Emulsions containing partially water-miscible solvents for the preparation of drug nanosuspensions

The aim of this study was to investigate the feasibility of partially water-miscible solvents, such as benzyl alcohol, butyl lactate and triacetin, to prepare drug nanosuspensions by a solvent quenching technique. Mitotane, which possesses very poor water solubility and low bioavailability, was used as model drug. Preparation was by emulsifying an organic solution of the drug in an aqueous solution of a stabilising agent followed by rapid displacement of the solvent from the internal into the external phase, provoking solid particle formation. To verify the influence of emulsion droplet size on the drug particle size, 0.1 or 0.2% of different emulsifiers (Tween 80, caprylyl-capryl glucoside or lecithin) and different homogenisation conditions (Ultra Turrax or a high pressure homogenizer at 200 or 1000 bar for three cycles) were used. In general, emulsion droplet size decreased with high pressure homogenization and on increasing the number of cycles. The size of drug particles, obtained after adding water at a constant rate, was dependent on the droplet size in the emulsion. Drug particles of ∼80 nm were obtained using butyl lactate, supporting the hypothesis that drug particle formation by the emulsification diffusion process involves generating regions of local supersaturation. Because of the increase in available surface area, the dissolution rate of diaultrafiltrated suspensions increased greatly compared to commercial product.