Application of Hot-Melt Extrusion in Modifying the Solubility of Lycopene
Source abstract
Abstract
Lycopene is a potent antioxidant carotenoid with significant health-promoting properties. However, its practical application is limited by poor water solubility. This study aimed to enhance lycopene dispersibility through the development of solid dispersions obtained by hot-melt extrusion (HME). Polymeric carriers composed of polyvinylpyrrolidone K30 (PVP K30), phosphatidylcholine, and xylitol were designed to achieve optimal processing conditions and thermal stability. Nine formulations containing 10–30% lycopene were prepared and characterized using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FT-IR), and dispersibility testing. TGA confirmed the thermal stability of lycopene at the extrusion temperature (150 °C). DSC and XRPD analyses indicated partial amorphization of lycopene in the extrudates, while FT-IR spectra revealed molecular interactions between lycopene and carrier components, particularly hydroxyl and carbonyl groups. Among the tested systems, the formulation containing PVP K30 and xylitol without phosphatidylcholine exhibited the highest dispersibility (1.0484 mg/mL after 3 h). Dispersibility decreased with increasing lycopene content. These findings demonstrate that HME is an effective technique for producing partially amorphous lycopene dispersions with improved dispersibility, and that polymer–polyol systems are particularly promising carriers for enhancing lycopene bioavailability.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Microencapsulation and Drying Processes · Food Chemistry and Fat Analysis · Nuts composition and effects
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland
Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznań, Poland
Phytopharm Klęka S.A., Klęka 1, 63-040 Nowe Miasto nad Wartą, Poland
Funding
Ministry of Science and Higher Education
References (48)
Show source-provided references
1. Imran, M., Ghorat, F., Ul-Haq, I., Ur-Rehman, H., Aslam, F., Heydari, M., Shariati, M.A., Okuskhanova, E., Yessimbekov, Z., and Thiruvengadam, M. (2020). Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders. Antioxidants, 9.10.3390/antiox9080706 ↗
2. Wang, H., Wang, S., Zhu, H., Wang, S., and Xing, J. (2019). Inclusion Complexes of Lycopene and β-Cyclodextrin: Preparation, Characterization, Stability and Antioxidant Activity. Antioxidants, 8.10.3390/antiox8080314 ↗
3. Kulawik, A., Cielecka-Piontek, J., and Zalewski, P. (2023). The Importance of Antioxidant Activity for the Health-Promoting Effect of Lycopene. Nutrients, 15.10.20944/preprints202308.0690.v1 ↗
4. Bin-Jumah, M.N., Nadeem, M.S., Gilani, S.J., Mubeen, B., Ullah, I., Alzarea, S.I., Ghoneim, M.M., Alshehri, S., Al-Abbasi, F.A., and Kazmi, I. (2022). Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases. Antioxidants, 11.10.3390/antiox11020232 ↗
5. Investigation of Cyclodextrin as Potential Carrier for Lycopene
6. Let Food Be Your Medicine: Nutraceutical Properties of Lycopene10.1039/C9FO00580C ↗
