Skip to main content
SpringerLink
Log in

Physicochemical characterization and stability of microbeads containing cod-liver oil encircled with natural cyclodextrins

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

The ability of cyclodextrins (CDs) to solubilize cod-liver oil in aqueous solutions was evaluated. Only the natural α-cyclodextrin (αCD) and γ-cyclodextrin (γCD) were able to fully disperse 10 % (v/v) cod-liver oil in aqueous solutions. Confocal imaging revealed that the oil was located in the center of the CD enveloped microbeads (<20 μm in diameter) where it was enclosed within nanocompartments (<1 μm in diameter). The aqueous microbead suspensions were lyophilized to produce dry powder microbeads with rough surfaces. To assess the stability of the cod-liver oil/γCD (3:1 molar ratio) microbead powder, three groups of samples were incubated over a period of 1, 2, 4, 12 and 84 weeks. Group 1 (G1) and group 2 (G2) were incubated at 25 °C and 60 % humidity. G1 was exposed to O2 for 10 min before sealing off the glass containers while G2 was kept under nitrogen. Group 3 was stored under accelerated conditions at 40 °C and 75 % humidity under nitrogen. The reference was pure cod-liver oil. Results indicated that encapsulating cod-liver oil with γCD delays oxidative degradation when oxygen is present, but does not significantly decrease or increase the long term stability of cod-liver oil under anaerobic conditions. Cod-liver oil/γCD microbeads could be compressed into tablets without decreasing the integrity of encapsulation. The cod-liver oil/γCD microbead powder might be of interest to the pharmaceutical industry as a carrier for lipophilic drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

CD:

Cyclodextrin

αCD:

α-Cyclodextrin

βCD:

β-Cyclodextrin

γCD:

γ-Cyclodextrin

HPαCD:

2-Hydroxypropyl-α-cyclodextrin

HPβCD:

2-Hydroxypropyl-β-cyclodextrin

HPγCD:

2-Hydroxypropyl-γ-cyclodextrin

PUFA:

Polyunsaturated fatty acid

EPA:

Eicosapentaenoic acid

DHA:

Docosahexaenoic acid

References

  1. Parker, H.M., Johnson, N.A., Burdon, C.A., Cohn, J.S., O’Connor, H.T., George, J.: Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J. Hepatol. 56(4), 944–951 (2012). doi:10.1016/j.jhep.2011.08.018

    Article  CAS  Google Scholar 

  2. Mozaffarian, D., Wu, J.H.Y.: Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J. Am. Coll. Cardiol. 58(20), 2047–2067 (2011). doi:10.1016/j.jacc.2011.06.063

    Article  CAS  Google Scholar 

  3. Wall, R., Ross, R.P., Fitzgerald, G.F., Stanton, C.: Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr. Rev. 68(5), 280–289 (2010). doi:10.1111/j.1753-4887.2010.00287.x

    Article  Google Scholar 

  4. Su, K.P.: Biological mechanism of antidepressant effect of omega-3 fatty acids: how does fish oil act as a ‘mind–body interface’? Neurosignals 17(2), 144–152 (2009)

    Article  CAS  Google Scholar 

  5. Innis, S.M.: Dietary omega 3 fatty acids and the developing brain. Brain Res. 1237, 35–43 (2008). doi:10.1016/j.brainres.2008.08.078

    Article  CAS  Google Scholar 

  6. Akter, K., Gallo, D.A., Martin, S.A., Myronyuk, N., Roberts, R.T., Stercula, K., Raffa, R.B.: A review of the possible role of the essential fatty acids and fish oils in the aetiology, prevention or pharmacotherapy of schizophrenia. J. Clin. Pharm. Ther. 37(2), 132–139 (2012). doi:10.1111/j.1365-2710.2011.01265.x

    Article  CAS  Google Scholar 

  7. Boran, G., Karaçam, H., Boran, M.: Changes in the quality of fish oils due to storage temperature and time. Food Chem. 98(4), 693–698 (2006). doi:10.1016/j.foodchem.2005.06.041

    Article  CAS  Google Scholar 

  8. Yoshimura, Y., Tanaka, H., Tamura, K., Oshawa, K., Imaeda, K.: Stability of fish oil as evaluated by oxygen absorption method. Anal. Sci. 2, 581–584 (1986)

    Article  Google Scholar 

  9. Thorgeirsdóttir, H., Valgeirsdóttir, H., Gunnarsdóttir, I., Gísladóttir, E., Gunnarsdóttir, B.E., Þórisdóttir, I., Stefánsdóttir, J., Steingrímsdóttir, L.: The diet of icelanders 2010–2011. In: Report from the Dictorate of Health, The Icelandic Food and Veterinary Authority and the Unit of Nutrition Research at the University of Iceland, Reykjavík (2011)

