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 (R1) and maximizing encapsulation efficiency (R2) and drug release (R3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R1, while factor A has a negative impact on R2 and R3. Interaction of AB was negative on R1 and R2 but positive on R3. The factor AC was having synergistic effect on R1 and on R3, while the same combination had a negative effect on R2. 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.