7. Amorim, A.d.G.N., Vasconcelos, A.G., Souza, J., Oliveira, A., Gullón, B., de Souza de Almeida Leite, J.R., and Pintado, M. (2022). Bio-Availability, Anticancer Potential, and Chemical Data of Lycopene: An Overview and Technological Prospecting. Antioxidants, 11.10.3390/antiox11020360 ↗
8. Nutraceutical Delivery Systems to Improve the Bioaccessibility and Bioavailability of Lycopene: A Review10.1080/10408398.2023.2168249 ↗
9. An Overview of Properties and Analytical Methods for Lycopene in Organic Nanocarriers
10. Leh, H.E., and Lee, L.K. (2022). Lycopene: A Potent Antioxidant for the Amelioration of Type II Diabetes Mellitus. Molecules, 27.10.3390/molecules27072335 ↗
11. Kulawik, A., Cielecka-Piontek, J., Czerny, B., Kamiński, A., and Zalewski, P. (2024). The Relationship Between Lycopene and Metabolic Diseases. Nutrients, 16.10.20944/preprints202409.2122.v1 ↗
12. A Review on Tomato Lycopene
13. Wdowiak, K., Pietrzak, R., Tykarska, E., and Cielecka-Piontek, J. (2023). Hot-Melt Extrusion as an Effective Technique for Obtaining an Amorphous System of Curcumin and Piperine with Improved Properties Essential for Their Better Biological Activities. Molecules, 28.10.3390/molecules28093848 ↗
14. Kim, D., Kim, Y., Tin, Y.-Y., Soe, M.-T.-P., Ko, B., Park, S., and Lee, J. (2021). Recent Technologies for Amorphization of Poorly Water-Soluble Drugs. Pharmaceutics, 13.10.3390/pharmaceutics13081318 ↗
15. Qiang, W., Löbmann, K., McCoy, C.P., Andrews, G.P., and Zhao, M. (2020). Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions. Pharmaceutics, 12.10.3390/pharmaceutics12070655 ↗
16. Stability-Enhanced Hot-Melt Extruded Amorphous Solid Dispersions via Combinations of Soluplus® and HPMCAS-HF10.1208/s12249-014-0269-6 ↗
17. Censi, R., Gigliobianco, M.R., Casadidio, C., and Di Martino, P. (2018). Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process. Pharmaceutics, 10.10.3390/pharmaceutics10030089 ↗
18. Contribution of Hot-Melt Extrusion Technology to Advance Drug Delivery in the 21st Century10.1517/17425247.2016.1126246 ↗
19. Hot-Melt Extrusion in the Pharmaceutical Industry: Toward Filing a New Drug Application10.1016/j.drudis.2019.05.013 ↗
20. Hot-Melt Extrusion: From Theory to Application in Pharmaceutical Formulation10.1208/s12249-015-0360-7 ↗
21. Melt Extrusion with Poorly Soluble Drugs—An Integrated Review10.1016/j.ijpharm.2017.10.056 ↗
22. Liu, W.-Y., Hsieh, Y.-S., Ko, H.-H., and Wu, Y.-T. (2023). Formulation Approaches to Crystalline Status Modification for Carotenoids: Impacts on Dissolution, Stability, Bioavailability, and Bioactivities. Pharmaceutics, 15.10.3390/pharmaceutics15020485 ↗
23. Moving Polyvinyl Pyrrolidone Electrospun Nanofibers and Bioprinted Scaffolds toward Multidisciplinary Biomedical Applications10.1016/j.eurpolymj.2020.109919 ↗
24. Pharmaceutical Assessment of Polyvinylpyrrolidone (PVP): As Excipient from Conventional to Controlled Delivery Systems with a Spotlight on COVID-19 Inhibition10.1016/j.jddst.2020.102046 ↗
25. Polyvinylpyrrolidone (PVP) in Nanoparticle Synthesis10.1039/C5DT02964C ↗
26. Rowe, R.C., Sheskey, P.J., and Quinn, M.E. (2009). Handbook of Pharmaceutical Excipients, Pharmaceutical Press. [6th ed.].
27. Liquisolid Technique for Dissolution Rate Enhancement of a High Dose Water-Insoluble Drug (Carbamazepine)10.1016/j.ijpharm.2007.03.034 ↗
28. Enhancement of Ketoconazole Dissolution Rate by the Liquisolid Technique10.2478/acph-2018-0025 ↗
29. Factors Affecting the Dissolution of Indomethacin Solid Dispersions10.1208/s12249-017-0813-2 ↗
30. Kulawik, A., Kulawik, M., Rosiak, N., Lu, W., Cielecka-Piontek, J., and Zalewski, P. (2025). Amorphous Lycopene–PVP K30 Dispersions Prepared by Ball Milling: Improved Solubility and Antioxidant Activity. Polymers, 17.10.3390/polym17212916 ↗
31. Evaluation of Novel Carriers for Enhanced Dissolution of Lycopene10.1007/s11694-024-02526-6 ↗
32. Solubility Enhancement of Lycopene by Lyophilized Polymeric Nanoparticles
33. Lycopene-Carrier Solid Dispersion Loaded Lipid Liquid Crystal Nanoparticle: In Vitro Evaluation and in Vivo Wound Healing Effects10.1080/10837450.2025.2504998 ↗
34. Tailoring the Multi-Functional Properties of Phospholipids for Simple to Complex Self-Assemblies10.1016/j.jconrel.2022.07.014 ↗
35. Improving Permeability and Oral Absorption of Mangiferin by Phospholipid Complexation10.1016/j.fitote.2013.10.016 ↗
36. Curcumin–Phospholipid Complex: Preparation, Therapeutic Evaluation and Pharmacokinetic Study in Rats10.1016/j.ijpharm.2006.09.025 ↗
37. A Novel Matrix Dispersion Based on Phospholipid Complex for Improving Oral Bioavailability of Baicalein: Preparation, in Vitro and in Vivo Evaluations10.1080/10717544.2017.1311968 ↗
38. Single Step Bottom-up Process to Generate Solid Phospholipid Nano-Particles10.3109/10837450.2013.778875 ↗
39. Jo, K., Cho, J.M., Lee, H., Kim, E.K., Kim, H.C., Kim, H., and Lee, J. (2019). Enhancement of Aqueous Solubility and Dissolution of Celecoxib through Phosphatidylcholine-Based Dispersion Systems Solidified with Adsorbent Carriers. Pharmaceutics, 11.10.3390/pharmaceutics11010001 ↗
40. Wdowiak, K., Tajber, L., Miklaszewski, A., and Cielecka-Piontek, J. (2024). Sweeteners Show a Plasticizing Effect on PVP K30—A Solution for the Hot-Melt Extrusion of Fixed-Dose Amorphous Curcumin-Hesperetin Solid Dispersions. Pharmaceutics, 16.10.3390/pharmaceutics16050659 ↗
41. Wdowiak, K., Tajber, L., Miklaszewski, A., and Cielecka-Piontek, J. (2025). Application of the Box–Behnken Design in the Development of Amorphous PVP K30–Phosphatidylcholine Dispersions for the Co-Delivery of Curcumin and Hesperetin Prepared by Hot-Melt Extrusion. Pharmaceutics, 17.10.3390/pharmaceutics17010026 ↗
42. Lycopene Purification with DMSO Anti-Solvent: Optimization Using Box-Behnken’s Experimental Design and Evaluation of the Synergic Effect between Lycopene and Ammi visnaga L. Essential Oil10.1007/s11696-022-02302-0 ↗
43. Effect of Water Vapor Sorption on Local Structure of Poly(Vinylpyrrolidone)10.1002/jps.22204 ↗
44. Rosiak, N., Tykarska, E., and Cielecka-Piontek, J. (2024). Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions. Int. J. Mol. Sci., 25.10.3390/ijms25052774 ↗
45. Zheng, T., Bielinski, D.F., Fisher, D.R., Zhang, J., and Shukitt-Hale, B. (2022). Protective Effects of a Polyphenol-Rich Blueberry Extract on Adult Human Neural Progenitor Cells. Molecules, 27.10.3390/molecules27196152 ↗
46. Development of a Highly Water-Soluble Lycopene Cyclodextrin Ternary Formulation by the Integrated Experimental and Modeling Techniques10.1208/s12249-020-01861-3 ↗
47. The Effect of Extrusion on the Functional Components and in Vitro Lycopene Bioaccessibility of Tomato Pulp Added Corn Extrudates10.1039/C5FO01185J ↗
48. Kulawik, A., Kulawik, M., Rosiak, N., Lu, W., Kryszak, A., Cielecka-Piontek, J., and Zalewski, P. (2025). Improving the Pharmaceutical Potential of Lycopene Using Hot-Melt Extrusion. Appl. Sci., 15.10.3390/app152212311 ↗