In Situ Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles.

Abstract

The world's population is getting older and the number of people suffering from arthritis is a major problem according to World Health Organization's data. In this respect, the need for more efficient treatment for arthritis becomes an urgent issue. In this research, nanoparticle bearing in situ gelling hydrogel formulation was developed for prolonged local delivery of diclofenac sodium (DS). Emulsion-solvent evaporation technique was used for the preparation of nanoparticles. Particle size, encapsulation efficiency, morphology, and drug release profile of DS loaded biodegradable nanoparticles as well as gel viscosity and gelation time of in situ gelling hydrogel formulations were optimized to increase the time interval between each dose application for enhanced patience compliance. The spherical nanoparticles with a mean particle diameter of 168 nm was obtained and confirmed by both transmission electron microscope and atomic force microscope. Different types of surfactants were tested in the first emulsification step of nanoparticle production process and Arlacel®-C significantly increased the encapsulation efficiency to 89.7%. Thirty days prolonged in vitro release of DS was achieved by using the combined formulation of polymeric nanoparticles and in situ hydrogel prepared by using poloxomer 407 and chitosan. Local administration of DS with this novel delivery system could be considered of having potential to minimize side effects associated with decreased amount of drug in dosage form compared to conventional oral dose.