An-Najah Staff

Biodegradable polymeric microcapsules can be produced through different methods of which emulsion solvent-evaporation/extraction is frequently used. In this technique, the polymer (often polylactide) is dissolved in a good solvent and is emulsified together with a poor solvent into a nonsolvent phase. The solvent is then removed through the nonsolvent phase by evaporation. This results in solidification of the polymer around an internal droplet of the poor solvent. The poor solvent may be removed later when hollow capsules are required. This paper discusses the fundamental aspects of the formation process of hollow polylactide microcapsules and its effects on the physical and chemical properties of the capsules, with emphasis on the solidification process of the polymer and the resulting properties of the shell. The scope for improvement and adaptation of the current process, including new emulsification techniques, is also discussed. The main message of this paper is that the properties of the capsules can be optimized through the solidification process of the polymer which can be highly influenced by the proper choice of the nonsolvent and oil. Since this field is hardly investigated in literature, there is room for improvement, especially if the capsules can be produced with the newest emulsification technologies that are becoming available.

The influence of nonsolvent, crystallinity of the polymer film, and addition of dodecane (a poor solvent for the polymer and for the nonsolvent) on the morphology of polylactides films has been investigated and was related to phase separation behavior. Both amorphous poly-DL-lactide (PDLLA) and crystalline poly-L-lactide (PLLA) were dissolved in dichloromethane, and subsequently films were made by immersion in nonsolvent baths. PDLLA gave dense films without any internal structure, since the structure was not solidified by crystallization or glassification. PLLA films show varying structure depending on the nonsolvent. With methanol, asymmetric morphologies were observed as a result from combined liquid-liquid demixing and crystallization, while with water symmetric spherulitic structures were formed. As a next step, dodecane was added, which is not miscible with the nonsolvent, and we found it to have a strong influence on the morphology of the films. The PDLLA films with dodecane did not collapse: a closed cell structure was obtained. In PLLA films, dodecane speeds up phase separation and induces faster crystallization in the films, and the porosity, size of the pores, and interconnectivity increased. When the PLLA solutions were subjected to a heat pretreatment, crystallization could be postponed, which yielded a cellular structure around dodecane, which did not contain spherulites anymore. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 959–971, 2007

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 μm) followed by ethanol (0.8 μm) and methanol (1.4 μm). 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.