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AAPS PharmSciTech. 2003 December; 4(4): 565–573.
Published online 2003 October 11. doi:  10.1208/pt040471
PMCID: PMC2750664

Optimization of polylactic-co-glycolic acid nanoparticles containing itraconazole using 23 factorial design

Abstract

This study investigated the utility of a 23 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 PLGAX1 (10, 100 mg/mL), benzyl benzoateX2 (5, 20 μg/mL), and itraconazoleX3 (200, 1800 μg/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, andX3 had a significant effect (P<.001) onY1,Y2, andY3. 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 whichY1 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 μg/mL of benzyl benzoate, and 1001.01 μg/mL of itraconazole. This approach allowed the selection of the optimum formulation ingredients for PLGA nanoparticles containing itraconazole of 500 μg/mL.

Keywords: itraconazole, nanoparticles, PLGA, 23 factorial design, formulation optimization

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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