Solubility of Polycaprolactone in Supercritical Carbon Dioxide with Ethanol as Cosolvent Soraya Rodríguez Rojo, A ´ ngel Martín,* Elisa Sa´ez Calvo, and María Jose´ Cocero High Pressure Processes Group, Department of Chemical Engineering and Environmental Technology, University of Valladolid, Facultad de Ciencias, Prado de la Magdalena s/n 47011 Valladolid, Spain The solubility of a polycaprolactone polymer with molecular weight of 1000 g · mol -1 (CAPA 2101A) in supercritical carbon dioxide with ethanol as cosolvent has been measured with a variable volume view cell according to the synthetic method. Three isotherms with temperatures ranging from (303 to 330) K were measured in the pressure range of (10 to 25) MPa, maintaining a constant ethanol molar fraction of 0.075. Polycaprolactone solubilities up to 0.2 % in mass were observed. Additionally, the perturbed hard-sphere- chain equation of state (PHSC EoS) has been used to correlate the experimental data. Introduction A new dimension for the use of polymeric materials as drug delivery devices involves the incorporation of biodegradability into the system. A number of degradable polymers are poten- tially useful for this purpose, including a variety of synthetic and natural substances. The use of degradable polymers in medicine has been highlighted as a platform for drug delivery systems. There are two main devices for controlled drug release: the production of a composite with the drug dispersed into a polymeric matrix, which controls the drug release, and the coating or encapsulation of micro- and nanoparticles of the active substance. 1 Polyesters, such as poly(lactic acid) (PLA), poly(glycolic acid) (PLG), and homo- and copolymers derived from them, have been widely employed in preparing carriers for controlled release of drugs and proteins. These polymers degrade by bulk hydrolysis of ester bonds, and their rate of degradation depends on several parameters such as chemical structure, crystallinity, hydrophobicity, and molecular weight. 2 Their therapeutic value has been enormously increased by the possibility of processing them as micro- and nanoparticles, which have distinct advan- tages for oral and parenteral administration. The successful use of these polymers in pharmaceutical applications has led to the evaluation of other aliphatic polyesters such as poly(ε-capro- lactone) (PCL). PCL is a synthetic biocompatible semicrystalline polymer. The linear aliphatic structure of its monomer is shown in Figure 1. PCL exhibits a low glass-transition temperature (from (-60 to -10) °C, depending on its molecular weight) that imparts a rubbery characteristic to the material, which results in high permeability. This property has been exploited for the delivery of low-molecular-weight drugs such as steroids and vaccines. 3 It has also been used as a platform for high-molecular-weight substances such as proteins, where protection against degradation has been proven to be better than the protection achieved with other polyesters. 4,5 Supercritical-fluid (SCF)-based technologies for the produc- tion of composites and encapsulates with biopolymers show several important advantages, such as the possibility of operating at mild temperatures without degradation or contamination of the product or the capacity to achieve a better control of product characteristics. Several of these formulation technologies have been proposed and developed in which the SCF plays different roles as solvent, antisolvent, or plasticizing and swelling agent. 6 For the development of all of these processes, knowledge of the phase behavior of the substances involved (supercritical fluid, active substance, and carrier) is essential. Previous works about the study of the phase behavior of polycaprolactone-supercritical fluid systems are scarce. Cotugno et al. 7 reported the solubility of near-critical CO 2 in PCL (molecular weight, 80 000 g · mol -1 ; melting temperature, 58 °C) at high temperature (from (70 to 85) °C). Leeke et al. 8 measured the solubility of supercritical CO 2 in the polymer in the temperature range from (40 to 60) °C with pressures up to 20 MPa. Domingo et al. 9 measured the solubility of a polymer blend (PMMA/PCL) in supercritical CO 2 without and with cosolvents (acetone, dichloromethane, and ethanol). In this work, the solubility of PCL (molecular weight, 1000 g · mol -1 ) in supercritical CO 2 using ethanol as cosolvent is reported. Moreover, a correlation of experimental data using the perturbed hard-sphere-chain equation of state (PHSC EoS) is presented. Experimental Section Materials. Carbon dioxide (purity, 99.5 %) was provided by S. E. Carburos Meta´licos S. A. (Spain). The cosolvent, absolute ethanol (purity > 99.9 %), was purchased from Panreac S.A. (Spain). Polycaprolactone (CAPA 2101A; molecular weight, 1000 g · mol -1 ; melting point interval, (30 to 40) °C) was kindly supplied by Solvay Caprolactones (Solvay Interox, United Kingdom). All products were used as received. * Corresponding author. E-mail: mamaan@iq.uva.es. Figure 1. Caprolactone monomer. J. Chem. Eng. Data 2009, 54, 962–965 962 10.1021/je8007364 CCC: $40.75  2009 American Chemical Society Published on Web 01/07/2009