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

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), C_max and T_max.

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 AUC_0-12hr and C_max when compared to the EE comparator (p<0.001), with AUC_0-12hr 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.

Keywords: Absorption; Bioavailability; DHA; EPA; Free fatty acids.