Enhancer effects on in vitro corneal permeation of timolol and acyclovir.
The aim of this study was to evaluate the ability of two non-toxic skin penetration enhancers, N-methylpyrrolidone (NMP) and a positively charged phospholipid mixture (PS), to increase in vitro corneal permeation of timolol maleate (TM) and acyclovir (AC) in comparison with two corneal absorption promoters, polyethylene glycol octadecyl ether (Brij 78) and sodium taurocholate (TA). In vitro experiments were performed on corneas from albino rabbits which were mounted in a perfusion apparatus. The concentrations of the enhancers being tested were: Brij 78 1%, PS 1%, TA 1%, NMP 5%, NMP 10%. The safety of the enhancers being tested was assessed in vitro by determining their effects on corneal hydration and in vivo by means of a modified Draize test. Calculating the amount of drug permeated at different time points (90 and 180 min) we observed that TA, PS and NMP 5% significantly increased the cumulative amount of AC permeated after 90 min but only PS was effective after 180 min. TA, Brij 78 and PS were able to increase significantly the amount of TM permeated after 90 min but after 180 min only Brij 78 retained its effect. TA, Brij 78 and NMP 10% significantly increased the percent hydration levels (% HL) compared to the control while PS and NMP 5% did not affect % HL. The results of in vivo ocular tolerability studies showed that the enhancers which caused an in vitro increase of % HL produced in vivo conjunctival and/or corneal damages. The results of this study suggest that PS could be regarded as a potential corneal enhancer to increase the intraocular bioavailability of AC and TM.
Montenegro
L
L
Department of Pharmaceutical Sciences, University of Catania, Catania, Italy. lmontene@unict.it
Bucolo
C
C
Puglisi
G
G
D000212:Acyclovir / Q000493:pharmacokinetics*; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005079:Excipients; D066298:In Vitro Techniques; D007249:Inflammation / Q000473:pathology; D010743:Phospholipids / Q000737:chemistry; D011760:Pyrrolidinones; D011817:Rabbits; D013268:Stimulation, Chemical; D013999:Timolol / Q000493:pharmacokinetics*
D000319:Adrenergic beta-Antagonists; D000998:Antiviral Agents; D005079:Excipients; D010743:Phospholipids; D011760:Pyrrolidinones; D013999:Timolol; C038678:N-methylpyrrolidone; D000212:Acyclovir