  10. Delgado, C.L., Wada, N., Rosengrant, M.W., Meijer, S., Ahmed, M.: Outlook for fish for 2020, meeting global demand. In: Food Policy Report, International Food Policy Research Institute (2003)

  11. Kralovec, J.A., Zhang, S., Zhang, W., Barrow, C.J.: A review of the progress in enzymatic concentration and microencapsulation of omega-3 rich oil from fish and microbial sources. Food Chem. 131(2), 639–644 (2012). doi:10.1016/j.foodchem.2011.08.085

    Article  CAS  Google Scholar 

  12. Kolanowski, W., Ziolkowski, M., Weißbrodt, J., Kunz, B., Laufenberg, G.: Microencapsulation of fish oil by spray drying—impact on oxidative stability. Part 1. Eur. Food Res. Technol. 222(3), 336–342 (2006). doi:10.1007/s00217-005-0111-1

    Article  CAS  Google Scholar 

  13. Uekama, K.: Design and evaluation of cyclodextrin-based drug formulation. Chem. Pharm. Bull. 52(8), 900–915 (2004)

    Article  CAS  Google Scholar 

  14. Del Valle, E.M.M.: Cyclodextrins and their uses: a review. Process Biochem. 39(9), 1033–1046 (2004). doi:10.1016/S0032-9592(03)00258-9

    Article  Google Scholar 

  15. Loftsson, T., Jarho, P., Masson, M., Jarvinen, T.: Cyclodextrins in drug delivery. Expert Opin. Drug Deliv. 2(2), 335–351 (2005). doi:10.1517/17425247.2.1.335

    Article  CAS  Google Scholar 

  16. Loftsson, T., Masson, M.: Cyclodextrins in topical drug formulations: theory and practice. Int. J. Pharm. 225(1–2), 15–30 (2001)

    Article  CAS  Google Scholar 

  17. Lopez-Garcia, M.A., Lopez, O., Maya, I., Fernandez-Bolanos, J.G.: Complexation of hydroxytyrosol with beta-cyclodextrins. An efficient photoprotection. Tetrahedron 66(40), 8006–8011 (2010). doi:10.1016/j.tet.2010.08.009

    Article  CAS  Google Scholar 

  18. Kayaci, F., Uyar, T.: Encapsulation of vanillin/cyclodextrin inclusion complex in electrospun polyvinyl alcohol (PVA) nanowebs: prolonged shelf-life and high temperature stability of vanillin. Food Chem. 133(3), 641–649 (2012). doi:10.1016/j.foodchem.2012.01.040

    Article  CAS  Google Scholar 

  19. Jansook, P., Kurkov, S.V., Loftsson, T.: Cyclodextrins as solubilizers: formation of complex aggregates. J. Pharm. Sci. 99(2), 719–729 (2010). doi:10.1002/jps.21861

    CAS  Google Scholar 

  20. Loftsson, T., Masson, M., Brewster, M.E.: Self-association of cyclodextrins and cyclodextrin complexes. J. Pharm. Sci. 93(5), 1091–1099 (2004). doi:10.1002/Jps.20047

    Article  CAS  Google Scholar 

  21. Messner, M., Kurkov, S.V., Brewster, M.E., Jansook, P., Loftsson, T.: Self-assembly of cyclodextrin complexes: aggregation of hydrocortisone/cyclodextrin complexes. Int. J. Pharm. 407(1–2), 174–183 (2011). doi:10.1016/j.ijpharm.2011.01.011

    Article  CAS  Google Scholar 

  22. Agnew, K.A., Mccarley, T.D., Agbaria, R.A., Warner, I.M.: Phase-transition pattern of 2,5-diphenyloxazole/gamma-cyclodextrin (PPO/gamma-CD) self-assembly aggregates. J. Photochem. Photobiol. A 91(3), 205–210 (1995)

    Article  CAS  Google Scholar 

  23. Gonzalez-Gaitano, G., Rodriguez, P., Isasi, J.R., Fuentes, M., Tardajos, G., Sanchez, M.: The aggregation of cyclodextrins as studied by photon correlation spectroscopy. J. Incl. Phenom. Macrocycl. Chem. 44(1–4), 101–105 (2002)

    Article  CAS  Google Scholar 

  24. Gabelica, V., Galic, N., De Pauw, E.: On the specificity of cyclodextrin complexes detected by electrospray mass spectrometry. J. Am. Soc. Mass Spectrom. 13(8), 946–953 (2002). doi:10.1016/s1044-0305(02)00416-6

