Evaluation of physicochemical properties of lipid parenteral emulsions stabilized with various phospholipids with contact of plastic containers
Dorota Watrobska-Swietlikowska
Medical University of Gdansk, Poland
: J Pharm Drug Deliv Res
Abstract
Introduction: Lipid emulsions stabilized mainly with egg lecithin are used as drug carriers and as a one of components of parenteral admixtures. Size of oily droplets of submicron emulsion is about 300 nm. Two significant parameters in lipid emulsion preparation are particle size and particle size distribution. Intravenous administration of fat droplets with diameters larger than 5 µm has been reported to be associated with severe adverse effects, such as emboli in the lungs. Appropriate container is mainly factor which determine stable lipid emulsion. Contact PCV with lipid emulsion given parenteral is considered as extremely unsafe. Physicochemical properties of lipid parenteral emulsions with contact of non-PVC plastic containers such as ethylvinylacetate (EVA), polipropylene (PP), low density polyethylene (LDPE), polyethyene (PE) were examined (immersion test). Methods: Submicron emulsions (10% of soya-bean oil) were prepared with the following phospholipids – type emulsifiers: Egg lecithin (1.2 and 5%), soya-bean lecithin (1.2 and 5%), phosphatidylcholine from egg lecithin (1.2%), hydrogenated phosphatidylcholine from egg lecithin (1.2%), hydrogenated phosphatidylcholine from soya-bean (1.2%) and dipalmitoyl-sn-glycero-3-phosphoethanolamine (1.2%). All emulsions were prepared using high pressure homogenization. The emulsions were observed for 6 months at 25 and 40°C. Visual and microscopic observations, pH, zeta potential and size of oily droplets (LD and PCS methods) measurements were performed. The stability of prepared emulsions with contact of different plastic containers such as: EVA, PP, LDPE and PE were also examined (immersion test). Influence of thermal sterilization on stability was also investigated with and without plastic materials immersed. Results: This study shows that it was possible to obtain two kinds of emulsions: Submicron type (droplet size below 1 µm) and traditional (droplet size upper 1 µm). Stable submicron emulsions,which were characterized by size of oil droplets about 300 nm, were prepared using egg lecithin (1.2%) or soya-bean lecithin (1.2 and 5%) as well as dipalmitoyl-sn-glycero-3-phosphoethanolamine (1.2%). Despite the fact that emulsions with 5% of egg lecithin and phosphatidylcholine from egg lecithin was not submicron type (d(90)below 1.76 µm), these emulsions were stable and can also be given parenterally for example intramuscular. However emulsions stabilized with hydrogenated phosphatidylcholines (d(90) about 3.81 µm) and very low zeta potetial (-12.5mV), were unstable due to increasing agglomeration. Despite two emulsions (5% of egg lecithin and 1.2% hydrogenated phosphatidylcholine from egg lecithin), all emulsions were stable when subjected to thermal sterilization. In unstable emulsions after autoclaving size of oily droplets increased from 300 nm up to 800 nm and agglomerates were observed. Lowering the temperature of thermal sterilization to 110°C eliminated this problem. No physical interaction in contact reaction between autoclaved lipid emulsions and investigated plastic containers was observed during storage up to six months in two temperatures. Increased oily droplets size in the emulsions with pure phospholipids being in contact with EVA material after 6 months at 40°C was only noticed. Conclusions: Our study indicates that there is possibility to obtain stable emulsions with pure phospholipids but nor for intravenous application. No contact interaction between thermally sterilized emulsions and investigated plastic containers was observed up to 6 months of storage except EVA containers with emulsions with pure phospholipids.
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