The Stability and Drug Release Characteristics of Multiple Emulsions

Abstract

Water-in-oil-in-water (W/O/W) or multiple emulsions have been studied by a number of methods. Bimodal particle size distributions were produced containing oil and multiple droplets. The proportions of these two types of droplets was important as it determined the degree to which the emulsion behaved as a multiple emulsion. The particle size distributions of the multiple emulsions were determined by optical microscopy. The relative sizes and proportions of the two types of droplets present could be determined from the distributions obtained. The effect of storage on the particle size distributions was followed. The equilibrium effect of an osmotic gradient on the multiple droplets was also determined. Freeze-etching of samples of multiple emulsions allowed electron microscopy to be performed. This revealed the structure of the internal aqueous droplets and made possible an approximate particle size distribution of these droplets. The kinetic behaviour of multiple droplets under an osmotic gradient was determined using a Coulter counter. Several rapid particle size analyses were made to follow the change in particle size distributions with time. The rate of change of the distribution enabled a mean diameter for the internal aqueous droplets to be calculated, once certain assumptions had been made. The change of the calculated diameters with storage was followed for a number of emulsions. Some preliminary experiments were carried out to directly determine the change in distribution of the internal aqueous phase. This was accomplished by using tritiated water as a radio-label. It was found that the main change on storage of multiple emulsions was diffusion of the internal aqueous droplets into the continuous phase. It is felt that the change in location of the internal aqueous phase especially under an osmotic gradient will be relevant to the release of drugs from multiple emulsions.