Soft-capsule formulation of a re-esterified triglyceride omega-3 employing self-emulsifying technology and bioavailability evaluation in healthy volunteers

Abstract

Despite the superior clinical efficacy of the re-esterified triglyceride (rTG) form compared to the ethylester form, few studies have been conducted on improving the bioavailability of the rTG form of omega-3 oil. The aim of study was to evaluate the effect of self emulsifying formulation on the improvement of bioavailability of rTG form of omega-3 oil. To develop a re-esterified triglyceride (rTG) soft capsule, an rTG-loaded self-emulsifying delivery system (SEDS) was designed using coconut oil, polysorbate 80, and lecithin. Candidate formulations were designed from a phase-diagram study and optimal SEDS formulations containing 85% of high omega-3 (ω−3) oils were screened from the evaluation of droplet size distribution, measurement of oil floating area and emulsion turbidity. The selected, optimized rTG SEDS formulation was filled into a soft capsule (NOVASEDS) and applied to a sequence-randomized, double-blind, single-dose, and two-way crossover clinical study (n = 44), and the the bioavailability of NOVASEDS was compared with that of a ‘raw’ rTG capsule (rTG OMEGA3) as control. The droplet size (D50) formed from the candidate formulations was approximately 30–45 μm, and the optimal formulation showed a unimodal particle distribution with the smallest oil floating area and small changes in turbidity after 24 h. Cmax and AUC from 0 to 24 h for NOVASEDS, calculated from docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and as the sum of DHA and EPA, were significantly higher (P < 0.05) than corresponding values for rTG OMEGA3. In conclusion, NOVASEDS formulated by SEDS technology enabled the manufacture of a high rTG payload soft capsule with improved bioavailability in human subjects. © 2023 The Authors