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

  • Fífa Konrádsdóttir
  • Thormódur Geirsson
  • Arnar Halldórsson
  • Skarphédinn Halldórsson
  • Thorsteinn Loftsson
Original Article

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.

Keywords

Cyclodextrins Encapsulation Stability Cod-liver oil Interfacial tension Tablets 

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. 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 CrossRefGoogle Scholar
  2. 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 CrossRefGoogle Scholar
  3. 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 CrossRefGoogle Scholar
  4. 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)CrossRefGoogle Scholar
  5. 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 CrossRefGoogle Scholar
  6. 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 CrossRefGoogle Scholar
  7. 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 CrossRefGoogle Scholar
  8. 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)CrossRefGoogle Scholar
  9. 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)Google Scholar
  10. 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)Google Scholar
  11. 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 CrossRefGoogle Scholar
  12. 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 CrossRefGoogle Scholar
  13. 13.
    Uekama, K.: Design and evaluation of cyclodextrin-based drug formulation. Chem. Pharm. Bull. 52(8), 900–915 (2004)CrossRefGoogle Scholar
  14. 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 CrossRefGoogle Scholar
  15. 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 CrossRefGoogle Scholar
  16. 16.
    Loftsson, T., Masson, M.: Cyclodextrins in topical drug formulations: theory and practice. Int. J. Pharm. 225(1–2), 15–30 (2001)CrossRefGoogle Scholar
  17. 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 CrossRefGoogle Scholar
  18. 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 CrossRefGoogle Scholar
  19. 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 Google Scholar
  20. 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 CrossRefGoogle Scholar
  21. 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 CrossRefGoogle Scholar
  22. 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)CrossRefGoogle Scholar
  23. 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)CrossRefGoogle Scholar
  24. 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 CrossRefGoogle Scholar
  25. 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 CrossRefGoogle Scholar
  26. 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 CrossRefGoogle Scholar
  27. 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)CrossRefGoogle Scholar
  28. 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)CrossRefGoogle Scholar
  29. 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 CrossRefGoogle Scholar
  30. 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 CrossRefGoogle Scholar
  31. 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 CrossRefGoogle Scholar
  32. 32.
    Bligh, E.G., Dyer, W.J.: A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917 (1959)CrossRefGoogle Scholar
  33. 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)Google Scholar
  34. 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)CrossRefGoogle Scholar
  35. 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 CrossRefGoogle Scholar
  36. 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)Google Scholar
  37. 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 CrossRefGoogle Scholar
  38. 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 CrossRefGoogle Scholar
  39. 39.
    WHO: Evaluation of certain food additives and contaminants. WHO Tech. Rep. Ser. 896, 26–27 (2000)Google Scholar
  40. 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 CrossRefGoogle Scholar
  41. 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)CrossRefGoogle Scholar
  42. 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 CrossRefGoogle Scholar
  43. 43.
    Lennernäs, H.: Human intestinal permeability. J. Pharm. Sci. 87(4), 403–410 (1998). doi:10.1021/js970332a CrossRefGoogle Scholar
  44. 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 CrossRefGoogle Scholar
  45. 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 2008Google Scholar
  46. 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)Google Scholar
  47. 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 CrossRefGoogle Scholar
  48. 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 CrossRefGoogle Scholar
  49. 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 CrossRefGoogle Scholar
  50. 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 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Fífa Konrádsdóttir
    • 1
  • Thormódur Geirsson
    • 1
  • Arnar Halldórsson
    • 2
  • Skarphédinn Halldórsson
    • 3
  • Thorsteinn Loftsson
    • 1
  1. 1.Faculty of Pharmaceutical SciencesUniversity of IcelandReykjavíkIceland
  2. 2.Lýsi hfReykjavíkIceland
  3. 3.Center for Systems BiologyUniversity of IcelandReykjavíkIceland

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