    Article  CAS  Google Scholar 

  25. Magnusdottir, A., Másson, M., Loftsson, T.: Self association and cyclodextrin solubilization of NSAIDs. J. Incl. Phenom. Macrocycl. Chem. 44(1), 213–218 (2002). doi:10.1023/a:1023079322024

    Article  CAS  Google Scholar 

  26. Bonini, M., Rossi, S., Karlsson, G., Almgren, M., Lo Nostro, P., Baglioni, P.: Self-assembly of beta-cyclodextrin in water. Part 1: Cryo-TEM and dynamic and static light scattering. Langmuir 22(4), 1478–1484 (2006). doi:10.1021/La052878f

    Article  CAS  Google Scholar 

  27. Regiert, M., Wimmer, T., Moldenhauer, J.P.: Application of gamma-cyclodextrin for the stabilization and/or dispersion of vegetable oils containing triglycerides of polyunsaturated acids. J. Incl. Phenom. Mol. Recogn. Chem. 25(1–3), 213–216 (1996)

    Article  CAS  Google Scholar 

  28. Shimada, K., Kawano, K., Ishii, J., Nakamura, T.: Structure of inclusion complexes of cyclodextrins with triglyceride at vegetable oil–water interface. J. Food Sci. 57(3), 655–656 (1992)

    Article  CAS  Google Scholar 

  29. Trichard, L., Fattal, E., Besnard, M., Bochot, A.: Alpha-cyclodextrin/oil beads as a new carrier for improving the oral bioavailability of lipophilic drugs. J. Control Release 122(1), 47–53 (2007). doi:10.1016/j.jconrel.2007.06.004

    Article  CAS  Google Scholar 

  30. Bochot, A., Trichard, L., Le Bas, G., Alphandary, H., Grossiord, J.L., Duchene, D., Fattal, E.: Alpha-cyclodextrin/oil beads: an innovative self-assembling system. Int. J. Pharm. 339(1–2), 121–129 (2007). doi:10.1016/j.ijpharm.2007.02.034

    Article  CAS  Google Scholar 

  31. Trichard, L., Fattal, E., Le Bas, G., Duchene, D., Grossiord, J.L., Bochot, A.: Formulation and characterisation of beads prepared from natural cyclodextrins and vegetable, mineral or synthetic oils. Int. J. Pharm. 354(1–2), 88–94 (2008). doi:10.1016/j.ijpharm.2007.10.029

    Article  CAS  Google Scholar 

  32. Bligh, E.G., Dyer, W.J.: A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917 (1959)

    Article  CAS  Google Scholar 

  33. AOCS: Official Methods and Recommended Practices of the American Oil Chemists’ Society. Method (Ce 1b-89) Fatty Acid Composition of Marine Oils and Marine Oil Esters by Capillary Column Gas–Liquid Chromatography (2001)

  34. Ringard-Lefebvre, C., Bochot, A., Memisoglu, E., Charon, D., Duchene, D., Baszkin, A.: Effect of spread amphiphilic beta-cyclodextrins on interfacial properties of the oil/water system. Colloids Surf. B 25(2), 109–117 (2002)

    Article  CAS  Google Scholar 

  35. Loftsson, T., Konradsdottir, F., Masson, M.: Development of octanol membranes for drug screening. J. Incl. Phenom. Macrocycl. Chem. 57(1–4), 613–617 (2007). doi:10.1007/s10847-006-9274-z

    Article  CAS  Google Scholar 

  36. Loftsson, T., Konradsdottir, F., Masson, M.: Influence of aqueous diffusion layer on passive drug diffusion from aqueous cyclodextrin solutions through biological membranes. Pharmazie 61(2), 83–89 (2006)

    CAS  Google Scholar 

  37. Li, Z., Wang, M., Wang, F., Gu, Z., Du, G., Wu, J., Chen, J.: γ-Cyclodextrin: a review on enzymatic production and applications. Appl. Microbiol. Biotechnol. 77(2), 245–255 (2007). doi:10.1007/s00253-007-1166-7

    Article  CAS  Google Scholar 

  38. Munro, I.C., Newberne, P.M., Young, V.R., Bar, A.: Safety assessment of gamma-cyclodextrin. Regul. Toxicol. Pharmacol. 39, S3–S13 (2004). doi:10.1016/j.yrtph.2004.05.008

    Article  CAS  Google Scholar 

  39. WHO: Evaluation of certain food additives and contaminants. WHO Tech. Rep. Ser. 896, 26–27 (2000)

    Google Scholar 

  40. De Bie, A.T.H.J., Van Ommen, B., Bär, A.: Disposition of [14C]γ-cyclodextrin in germ-free and conventional rats. Regul. Toxicol. Pharmacol. 27(2), 150–158 (1998). doi:10.1006/rtph.1998.1219

