title: Ocular bioavailability of ciprofloxacin in sustained release formulations.
abstract: A novel sustained release delivery system of ciprofloxacin for the eye was developed. The system consists of a viscosity enhancer (carbopol gel or hydroxypropylmethylcellulose solution) plus a penetration enhancer (dodecylmaltoside) to overcome penetration barriers and loss due to wash-out and thus achieve the desired ciprofloxacin ocular absorption. The present studies were designed to assess the ocular penetration and bioavailability of ciprofloxacin in sustained release formulations. In vitro studies in rabbits indicated an approximate 10-fold increase in drug penetration through the rabbit cornea using the penetration enhancer, dodecylmaltoside. In vivo bioavailability studies demonstrate that these formulations provided a long drug duration in the cornea. After administration of a single topical dose of ciprofloxacin (0.3%/30 microL), corneal levels greater than the Minimum Inhibitory Concentration (MIC90) (0.5 microg/g) were observed through eight hours. These sustained release formulations delivered 10-fold more drug into the aqueous humor than the standard solution formulation. Maximum ciprofloxacin concentrations in the aqueous humor (0.5-0.7 microg/mL) were attained between one and two hours after dosing. Using these sustained release formulations, ciprofloxacin can penetrate to the anterior chamber of the eye in concentrations that are inhibitory for most gram-negative and gram-positive organisms. These topical ocular formulations have prophylactic utility for prevention of post-surgical infection, offering greater efficacy and safety than currently available treatments.
authors.affiliation: Alcon Research, Ltd., Fort Worth, Texas 76134, USA. tai-lee.ke@AlconLabs.com
authors.forename: T L
authors.initials: TL
authors.lastname: Ke
authors.forename: G
authors.initials: G
authors.lastname: Cagle
authors.forename: B
authors.initials: B
authors.lastname: Schlech
authors.forename: O J
authors.initials: OJ
authors.lastname: Lorenzetti
authors.forename: J
authors.initials: J
authors.lastname: Mattern
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000737:chemistry; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003228:Conjunctiva / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D066298:In Vitro Techniques; D010539:Permeability; D011817:Rabbits; D012590:Sclera / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D002939:Ciprofloxacin