Design of Topical Ocular Ciprofloxacin Nanoemulsion for the Management of Bacterial Keratitis

Abstract

Bacterial keratitis (BK) is a critical ocular infection that can lead to serious visual disability. Ciprofloxacin (CIP), moxifloxacin (MOX), and levofloxacin (LFX) have been accepted as monotherapies by the US Food and Drug Administration for BK treatment. CIP is available commercially at 0.3% w/v concentration as an ophthalmic solution and as an ointment for ocular delivery. Because of solubility issues at physiological pH, CIP precipitation can occur at the corneal surface post instillation of the solution dosage form. Consequently, the ocular bioavailability of CIP is reduced. The ointment dosage form is associated with side effects such as blurred vision, itching, redness, eye discomfort, and eye dryness. This study aimed to design a CIP loaded nanoemulsion (NE; CIP-NE) to facilitate drug penetration into the corneal layers for improved therapeutic outcomes as well as to overcome the drawbacks of the current commercial ophthalmic formulations. CIP-NE formulations were prepared by hot homogenization and ultrasonication, using oleic acid (CIP-O-NE) and Labrafac® Lipophile WL 1349 (CIP-L-NE) as the oily phase, and Tween® 80 and Poloxamer 188 as surfactants. Optimized CIP-NE was further evaluated with respect to in vitro release, ex vivo transcorneal permeation, and moist heat sterilization process, using commercial CIP ophthalmic solution as a control. Optimized CIP-O-NE formulation showed a globule size, polydispersity index, and zeta potential of 121.6 ± 1.5 nm, 0.13 ± 0.01, and −35.1 ± 2.1 mV, respectively, with 100.1 ± 2.0% drug content and was spherical in shape. In vitro release and ex vivo transcorneal permeation studies exhibited sustained release and a 2.1-fold permeation enhancement, respectively, compared with commercial CIP ophthalmic solution. Autoclaved CIP-O-NE formulation was found to be stable for one month (last time-point tested) at refrigerated and room temperature. Therefore, CIP-NE formulation could serve as an effective delivery system for CIP and could improve treatment outcomes in BK.

Keywords

• bacterial keratitis
• ciprofloxacin
• nanoemulsion
• stability
• transcorneal permeability
• surfactant