A self-emulsifying Omega-3 ethyl ester formulation (AquaCelle) significantly improves eicosapentaenoic and docosahexaenoic acid bioavailability in healthy adults
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.
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.
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.
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.
KeywordsOmega-3 Eicosapentaenoic acid ethyl ester Docosahexaenoic acid ethyl ester Bioavailability Self-emulsifying delivery systems
This study was funded by Pharmako Biotechnologies, Pty Ltd, Australia.
Compliance with ethical standards
Conflict of interest
The author declares that they have no competing interests.
The manuscript was written through contribution from all authors who have given approval for the final manuscript.
- 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle Scholar
- 19.PharmakoBiotechnologies (2019) http://www.pharmako.com.au. Accessed 9 April 2019
- 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 106:3143–3421CrossRefGoogle Scholar