changes in the Gibbs Free energy for SBEβCD and HPβCD were −14.3 KJ/mol and −8.96 KJ/mol, respectively, which indicated rapid spontaneous complex formation between the drug and the cyclodextrin [33]. The comparison is discussed in Table 1.…”