In Vitro and In Vivo Performance of Pickering Emulsion-Based Powders of Omega-3 Polyunsaturated Fatty Acids.

Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are essential nutrients for human health and have been linked to a variety of health benefits, including reducing the risk of cardiovascular diseases. In this paper, a spray-dried powder formulation based on Pickering emulsions stabilized with cellulose nanocrystals (CNC) and hydroxypropyl methylcellulose (HPMC) has been developed. The formulation was compared in vitro and in vivo to reference emulsions (conventional Self-Emulsifying Drug Delivery System, SEDDS) to formulate n-3 PUFA pharmaceutical products, specifically in free fatty acid form. The results of in vivo studies performed in fasted dogs showed that Pickering emulsions reconstituted from powders are freely available (fast absorption) with a similar level of bioavailability as reference emulsions. In the studies performed with dogs in the fed state, the higher bioavailability combined with slower absorption observed for the Pickering emulsion, compared to the reference, was proposed to be the result of the protection of the n-3 PUFAs (in free fatty acid form) against oxidation in the stomach by the solid particles stabilizing the emulsion. This observation was supported by promising results from short-term studies of chemical stability of powders with n-3 PUFA loads as high as 0.8 g oil/g powder that easily regain the original emulsion drop sizes upon reconstitution. The present work has shown that Pickering emulsions may offer a promising strategy for improving the bioavailability and stability as well as providing an opportunity to produce environmentally friendly (surfactant free) and patient-acceptable solid oral dosage forms of n-3 PUFA in the free fatty acid form.