Skip to main content
SpringerLink
Log in

A self-emulsifying Omega-3 ethyl ester formulation (AquaCelle) significantly improves eicosapentaenoic and docosahexaenoic acid bioavailability in healthy adults

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Application of intelligent formulation design has the ability to address the poor bioavailability and improve the fasted state bioavailability of fish oils. In this study we assessed the ability of a self-emulsifying drug delivery system (SEDDS), AquaCelle®, as an additive to enhance the oral absorption of Omega-3 ethyl esters (EE) in healthy subjects under low-fat diet conditions.

Methods

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) EE were formulated with AquaCelle®. A single dose (680 mg dose of oil containing 272 mg of EPA EE and 204 mg of DHA EE), randomized, double-blind, study measured uptake of EPA and DHA over 24 h in healthy adults. Participants were randomized into two groups, receiving either the SEDDS AquaCelle® fish oil formulation or the unformulated fish oil EE as control.

Results

The AquaCelle® fish oil EE formulation demonstrated instant and complete emulsification on addition to water to produce an emulsion with an average diameter of 43 μm, compared to the oil alone which did not emulsify. The study revealed a significant difference in absorption (Cmax and AUC0–24h) between the AquaCelle® group and the control group. The AquaCelle® group was capable of increasing maximum plasma concentrations and absorption (AUC0–24h) of total Omega-3 (EPA + DHA) 3.7- and 7.1-fold, respectively, compared to the control.

Conclusion

Formulating Omega-3 EE with a SEDSS concentrate (AquaCelle®) demonstrated a significant improvement in the oral absorption of Omega-3 fatty acids without requiring a high-fat meal.

Graphic abstract

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. AbuMweis S, Jew S, Tayyem R, Agraib L (2018) Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials. J Hum Nutr Diet 31(1):67–84. https://doi.org/10.1111/jhn.12493

    Article  CAS  PubMed  Google Scholar 

  2. Chandra A, Røsjø H, Eide IA, Vigen T, Ihle-Hansen H, Orstad EB, Rønning OM, Lyngbakken MN, Berge T, Schmidt EB, Omland T, Tveit A, Svensson M (2019) Plasma marine n-3 polyunsaturated fatty acids and cardiovascular risk factors: data from the ACE 1950 study. Eur J Nutr. https://doi.org/10.1007/s00394-019-02007-3

    Article  PubMed  Google Scholar 

  3. Calder PC (2017) Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans 45(5):1105–1115. https://doi.org/10.1042/bst20160474

    Article  CAS  PubMed  Google Scholar 

  4. Sinclair AJ, Begg D, Mathai M, Weisinger RS (2007) Omega 3 fatty acids and the brain: review of studies in depression. Asia Pac J Clin Nutr 16(Suppl 1):391–397

    CAS  PubMed  Google Scholar 

  5. Mozaffarian D, Wu JHY (2012) (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr 142(3):614S–625S. https://doi.org/10.3945/jn.111.149633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Davidson MH, Johnson J, Rooney MW, Kyle ML, Kling DF (2012) A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova® compared to Lovaza® in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol 6(6):573–584. https://doi.org/10.1016/j.jacl.2012.01.002

    Article  PubMed  Google Scholar 

  7. Shimada H, Nilsson C, Noda Y, Kim H, Lundström T, Yajima T (2017) Effects of food on the pharmacokinetics of Omega-3-carboxylic acids in healthy Japanese male subjects: a phase I, randomized, open-label, three-period, crossover trial. J Atheroscler Thromb 24(9):980–987. https://doi.org/10.5551/jat.38737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pouton CW (2006) Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 29(3):278–287. https://doi.org/10.1016/j.ejps.2006.04.016

    Article  CAS  PubMed  Google Scholar 

  9. McClements DJ, Decker EA, Park Y, Weiss J (2008) Designing food structure to control stability, digestion, release and absorption of lipophilic food components. Food Biophys 3(2):219–228. https://doi.org/10.1007/s11483-008-9070-y

    Article  Google Scholar 

  10. Garaiova I, Guschina IA, Plummer SF, Tang J, Wang D, Plummer NT (2007) A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification. Nutr J 6(1):4. https://doi.org/10.1186/1475-2891-6-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chang Y, McClements DJ (2016) Influence of emulsifier type on the in vitro digestion of fish oil-in-water emulsions in the presence of an anionic marine polysaccharide (fucoidan): caseinate, whey protein, lecithin, or Tween 80. Food Hydrocoll 61:92–101. https://doi.org/10.1016/j.foodhyd.2016.04.047

    Article  CAS  Google Scholar 

  12. Joyce P, Gustafsson H, Prestidge CA (2018) Enhancing the lipase-mediated bioaccessibility of omega-3 fatty acids by microencapsulation of fish oil droplets within porous silica particles. J Funct Foods 47:491–502. https://doi.org/10.1016/j.jff.2018.06.015

    Article  CAS  Google Scholar 

  13. Singh B, Bandopadhyay S, Kapil R, Singh R, Katare OP (2009) Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications. Crit Revi Ther Drug Carr Syst 26(5):427–451. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v26.i5.10

