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ED50 95% confidence limits

HPMC, 0.5% 0.50 0.403-0.620 PVA, 1.4% 1.00 0.750-1.330 PVP, 1.4% 1.10 0.89-1.35 Distilled water 1.03 0.84-1.27

0 Reproduced from F. C. Bach et a/., Am. J. Ophthalmol., 69, 659 (1970).

0 Reproduced from F. C. Bach et a/., Am. J. Ophthalmol., 69, 659 (1970).

Some ingredients of eye medications may increase the permeability of the cornea. Surface-active agents are known to interact with membranes to increase the permeability: benzalkonium chloride has surfactant properties and may well have some effect on corneal permeability, although its primary purpose is as a bacteriostat and bactericide. Chlorhexidine acetate and cetrimide, both of which are surface-active, are also used.

Log P

The influence of log P of beta-blockers (Table 9.12) on their permeation coefficients into conjunctiva and cornea is shown in Fig. 9.37. In humans, the conjunctiva has 17 times the surface area of the cornea and therefore it absorbs significant amounts of drug. Work has centred on increasing corneal permeability or retention of the drug (or product) in the conjunctiva sac. Appropriate doses of drug can achieve a degree of corneal or conjunctival selectivity, represented in Fig. 9.37(c) by the ratio (C/J). Increasing lipophilicity increases the C/J ratio from <0.1 to approximately 0.5.

The prodrug approach

Attempts have been made to improve the performance of drugs used in the eye. One approach has been to modify the drug substance to increase its ability to penetrate the

Table 9.12 Log P values of beta-blockers (in increasing order of lipophilicity)

Compound

Log P

Sotalol

0 0

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