ABSTRACT
PURPOSE: Intravenous lipid emulsion (IVLE) was first used to prevent essential fatty acids deficiency. IVLE with α-tocopherol was reported to provide protection against parenteral nutrition-associated liver disease. This study aims to determine the optimal parameters and conditions in developing a physically stable IVLE from superolein palm oil (SoLE 20%) and its effect on lipid and liver profiles in an animal model. METHODS: SoLE 20% was prepared using superolein oil and MCT oil (1:1), stabilized with egg lecithin and homogenized using a high pressure homogenizer. Mean droplet size was used as the response variable and was measured using laser diffraction and dynamic light scattering method. Physical stability at 4 °C, 25 °C and 40 °C storage temperatures were determined based on particle size and distribution, polydispersity index, zeta potential, viscosity, vitamin E contents and pH. Sterility and pyrogenicity were also investigated. Rabbits were administered with 1.0 g/kg SoLE 20% for 5 h and repeated daily for 3 days to investigate its effect on blood lipid and liver enzymes profile. RESULTS: SoLE 20% was succesfully prepared using the optimized parameters of 800 psi, 7 cycles and 1.2 g lecithin. The IVLE prepared had a particle size of 252.60 ± 4.88 nm and was physically stable for 4 weeks at different storage temperatures. SoLE 20% had a high content of natural vitamin E, remained sterile and pyrogen free. It was also safe for intravenous administration and did not alter the blood lipid (p > 0.05) and liver enzymes profiles (p > 0.05) of the rabbits. CONCLUSION: The optimal parameters to develop a stable superolein based IVLE are 800 psi homogenization pressure, 7 homogenization cycles and using 1.2 g lecithin as the emulsifier. SoLE 20% is safe for intravenous administration and does not significantly alter lipid and liver enzymes profiles of the rabbits.
Subject(s)
Fat Emulsions, Intravenous/chemical synthesis , Lipids/blood , Liver/chemistry , Plant Oils/chemistry , Animals , Coconut Oil/chemistry , Drug Stability , Fat Emulsions, Intravenous/administration & dosage , Fat Emulsions, Intravenous/chemistry , Lecithins/chemistry , Lipid Droplets , Male , Models, Animal , Palm Oil/chemistry , Parenteral Nutrition Solutions , Particle Size , RabbitsABSTRACT
Oil in water (O/W) emulsions for parenteral nutrition can be employed as intravenous (i.v.) carriers for drugs that are poorly soluble in water and in oil by localising the drug in the interfacial lecithin layer, e.g. Amphotericin B emulsions. By now, the emulsion production required organic solvents. SolEmuls technology localises the drug in the interfacial layer by a solvent-free high-pressure homogenisation process. SolEmuls was applied to produce Carbamazepine emulsions at increasing drug concentrations from 0.5 to 10mg/ml. Drug powder and Lipofundin emulsion were mixed and homogenised at 1500bar. Characterisation of emulsions and short-term stability were performed by photon correlation spectroscopy (PCS) and laser diffractometry. Drug incorporation (absence of non-dissolved drug crystals) was investigated by light microscopy and a centrifugation test. The emulsions were physically stable and complete drug dissolution is possible up to 3mg/ml. Up to 10mg/ml drug hybrid dispersions of emulsion droplets and ultrafine nanocrystals were obtained. Both, emulsions and hybrid dispersions are suitable as i.v. injectables regarding size and stability.
