II. An ocular bioavailability comparison in rabbits of prednisolone acetate after repeated topical applications formulated as a high‐viscosity gel and as an aqueous suspension

Abstract

To increase contact time between drug and ocular surface and thus improve the ocular bioavailability, we used the high-viscous, water-soluble polymer carbomer Leogel (carbomer 0.5%). We compared the bioavailability of prednisolone acetate 0.5% given in 1) Leogel using fusidic acid 1% with that obtained using 2) aqueous sulfacetamide sodium 10% as vehicle. We applied the drugs to Copenhagen white rabbits as repeated topical applications (gel preparation: twice daily; aqueous preparation: four times daily) for one week. Dosis regimen was chosen according to earlier investigations (Johansen et al. 1995). Prednisolone concentrations in cornea, conjunctiva and aqueous humour were shown to be higher using the Leogel vehicle than using the aqueous suspension. Fusidic acid and sulfacetamide sodium values were compared with values from a single application (Johansen et al. 1995). Fusidic acid reached higher concentration levels in cornea, conjunctiva and aqueous humour after repeated applications than after a single application. Sulfacetamide sodium concentrations did not rise when applied four times daily for one week. Leogel increases the ocular bioavailability of substance(s) in the gel and allows lower drug concentrations and/or application frequencies.

Biodegradable ocular implant for sustained drug delivery

“…Patients who receive anti-glaucoma topical treatment for long period of time were reported to have chronic inflammation [34]. In addition, majority of the drug following topical administration is lost through lacrimation, tear dilution, tear turnover and nasolacrimal drainage [43] due to very low bioavailability of the administered drug, typically less than 5% [9,44], which prompts the ophthalmologists searching for alternative routes of drug administration.…”

“…However, due to the bulk degradation mechanism of PLC7030, when the critical M w for the onset of mass loss of PLC7030 has reached [17], the drug release would be increased drastically, which is highly above the toxic level, thus lead to undesirable side effects. [7,111] of the drug optimistically, then only 0.012mg of the drug can actually reach the targeted site. The amount of drug required is quite close to the amount released daily from 20%…”