Characterization of Hesperidin-PEG 1000 Solid Dispersion Prepared by Freeze Drying Method
DOI:
https://doi.org/10.24036/eksakta/vol27-iss04/702Keywords:
hesperidin, peg 1000, solubility, solid dispersion system, freeze dryingAbstract
Hesperidin is a disaccharide-derivative bioflavonoid in BCS class II, insoluble in water but soluble in propylene glycol and polyethylene glycol, and its poor aqueous solubility may impair bioavailability, necessitating modification via solid dispersion. In this study, a hesperidin–PEG 1000 system was prepared at 1:1 and 1:6 hesperidin:PEG 1000 ratios using freeze‑drying. The systems were characterised for crystallinity, thermal behaviour, vibrational transitions, and particle morphology. PXRD patterns recorded over 2θ = 5–40° showed that both solid dispersions retained the main diffraction peaks of pure hesperidin with reduced intensities, indicating preservation of a predominantly crystalline structure. DSC thermograms revealed a hesperidin melting peak at 261.0 °C for the pure drug, which shifted to 248.6 °C and 241.0 °C for the 1:1 and 1:6 systems, respectively, without disappearance of the drug melting event. Data from FTIR and SEM further indicated only minor molecular interactions and limited morphological changes, and the characterisation results for both ratios were essentially identical. Taken together, these findings indicate that freeze‑drying hesperidin with PEG 1000 under the applied conditions did not convert hesperidin into an amorphous, molecularly dispersed solid dispersion, but yielded a predominantly crystalline, hesperidin‑dominated system with minimal PEG 1000 incorporation.
Downloads
References
[1] Bhalani, D. V., Nutan, B., Kumar, A., & Singh Chandel, A. K. (2022). Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics. Biomedicines, 10(9).
[2] Kumar, S. V. P., Vishwanath, B. A., & Swapna, D. (2024). Enhancement of solubility and dissolution rate of BCS class II drugs. International Journal of Pharmaceutical Sciences Review and Research, 84(7).
[3] Shekaari, H., Zafarani-Moattar, M. T., Mokhtarpour, M., & Faraji, S. (2023). Solubility of hesperidin drug in aqueous biodegradable acidic choline chloride-based deep eutectic solvents. Scientific Reports, 13(1).
[4] Swarup, P., & Agrawal, G. P. (2024). Development of hesperidin solid dispersion for improved solubility and dissolution using mannitol and PVP K30 as carriers. Journal of Applied Pharmaceutical Research, 12(6), 192–202.
[5] Xie, B., Liu, Y., Li, X., Yang, P., & He, W. (2024). Solubilization techniques used for poorly water-soluble drugs. Acta Pharmaceutica Sinica B, 14(11), 4683–4716.
[6] Hashmi, A. R., Sekar, M., Zahra, F., Molugulu, N., & Wong, L. S. (2025). Advanced drug delivery strategies to overcome solubility and permeability challenges: Driving biopharmaceutical advancements toward commercial success. ACS Omega, 10(36), 40769–40792.
[7] Tekade, A. R., & Yadav, N. J. (2020). A review on solid dispersion and carriers used therein for solubility enhancement of poorly water soluble drugs. Advanced Pharmaceutical Bulletin, 359–369.
[8] Pisano, R., & Fissore, D. (2023). New trends in freeze-drying of pharmaceutical products. Pharmaceutics, 15(7).
[9] Bessarabov, V., Lisovyi, V., Lyzhniuk, V., Kostiuk, V., Smishko, R., Yaremenko, V., ... & Melnyk, V. (2025). Development and characterisation of polymeric solid dispersed systems of hesperidin, obtained by centrifugal fibre formation. Heliyon, 11(4).
[10] Pardeshi, S. R., Deshmukh, N. S., Telange, D. R., Nangare, S. N., Sonar, Y. Y., Lakade, H. S., ... & Sangshetti, J. N. (2023). Process development and quality attributes for the freeze-drying process in pharmaceuticals, biopharmaceuticals and nanomedicine delivery: A state-of-the-art review. Future Journal of Pharmaceutical Sciences, 9(1).
[11] Khorasanian, A. S., Fateh, S. T., Gholami, F., Rasaei, N., Gerami, H., Khayyatzadeh, S. S., ... & Asbaghi, O. (2023). The effects of hesperidin supplementation on cardiovascular risk factors in adults: A systematic review and dose–response meta-analysis. Frontiers in Nutrition, 10.
[12] Paczkowska-Walendowska, M., Miklaszewski, A., & Cielecka-Piontek, J. (2023). Improving solubility and permeability of hesperidin through electrospun orange-peel-extract-loaded nanofibers. International Journal of Molecular Sciences, 24(9).
[13] Gerasimov, A. V., Ziganshin, MA., Gorbatchuk, V. V., & Usmanova, L. S. (2013). Formation of solid dispersion of PEG-1000 with phenacetin according to differential scanning calorimetry. Der Pharma Chemica, 5(4), 133–139.
[14] Mundada, A. S. (2021). Solid dispersion: A review. International Journal of Pharmacy Research & Technology, 11(2).
[15] Almeida, H., Ferreira, B., Fernandes-Lopes, C., Araújo, F., Bonifacio, M. J., Vasconcelos, T., ... & Soares-da-Silva, P. (2024). Third-generation solid dispersion through lyophilization enhanced oral bioavailability of resveratrol. ACS Pharmacology & Translational Science, 7(3), 888–898.
[16] Bessarabov, V., Lisovyi, V., Lyzhniuk, V., Kostiuk, V., Smishko, R., Yaremenko, V., ... & Melnyk, V. (2025). Development and characterisation of polymeric solid dispersion systems of hesperidin obtained by the method of centrifugal fibre formation.
