Gellan-based systems for ophthalmic sustained delivery of methylprednisolone

Abstract

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 normal saline. In vitro release ofMP from the test dosage forms was determined in a pH 7.4 phosphate buffer at 32 °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, AUC 0–8h, 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 AUC 0–8h values approximately equal to the control values. The gellan eye drops containing MP yielded 2.6-fold higher AUC 0–8h 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.