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The present research was designed to improve the permeability of sulfasalazine by loading it into chitosan nanoparticles using the ionic gelation method. The process parameters were screened and optimized through Box-Behnken design. 13 formulations containing sulfasalazine chitosan-based nanoparticles (SCSNPs) were optimized using particle size, zeta potential, and % encapsulation efficiency as responses. Results were optimized based on the desirability function shown in 2D contour plots and 3D response surface plots. The effect of every factor on responses was statistically analyzed using ANOVA and p-Value, and the correlation coefficient of all the responses was found to be >0.99 and >0.96 for optimized CSNPs and optimized SCSNPs respectively with p<0.05. From the predicted and observed values of responses, the optimized formulation (SCSNPs) has a particle size of 261±3.06 nm, with an encapsulation efficiency of 81.3±5.3%. Morphology of the particles using scanning electron microscopy reveals nearly spherical shaped particles with a zeta potential of +41.4±0.5 mV. In-vitro studies acknowledge that sulfasalazine was released in a sustained manner for about 24 hrs in simulated colonic fluid pH 7 and phosphate buffer pH 7.4, when compared to a simulated colonic fluid at fed (pH 6) and fasted state (pH 7.8). Optimized SCSNPs followed Korsmeyer Peppas kinetics with a drug release mechanism as non-fickian diffusion (anomalous transport).
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