

Taguchi method-based optimization of key parameters for the preparation of poly(lactic-co-glycolic acid) microspheres to enhance betamethasone acetate loading
https://doi.org/10.26896/1028-6861-2025-91-9-19-27
Abstract
This study presents an investigation into the effects of key process parameters on the encapsulation of betamethasone acetate (BA) in poly(lactic-co-glycolic acid) (PLGA) microspheres. The Taguchi method was employed to identify the most influential factors affecting microsphere characteristics. The experimental design included variation of several parameters: PLGA concentration, BA concentration, the aqueous-to-organic phase ratio and stirring speed. The results indicate that BA loading is primarily influenced by its own concentration and the polymer concentration. High-performance liquid chromatography was used for determination of betamethasone acetate. Optimal loading was achieved at PLGA and drug concentrations of 100 and 20 mg/mL, respectively, an aqueous-to-organic phase ratio of 50:1, and a stirring speed of 500 rpm. Under these conditions, the drug loading reached 4.35%, compared to 1.44% prior to optimization. These findings may support the refinement of PLGA microsphere preparation techniques for other active pharmaceutical ingredients with similar physicochemical properties.
About the Authors
Yu. V. UlianovaRussian Federation
Yulia V. Ulianova
9, Miusskaya pl., Moscow, 125047
E. G. Vinokurov
Russian Federation
Evgeny G. Vinokurov
9, Miusskaya pl., Moscow, 125047
31, Leninsky prosp., Moscow, 119071
20, ul. Usievicha, Moscow, 125190
Yu. V. Ermolenko
Russian Federation
Yulia V. Ermolenko
9, Miusskaya pl., Moscow, 125047
A. N. Morozov
Russian Federation
Aleksandr N. Morozov
9, Miusskaya pl., Moscow, 125047
References
1. Shetab Boushehri M. A., Dietrich D., Lamprecht A. Nanotechnology as a platform for the development of injectable parenteral formulations: a comprehensive review of the know-hows and state of the art / Pharmaceutics. 2020. Vol. 12. No. 6. 510. DOI: 10.3390/pharmaceutics12060510.
2. Muddineti O. S., Omri A. Current trends in PLGA based long-acting injectable products: the industry perspective / Expert Opin. Drug Delivery. 2022. Vol. 19. No. 5. P. 559 – 576. DOI: 10.1080/17425247.2022.2075845
3. Wan B., Bao Q., Burgess D. Long-acting PLGA microspheres: Advances in excipient and product analysis toward improved product understanding / Adv. Drug Delivery Rev. 2023. Vol. 198. 114857. DOI: 10.1016/j.addr.2023.114857
4. Huang H., Zijian L., Shimin Z., et al. Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage / Drug Delivery. 2022. Vol. 29. No. 1. P. 767 – 791. DOI: 10.1080/10717544.2022.2048130
5. Bhujel R., Maharjan R., Kim N., Jeong S. Practical quality attributes of polymeric microparticles with current understanding and future perspectives / J. Drug Delivery Sci. Technol. 2021. Vol. 64. 102608. DOI: 10.1016/j.jddst.2021.102608
6. Berkland C., King M., Cox A., et al. Precise control of PLG microsphere size provides enhanced control of drug release rate / J. Controlled Release. 2002. Vol. 82. No. 1. P. 137 – 147. DOI: 10.1016/s0168-3659(02)00136-0
7. Siepmann J., Faisant N., Akiki J., et al. Effect of the size of biodegradable microparticles on drug release: experiment and theory / J. Controlled Release. 2004. Vol. 96. No. 1. P. 123 – 134. DOI: 10.1016/j.jconrel.2004.01.011
8. Wee C. Y., Tjieh Q. R., Zhao Y., et al. Optimizing fabrication parameters via Taguchi method for production of high yield hydroxyapatite microsphere scaffolds using Drop-on-Demand inkjet method / J. Biomed. Mater. Res., Part B. 2023. Vol. 111. No. 11. P. 1938 – 1955. DOI: 10.1002/jbm.b.35297
9. Vinokurov E. G., Gainetdinov C. R., Grafushin R. V., et al. Study of crucial factors for minimizing the roughness of chemical coatings with Ni – P and Ni – Cu – P alloys / Industr. Lab. Mater. Diagn. 2024. Vol. 90. No. 2. P. 29 – 38 [in Russian]. DOI: 10.26896/1028-6861-2024-90-2-29-38
10. Leon R., Shoemaker A., Kackar R., et al. Quality control, robust design, and the taguchi method. — Moscow: Seify, 2002. — 384 p. [Russian translation].
