Increased corneal hydration induced by potential ocular penetration enhancers: assessment by differential scanning calorimetry (DSC) and by desiccation.
The corneal toxicity of some surfactants of possible use as ocular penetration enhancers was investigated by measuring their effect on hydration of rabbit corneas 'in vitro'. The tested substances were benzalkonium chloride (BAC), cetylpyridinium chloride (CPC), ethylenediaminetetraacetic acid disodium salt (EDTA), polyoxyethylene-20-stearyl ether (Brij 78, PSE), polyethoxylated castor oil (Cremophor EL, PCO) and sodium deoxycholate (DC). Freshly excised corneas, mounted in perfusion cells, were kept in contact for 1 h with solutions of these agents; corneal hydration was then evaluated by measuring: (a) their total (free+bound) water content by desiccation (gravimetric analysis); and (b) their free water content by differential scanning calorimetry (DSC). The DSC measurements also provided a rough quantitative estimate of corneal solutes. All tested agents significantly influenced corneal hydration, evidently as a consequence of alteration of the corneal epithelium. Although a brief contact with the precorneal tissues 'in vivo' may not prove harmful, the use of these compounds as potential ocular permeation enhancers or otherwise as ingredients of topical ocular formulations for long-term use should be considered with caution.
Monti
D
D
Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Via Bonanno 33, I-56126, Pisa, Italy. montid@farm.unipi.it
Chetoni
P
P
Burgalassi
S
S
Najarro
M
M
Saettone
M F
MF
D000704:Analysis of Variance; D000818:Animals; D002152:Calorimetry, Differential Scanning; D003315:Cornea / Q000187:drug effects*; D003890:Desiccation / Q000379:methods; D008297:Male; D009883:Ophthalmic Solutions / Q000009:adverse effects*; D011817:Rabbits
D009883:Ophthalmic Solutions