GELLAN-BASED SYSTEMS FOR OPHTHALMIC SUSTAINED DELIVERY OF METHYLPREDNISOLONE

Gellan is an anionic exocellular polysaccharide of microbial origin, h aving a characteristic property of cation-induced gellation. In the cu rrent study, gellan was evaluated for applications in ocular sustained release devices. A methylprednisolone (MP) ester of gellan (gellan-MP ) was synthesized. Sustained release dosage forms evaluated were gella n-MP films, gellan films with physically incorporated MP and eye drops of MP suspended in a 0.6% w/w gellan dispersion in water. The control dosage form was a suspension of MP in nor-mal saline. In vitro releas e of MP from the test dosage forms was determined in a pH 7.4 phosphat e buffer at 32-degrees-C using a rotating bottle apparatus. MP concent rations in the tear fluid of New Zealand white rabbits were measured a fter ocular application of the dosage forms. In vitro, the gellan-MP f ilms released covalently bound MP in an approximate zero-order pattern , whereas the release of physically incorporated MP from the gellan ey e drops and films followed a square root of time relationship and anom alous kinetics, respectively. Compared with the MP suspension control, the gellan-MP films yielded an approximately 4-fold higher area under tear fluid concentration vs time curve, AUC0-8h, but exhibited a tend ency to slip out of the eye due to a high degree of swelling. The in v ivo release from films containing physically incorporated MP showed hi gher variability and provided mean AUC0-8h Values approximately equal to the control values. The gellan eye drops containing MP yielded 2.6- fold higher AUC0-8h values than the control and also provided ease of administration. Gellan solutions might thus provide a versatile vehicl e for ocular sustained release of drugs. The results also show that th e gellan-MP ester can be used to increase the residence time of methyl prednisolone in the tear fluid of rabbits.