Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelation-ultrasonication method and evaluation of dispersion stability

Setenay Özer-önder; Timuçin Uğurlu

Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelation-ultrasonication method and evaluation of dispersion stability

Abstract

The main objective of this study was to optimize chitosan nanoparticles by exploring the relationship between design factors and experimental data through response surface methodology. A Box-Behnken design was employed, considering chitosan: tripolyphosphate ratio (X1), pH of the chitosan solution (X2), and ultrasonication amplitude (X3) as independent factors. Particle size, polydispersity index (PDI), and zeta potential served as the dependent variables. Nanoparticles were successfully prepared using a modified ionic gelation method incorporating an ultrasonic homogenizer and evaluated by models according to Box-Behnken Design. Surface plots were utilized to enhance the understanding of interactions between different variables. Results indicated that the chitosan ratio played the most significant role on both particle size and polydispersity, while the ultrasonic homogenizer amplitude predominantly influenced zeta potential. The models for particle size and polydispersity exhibited high accuracy (R², 0.9992 and 0.9955, respectively), whereas the zeta potential model demonstrated a lower R² value (0.7857) and lack of statistical significance. Comparison of predicted and actual data revealed larger error% values in the zeta potential model, exceeding the acceptable 15% threshold. Consequently, it was concluded that the ionic gelation-ultrasonic homogenizer technique, coupled with the Box-Behnken Design, is a rapid and effective approach for chitosan nanoparticle preparation and optimization. Additionally, aqueous dispersions of nanoparticles exhibited significant changes in particle size, polydispersity, and zeta potential values over one month at temperature and relative humidity conditions in accordance with ICH stability guidelines. This reinforced the recommendation that nanoparticles should be lyophilized and stored in a dry form.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Delivery Technologies

Journal Section

Research Article

Authors

Setenay Özer-önder This is me
0000-0002-1152-1333
Türkiye

Timuçin Uğurlu ^*
0000-0002-8874-5941
Türkiye

Publication Date

June 28, 2025

Submission Date

February 12, 2024

Acceptance Date

March 11, 2024

Published in Issue

Year 2024 Volume: 28 Number: 4

IZ

https://izlik.org/JA77KS29TS

Cite

RIS / Bibtex

APA

Özer-önder, S., & Uğurlu, T. (2025). Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelation-ultrasonication method and evaluation of dispersion stability. Journal of Research in Pharmacy, 28(4), 1057-1068. https://izlik.org/JA77KS29TS

AMA

1.Özer-önder S, Uğurlu T. Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelation-ultrasonication method and evaluation of dispersion stability. J. Res. Pharm. 2025;28(4):1057-1068. https://izlik.org/JA77KS29TS

Chicago

Özer-önder, Setenay, and Timuçin Uğurlu. 2025. “Application of Box-Behnken Design in the Optimization of Chitosan Nanoparticles Prepared by the Ionic Gelation-Ultrasonication Method and Evaluation of Dispersion Stability”. Journal of Research in Pharmacy 28 (4): 1057-68. https://izlik.org/JA77KS29TS.

EndNote

Özer-önder S, Uğurlu T (July 1, 2025) Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelation-ultrasonication method and evaluation of dispersion stability. Journal of Research in Pharmacy 28 4 1057–1068.

IEEE

[1]S. Özer-önder and T. Uğurlu, “Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelation-ultrasonication method and evaluation of dispersion stability”, J. Res. Pharm., vol. 28, no. 4, pp. 1057–1068, July 2025, [Online]. Available: https://izlik.org/JA77KS29TS

ISNAD

Özer-önder, Setenay - Uğurlu, Timuçin. “Application of Box-Behnken Design in the Optimization of Chitosan Nanoparticles Prepared by the Ionic Gelation-Ultrasonication Method and Evaluation of Dispersion Stability”. Journal of Research in Pharmacy 28/4 (July 1, 2025): 1057-1068. https://izlik.org/JA77KS29TS.

JAMA

1.Özer-önder S, Uğurlu T. Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelation-ultrasonication method and evaluation of dispersion stability. J. Res. Pharm. 2025;28:1057–1068.

MLA

Özer-önder, Setenay, and Timuçin Uğurlu. “Application of Box-Behnken Design in the Optimization of Chitosan Nanoparticles Prepared by the Ionic Gelation-Ultrasonication Method and Evaluation of Dispersion Stability”. Journal of Research in Pharmacy, vol. 28, no. 4, July 2025, pp. 1057-68, https://izlik.org/JA77KS29TS.

Vancouver

1.Setenay Özer-önder, Timuçin Uğurlu. Application of Box-Behnken design in the optimization of chitosan nanoparticles prepared by the ionic gelation-ultrasonication method and evaluation of dispersion stability. J. Res. Pharm. [Internet]. 2025 Jul. 1;28(4):1057-68. Available from: https://izlik.org/JA77KS29TS