Experimental Study of the Synergistic Plasticizing Effect of Carbon

Article pubs.acs.org/IECR

Experimental Study of the Synergistic Plasticizing Effect of Carbon Dioxide and Ibuprofen on the Glass Transition Temperature of Poly(methyl methacrylate) Xue-Kun Li, Hui Lu, Gui-Ping Cao,* Ying-Hui Qian, Li-Hua Chen, Ren-Han Zhang, Hong-Lai Liu, and Yun-Hai Shi UNILAB, State Key Lab of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China ABSTRACT: The solubility of small molecules in a polymer and the consequent glass transition temperature reduction of the polymer with a plasticizing effect are two of the most important thermodynamic properties of small molecule−polymer systems. In this study, with an improved dual QCM device and corresponding method for determination, the solubilities of CO2 in poly(methyl methacrylate) (PMMA) film, ibuprofen (IBU) in supercritical carbon dioxide (SCCO2), and the CO2/IBU compound into PMMA film at different temperatures and pressures were determined, respectively, and then the solubility of IBU in PMMA film was calculated according to the theory of infinite dilute solution. Both CO2 and IBU molecules can plasticize the polymer in CO2−polymer and drug−polymer systems. For the CO2−IBU−PMMA ternary system, the glass transition temperature reduction behavior of PMMA versus the pressure of CO2 and proportion of IBU in PMMA was investigated, which would illustrate the synergistic plasticizing effect of CO2 and IBU on the glass transition temperature of PMMA.

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superior to other conventional methods. Yoganathan et al.18 used SCCO2 to impregnate IBU into polycaprolactone (PCL) by placing two glass beakers, containing IBU and PCL respectively, in a high-pressure stainless steel reactor at two different temperatures and CO2 pressures; the amount of loading IBU was quantified by reverse-phase high pressure liquid chromatography. They indicated that the capability of the drug dissolved into the polymer should be taken into account for the solubility of the drug in CO2, the ability of CO2 to penetrate the polymer, and the partitioning coefficient of the drug between the polymer and CO2. Nikitin et al.19 determined the solubility of ethyl-2-cyano-3-(4′-dimethylaminophenyl) acrylate (ECDA) in polystyrene film by introducing a saturated solution of ECDA in the SCCO2 impregnation process with a conventional gravimetric technique. They also obtained the solubility of ECDA in SCCO2 with UV spectroscopy. Diankov and co-workers20 used SCCO2 as a carrier and swelling agent to investigate the impregnation of o-hydroxybenzoic acid (o-HBA) into poly(methyl methacrylate) (PMMA). Their experiments were carried out in a stirred batch reactor by the static method. The uptakes of o-HBA on PMMA were determined at the temperature of 40 °C and three different pressures (12, 16, and 20 MPa). The results revealed that the solute uptakes changed in a small range of order, i.e., 20−27 mg(o-HBA)/g(PMMA), as the pressure changed, which suggested that pressure had little effect on the drug uptake on polymer compared to the concentration of drug in the high-pressure fluid phase. Uzer et al.21 also investigated the influence of temperature and pressure on the impregnation process in a CO2−drug−polymer system. Their results showed that the amounts of naphthalene

INTRODUCTION Supercritical impregnation is, in essence, the converse of supercritical extraction. Three major steps can be used to describe the impregnation process: a solute is primarily dissolved in the supercritical fluid and the supercritical fluid swells the polymer substrate, then the solution penetrates into the swollen substrate, and finally the solute is deposited on or dissolves in the substrate by releasing the supercritical fluid in a controlled manner. It is well-known that carbon dioxide is the most common fluid in supercritical applications.1−7 Most studies focused on the impregnation of various additives (such as polymer modifiers, dyes, and drugs) into biodegradable polymers using supercritical carbon dioxide (SCCO2),8 because of the potential of SCCO2 for providing precise control of the particle size, porosity, crystallinity, and surface structure by tuning CO2 properties through easily adjusting its temperature and pressure.9−12 During the process of impregnation of additive into polymer, the polymer exposed to CO2 would undergo swelling as well as the enhancement of chain mobility with CO2 plasticization, which significantly accelerates the transport of additive and increases the rate of impregnation.13 The solubility of CO2 in polymer and the glass transition temperature reduction of polymer with CO2 plasticization are two of the most important thermodynamic properties of CO2− polymer binary systems;14,15 however, what play more important roles in CO2−additive−polymer ternary systems are the solubility of the additive in the polymer and the effect of the additive on the glass transition temperature of the polymer.16 Many studies have been reported on the investigation of additives dissolved into polymers using SCCO2 as a carrier agent. Hussein et al.17 prepared an IBU (ibuprofen)/CD (cyclodextrin) complex using SCCO2 and then investigated the dissolved amount and dissolution rate of IBU into CD with the controlled particle deposition (CPD) method, which was © 2014 American Chemical Society

