# Synergic Effect of Methyl-β-Cyclodextrin and Hydrophilic Polymers on Nepafenac Solubilization: Development of a 0.3% Ophthalmic Solution

## TL;DR

This study develops a stable ophthalmic solution of nepafenac using methyl-β-cyclodextrin and hydrophilic polymers, offering a safer and more effective alternative to the current suspension.

## Contribution

The study introduces a novel formulation using 5% RAMEB and hydrophilic polymers to solubilize 0.3% nepafenac, enabling a stable ophthalmic solution.

## Key findings

- Nepafenac solubilization was achieved with 5% RAMEB and hydrophilic polymers.
- The solution was chemically and physically stable for 12 months at 25 °C.
- The formulation showed no cytotoxicity on human corneal epithelial cells.

## Abstract

Nepafenac is an anti-inflammatory drug used in ophthalmology, marketed as a suspension due to its low aqueous solubility. A solution formulation could provide better bioavailability than suspension and facilitate single unit doses, avoiding the use of preservatives which are required to maintain sterility in multidose packaging. In this study, solubilization of nepafenac was achieved in the presence of randomly methylated β-cyclodextrin (RAMEB) and the actual complexation was assessed by NMR and phase-solubility studies. It was also found that the addition of hydrophilic polymers plays an important role in allowing increased solubilization of nepafenac at the same cyclodextrin concentration. Compared to complexes of nepafenac with other cyclodextrins, only 5% RAMEB was sufficient to solubilize 0.3% (w/v) nepafenac, enabling for the first time the development of an ophthalmic solution that proved chemically and physically stable for 12 months at 25 °C. The formulated solutions of nepafenac were tested for cytotoxicity on human corneal epithelial cells (HCE-2) and the results suggest their potential as a valuable and safe alternative to the commercially available 0.3% (w/v) suspension of the drug.