FORMULATION, STABILITY AND PHARMACOKINETICS OF TISSUE TARGETING EMULSIONS (DISTRIBUTION EMULSION, FACTOR ANALYSIS, PATTERN RECOGNITION, CLUSTER ANALYSIS).

摘要

Many of the physical and biological problems associated with the intravenous administration of poorly water soluble drugs can be overcome by dissolving drugs into the oil phase of an emulsion. The physico-chemical stability of a safflower or soybean oil emulsion, with or without drug and made either by sonicator or homogenizer was tested by particle size distribution, ultracentrifugation, elevated temperature and phase separation methods. The emulsions were found to be stable over a 3 year period at room temperature. The stability and particle size of these emulsions were not influenced by sterilization. The particle size did not significantly change within 10 days at 60(DEGREES)C.;A 6- ('75)SE -methyl-selenomethyl-19-nor-cholest-5(10)-en-3-beta-ol (SECHL) emulsion, formulated from the previous stability tests, was administered to rats in order to study its ability to be targeted to the lymphatic system. During the first 5 days after intramuscular or subcutaneous injection of the emulsions, a higher concentration of radioactivity was detected in the lymph nodes than in other tissues. Nonparametric methods (cluster analysis, factor analysis and pattern recognition) were used to analyze the data. These innovative methods gave more insight into the physiological distribution of drug by uncovering residing structures or patterns in data. Several physiological models were also used to reveal the absorption pattern into blood and the lymphatic system in the rats. From all the methods of analysis, there appeared to be preferential uptake of drug by the lymphatic system when injected intramuscular or subcutaneous as an emulsion.