Investigation on Potential of Chitosan Nanoparticles for Oral Bioavailability Enhancement of Risedronate Sodium

Risedronate sodium (RS) is used in osteoporosis for bone reabsorption. It is a BCS class III drug having poor oral bioavailability (<0.63%) due to low permeability. In the present study, RS-loaded chitosan nanoparticles were developed to increase oral bioavailability and evaluated for various parameters. The DSC study indicated compatibility of RS with excipients in their physical mixture. The nanoparticles were prepared by ionotropic gelation technique and lyophilized. The optimized batch (RS-CNs) was found to have particles of size 268.7 nm and zeta potential of 24.9 mV. The TEM image of RS-CNs revealed discrete spherical particles. Angle of repose of 27.02 indicates good flow property of nanoparticles. FT-IR spectra of RS-CNs showed characteristic peaks of RS indicating compatibility of RS with the excipients. The mucin binding efficiency of RS-CNs was obtained as 63.42%. The in vitro release study of RS indicated controlled delivery from RS-CNs over 22 h. The release mechanism was found to be diffusion- and erosion-controlled release. Ex vivo study using rat intestine revealed faster permeation of 32.78% in 6 h from RS-CNs compared to plain drug solution. In vivo pharmacokinetic study in rats showed increased C_max (1.8 fold) from RS-CNs compared to marketed formulation. The relative bioavailability of 193% from RS-CNs indicated significant enhancement in bioavailability upon nanoparticle formulation. The RS-CNs were found to be stable at room and refrigerated conditions. In conclusion, developed RS-loaded chitosan nanoparticles seem to be a promising approach to increase oral bioavailability and can avoid upper GI tract side effects.