(W1030-05-33) Study on the Permeability of Ophthalmic Tissues In Vitro

Purpose: Under current clinical background, local administration of conjunctival sac is the most common route of administration in ophthalmology.^[3]Due to the absorption barrier formed by the special structure of the cornea, the bioavailability of drugs via the corneal absorption is low.^[4]It is definitely challenging to improve the bioavailability of ocular topical drugs. Study on the permeability of excised ophthalmic tissues can evaluate the absorption property of drugs in different ophthalmic tissues by directional simulation of the osmotic environment of the dedicated tissues, and provide more possibilities for optimizing the corneal absorption pathway scheme and exploring the application of non-corneal absorption pathway.^[1,2]

Methods: Intact cornea and sclera of healthy male New Zealand White rabbits were used and placed on the Franz diffusion cell for the experiment, respectively. The commercial available drug 0.3% gatifloxacin eye drops and gel were used as the test drugs. Samples were collected at predetermined time points (0.5, 1, 1.5, 2, 2.5, 3, 3.5 and 4 h). The cornea was weighed at the endpoint of the experiment to calculate the corneal hydration levels (HL) to evaluate the cornea status. ^[5]The change curve was drawn according to the cumulative permeability of drugs, and the permeability of different dosage forms of drugs with the same concentration in different eye tissues was evaluated by Q_n and P<sub>app.

Results: According to calculate the corneal hydration level, there was no corneal injured before the experiment (81.7% ± 0.77%, HL ranges are typically 76% ⁓ 83%). ^[5] The Q_n and P<sub>app of gatifloxacin eye drops in cornea and sclera were 244.49 ± 16.95 µg/cm² and 799.74 ± 187.45 µg/cm, 5.66 ± 0.39×10^-6 cm/s and 18.51 ± 4.34×10^-6 cm/s, respectively. Meanwhile, the Q_n and P<sub>app of gatifloxacin eye gel in cornea and sclera were 122.02 ± 10.49 µg/cm² and 292.03 ± 30.11 µg/cm², 2.82 ± 0.24×10^-6 cm/s and 6.76±0.70×10^-6 cm/s, respectively.

Conclusion: The P<sub>app in cornea and sclera in the eye drops group were higher than that of in the eye gel group. Previous studies have shown that excipients could prolong the drug release and retention in target tissues, but it may affect the rate at which the drug penetration through the ophthalmic tissue. ^[3]The Q_n and P<sub>app of sclera group were significantly higher than these of cornea group. Therefore, the development of new ocular delivery modes (such as periocular injection) has potential advantages. The preliminary evaluation of ophthalmic tissue permeability has important screening and evaluation value for the preclinical study of ophthalmic drug.

References: [1] Zhao X, Lu H, Wang X T et al. Study on the permeability of cornea and sclera in vitro by cyclodextrin-coated eye drops. Liaoning Chemical Industry. 2018,47(07):636-638.
[2] Dave V, Paliwal S, Yadav S, Sharma S. Effect of in vitro transcorneal approach of aceclofenac eye drops through excised goat, sheep, and buffalo corneas. Scientific World Journal. 2015;2015:432376.
[3] Ge J, Wang N L. Ophthalmology [M]. Beijing, People's Medical Publishing House, 2015:528-531.
[4] Ramsay E, Del Amo EM, Toropainen E, et al. Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye. Eur J Pharm Sci. 2018;119:83-89.
[5] Yu N, Xun Y, Jin D, Yang H, Hang T, Cui H. Effect of sperminated pullulans on drug permeation through isolated rabbit cornea and determination of ocular irritation. J Int Med Res. 2010;38(2):526-535.

Acknowledgements: Conflict of interest: No conflicting relationship exists for any author.

Figure 1. Experimental endpoint cornea (left) and sclera (right).

Table 1. Comparison of permeability parameters of gatifloxacin in different dosage forms on cornea and sclera.

Figure 2. The cumulative permeability (Qn ) of gatifloxacin eye drops (left) and gels (right) in cornea or sclera of rabbits.