The Formulation And Characterisation of Polyglycolysed Glyceride Self-emulsifying Drug Delivery Systems

Self-Emulsifying Drug Delivery Systems (SEDDS) are specific mixtures o f oil and surfactant which readily emulsify in water with little or no agitation. These systems have been reported to increase the extent and reproducibility o f poorly water-soluble compounds. The rate limiting dissolution step is avoided by presenting the compound in solution. In addition, SEDDS deliver the compound as a fine emulsion giving a large surface area for diffusion and release by lipid digestion. Similarly, solubilisation in the core of mixed micelles (bile salts and lipid digestion products) maintains the compound in solution. This study has been performed to evaluate self-emulsifying multiple w/o/w and simple o/w emulsions for their potential as delivery systems. Medium or long chain triglycerides often reacted with PEG with non-ionic surfactants were investigated. Hydrophilic formulations showed the clearest tendency to self-emulsify, forming predominantly simple o/w emulsions whereas hydrophobic formulations displayed poor self-emulsifying properties but tended to form multiple emulsions. Stability studies for multiple emulsions were carried out in water and simulated gastric and intestinal media. The most stable formulations contained 90% oil/10% surfactant. Unfortunately phase inversion to simple o/w droplets or complete breakdown occurred in simulated intestinal media. The mechanism of self-emulsification was studied. This remains unclear although it appears that simple emulsions may be formed by phase inversion fi-om a multiple emulsion system. As the phase inversion process requires little or no external energy this process appears to be self-emulsifying. Liquid crystal formation may also be involved. In addition, interfacial features previously reported for spontaneous émulsification were observed for some formulations. The digestibility o f selective oil/surfactant mixes were analysed in vitro using a pH stat technique. Medium chain triglycerides were digested to a greater extent than long chain trigylcerides. In addition. Tween 80 concentrations greater than 10%v/v and oils with large PEG groups inhibited lipolysis. This was overcome by employing a digestible surfactant. Finally the solubility o f two model poorly water-soluble compounds in the oils and several formulations was examined to determine the dose loading potential. In general, hydrophilic formulations displayed a greater solubilising capacity than hydrophobic formulations