Formulation and characterization of ezetimibe nanoparticles for hyperlipidemia treatment

Authors

DOI:

https://doi.org/10.15587/2519-4852.2026.359581

Keywords:

Ezetimibe, HPLC, sodium alginate, nanoparticles

Abstract

The aim of the work. Ezetimibe (EZ) is categorized as a Biopharmaceutics Classification System class II (BCS II) agent that possesses poor solubility and is highly permeable. This work aimed to incorporate EZ into nanoparticles (NPs) to accelerate release and to enhance its bioavailability.

Materials and Methods. A stability-indicating method for the computation of EZ was developed to compute EZ in NPs in fresh and stored samples. Nine formulations of EZ-NPs were developed by solvent evaporation using HPMC 6 cps, sodium alginate, and Tween 80 in various proportions. A HPLC method was designed to estimate EZ in NPs. EZ-NPs were tested chemically and characterized.

Results. The developed method was fully validated, and EZ NPs comprising HPMC and tween 80 had zeta potential (ZP) ranging from -21.6 mV to -30.1 mV, higher than other formulae, and their release was enhanced. The formulation (HP4) had an elevated ZP (-30.1 mV) and released about 91% of EZ within 20 min. HP4 was chosen for stability assessment and proved to be stable.

Conclusion. The formulation (HP4), including 0.1:0.5:0.4 ratios of the EZ: HPMC: sodium alginate, was the optimized EZ-NPs formulation. Microencapsulation of EZ with HPMC: sodium alginate in a 0.1:0.5:0.4 ratio could enhance the release and achieve stability

