Improvement in Ocular Bioavailability and Prolonged Delivery of Tobramycin Sulfate Following Topical Ophthalmic Administration of Drug-Loaded Mucoadhesive Microparticles Incorporated in Thermosensitive In Situ Gel.

PURPOSE: Conventional topical delivery in hyperacute bacterial conjunctivitis and endophthalmitis is associated with low drug bioavailability due to rapid precorneal clearance. Hence, in the present investigation, an attempt has been made to enhance ocular bioavailability of tobramycin sulfate by formulating drug-loaded microparticles dispersed in thermosensitive in situ gel.

METHODS: Microparticles prepared by emulsion-ionic gelation technique were characterized for drug loading, entrapment efficiency, particle size, surface morphology, and in vitro drug release. Consequently microparticles (F2 prepared with 1.5%w/v chitosan, 0.2%w/v tripolyphosphate, and drug, 30%w/w of polymer) with high drug loading and encapsulation efficiency were dispersed in thermosensitive in situ gel containing poloxamer 407 and varying percentage of chitosan. In situ gel containing drug-loaded microparticles were evaluated for gelation temperature, rheological behavior, mucoadhesive strength, in vitro drug release, in vitro permeation, ocular irritation, and bioavailability in aqueous humor of rabbits.

RESULTS: Formulation containing 17%w/v poloxamer 407 and 0.5%w/v chitosan (P2) gelled at 32°C ± 1.5°C gave pseudoplastic behavior. In vitro permeability of tobramycin from the formulation P2 was found 2-folds greater than eye drops. It also gave significantly higher aqueous humor concentration of tobramycin compared with eye drops with no signs of ocular irritation.

CONCLUSION: Thus, the formulation possesses high potential for treating ocular infections.