J. of Supercritical Fluids 33 (2005) 275–281 Formation of l-poly(lactic acid) microspheres by rapid expansion of CO 2 saturated polymer suspensions Kiyoshi Matsuyama a,∗ , Zhang Donghui b , Takashi Urabe a , Kenji Mishima a,b a Department of Chemical Engineering, Faculty of Engineering, Fukuoka University, 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180, Japan b Innovation Plaza Fukuoka, Japan Science and Technology Corporation, 3-8-34 Momochihama, Sawara-ku, Fukuoka 814-0001, Japan Accepted 2 September 2004 Abstract l-Poly(lactic acid) (PLA) microspheres were produced by rapid expansion of carbon dioxide (CO 2 ) saturated polymer suspensions. The suspensions of CO 2 saturated polymer solution containing ethanol were sprayed through a nozzle to the atmosphere or into water. In this work, to control the particle morphology, the gas-saturated polymer suspensions were expanded through the nozzle to water. After spraying solutions through a nozzle to the atmosphere, polymeric fibers and/or coalesced particles were obtained. On the other hand, polymeric microspheres were obtained after spraying through a nozzle to water. The obtained particles were smaller than those produced by expansion to atmosphere. The expansion of polymer suspensions to water impedes particle’s growth and agglomeration. The particles do not tend to agglomerate after expansion, since the ethanol used as co-solvent on the surface of particles diffuses through the water phase. Furthermore, the interfacial tension between the polymer droplets and water phase contributes to the microspheres formation. Changing the pre-expansion pressure and injection distance between the nozzle and water interface, controls the particle size distribution and morphology of microparticles. © 2004 Elsevier B.V. All rights reserved. Keywords: Polymeric microspheres; Rapid expansion; Interfacial tension; Poly(lactic acid) 1. Introduction Recently, supercritical carbon dioxide (CO 2 )-based pro- duction of microparticles and nanoparticles is attracting much attention in the pharmaceutical, nutraceutical, cosmetic, and specialty chemistry industry [1–5]. A considerable number of studies have been made on the preparation of microparticles and/or microcapsules of bridgeable polymer for pharmaceu- tical applications. To obtain the polymer particles, several techniques have been reported [6]. Current techniques in- clude spray drying, emulsion, and processes based on the high shear. However, there are several drawbacks, such as broad-particles size distribution in these techniques. And the solvent impurities and surfactants are often toxic and also degrade medicines within polymer matrix. ∗ Corresponding author. Tel.: +81 92 871 6631x6449; fax: +81 92 865 6031. E-mail address: matuyama@cis.fukuoka-u.ac.jp (K. Matsuyama). Therefore, we have been challenged to develop the for- mation method polymer microspheres that emits no such chemicals into our environment and controls the particles size using the supercritical fluids (SCF), especially CO 2 . Car- bon dioxide may be utilized as an environmentally benign- solvent substitute because CO 2 is non-toxic, non-flammable, and has easily accessible critical conditions, i.e., T c = 304 K and P c = 7.37 MPa. Recently, several principles based on the supercritical CO 2 are used as the formation method of poly- meric microspheres. Supercritical solutions have been used in a process called rapid expansion from supercritical solu- tion (RESS) to produce a variety of powders and fibers [7]. In RESS, a supercritical fluid solution is expanded through the nozzle with formation of solid particles. However, RESS of polymer solutions in CO 2 has been scarcely reported [8–14] because of the low polymer solubility in supercritical CO 2 . In general, solubility of high molecular weight of polymer in CO 2 is very low at a temperature below 80 ◦ C [15,16]. CO 2 dissolves only polymers with very low cohesive energy 0896-8446/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.supflu.2004.09.001