A METHOD FOR THE PREPARATION OF SUBMICRON PARTICLES OF SPARINGLY WATER-SOLUBLE DRUGS BY PRECIPITATION IN OIL-IN-WATER EMULSIONS .2. INFLUENCE OF THE EMULSIFIER, THE SOLVENT, AND THE DRUG SUBSTANCE

Small particles of two steroids, cholesteryl acetate and beta-sitoster ol, were prepared by the following technique. The steroid was dissolve d in an organic solvent, which was emulsified in water in the presence of surfactant, thus giving a water-continuous emulsion. As the organi c solvent was evaporated, the steroid precipitated. One particle was f ound to form in each emulsion droplet. Particle sizes down to 25 nm we re obtained by this method. Particles were prepared from emulsions con taining different organic solvents and surfactants, and the effect on the size and the colloidal stability of the particles was examined. Th e final particle suspension is relatively stable provided the initial emulsion is stable. Furthermore, there is a close correlation between the initial droplet size and the final particle size. The particle siz e, therefore, can be varied in the same manner as the size of emulsion droplets; that is, by changing the emulsification process parameters and the amount and choice of surfactant and the oil-to-water ratio. Fi nally, the particle size depends on the choice of solvent and only sli ghtly on the concentration of drug in the oil phase of the emulsion.