11. Haidar M. K., Yamashita F., Hashida M. Minocycline hydrochloride controlled-release microsphere preparation process optimization based on the robust design method / Turk. J. Pharm. Sci. 2021. Vol. 18. No. 6. P. 752 – 760. DOI: 10.4274/tjps.galenos.2021.56492
12. Vysloužil J., Doležel P., Kejdušová M., et al. Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis / Acta Pharm. 2014. Vol. 64. No. 4. P. 403 – 417. DOI: 10.2478/acph-2014-0032
13. Zhai J., Ou Z., Zhong L., et al. Exenatide-loaded inside-porous poly(lactic-co-glycolic acid) microspheres as a long-acting drug delivery system with improved release characteristics / Drug Delivery. 2020. Vol. 27. No. 1. P. 1667 – 1675. DOI: 10.1080/10717544.2020.1850919
14. Ramazani F., Chen W., van Nostrumet C., et al. Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: state-of-the-art and challenges / Int. J. Pharm. 2016. Vol. 499. P. 358 – 367. DOI: 10.1016/j.ijpharm.2016.01.020
15. Orlov A. I. System fuzzy interval mathematics: the basis of tools of mathematical research methods / Industr. Lab. Mater. Diagn. 2022. Vol. 88. No. 7. P. 5 – 7 [in Russian]. DOI: 10.26896/1028-6861-2022-88-7-5-7
16. Orlov A. I. On the requirements for statistical methods of data analysis (generalizing article) / Industr. Lab. Mater. Diagn. 2023. Vol. 89. No. 11. P. 98 – 106 [in Russian] DOI: 10.26896/1028-6861-2023-89-11-98-106
17. Roy R. Design of experiments using the Taguchi approach. 16 steps to product and process improvement. — Hoboken: John Wiley & Sons, Ltd, 2001. — 569 p.
18. Park K., Skidmore S., Hadar J., et al. Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation / J. Controlled Release. 2019. Vol. 304. P. 125 – 134. DOI: 10.1016/j.jconrel.2019.05.003
19. Sarmadi M., Behrens A., McHugh K., et al. Modeling, design, and machine learning-based framework for optimal injectability of microparticle-based drug formulations / Sci. Adv. 2022. Vol. 6. No. 28. eabb6594. DOI: 10.1126/sciadv.abb6594
20. Dinarvand R., Moghadam S., Mohammadyari-Fard L., Atyabi F. Preparation of biodegradable microspheres and matrix devices containing naltrexone / AAPS Pharm. Sci. Tech. 2003. Vol. 4. No. 3. P. 34. DOI: 10.1208/pt040334
21. Chen W., Palazzo A., Hennink W. E., Kok R. J. Effect of particle size on drug loading and release kinetics of gefitinib-loaded PLGA microspheres / Mol. Pharm. 2017. Vol. 14. No. 2. P. 459 – 467. DOI: 10.1021/acs.molpharmaceut.6b00896
Review
For citations:
Ulianova Yu.V., Vinokurov E.G., Ermolenko Yu.V., Morozov A.N. Taguchi method-based optimization of key parameters for the preparation of poly(lactic-co-glycolic acid) microspheres to enhance betamethasone acetate loading. Industrial laboratory. Diagnostics of materials. 2025;91(9):19-27. (In Russ.) https://doi.org/10.26896/1028-6861-2025-91-9-19-27