Received: Revised: Accepted: Published: 5873

December 17, 2013 February 25, 2014 March 11, 2014 March 11, 2014 dx.doi.org/10.1021/ie404270g | Ind. Eng. Chem. Res. 2014, 53, 5873−5885

Industrial & Engineering Chemistry Research

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in a CO2−drug−polymer ternary system had not been previously reported. What limited the investigation of the thermodynamic properties (solubility of drug in polymer and Tg reduction of polymer) in CO2−drug−polymer ternary systems under elevated pressure was the deficiency of the valid experimental technique. Although DSC is the most convenient, fast, and accurate technique to determine the Tg of a polymer, the available high-pressure cell for DSC has a typical pressure limitation of about 6.9 MPa and the baseline stability becomes erratic under elevated pressure. These two factors limit the use of DSC in investigating the Tg reduction of polymer under an elevated pressure.28 In situ spectroscopy has been successfully used to investigate the interactions among CO2, drug, and polymer materials in ternary systems.29−31 Here we also need other in situ techniques to determine the solubility of a drug in a polymer with a supercritical impregnation process as well as the Tg reduction of the polymer in a CO2−drug−polymer system under elevated pressure. The quartz crystal microbalance (QCM) technique has been used widely to explore fluid−polymer binary systems for several decades, but the conventional QCM device (single measurement cell) might not be the optimal method for the convenient and accurate investigation of ternary systems, since it is difficult to make the sorption process occur in the atmosphere of a saturated solution to obtain the solubility of a drug in the polymer. Therefore, on the basis of the dual cell device for microgravimetric impregnation studies,22 an improved dual cell QCM device and a corresponding method for determination will be introduced to monitor the sorption of CO2 or a CO2/ drug compound into a polymer. The Tg reduction of the polymer in binary or ternary systems will be investigated by determining the volume change of different samples versus increasing temperature under isopiestic condition using a horizontal high-pressure visual cell, and this technique is based on the free volume theory. This work will focus on an experimental investigation of the sorption of CO2 and CO2/IBU compound into PMMA with the dual cell QCM technique, and the Tgs of PMMA and PMMA/IBU blends under CO2 atmosphere with the highpressure visual technique. Using the multifunctional dual cell QCM device, the sorption behavior of CO2 and CO2/IBU compound into PMMA films and the solubility of IBU in SCCO2 at different temperatures and pressures can be determined, respectively. With an improved data calculation and correction method, the accurate solubility data of CO2 or IBU in PMMA over the entire experimental conditions will be obtained, and then the partitioning coefficient of IBU between PMMA and CO2 also can be calculated. The PMMA will be prepared as a regular plate to investigate the effect of dissolved CO2 on the Tg of PMMA. Especially, due to the stronger miscibility of IBU and PMMA, the IBU/PMMA blend will also be prepared as a regular plate to investigate the synergistic plasticizing effect of CO2 and IBU on the Tg of PMMA with different proportions of IBU in PMMA and pressures of CO2.

