GELLAN-BASED SYSTEMS FOR OPHTHALMIC SUSTAINED DELIVERY OF METHYLPREDNISOLONE

Gellan is an anionic exocellular polysaccharide of microbial origin, having a characteristic property of cation-induced gellation. In the current 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 gellan-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 release of MP from the test dosage forms was determined in a pH 7.4 phosphate buffer at 32-degrees-C using a rotating bottle apparatus. MP concentrations in the tear fluid of New Zealand white rabbits were measured after ocular application of the dosage forms. In vitro, the gellan-MP films released covalently bound MP in an approximate zero-order pattern, whereas the release of physically incorporated MP from the gellan eye drops and films followed a square root of time relationship and anomalous 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 tendency to slip out of the eye due to a high degree of swelling. The in vivo release from films containing physically incorporated MP showed higher 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 vehicle for ocular sustained release of drugs. The results also show that the gellan-MP ester can be used to increase the residence time of methylprednisolone in the tear fluid of rabbits.