Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box-Behnken experimental design

Indomethacin chitosan nanoparticles (NPs) were developed by ionotropic gelation and optimized by concentrations of chitosan and tripolyphosphate (TPP) and stirring time by 3-factor 3-level Box-Behnken experimental design. Optimal concentration of chitosan (A) and TPP (B) were found 0.6 mg/mL and 0.4 mg/mL with 120 min stirring time (C), with applied constraints of minimizing particle size (R-1) and maximizing encapsulation efficiency (R-2) and drug release (R-3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R-1, while factor A has a negative impact on R-2 and R-3. Interaction of AB was negative on R-1 and R-2 but positive on R3. The factor AC was having synergistic effect on R-1 and on R-3, while the same combination had a negative effect on R-2. The interaction BC was positive on the all responses. NPs were found in the size range of 321-675 nm with zeta potentials (+25 to +32 mV) after 6 months storage. Encapsulation, drug release, and content were in the range of 56-79%, 48-73% and 98-99%, respectively. In vitro drug release data were fitted in different kinetic models and pattern of drug release followed Higuchi-matrix type. (C) 2016 Elsevier B.V. All rights reserved.