23 Full Factorial Model for Particle Size Optimization of Methotrexate Loaded Chitosan Nanocarriers: A Design of Experiments (DoE) Approach

Purpose. To build and inquire a statistically significant mathematical model for manufacturing methotrexate loaded chitosan nanoparticles (CsNP) of desired particle size. The study was also performed to evaluate the effect of formulation variables in the explored design space. Method. Ionotropic gelation technique was followed for chitosan nanocarriers by changing formulation variables suggested as per Design Expert software. Altering the levels of Chitosan, tripolyphosphate, methotrexate by 2(3) factorial design served the purpose. The CsNP were characterized for nanocarrier formation, particle size, and statistical analysis. 'Ten mathematical model was statistically analyzed for fabricating desired formulation having particle size less than 200nm. Results. FT-IR, XRD reports confirmed the structural change in chitosan which lead to the formation of CsNP. For particle size, linear model was found to be best fit to explain effect of variables. Besides, high R-2 (0.9958) defends the constancy of constructed model. Chitosan exhibited higher t-value in Pareto chart and a p-value <0.0001. Based on maximum desirability, optimization was performed and amount of variables for preparing CsNP of 180nm was predicted. The experiment was carried out with software suggested combination and particle size was found to be 176 +/- 4nm. Conclusion. Low p-value endorsed the greater dominance of chitosan on particle size. Good model adequacy and small percentage error between predicted and experimented value established the reliability of constructed model for robust preparation of CsNP.