Abstract

EVAPORATIVE NANOCRYSTALLIZATION FOR ENHANCED SOLUBILITY AND BIOAVAILABILITY OF SULFASALAZINE

Monica Rp. Rao* and V.M. Pawar

Abstract

The purpose of the present study was to increase the aqueous solubility of sulfasalazine (0.045mg/ml) by nanaocrystallization and preparation of controlled multiparticulate drug delivery. Sulfasalazine is mainly used for inflammatory bowel diseases (Crohn’s colitis and ulcerative colitis). Sulfasalazine nanosuspensions were prepared by bottom up i.e. antisolvent precipitation technique using stabilizers such as tocopherolpolythytlene glycol succinate and polyvinylpyrrolidone K30 in combination (30%:70%). Nanosuspensions were characterized for particle size distribution, polydispersity index and zeta potential. Plain sulfasalazine and lyophilized sulfasalazine were evaluated and compared to each other by FTIR, PXRD, FESEM, saturation solubility and wettability. A 32factorial design was used to examine the effect of independent variables like stabilizer concentration and speed of stirring on particle size. Optimized batch had particle size of 251 ±6.23 nm and polydispersity index of 0.171. Zeta potential values ranged from -5 to -13 mV. Optimized nanosuspension was loaded on Espheres by pan coating, followed by coating with pH responsive polymers Eudragit S100 and Eudragit L100 for controlled drug release. Espheres were evaluated for drug content, (i.e. 91% to 94% for sulfasalazine suspension and 100% to 101% for sulfasalazine) and drug release kinetics (Sulfasalazine suspension secondary coated Espheres were found to 99.20 % drug release and Sulfasalazine nanosuspension secondary coated Espheres released 94.3 % of drug in 10 h). Results of evaluations indicate that multiparticulate systems are beneficial for treatment of inflammatory bowel diseases (IBD). It was concluded from the study that Eudragit-coated Espheres were promising carriers for faster but controlled and uniform drug release.

Keywords: Solubility, Nanocrystals, Stabilization, Coating, Controlled drug delivery.