In vitro dissolution behaviour and absorption in humans of a novel mixed L-lysine salt formulation of EPA and DHA

Koen Manusama, Michiel Balvers, Marlies Diepeveen-de Bruin, Laura Headley, Roberta Bosi, Michael Schwarm, Renger Witkamp*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Supplements with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are generally oil-based formulations containing their triacylglycerols, phospholipids or ethyl-esters (EE). Recently, a L-lysine salt of carboxylic EPA and DHA became available (Lys-FFA), which necessitated to study its oral absorption and plasma kinetics in humans. Objectives: The in vitro dissolution characteristics, oral bioavailability and 48 h plasma profiles of EPA and DHA (as triacylglycerides) of Lys-FFA, relative to a commercially available oil-based EE supplement. Methods: Dissociation of the lysine from the FFAs was studied in vitro applying simulated gastric (12 h) and intestinal (3 h) conditions. In an open label, randomized, two-way cross-over design, oral administration of Lys-FFA (500 mg EPA plus 302 mg DHA) versus EE (504 mg EPA plus 378 mg DHA) was studied over 48 h, in eight female volunteers. Plasma profiles of EPA and DHA were described by Area Under the Curve (AUC; 0–12 h), Cmax and Tmax. Results: Dissolution studies with Lys-FFA showed complete dissociation under both conditions. In volunteers Lys-FFA showed rapid absorption and high bioavailability indicated by significant differences in both the AUC0–12hr and Cmax when compared to the EE comparator (p<0.001), with AUC0–12hr which was for EPA 5 times higher with Lys-FFA than with the EE formulation. Conclusion: This first-in-man study of Lys-FFA demonstrated rapid absorption of EPA and DHA and a considerably higher bioavailability compared to an EE supplement under fasting conditions. The release and absorption characteristics from this solid form offer several new options in terms of formulation technology and dosing.

Original languageEnglish
Article number102232
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume164
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Absorption
  • Bioavailability
  • DHA
  • EPA
  • Free fatty acids

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