    Article  CAS  Google Scholar 

  14. Qin Y, Nyheim H, Haram EM, Moritz JM, Hustvedt SO (2017) A novel self-micro-emulsifying delivery system (SMEDS) formulation significantly improves the fasting absorption of EPA and DHA from a single dose of an omega-3 ethyl ester concentrate. Lipid Health Dis 16(1):204. https://doi.org/10.1186/s12944-017-0589-0

    Article  CAS  Google Scholar 

  15. Lopez-Toledano MA, Thorsteinsson T, Daak A, Maki KC, Johns C, Rabinowicz AL, Sancilio FD (2017) A novel ω-3 acid ethyl ester formulation incorporating advanced lipid technologiesTM (ALT®) improves docosahexaenoic acid and eicosapentaenoic acid bioavailability compared with lovaza®. Clin Ther 39(3):581–591. https://doi.org/10.1016/j.clinthera.2017.01.020

    Article  CAS  PubMed  Google Scholar 

  16. West AL, Kindberg GM, Hustvedt SO, Calder PC (2018) A novel self-micro-emulsifying delivery system enhances enrichment of eicosapentaenoic acid and docosahexaenoic acid after single and repeated dosing in healthy adults in a randomized trial. J Nutr 148(11):1704–1715. https://doi.org/10.1093/jn/nxy127

    Article  PubMed  Google Scholar 

  17. Maki KC, Palacios OM, Buggia MA, Trivedi R, Dicklin MR, Maki CE (2018) Effects of a self–micro-emulsifying delivery system formulation versus a standard ω-3 acid ethyl ester product on the bioavailability of eicosapentaenoic acid and docosahexaenoic acid: a study in healthy men and women in a fasted state. Clin Ther 40(12):2065–2076. https://doi.org/10.1016/j.clinthera.2018.10.014

    Article  CAS  PubMed  Google Scholar 

  18. Lopez-Toledano MA, Thorsteinsson T, Daak AA, Maki KC, Johns C, Rabinowicz AL, Sancilio FD (2017) Minimal food effect for eicosapentaenoic acid and docosahexaenoic acid bioavailability from omega-3–acid ethyl esters with an Advanced Lipid TechnologiesTM (ALT)–based formulation. J Clin Lipidol 11:394–405. https://doi.org/10.1016/j.jacl.2017.01.017

    Article  PubMed  Google Scholar 

  19. PharmakoBiotechnologies (2019) http://www.pharmako.com.au. Accessed 9 April 2019

  20. Vasconcelos T, Marques S, Sarmento B (2018) Measuring the emulsification dynamics and stability of self-emulsifying drug delivery systems. Eur J Pharm Biopharm 123:1–8. https://doi.org/10.1016/j.ejpb.2017.11.003

    Article  CAS  PubMed  Google Scholar 

  21. Raatz SK, Johnson LK, Bukowski MR (2016) Enhanced bioavailability of EPA from emulsified fish oil preparations versus capsular triacylglycerol. Lipids 51(5):643–651. https://doi.org/10.1007/s11745-015-4100-2

    Article  CAS  PubMed  Google Scholar 

  22. Sarkar A, Ye A, Singh H (2016) On the role of bile salts in the digestion of emulsified lipids. Food Hydrocoll 60:77–84. https://doi.org/10.1016/j.foodhyd.2016.03.018

    Article  CAS  Google Scholar 

  23. Lawson LD, Hughes BG (1988) Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters. Biochem Biophys Res Commun 152(1):328–335. https://doi.org/10.1016/S0006-291X(88)80718-6

    Article  CAS  PubMed  Google Scholar 

  24. National Cholesterol Education Program (NCEP) Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) Final Report. Circulation 106:3143–3421

    Article  Google Scholar 

  25. Neslihan Gursoy R, Benita S (2004) Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother 58(3):173–182. https://doi.org/10.1016/j.biopha.2004.02.001

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by Pharmako Biotechnologies, Pty Ltd, Australia.

Author information

Authors and Affiliations

  1. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia

    Kristen E. Bremmell, Tahlia R. Meola & Clive A. Prestidge

  2. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of South Australia, Mawson Lakes Campus, Mawson Lakes, 5095, Australia

    Kristen E. Bremmell, Tahlia R. Meola & Clive A. Prestidge

  3. RDC Clinical Pty Ltd, Brisbane, QLD, 4005, Australia

    David Briskey & Amanda Rao

  4. School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, QLD, 4072, Australia

    David Briskey & Alistair Mallard

Authors
  1. Kristen E. Bremmell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Briskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tahlia R. Meola
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alistair Mallard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clive A. Prestidge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amanda Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristen E. Bremmell.

Ethics declarations

Conflict of interest

The author declares that they have no competing interests.

Ethical standards

The manuscript was written through contribution from all authors who have given approval for the final manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bremmell, K.E., Briskey, D., Meola, T.R. et al. A self-emulsifying Omega-3 ethyl ester formulation (AquaCelle) significantly improves eicosapentaenoic and docosahexaenoic acid bioavailability in healthy adults. Eur J Nutr 59, 2729–2737 (2020). https://doi.org/10.1007/s00394-019-02118-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-019-02118-x

Keywords

Search

Navigation