[Effect of pH on the permeability of timolol maleate across isolated rabbit cornea].
OBJECTIVE
To study the effect of pH on the transcorneal permeability of timolol maleate (TM).


METHODS
The apparent distribution coefficients of TM were determined. The permeability of TM across isolated rabbit cornea was measured using in vitro method at various pH.


RESULTS
The partition coefficient and pKa of TM were 63.63 and 9.17 respectively. At neutral pH, the apparent permeation coefficient of TM was 1.43 x 10(-5) cm.s-1. When the pH varied from 6.65 to 9.20, the cumulative amount for timolol transcorneal penetration increased 1.3 times and the lag time decreased more than 19-folds. The calculated permeability coefficients of ionized and un-ionized timolol were 1.29 x 10(-5) cm.s-1 and 4.22 x 10(-5) cm.s-1, respectively.


CONCLUSIONS
Timolol penetrated corneal membrane mainly as free base by intracellular pathway, and corneal epithelium was the rate-limiting barrier.
Wei
G
G
Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. weigangmail@sina.com.cn
Xu
H
H
Ma
Y
Y
Li
S M
SM
Zheng
J M
JM
D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D010539:Permeability; D011817:Rabbits; D013999:Timolol / Q000493:pharmacokinetics*
D000959:Antihypertensive Agents; D013999:Timolol