Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation.

Area of Science:

• Ophthalmology
• Pharmaceutics
• Drug Delivery

Background:

• Nepafenac is a nonsteroidal anti-inflammatory drug (NSAID) used for ophthalmic conditions.
• Current formulations of nepafenac are limited by poor water solubility and ocular penetration.
• Hydroxypropyl-β-cyclodextrin (HPBCD) is a known excipient for improving drug solubility and bioavailability.

Purpose of the Study:

• To enhance the water solubility and trans-corneal permeation of nepafenac using HPBCD.
• To formulate a novel nepafenac ophthalmic solution with improved ocular drug delivery.
• To compare the permeation, retention, and tissue distribution of the new formulation against the existing nepafenac suspension.

Main Methods:

• Nepafenac-HPBCD complexation was confirmed using phase solubility, DSC, XRD, FT-IR, and NMR.
• A nepafenac 0.1% ophthalmic solution was formulated with HPBCD, matching Nevanac®'s pH and osmolality.
• Trans-corneal permeation and ocular tissue distribution were evaluated in isolated pig eye models.

Main Results:

• The HPBCD complexation successfully increased nepafenac's water solubility.
• The nepafenac-HPBCD ophthalmic solution demonstrated an 18-fold higher permeation rate compared to Nevanac®.
• Corneal retention was 11 times higher, and detectable drug levels were found in various ocular tissues, unlike the Nevanac® suspension.

Conclusions:

• HPBCD significantly enhances nepafenac's solubility and ocular permeation.
• The developed nepafenac ophthalmic solution offers superior drug delivery to ocular tissues compared to the current suspension.
• This formulation holds promise for improved therapeutic efficacy in treating ocular inflammatory conditions.