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2000
Volume 15, Issue 3
  • ISSN: 2210-3031
  • E-ISSN: 2210-304X

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
2025-12-15

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References

  1. AhmadM. Ziaullah IslamN.U. AliM. KhanS. Metal complexes of fluoroquinolones with selected transition metals, their synthesis, characterizations, and therapeutic applications.Chemistry Africa2024784139415610.1007/s42250‑024‑01059‑1
     [Google Scholar]
  2. NazliA. MalangaM. SohajdaT. BéniS. Cationic cyclodextrin-based carriers for drug and nucleic acid delivery.Pharmaceutics20251718110.3390/pharmaceutics1701008139861729
     [Google Scholar]
  3. SarafskaT. IvanovaS. DudevT. TzachevC. PetrovV. SpassovT. Enhanced solubility of Ibuprofen by complexation with β-cyclodextrin and citric acid.Molecules2024297165010.3390/molecules2907165038611930
     [Google Scholar]
  4. AngelovaS. PerevaS. DudevT. SpassovT. Cyclodextrins’ internal cavity hydration: Insights from theory and experiment.Inorganics20251312810.3390/inorganics13010028
     [Google Scholar]
  5. KaleM. PatilS. KambleR. 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.202510610672610.1016/j.jddst.2025.106726
     [Google Scholar]
  6. BaumgartnerA. DobajN. PlaninšekO. Investigating the influence of processing conditions on dissolution and physical stability of solid dispersions with Fenofibrate and Mesoporous Silica. Pharmaceutics202416557510.3390/pharmaceutics1605057538794237
     [Google Scholar]
  7. GanapathyB. RedasaniV. DebnathS. GuptaN. KadamA. WangF. NarwankarP. Bioavailability improvement by atomic layer coating: Fenofibrate a case study.J. Pharm. Sci.2025114161762510.1016/j.xphs.2024.10.05239489377
     [Google Scholar]
  8. KankalaR.K. LiuC.G. ChenA.Z. WangS.B. XuP.Y. MendeL.K. LiuC.L. LeeC.H. HuY.F. Overcoming multidrug resistance through the synergistic effects of hierarchical pH-sensitive, ROS-generating nanoreactors.ACS Biomater. Sci. Eng.20173102431244210.1021/acsbiomaterials.7b0056933445301
     [Google Scholar]
  9. TsunodaC. GotoS. HiroshigeR. KasaiT. OkumuraY. YokoyamaH. 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.202363812291310.1016/j.ijpharm.2023.12291337024067
     [Google Scholar]
  10. MoreM. VinjamurM. MukhopadhyayM. 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.202520811012810.1016/j.cep.2024.110128
     [Google Scholar]
  11. DarweeshR.S. ShriemL.A. Al-NemrawiN.K. Intranasal nanocrystals of tadalafil: in vitro characterisation and in vivo pharmacokinetic study.Pharmacia20247111510.3897/pharmacia.71.e120458
     [Google Scholar]
  12. BhattacharjeeT. RahmanS. DekaD. PurkaitM.K. ChowdhuryD. MajumdarG. Synthesis and characterization of exfoliated beta-cyclodextrin functionalized graphene oxide for adsorptive removal of atenolol.Mater. Chem. Phys.202228812641310.1016/j.matchemphys.2022.126413
     [Google Scholar]
  13. AtneriyaU. KapoorD. SainyJ. MaheshwariR. in vitro profiling of fenofibrate solid dispersion mediated tablet formulation to treat high blood cholesterol.Ann. Pharm. Fr.202381228429910.1016/j.pharma.2022.08.00936037932
     [Google Scholar]
  14. KankalaR.K. TsaiP.Y. KuthatiY. WeiP.R. LiuC.L. LeeC.H. Overcoming multidrug resistance through co-delivery of ROS-generating nano-machinery in cancer therapeutics.J. Mater. Chem. B Mater. Biol. Med.2017571507151710.1039/C6TB03146C32264641
     [Google Scholar]
