Emulsions containing partially water-miscible solvents for the preparationof 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, w hich possesses very poor water solubility and low bioavailability, was used as model drug. Preparation was by emulsifying an organic solution of the d rug in an aqueous solution of a stabilising agent followed by rapid displac ement of the solvent from the internal into the external phase, provoking s olid particle formation. To verify the influence of emulsion droplet size o n the drug particle size, 0.1 or 0.2% of different emulsifiers (Tween 80, c aprylyl-capryl glucoside or lecithin) and different homogenisation conditio ns (Ultra Turrax or a high pressure homogenizer at 200 or 1000 bar for thre e 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 depend ent on the droplet size in the emulsion. Drug particles of similar to 80 nm were obtained using butyl lactate, supporting the hypothesis that drug par ticle formation by the emulsification diffusion process involves generating regions of local supersaturation. Because of the increase in available sur face area, the dissolution rate of diaultrafiltrated suspensions increased greatly compared to commercial product. (C) 2001 Elsevier Science B.V. All rights reserved.