Article pubs.acs.org/IECR
New Equilibrium Autoclave for Determining Solubility and Melting Point of Solid Solute in Supercritical Fluids. 1. Determination of Solubility of Levonorgestrel in Supercritical Carbon Dioxide Jianpeng Ren, Shiping Zhan,* Jinxia Zhou, and Miaomiao Zhang College of Environmental and Chemical Engineering, Dalian University, Dalian, China 116622 ABSTRACT: A new equilibrium autoclave has been designed for determining the solubility of a solid solute and its melting point in supercritical carbon dioxide (ScCO2) with static method inexpensively but accurately. The solubility of levonorgestrel in ScCO2 was measured in this vessel at temperatures ranging from 313 to 323 K and pressures ranging from 10 to 18 MPa. The solubility of levonorgestrel was determined to rise with the increase of pressure at a constant temperature. The crossover point occurred between 14 and 15 MPa. Experimental data were correlated by three semiempirical models (Chrastil, Bartle, and Mendez-Santiago−Teja models). All models achieve excellent correlations to the solubility data with an average absolute relative deviation (AARD (%)) ranging from 7.92 to 9.51%.
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INTRODUCTION Supercritical fluid (SCF) technology has a great potential application in many processes, such as in food, pharmaceutical, and biochemical industries, and polymer processing.1−6 In recent decades, supercritical carbon dioxide (ScCO2) has become the most used SCF owing to its superior physical and toxicological inertness. The solubility of a solute in a supercritical fluid is the most important thermophysical property that has to be determined and modeled as the first step in developing any SCF technology. From a general point of view, experimental techniques for solubility evaluation can be divided into “static” and “dynamic”.7,8In the “dynamic” method, it is difficult to know if the phase equilibrium has been reached. Thus, the sampling for analysis shall often be conducted 1 h after the beginning of the determination.8 In the “static” method, a key problem is how to withdraw a large sample for analysis from an autoclave without disturbing the phase equilibrium. To solve this problem, various methods have been used in the literature, such as by using a buffer autoclave in combination with a syringe pump, by using capillaries or special sampling valves, and even by using optic analytical equipments with two sapphire windows in autoclave, etc.8−12 Levonorgestrel (13β-ethyl-17α-ethynyl-17βhydroxy-4-gonen3one) has been demonstrated to be an effective emergency contraceptive; in 1999, it received an approval from the Food and Drug Administration for this indication.13 To prepare the controlled release product of levonorgestrel, SCF technology, especially ScCO2-based technology will be definitely regarded as a good alternative to volatile organic solvent. Therefore, the knowledge of levonorgestrel’s solubility and melting point in ScCO2 could be of great interest to the researchers and producers of such medication. In the present study, a new equilibrium autoclave was designed for determining the solubility and melting point of a solid solute in a supercritical fluid easily and inexpensively. Solubility of levonorgestrel in ScCO2 was measured at 313, 318, and 323 K between 10 and 18 MPa. The solubility results were © 2012 American Chemical Society
correlated with three density-based models (Chrastil, Bartle, and Mendez-Santigo−Teja (M−T) models). The measurement of melting point of levonorgestrel in ScCO2 is ongoing.
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EXPERIMENTAL SECTION Materials. Levonorgestrel (CAS 797-63-7, product content > 98.5%, loss on drying ≤ 0.5%, residue on ignition ≤ 0.3%, chromatographic purity: single impurity
