Evaluation of ocular permeation enhancers: In vitro effects on corneal transport of four β-blockers, and in vitro/in vivo toxic activity
International Journal of Pharmaceutics, ISSN: 0378-5173, Vol: 142, Issue: 1, Page: 103-113
1996
- 136Citations
- 55Captures
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Article Description
The efficacy and toxicity of a series of prospective ocular penetration enhancers (benzalkonium chloride, EDTA, non-ionic surfactants, surface-active heteroglycosides and bile salts) was investigated in vitro, using isolated rabbit corneas. As test drugs four β-blocking agents were used, chosen in order of increasing lipophilicity: atenolol (AT), timolol (TM), levobunolol (LB) and betaxolol (BX). The increased corneal hydration induced by the enhancers was taken as an index of cellular and tissue damage; the ocular irritancy of the agents was also tested in rabbits in vivo. In the absence of enhancers, the apparent corneal permeability coefficients of the four drugs were in the order AT ⋍ TM < LB ≥ BX; in general, the enhancers increased the permeation rates of the more hydrophilic drugs, AT and TM, more than those of the other two, more lipophilic ones, LB and BX. The study pointed to some agents (in particular, polyoxyethylene alkyl ethers and bile salts) as effective and safe penetration promoters for AT and TM. Their apparent safety at the tested concentrations was confirmed by their failure to increase the corneal hydration level beyond the ‘normal’ value, and by their lack of irritant effect in vivo, as evidenced by a Draize test.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/0378517396046637; http://dx.doi.org/10.1016/0378-5173(96)04663-7; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0030604042&origin=inward; https://linkinghub.elsevier.com/retrieve/pii/0378517396046637; https://api.elsevier.com/content/article/PII:0378517396046637?httpAccept=text/xml; https://api.elsevier.com/content/article/PII:0378517396046637?httpAccept=text/plain; http://dx.doi.org/10.1016/0378-5173%2896%2904663-7; https://dx.doi.org/10.1016/0378-5173%2896%2904663-7
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