Author Biographies

Asmaa Abdelaziz Mohamed, Al-Zahraa University for Women

PhD of Pharmaceutics, Lecturer

College of Pharmacy

Olla Maan, Al-Mansour University College

Master's in Pharmaceutics, Assistant Lecturer

Department of Pharmacy

Firas Aziz Rahi, Al-Mansour University College

Professor Doctor in Pharmaceutics, Head of Department

Department of Pharmacy

Doaa Zakaria Elkashif, Queensway Carleton Hospital

Master’s in Medical Laboratory Sciences, Medical Laboratory Scientist

References

  1. Nițu, E.-T., Jianu, N., Merlan, C., Foica, D., Sbârcea, L., Buda, V. et al. (2025). A Comprehensive Review of the Latest Approaches to Managing Hypercholesterolemia: A Comparative Analysis of Conventional and Novel Treatments: Part I. Life, 15 (8), 1185. https://doi.org/10.3390/life15081185
  2. Kumari, L., Rani, D. (2025). A Concise overview of diverse analytical techniques for ezetimibe estimation. Microchemical Journal, 209, 112561. https://doi.org/10.1016/j.microc.2024.112561
  3. Torrado-Salmerón, C., Guarnizo-Herrero, V., Gallego-Arranz, T., del Val-Sabugo, Y., Torrado, G., Morales, J., Torrado-Santiago, S. (2020). Improvement in the Oral Bioavailability and Efficacy of New Ezetimibe Formulations – Comparative Study of a Solid Dispersion and Different Micellar Systems. Pharmaceutics, 12 (7), 617. https://doi.org/10.3390/pharmaceutics12070617
  4. Lipinski, C. A. (2000). Drug-like properties and the causes of poor solubility and poor permeability. Journal of Pharmacological and Toxicological Methods, 44 (1), 235–249. https://doi.org/10.1016/s1056-8719(00)00107-6
  5. Zhuo, Y., Zhao, Y.-G., Zhang, Y. (2024). Enhancing Drug Solubility, Bioavailability, and Targeted Therapeutic Applications through Magnetic Nanoparticles. Molecules, 29 (20), 4854. https://doi.org/10.3390/molecules29204854
  6. A. Ali, Y., N. Abd-Alhammid, S. (2017). Formulation and Evaluation of Ezetimibe Nanoparticles. Iraqi Journal of Pharmaceutical Sciences, 24 (2), 11–21. https://doi.org/10.31351/vol24iss2pp11-21
  7. Q 2 (R1) Validation of Analytical Procedures: Text and Methodology (1995). European Medicines Agency. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-q2r1-validation-analytical-procedures-text-methodology-step-5-first-version_en.pdf
  8. The Pharmacopoeia of United States of America (2020). National Formulary 38, Mack publishing Co. Easton, vol. 2. Available at: http://182.160.97.198:8080/xmlui/handle/123456789/1493
  9. Singh, R., Popli, H., Suryawanshi, M. (2025). Development and validation of an HPLC analytical method for the simultaneous estimation of vitamin B12 and folic acid. Essential Chem, 2 (1), 1–9. https://doi.org/10.1080/28378083.2025.2462931
  10. Rostami, E. (2021). Recent achievements in sodium alginate-based nanoparticles for targeted drug delivery. Polymer Bulletin, 79 (9), 6885–6904. https://doi.org/10.1007/s00289-021-03781-z
  11. Filimon, A., Onofrei, M. D., Bargan, A., Stoica, I., Dunca, S. (2023). Bioactive Materials Based on Hydroxypropyl Methylcellulose and Silver Nanoparticles: Structural-Morphological Characterization and Antimicrobial Testing. Polymers, 15 (7), 1625. https://doi.org/10.3390/polym15071625
  12. Li, H.-J., Zhang, A.-Q., Hu, Y., Sui, L., Qian, D.-J., Chen, M. (2012). Large-scale synthesis and self-organization of silver nanoparticles with Tween 80 as a reductant and stabilizer. Nanoscale Research Letters, 7 (1). https://doi.org/10.1186/1556-276x-7-612
  13. Elhassan, E., Omolo, C. A., Gafar, M. A., Ismail, E. A., Ibrahim, U. H., Khan, R. et al. (2025). Multifunctional hyaluronic acid-based biomimetic/pH-responsive hybrid nanostructured lipid carriers for treating bacterial sepsis. Journal of Biomedical Science, 32 (1). https://doi.org/10.1186/s12929-024-01114-6
  14. Jafar, M., Sajjad Ahmad Khan, M., Salahuddin, M., Zahoor, S., MohammedHesham Slais, H., Ibrahim Alalwan, L., Radhi Alshaban, H. (2023). Development of apigenin loaded gastroretentive microsponge for the targeting of Helicobacter pylori. Saudi Pharmaceutical Journal, 31 (5), 659–668. https://doi.org/10.1016/j.jsps.2023.03.006
  15. Castro, S. R., Ribeiro, L. N. M., Breitkreitz, M. C., Guilherme, V. A., Rodrigues da Silva, G. H., Mitsutake, H. et al. (2021). A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers. Scientific Reports, 11 (1). https://doi.org/10.1038/s41598-021-99743-6
  16. Dissolution Methods. FDA. Available at: https://www.accessdata.fda.gov/scripts/cder/dissolution/dsp_SearchResults.cfm
  17. Rahi, F. A., Mohammed Ameen, M. S., Fayyadh, M. S. (2021). Linagliptin and gliclazide di-loaded extended-release nanoparticles: formulation and evaluation. Wiadomości Lekarskie, 74 (9), 2315–2322. https://doi.org/10.36740/wlek202109212
  18. Rahi, F. A., Ameen, M. S. M., Jawad, K. K. M. (2022). Preparation and evaluation of lipid matrix microencapsulation for drug delivery of azilsartan kamedoxomil. ScienceRise: Pharmaceutical Science, 6 (40), 21–28. https://doi.org/10.15587/2519-4852.2022.270306
  19. Singh, N., Akhtar, M. J., Anchliya, A. (2021). Development and Validation of HPLC Method for Simultaneous Estimation of Reduced and Oxidized Glutathione in Bulk Pharmaceutical Formulation. Austin Journal of Analytical and Pharmaceutical Chemistry, 8 (1). https://doi.org/10.26420/austininternmed.2021.1129
  20. Sudha, T., Sumithra, M., Ajith, U. (2024). A review of analytical method development and validation of labetalol hydrochloride. Annals of Phytomedicine an International Journal, 13 (1). https://doi.org/10.54085/ap.2024.13.1.38
  21. Mahapatra, A., Sreedhar, C. (2018). HPLC and analytical method validation: a review. Indian Research Journal of Pharmacy and Science, 5 (1), 1399–1414. https://doi.org/10.21276/irjps.2018.5.1.18
  22. Nakatuka, Y., Yoshida, H., Fukui, K., Matuzawa, M. (2015). The effect of particle size distribution on effective zeta-potential by use of the sedimentation method. Advanced Powder Technology, 26 (2), 650–656. https://doi.org/10.1016/j.apt.2015.01.017
  23. Elkhayat, D., Abdelmalak, N. S., Amer, R., Awad, H. H. (2025). Ezetimibe Loaded Nanostructured Lipid Carriers Tablets: Response Surface Methodology, In-vitro Characterization, and Pharmacokinetics Study in Rats. Journal of Pharmaceutical Innovation, 20 (1). https://doi.org/10.1007/s12247-024-09911-0
  24. Tulain, U. R., Mahmood, A., Aslam, S., Erum, A., Shamshad Malik, N., Rashid, A. et al. (2021). Formulation and Evaluation of Linum usitatissimum Mucilage-Based Nanoparticles for Effective Delivery of Ezetimibe. International Journal of Nanomedicine, 16, 4579–4596. https://doi.org/10.2147/ijn.s308790
Formulation and characterization of ezetimibe nanoparticles for hyperlipidemia treatment

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Published

2026-04-30

How to Cite

Mohamed, A. A., Maan, O., Rahi, F. A., & Elkashif, D. Z. (2026). Formulation and characterization of ezetimibe nanoparticles for hyperlipidemia treatment. ScienceRise: Pharmaceutical Science, (2 (60), 111–117. https://doi.org/10.15587/2519-4852.2026.359581

Issue

No. 2 (60) (2026)

Section

Pharmaceutical Science

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Copyright (c) 2026 Asmaa Abdelaziz Mohamed, Olla Maan, Firas Aziz Rahi, Doaa Zakaria Elkashif

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