    Article  Google Scholar 

  41. Van Ommen, B., De Bie, A., Bär, A.: Disposition of 14C-alpha-cyclodextrin in germ-free and conventional rats. Regul. Toxicol. Pharmacol. 39(Suppl 1), 57–66 (2004)

    Article  Google Scholar 

  42. Loftsson, T., Konradsdottir, F., Masson, M.: Development and evaluation of an artificial membrane for determination of drug availability. Int. J. Pharm. 326(1–2), 60–68 (2006). doi:10.1016/j.ijpharm.2006.07.009

    Article  CAS  Google Scholar 

  43. Lennernäs, H.: Human intestinal permeability. J. Pharm. Sci. 87(4), 403–410 (1998). doi:10.1021/js970332a

    Article  Google Scholar 

  44. Karlsson, J., Artursson, P.: A method for the determination of cellular permeability coefficients and aqueous boundary layer thickness in monolayers of intestinal epithelial (Caco-2) cells grown in permeable filter chambers. Int. J. Pharm. 71(1–2), 55–64 (1991). doi:10.1016/0378-5173(91)90067-x

    Article  CAS  Google Scholar 

  45. Lai, C.S., Chow, J., Wolf, B.W.: Method of using gamma cyclodextrin to control blood glucose and insulin secretion. United States of America Patent 7423027, 9 Sept 2008

  46. Dalli, J.: Commission implementing decision of 1 June 2012 authorising the placing on the market of gamma-cyclodextrin as a novel food ingredient under regulation (EC) No 258/97 of the European Parliament and of the Council. In: Commission, E.E. (ed.) vol. L 144, pp. 41–42. Official Journal of the European Union, Brussels (2012)

  47. Rajewski, R.A., Stella, V.J.: Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery. J. Pharm. Sci. 85(11), 1142–1169 (1996). doi:10.1021/js960075u

    Article  CAS  Google Scholar 

  48. Andreu-Sevilla, A.J., Lopez-Nicolas, J.M., Carbonell-Barrachina, A.A., Garcia-Carmona, F.: Comparative effect of the addition of alpha-, beta-, or gamma-cyclodextrin on main sensory and physico-chemical parameters. J. Food Sci. 76(5), S347–S353 (2011). doi:10.1111/j.1750-3841.2011.02190.x

    Article  CAS  Google Scholar 

  49. Lantz, A.W., Rodriguez, M.A., Wetterer, S.M., Armstrong, D.W.: Estimation of association constants between oral malodor components and various native and derivatized cyclodextrins. Anal. Chim. Acta 557(1–2), 184–190 (2006). doi:10.1016/j.aca.2005.10.005

    Article  CAS  Google Scholar 

  50. Frankel, E.N.: Antioxidants in lipid foods and their impact on food quality. Food Chem. 57(1), 51–55 (1996). doi:10.1016/0308-8146(96)00067-2

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Financial support from the Icelandic Technology Development Fund (RANNÍS), The Icelandic Research Fund-for students (RANNÍS), The Bergþóru and Þorsteinn Schewing Þorsteinsson award grant, Íslandsbanki educational fund, BHMR educational fund and University of Iceland travel fund and materials provided by Lýsi hf are gratefully acknowledged. We thank Anna Birna Björnsdóttir and Eiríkur Kristinsson for assistance with the methods of oil extraction, peroxide titration, fatty acid extraction and analysis, Skúli Skúlason for assistance with the tabletting processes, Hjordis Audunsdóttir at Filmverk and finally Thorunn Ósk Thorgeirsdóttir at Invent Pharma for allowing us the use of their regulated incubators.

Author information

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík, Iceland

    Fífa Konrádsdóttir, Thormódur Geirsson & Thorsteinn Loftsson

  2. Lýsi hf, Reykjavík, Iceland

    Arnar Halldórsson

  3. Center for Systems Biology, University of Iceland, Reykjavík, Iceland

    Skarphédinn Halldórsson

Authors
  1. Fífa Konrádsdóttir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thormódur Geirsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arnar Halldórsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Skarphédinn Halldórsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thorsteinn Loftsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thorsteinn Loftsson.

Additional information

Thormódur Geirsson, the co-author passed away on October 2009.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Konrádsdóttir, F., Geirsson, T., Halldórsson, A. et al. Physicochemical characterization and stability of microbeads containing cod-liver oil encircled with natural cyclodextrins. J Incl Phenom Macrocycl Chem 78, 485–499 (2014). https://doi.org/10.1007/s10847-013-0331-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-013-0331-0

Keywords

Search

Navigation