Optimization of polylactic-co-glycolic acid nanoparticles containing itraconazole using 2(3) factorial design.

This study investigated the utility of a 2(3) factorial design and optimization process for polylactic-co-glycolic acid (PLGA) nanoparticles containing itraconazole with 5 replicates at the center of the design. Nanoparticles were prepared by solvent displacement technique with PLGA X1 (10, 100 mg/mL), benzyl benzoate X2 (5, 20 microg/mL), and itraconazole X3 (200, 1800 microg/mL). Particle size (Y1), the amount of itraconazole entrapped in the nanoparticles (Y2), and encapsulation efficiency (Y3) were used as responses. A validated statistical model having significant coefficient figures (P < .001) for the particle size (Y1), the amount of itraconazole entrapped in the nanoparticles (Y2), and encapsulation efficiency (Y3) as function of the PLGA (X1), benzyl benzoate (X2), and itraconazole (X3) were developed: Y1 = 373.75 + 66.54X1+ 52.09X2 + 105.06X3 - 4.73X1X2 + 46.30X1X3; Y2 = 472.93 + 73.45X1 + 169.06X2 + 333.03X3 + 62.40X1X3 + 141.49X2X3; Y3 = 57.36 + 6.53X1 + 15.52X2 - 12.59X3 + 1.01X1X3 + 1.73X2X3. X1, X2, and X3 had a significant effect (P < .001) on Y1, Y2, and Y3. The particle size, the amount of itraconazole entrapped in the nanoparticles, and the encapsulation efficiency of the 4 formulas were in agreement with the predictions obtained from the models (P < .05). An overlay plot for the 3 responses shows the boundary in which Y1 shows the boundary in which a number of combinations of concentration of PLGA, benzyl benzoate, and itraconazole will result in a satisfactory process. Using the desirability approach with the same constraints, the solution composition having the highest overall desirability (D = 0.769) was 10 mg/mL of PLGA, 16.94 microg/mL of benzyl benzoate, and 1001.01 microg/mL of itraconazole. This approach allowed the selection of the optimum formulation ingredients for PLGA nanoparticles containing itraconazole of 500 microg/mL.