Hollow polylactide microcapsules that can be used as ultrasound contrast agents were prepared using premix membrane emulsification. Polylactide/dichloromethane and dodecane solutions were emulsified together with a nonsolvent phase (water or a water¿alcohol mixture) by repeated passage through a glass fibre membrane. The solvent, dichloromethane, diffuses out of the droplets and the polylactide solidifies around a droplet of dodecane. To investigate the effect of the nonsolvent properties on the size and span of the microcapsules, different methanol¿water, ethanol¿water and 2-propanol¿water mixtures were used as nonsolvents. The alcohol lowers the interfacial tension and increases the viscosity of the nonsolvent, and therewith it decreases the size and the span of the microcapsules. It was remarkable that 2-propanol yields the smallest size (0.35 ¿m) followed by ethanol (0.8 ¿m) and methanol (1.4 ¿m). In contrast, the smallest span was obtained with methanol (0.7), whereas 2-propanol gave the largest span (1.5). The results further show that the size and the span of the microcapsules decreases with increasing number of emulsification passes and transmembrane flux. The presence of alcohol in the nonsolvent phase increases the efficiency of the emulsification process and decreases the optimum number of passes required to obtain the minimum average size of the droplets. A three-parameter correlation was defined that could quantitatively describe the effects of all the aforementioned parameters on the size of the microcapsules.
- contrast agents