  15. KayaA. ArafatB. ChichgerH. TolaymatI. PierscionekB. KhoderM. NajlahM. Preparation and characterisation of Zinc diethyldithiocarbamate–cyclodextrin inclusion complexes for potential lung cancer treatment.Pharmaceutics20231616510.3390/pharmaceutics1601006538258076
     [Google Scholar]
  16. MahmoodT. SarfrazR.M. IsmailA. AliM. KhanA.R. Pharmaceutical methods for enhancing the dissolution of poorly water- soluble drugs.Assay Drug Dev. Technol.2023212657910.1089/adt.2022.11936917562
     [Google Scholar]
  17. LiuC.G. HanY.H. ZhangJ.T. KankalaR.K. WangS.B. ChenA.Z. Rerouting engineered metal-dependent shapes of mesoporous silica nanocontainers to biodegradable Janus-type (sphero-ellipsoid) nanoreactors for chemodynamic therapy.Chem. Eng. J.20193701188119910.1016/j.cej.2019.03.272
     [Google Scholar]
  18. AliM.S. ShahromN.S.Z. RajanderanT. SalawiA. SabeiF.Y. AlbariqiA.H. SultanM.H. AlamM.I. AlshamraniA.A. KumarA. ZhouL.R. MajeedS. AnsariM.T. A stable curcumin/β-cyclodextrin/ascorbic acid ternary inclusion complexes, docking studies, antimicrobial and anticancer assays.J. Incl. Phenom. Macrocycl. Chem.2025281410.1007/s10847‑025‑01290‑4
     [Google Scholar]
  19. LucaciuRL. HanganAC. SevastreB. OpreanLS. Metallo- drugs in cancer therapy: Past, present and future.Molecules.20222719648510.3390/molecules27196485
     [Google Scholar]
  20. MansouriF. BuysR. EliasA. In the pursuit of social justice during political transitions: the practices of CSOs in post-Arab Spring Tunisia.Cogent Soc. Sci.2024101234083410.1080/23311886.2024.2340834
     [Google Scholar]
  21. NavaleG.R. AhmedI. LimM.H. GhoshK. Transition metal complexes as therapeutics: A new frontier in combatting neurodegenerative disorders through protein aggregation modulation.Adv. Healthc. Mater.20241331240199110.1002/adhm.20240199139221545
     [Google Scholar]
  22. XuY. WangY. LiC. HanT. ChenH. ChenW. ZhongQ. PeiJ. HaenenG.R.M.M. LiZ. MoalinM. ZhangM. ChenW. Preparation, characterization, and biological activity of the inclusion complex of dihydroquercetin and β-Cyclodextrin.AAPS Open2023911610.1186/s41120‑023‑00083‑8
     [Google Scholar]
  23. PatilS.M. BarjiD.S. ChavanT. PatelK. CollazoA.J. PrithipaulV. MuthA. KundaN.K. Solubility enhancement and inhalation delivery of cyclodextrin-based inclusion complex of delamanid for pulmonary tuberculosis treatment.AAPS PharmSciTech20232414910.1208/s12249‑023‑02510‑136702977
     [Google Scholar]
  24. AlramadhanH. ElbashirA.A. AlnajjarA.O. Supramolecular interaction of atenolol and propranolol with β-Cyclodextrin spectroscopic characterization and analytical application.Molecules20242912287510.3390/molecules2912287538930938
     [Google Scholar]
  25. LeT.V.H. TruongT.N. LeT.T.T. PhanD.T. Optimization of the synthesis reaction and establishing the reference standard of Fenofibrate impurity C (USP).MedPharmRes202591496110.32895/UMP.MPR.9.1.5
     [Google Scholar]
  26. LimaniG.N. ShaikhN.K. BhangaleP.J. BhangaleJ.O. MakwanaK.C. Development and validation of analytical methods for estimation of simvastatin and fenofibrate.J. Adv. Zool2024451262810.53555/jaz.v45i1.3197
     [Google Scholar]
  27. PiatC. BeckersM. BloemB.R. MenezesA.L. BenarrochE.E. Molecular variability in levodopa absorption and clinical implications for the management of Parkinson’s disease.J. Parkinsons Dis.20241471353136810.3233/JPD‑24003639240647
     [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
Drug Deliv Lett 15, 347 (2025); 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
Keyword(s): beta-cyclodextrin; cupper acetate; Fenofibrate; molecular docking; transition metals, solubility

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