Development and Evaluation of Diclofenac Sodium Loaded-N-Trimethyl Chitosan Nanoparticles for Ophthalmic Use.

Abstract

The ophthalmic preparation of diclofenac sodium (DC) for relieving ocular inflammation is presently available in the market only as an eye drop solution. Due to its low occular bioavailability, it requires frequent application leading to low patients' compliance and quality of life. This study was conducted to develop formulations of DC loaded-N-trimethyl chitosan nanoparticles (DC-TMCNs) for ophthalmic use to improve ocular biavailabiltiy of DC. DC-TMCNs varied in formulation compositions were prepared using ionic gelation technique and evaluated for their physicochemical properties, drug release, eye irritation potential, and ophthalmic absorption of diclofenac sodium. N-Trimethyl chitosan (TMC) with a 49.8% degree of quaternization was synthesized and used for DC-TMCNs production. The obtained DC-TMCNs had particle size in a range of 130-190 nm with zeta potential values of +4 to +9 mV and drug entrapment efficiencies of more than 70% depending on the content of TMC and sodium tripolyphosphate (TPP). The optimized DC-TMCNs formulation contained TMC, DC, and TPP at a weight ratio of TMC/DC/TPP = 3:1:1. Their lyophilized product reconstituted with phosphate buffer solution pH 5.5 possessed a drug release pattern that fitted within the zero-order model. The eye irritation tests showed that DC-TMCNs were safe for ophthalmic use. The in vivo ophthalmic drug absorption study performed on rabbits indicated that DC-TMCNs could improve ophthalmic bioavailability of DC. Results of this study suggested that DC-TMCNs had potential for use as an alternative to conventional DC eye drops for ophthalmic inflammation treatment.