Determination of permeability coefficients of ophthalmic drugs through different layers of porcine, rabbit and bovine eyes.
To treat ophthalmic diseases like glaucoma or inflammatory disorders topically applied ophthalmic formulations such as eye drops are usually used. In addition, novel ophthalmic implants releasing drug substances locally into different parts of the eye are available today. In the work presented here, the permeability coefficients of selected drugs (ciprofloxacin hydrochloride, lidocaine hydrochloride, timolol maleate) for ophthalmic tissues were determined using side-by-side diffusion chambers (so-called Ussing chambers). Sclera, conjunctiva, cornea, choroidea-retina-complex and a complex of conjunctiva-sclera-choroidea-retina were excised from fresh porcine, rabbit and bovine eyes. In the porcine eye tissues the highest P(app) values were obtained for conjunctiva with the exception of lidocaine. Therefore, it can be estimated that a certain amount of drug diffuses or is transported through conjunctiva after application. The P(app) values for sclera were also higher than those for cornea and even more, the surface area of sclera which is available for drug absorption is much larger than that of cornea when applying an implant. The obtained permeability coefficients for sclera and conjunctiva indicate that the administration of periocular implants can be an alternative to topically applied formulations. The complexes of the tissues were a significantly (p<0.01) stronger barrier to the investigated substances than the separated tissues. Distinct differences in permeability coefficients between the investigated animal tissues were observed. Overall the highest P(app) values for all mounted tissues were obtained with the rabbit, followed by porcine and bovine eyes. Because of these distinct interspecies differences one must be very careful when selecting the proper animal model for the permeability experiments.
Institute of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, EMA University of Greifswald, 17487 Greifswald, Germany.
Christian
C
Loch
Simon
S
Zakelj
Albin
A
Kristl
Stefan
S
Nagel
Rudolf
R
Guthoff
Werner
W
Weitschies
Anne
A
Seidlitz
D000818:Animals; D002417:Cattle; D002829:Choroid / Q000187:drug effects / Q000378:metabolism; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion; D005123:Eye / Q000187:drug effects* / Q000378:metabolism*; D005128:Eye Diseases / Q000188:drug therapy / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010539:Permeability; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012590:Sclera / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D014018:Tissue Distribution
D009883:Ophthalmic Solutions