Beta-cyclodextrins as vehicles in eye-drop formulations: an evaluation of their effects on rabbit corneal epithelium.
Beta-cyclodextrins are cyclic molecules with a hydrophilic outer side and a central hydrophobic cavity. Through the inclusion of drug molecules into their cavities, i.e. the formation of inclusion complexes, cyclodextrins are able to modify the physical and chemical properties of these molecules. When used in pharmaceutical formulations, they can improve the aqueous solubility, stability, dissolution rate, bioavailability and/or local tolerance of certain drugs. To make an initial evaluation of the potential use of beta-cyclodextrins as vehicles in ophthalmic eye-drop formulations, we studied the effect of a single and of multiple applications of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) 12.5% and of dimethyl-beta-cyclodextrin (DM-beta-CD) 5 and 12.5% solutions on the corneal epithelium of albino and pigmented rabbits with slit lamp biomicroscopy (SLB) and scanning electron microscopy (SEM). We can conclude from this study that DM-beta-CD at concentrations of 5 and 12.5% is not a suitable vehicle for ophthalmic formulations since it is toxic to the corneal epithelium and that HP-beta-CD at a concentration of 12.5% is well tolerated by the rabbit eye and is not toxic to the corneal epithelium when evaluated by SLB and SEM.
Jansen
T
T
Department of Life Sciences, Janssen Research Foundation, Beerse, Belgium.
Xhonneux
B
B
Mesens
J
J
Borgers
M
M
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000287:Administration, Topical; D000818:Animals; D003228:Conjunctiva / Q000187:drug effects; D003315:Cornea / Q000187:drug effects* / Q000648:ultrastructure; D003505:Cyclodextrins / Q000633:toxicity*; D004337:Drug Carriers; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D005069:Evaluation Studies as Topic; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin