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Abstract

Background

Fenofibrate, a widely used lipid-lowering agent, exhibits limited bioavailability due to its BCS Class II status and poor aqueous solubility. Enhancing its solubility is crucial to improving therapeutic efficacy.

Methods

This study explored solubility enhancement molecular docking-guided screening of transition metal complexes and inclusion complexes with beta-cyclodextrin (β-CD). Transition complexes of fenofibrate with copper acetate were synthesized at a 1:1 molar ratio in a methanol-water mixture (2:1). Additionally, inclusion complexes of these metal complexes with β-CD were prepared in a 1:1 molar ratio and dried. Physicochemical characterization was performed using FTIR, XRD, and SEM analyses. Molecular docking identified potential interactions and conformational stability of the complexes.

Results

The aqueous solubility of fenofibrate increased significantly, 17-fold in the transition metal complex and 25-fold in the β-CD inclusion complex compared to the pure drug. The complexes demonstrated structural changes, including amorphization, which likely contributed to enhanced solubility. Molecular docking revealed strong interactions between fenofibrate, copper acetate, and β-CD, supporting the formation of stable complexes.

Conclusion

The results indicate that fenofibrate’s solubility can be markedly enhanced through complexation with transition metals and β-CD. These approaches, particularly the β-CD inclusion complexes, hold the potential for improving fenofibrate's bioavailability and therapeutic outcomes, offering a promising strategy for addressing solubility challenges in poorly water-soluble drugs.

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2025-05-16
2025-09-13

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References

  1. Ahmad M. Ziaullah Islam N.U. Ali M. Khan S. Metal complexes of fluoroquinolones with selected transition metals, their synthesis, characterizations, and therapeutic applications. Chemistry Africa 2024 7 8 4139 4156 10.1007/s42250‑024‑01059‑1
    [Google Scholar]
  2. Nazli A. Malanga M. Sohajda T. Béni S. Cationic cyclodextrin-based carriers for drug and nucleic acid delivery. Pharmaceutics 2025 17 1 81 10.3390/pharmaceutics17010081 39861729
    [Google Scholar]
  3. Sarafska T. Ivanova S. Dudev T. Tzachev C. Petrov V. Spassov T. Enhanced solubility of Ibuprofen by complexation with β-cyclodextrin and citric acid. Molecules 2024 29 7 1650 10.3390/molecules29071650 38611930
    [Google Scholar]
  4. Angelova S. Pereva S. Dudev T. Spassov T. Cyclodextrins’ internal cavity hydration: Insights from theory and experiment. Inorganics 2025 13 1 28 10.3390/inorganics13010028
    [Google Scholar]
  5. Kale M. Patil S. Kamble R. Fabrication of chitosan-coated tadalafil nanocrystals by Box-Behnken design to enhance its solubility and oral bioavailability via sonoprecipitation technique. J. Drug Deliv. Sci. Technol. 2025 106 106726 10.1016/j.jddst.2025.106726
    [Google Scholar]
  6. Baumgartner A. Dobaj N. Planinšek O. Investigating the influence of processing conditions on dissolution and physical stability of solid dispersions with Fenofibrate and Mesoporous Silica. Pharmaceutics 2024 16 5 575 10.3390/pharmaceutics16050575 38794237
    [Google Scholar]
  7. Ganapathy B. Redasani V. Debnath S. Gupta N. Kadam A. Wang F. Narwankar P. Bioavailability improvement by atomic layer coating: Fenofibrate a case study. J. Pharm. Sci. 2025 114 1 617 625 10.1016/j.xphs.2024.10.052 39489377
    [Google Scholar]
  8. Kankala R.K. Liu C.G. Chen A.Z. Wang S.B. Xu P.Y. Mende L.K. Liu C.L. Lee C.H. Hu Y.F. Overcoming multidrug resistance through the synergistic effects of hierarchical pH-sensitive, ROS-generating nanoreactors. ACS Biomater. Sci. Eng. 2017 3 10 2431 2442 10.1021/acsbiomaterials.7b00569 33445301
    [Google Scholar]
  9. Tsunoda C. Goto S. Hiroshige R. Kasai T. Okumura Y. Yokoyama H. Optimization of the stability constants of the ternary system of diclofenac/famotidine/β-cyclodextrin by nonlinear least-squares method using theoretical equations. Int. J. Pharm. 2023 638 122913 10.1016/j.ijpharm.2023.122913 37024067
    [Google Scholar]
  10. More M. Vinjamur M. Mukhopadhyay M. An improved process for enhancement of loading of fenofibrate using pre-mixed feed with mesoporous silica particles by supercritical carbon dioxide-assisted diffusion. Chem. Eng. Process. 2025 208 110128 10.1016/j.cep.2024.110128
    [Google Scholar]
  11. Darweesh R.S. Shriem L.A. Al-Nemrawi N.K. Intranasal nanocrystals of tadalafil: in vitro characterisation and in vivo pharmacokinetic study. Pharmacia 2024 71 1 15 10.3897/pharmacia.71.e120458
    [Google Scholar]
  12. Bhattacharjee T. Rahman S. Deka D. Purkait M.K. Chowdhury D. Majumdar G. Synthesis and characterization of exfoliated beta-cyclodextrin functionalized graphene oxide for adsorptive removal of atenolol. Mater. Chem. Phys. 2022 288 126413 10.1016/j.matchemphys.2022.126413
    [Google Scholar]
  13. Atneriya U. Kapoor D. Sainy J. Maheshwari R. in vitro profiling of fenofibrate solid dispersion mediated tablet formulation to treat high blood cholesterol. Ann. Pharm. Fr. 2023 81 2 284 299 10.1016/j.pharma.2022.08.009 36037932
    [Google Scholar]
  14. Kankala R.K. Tsai P.Y. Kuthati Y. Wei P.R. Liu C.L. Lee C.H. Overcoming multidrug resistance through co-delivery of ROS-generating nano-machinery in cancer therapeutics. J. Mater. Chem. B Mater. Biol. Med. 2017 5 7 1507 1517 10.1039/C6TB03146C 32264641
    [Google Scholar]
  15. Kaya A. Arafat B. Chichger H. Tolaymat I. Pierscionek B. Khoder M. Najlah M. Preparation and characterisation of Zinc diethyldithiocarbamate–cyclodextrin inclusion complexes for potential lung cancer treatment. Pharmaceutics 2023 16 1 65 10.3390/pharmaceutics16010065 38258076
    [Google Scholar]
  16. Mahmood T. Sarfraz R.M. Ismail A. Ali M. Khan A.R. Pharmaceutical methods for enhancing the dissolution of poorly water- soluble drugs. Assay Drug Dev. Technol. 2023 21 2 65 79 10.1089/adt.2022.119 36917562
    [Google Scholar]
  17. Liu C.G. Han Y.H. Zhang J.T. Kankala R.K. Wang S.B. Chen A.Z. Rerouting engineered metal-dependent shapes of mesoporous silica nanocontainers to biodegradable Janus-type (sphero-ellipsoid) nanoreactors for chemodynamic therapy. Chem. Eng. J. 2019 370 1188 1199 10.1016/j.cej.2019.03.272
    [Google Scholar]
  18. Ali M.S. Shahrom N.S.Z. Rajanderan T. Salawi A. Sabei F.Y. Albariqi A.H. Sultan M.H. Alam M.I. Alshamrani A.A. Kumar A. Zhou L.R. Majeed S. Ansari M.T. A stable curcumin/β-cyclodextrin/ascorbic acid ternary inclusion complexes, docking studies, antimicrobial and anticancer assays. J. Incl. Phenom. Macrocycl. Chem. 2025 28 1 4 10.1007/s10847‑025‑01290‑4
    [Google Scholar]
  19. Lucaciu RL. Hangan AC. Sevastre B. Oprean LS. Metallo- drugs in cancer therapy: Past, present and future. Molecules. 2022 27 19 6485 10.3390/molecules27196485
    [Google Scholar]
  20. Mansouri F. Buys R. Elias A. In the pursuit of social justice during political transitions: the practices of CSOs in post-Arab Spring Tunisia. Cogent Soc. Sci. 2024 10 1 2340834 10.1080/23311886.2024.2340834
    [Google Scholar]
  21. Navale G.R. Ahmed I. Lim M.H. Ghosh K. Transition metal complexes as therapeutics: A new frontier in combatting neurodegenerative disorders through protein aggregation modulation. Adv. Healthc. Mater. 2024 13 31 2401991 10.1002/adhm.202401991 39221545
    [Google Scholar]
  22. Xu Y. Wang Y. Li C. Han T. Chen H. Chen W. Zhong Q. Pei J. Haenen G.R.M.M. Li Z. Moalin M. Zhang M. Chen W. Preparation, characterization, and biological activity of the inclusion complex of dihydroquercetin and β-Cyclodextrin. AAPS Open 2023 9 1 16 10.1186/s41120‑023‑00083‑8
    [Google Scholar]
  23. Patil S.M. Barji D.S. Chavan T. Patel K. Collazo A.J. Prithipaul V. Muth A. Kunda N.K. Solubility enhancement and inhalation delivery of cyclodextrin-based inclusion complex of delamanid for pulmonary tuberculosis treatment. AAPS PharmSciTech 2023 24 1 49 10.1208/s12249‑023‑02510‑1 36702977
    [Google Scholar]
  24. Alramadhan H. Elbashir A.A. Alnajjar A.O. Supramolecular interaction of atenolol and propranolol with β-Cyclodextrin spectroscopic characterization and analytical application. Molecules 2024 29 12 2875 10.3390/molecules29122875 38930938
    [Google Scholar]
  25. Le T.V.H. Truong T.N. Le T.T.T. Phan D.T. Optimization of the synthesis reaction and establishing the reference standard of Fenofibrate impurity C (USP). MedPharmRes 2025 9 1 49 61 10.32895/UMP.MPR.9.1.5
    [Google Scholar]
  26. Limani G.N. Shaikh N.K. Bhangale P.J. Bhangale J.O. Makwana K.C. Development and validation of analytical methods for estimation of simvastatin and fenofibrate. J. Adv. Zool 2024 45 1 26 28 10.53555/jaz.v45i1.3197
    [Google Scholar]
  27. Piat C. Beckers M. Bloem B.R. Menezes A.L. Benarroch E.E. Molecular variability in levodopa absorption and clinical implications for the management of Parkinson’s disease. J. Parkinsons Dis. 2024 14 7 1353 1368 10.3233/JPD‑240036 39240647
    [Google Scholar]
/content/journals/ddl/10.2174/0122103031388141250512072012
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Molecular Docking Aided Study of Transient Metal Inclusion and Tertiary Complexation of Fenofibrate: Effect on Solubility
Bentham Science Publishers ; https://doi.org/10.2174/0122103031388141250512072012
/content/journals/ddl/10.2174/0122103031388141250512072012
/content/journals/ddl/10.2174/0122103031388141250512072012
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  • Article Type:     Research Article
Keywords: beta-cyclodextrin ; molecular docking ; transition metals ; Fenofibrate ; cupper acetate

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