title: Differential effect of chelation on the pH tolerance of corneal epithelium in tissue culture.
abstract: The impact of chelation on the biocompatibility of various vehicles was determined after 1- to 32-min exposures using stratified rabbit corneal epithelial cultures. Each formulation was tested at either pH 5.0 or 7.5 to mimic the specifications of most commercial ophthalmic preparations. Adding ethylenediamine tetraacetic acid (EDTA) to balanced salt solutions was unremarkable, and all of the formulations were essentially nontoxic. In contrast, EDTA moderately reduced the toxicity of the acidic acetate/citrate-buffered vehicles, but enhanced the toxicity of the alkaline solutions. The preservative, on the other hand, had little impact on the biotolerance of acidic unbuffered and phosphate-buffered vehicles, although it also increased the toxicity of the alkaline formulations. These findings are interpreted in terms of the different pKa values of the chelating agents, and an unsuspected interaction between citrate and the preservative. We believe that this type of testing can be used to develop guidelines for the use of buffers, excipients and preservatives in commercial formulations.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: D R
authors.initials: DR
authors.lastname: Meyer
authors.forename: J P
authors.initials: JP
authors.lastname: McCulley
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002614:Chelating Agents; D003315:Cornea / Q000166:cytology / Q000187:drug effects*; D004337:Drug Carriers; D004361:Drug Tolerance; D004492:Edetic Acid / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D009883:Ophthalmic Solutions / Q000494:pharmacology*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D011817:Rabbits
chemical_list: D002614:Chelating Agents; D004337:Drug Carriers; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D004492:Edetic Acid