Formulation of intravenous lipid emulsion containing oil-soluble vitamins

Abstract

The oil-soluble vitamins could be parenterally administered via oil-in-water emulsion. Factors affecting the Physicochemical properties of lipid emulsion were investigated, i.e., cycles of homogenization, emulsion compositions, including sterilization method. The combination of medium chain triglycerides (Miglyol 812) and long chain triglycerides (soybean oil) or only soybean oil was used as oil phase in lipid emulsion preparation at concentration of 10% or 20%. The main emulsifiers used were soy lecithin (SPC) or egg lecithin (EPC). The co-emulsifiers used were phosphatidylglycerol (PG), stearylamine (SA) and Tween 80 (T80). The main emulsifier was used either alone or in combination with co-emulsifier or a mixture of co-emulsifiers. The methods of preparation were varied in number of cycle times of emulsion through the high pressure homogenizer (3, 5, 7 or 10 cycles). The studies revealed that 10 cycles of homogenization provided the snakkest drioket suzem wgucg was aoorixunatekt 9,2 U m. Lipid emulsions formulated using 10% sybean oil, stabilized by the combination of EPC (or SPC), T80 and SA showed the best stability upon 4-month storage in a refrigerator. The mean droplet sizes of such autoclaved formulations were approximately 0.2 Um. The pH values of emulsions were approximately neutral. Emulsion using EPC+T80+SA exhibited higher positive zeta potential than that found in emulsion using SPC+T80+SA, hence it was used to incorporate vitamins (V) that were vitamins A palmitate, D3 E acetate and K1 Emulsion containing SPC+T80+SA+V had the similar physicochemical properties to prepared emulsion without vitamins. After 1-month storage, zeta potential of autoclaved formulations using SPC+T80+SA+V were 14,21 mV and the particle size was 0.2 Um. The pH of the formulation was approximately neutral and the osmolality was approximately 300 mOsm/kg. Comparison between methods of sterilization, filtration and autoclaving, was found that they insignificantly affected the amount of vitamins remaining in the emulsion (P>0.05). The loss of oil-soluble vitamins in the emulsion was observed and seemed to depend on the type of vitamins and storage time.Viamin E acetate was the most stable vitamin compared to others. From the overall results, it would be concluded that stability of emulsion containing EPC could be increased using a mixture of nonionic surfactant (T80) and positively-charged agent (SA). The prepared emulsion provided a promising properties for intravenous delivery of oil-soluble vitamins.