Validation of a device for transcorneal drug permeation measure.
A model of a corneal apparatus for the study of drug permeation across the corneal tissues is evaluated. The instrument was designed to measure drug transport in living rabbit corneas, which are placed hermetically into a chamber, separating it into two compartments (epithelial and endothelial). The device also allows the measurement and recording of the corneal potential, providing information on the vitality of the cornea. The validation of the instrument was carried out by introducing variable amounts of fluorescein into the epithelial compartment of the chamber, and measuring the concentration of the dye by the fluorescence obtained in the endothelial compartment. The fluorescein concentration in the endothelial compartment increased exponentially over time, with a good correlation between the epithelial and endothelial concentrations. The repeatability of the measurements is strongly influenced by the maintenance and regularity of the initial concentration, the time that has passed from the beginning of the experiment, and the corneal potential (vitality of the cornea). Less important are slight modifications to temperature, the agitation system and hydrostatic pressure (robustness). The proposed experimental system shows good precision when measuring the permeation through rabbit cornea at different drug concentrations, and good repeatability and intermediate precision with non-significant differences among operators in repeated experiments. It is a good approach for comparing corneal transport of different formulations of the same drug. To test the method with real samples, different formulations of the NSAID sodium diclofenac where assayed. Corneal permeation was remarkably enhanced when diclofenac was formulated as a beta-cyclodextrin complex. Other additives, such as the surfactants used in commercial eye drops, also enhanced corneal drug transport.
Valls
R
R
Physical-Chemistry Department, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII, s.n. 08028 Barcelona, Spain.
García
M L
ML
Egea
M A
MA
Valls
O
O
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D004008:Diclofenac / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004867:Equipment Design; D019793:Fluorescein / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000008:administration & dosage; D010539:Permeability; D011817:Rabbits; D015203:Reproducibility of Results
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005456:Fluorescent Dyes; D004008:Diclofenac; D019793:Fluorescein