[17] Yaghoubi, N., Gholamzad, A., Naji, T., & Gholamzad, M. (2024). In vitro evaluation of PLGA loaded hesperidin on colorectal cancer cell lines: An insight into nano delivery system. BMC Biotechnology, 24(1).
[18] Brogly, M., Bistac, S., & Bindel, D. (2024). Adsorption and structuration of PEG thin films: Influence of the substrate chemistry. Polymers, 16(9).
[19] Rosiak, N., Wdowiak, K., Tykarska, E., & Cielecka-Piontek, J. (2022). Amorphous solid dispersion of hesperidin with polymer excipients for enhanced apparent solubility as a more effective approach to the treatment of civilization diseases. International Journal of Molecular Sciences, 23(23).
[20] Invernizzi, C., Rovetta, T., Licchelli, M., & Malagodi, M. (2018). Mid and near-infrared reflection spectral database of natural organic materials in the cultural heritage field. International Journal of Analytical Chemistry, 2018.
[21] Sip, S., Sip, A., Miklaszewski, A., Żarowski, M., & Cielecka-Piontek, J. (2023). Zein as an effective carrier for hesperidin delivery systems with improved prebiotic potential. Molecules, 28(13).
[22] Dai, F., Zhuang, Q., Huang, G., Deng, H., & Zhang, X. (2023). Infrared spectrum characteristics and quantification of OH groups in coal. ACS Omega, 8(19), 17064–17076.
[23] Campanale, C., Savino, I., Massarelli, C., & Uricchio, V. F. (2023). Fourier transform infrared spectroscopy to assess the degree of alteration of artificially aged and environmentally weathered microplastics. Polymers, 15(4).
[24] Patel, K., Shah, S., & Patel, J. (2022). Solid dispersion technology as a formulation strategy for the fabrication of modified release dosage forms: A comprehensive review. DARU Journal of Pharmaceutical Sciences, 165–189.
[25] De Oliveira Cardoso Melo, M. E., Castro da Silva, C., Dos Santos Dantas, T., Barbosa Machado, JC., Assunção Ferreira, M. R., & Lira Soares, L. A. (2026). Amorphous solid dispersions as a strategy to enhance the bioavailability and stability of formulations containing plant active ingredients: An integrative review. DARU Journal of Pharmaceutical Sciences.
[26] Xiao, H., Feng, Y., Goundry, W. R. F., & Karlsson, S. (2024). Organic solvent nanofiltration in pharmaceutical applications. Organic Process Research & Development, 891–923.
[27] Rosiak, N., Wdowiak, K., Tykarska, E., & Cielecka-Piontek, J. (2022). Amorphous solid dispersion of hesperidin with polymer excipients for enhanced apparent solubility as a more effective approach to the treatment of civilization diseases. International Journal of Molecular Sciences, 23(23).
[28] Bertoni, S., Albertini, B., & Passerini, N. (2023). Investigating the physicochemical properties of solid dispersions based on semicrystalline carriers: A case study with ketoprofen. International Journal of Pharmaceutics, 632.
[29] Malkawi, R., Malkawi, W. I., Al-Mahmoud, Y., & Tawalbeh, J. (2022). Current trends on solid dispersions: Past, present, and future. Advances in Pharmacological and Pharmaceutical Sciences, 2022.
[30] De Mohac, L. M., Caruana, R., Cavallaro, G., Giammona, G., & Licciardi, M. (2020). Spray-drying, solvent-casting and freeze-drying techniques: A comparative study on their suitability for the enhancement of drug dissolution rates. Pharmaceutical Research, 37(3).
[31] Thomas, M., Nabais, A. R., Burggraef, M. J., Peeva, L., Murray, J., & Livingston, A. G. (2025). Enabling High-Boiling-Point Green Solvent Recycling Using Organic Solvent Nanofiltration Membranes. ChemSusChem, 18(21), e202501117.
[32] Xie, B., Liu, Y., Li, X., Yang, P., & He, W. (2024). Solubilization techniques used for poorly water-soluble drugs. Acta Pharmaceutica Sinica B, 4683–4716.
[33] Le Khanh, H. P., Haimhoffer, Á., Nemes, D., Józsa, L., Vasvári, G., Budai, I., ... & Fenyvesi, F. (2023). Effect of molecular weight on the dissolution profiles of PEG solid dispersions containing ketoprofen. Polymers, 15(7).
[34] Jelić, D. (2021). Thermal stability of amorphous solid dispersions. Molecules, 26(1).
[35] Joshi, S., Dhingra, A. K., Chopra, B., Dass, R., Guarve, K., & Sapra, S. (2023). Formulation and evaluation of solid dispersions of poorly water-soluble drug-hesperidin. Letters in Applied NanoBioScience, 12(2).
[36] Kanaze, F. I., Kokkalou, E., Niopas, I., Georgarakis, M., Stergiou, A., & Bikiaris, D. (2006). Dissolution enhancement of flavonoids by solid dispersion in PVP and PEG matrixes: A comparative study. Journal of Applied Polymer Science, 102(1), 460–471.
[37] Akram, A., Irfan, M., Abualsunun, W. A., Bukhary, D. M., & Alissa, M. (2022). How to improve solubility and dissolution of irbesartan by fabricating ternary solid dispersions: Optimization and in-vitro characterization. Pharmaceutics, 14(11).
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Aga Mikail, Aditya Trias Pradana, Endang Wahyu Fitriani, Agnes Nuniek Winantari, Astridani Rizky Putranti, Xandramela Limala Alicya Junaidi Lee

This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted non-commercial use, distribution and reproduction in any medium
