deposited in PMMA changed between 100 and 300 mg(naphthalene)/g(PMMA) at temperatures of 35, 40, and 45 °C and pressures of 8, 9, 12, and 15 MPa. They suggested that the difference in the impregnated amount of different drugs in the same polymer under identical conditions might be attributed to the different interactions among polymer, drugs, and fluid, which were also affected by the temperature and pressure. Hussain and Grant22 highlight the influence of temperature and pressure on the determination of drug uptake on polymer. They adjusted the CO2 density by changing the temperature and pressure to control the change in the IBU uptake from 10 to 30% as the condition ranged from 40 °C and 20.7 MPa to 50 °C and 13.8 MPa using the dual quartz crystal microbalance (QCM) method. They concluded that temperature played the most important role in the partitioning coefficient and the diffusivity of IBU between PMMA and CO2. Ma et al.23 used the conventional single QCM technique to obtain the drug uptake in poly(lactic acid) (PLA) by subtracting the solubility of CO2 in PLA from the coabsorption of drug and CO2 in PLA. They concluded that the partitioning coefficients of drugs between PLA and SCCO2 were greatly affected by the intermolecular interactions between drugs and PLA. According to these determinations of additives dissolved into polymers, we believe that it is better to use a saturated solution of additive in SCCO2 to determine the solubility of additive in polymer with the SCCO2 impregnation process, which should be distinguished from the definitions of “concentration”, “uptake”, or “loading”. As we know, the glass transition temperature (Tg) of a polymer will be reduced when the compressed fluid penetrates the space between polymer chains to alter the chain mobility and free volume of the polymer, while this kind of plasticizing effect may also apply equally to additives such as drugs. Velasco et al.24 determined the Tg of PMMA incorporated with IBU by differential scanning calorimetry (DSC). All the PMMA−IBU samples were treated in SCCO2 at the temperature of 60 °C and pressure of 16 MPa for 24 h. They suggested that IBU initially was crystallized in the PMMA matrix and, as the temperature increased, IBU was melted and diffused into the amorphous state acting as a plasticizer of PMMA, leading to the reduction of the Tg.25 Nair and co-workers16 investigated the influence of several drugs on the Tg of poly(vinylpyrrolidone) using the DSC technique. They also suggested that the Tg reduction of PVP could be attributed to the plasticizing effect of different drugs. Simultaneously, the interactions between drugs and PVP were characterized by Fourier transform infrared (FTIR) spectroscopy, and the results presented that the drugs which formed hydrogen bonding with the carbonyl groups of PVP could reduce the Tg more than those without any interaction with PVP. Matsumoto and Zografi26 also investigated the influence of interaction between indomethacin and PVP on the molecular dispersions. Their results expressed that the Tg reduction of PVP was related not to the molecular weight of PVP but to the characteristics of the drug, especially for carboxylic acid dimers, which could form hydrogen bonding with PVP. On the other hand, the molecular size of impregnated drugs might influence the Tg reduction of the polymer: the smaller molar volume the drug had, the easier the drug diffused into polymer chains and interacted with the functional groups of the polymer, reducing the Tg of the polymer.27 All these studies were based on drug−polymer binary systems; however, the research on the Tg reduction of polymer with the synergistic plasticizing effect of CO2 and drug

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FUNDAMENTAL THEORY OF DETERMINATION QCM Determination. Due to the high sensitivity of the QCM, several factors will affect the QCM frequency determination, which can be classified into two categories: the physical parameters of the surrounding fluid (temperature, pressure, viscosity, and density of the fluid) and the structural parameters of the crystal (mass loading and surface roughness 5874

dx.doi.org/10.1021/ie404270g | Ind. Eng. Chem. Res. 2014, 53, 5873−5885


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Figure 1. Schematic illustration of the high-pressure dual cell QCM associated with high-pressure visual cell and apparatus. (A) CO2 cylinder; (B) buffer tank; (C) vacuum pump; (D1−D4) thermocouples; (E1−E4) pressure transducers; (F) air bath; (G) preheating coil; (H) QCM measurement cell; (I) feed-through leads; (J) quartz crystal; (K) oscillator circuit; (L) frequency counter; (M) PC; (N) safety valves; (O1−O13) needle valves; (P) CCD camera; (Q1) vertical high-pressure visual cell; (Q2) horizontal high-pressure visual cell; (R) calibration holder; (S1, S2) quartz windows; (T) polymer sample; (U) back-pressure valve; (V) elastic filter; (W) high-pressure circulation device; (X) magnetic stirrer; (Y1, Y2) mesh filters; (Z) electric machinery.

1011 g·cm−1·s−2) are the density and shear modulus of quartz, respectively, and Δm is the mass shift per surface area (g·cm−2). It is difficult for an empirical equation to precisely calculate the frequency shift caused by the roughness effect because of the diversity of the morphology of the polymer film coated on the crystal, as it will change in the CO2 sorption process. In other words, the surface roughness effect can be estimated only by the real morphology of the polymer film; i.e., it needs some effective analysis of surface morphology, such as by atomic force microscopy or scanning electron microscopy. A detailed description can be found in our recent work.33 When a QCM is used to investigate the sorption of CO2 into a polymer film, the parameter of Δm in eq 4 contains the mass of CO2 adsorbed on the surface of the polymer film (mA) and the CO2 absorbed in the bulk of the polymer film (mB, mB = Smp, mp is the mass of the coated polymer film). In order to obtain more accurate data, we introduced a concept, the true frequency shift (ΔF′), which was defined as33

of the crystal). The apparent frequency shift (ΔF) in QCM determination can be defined as ΔF = Fi − Ff = ΔFT + ΔFP + ΔFη + ΔFm + ΔFr

(1)

where Fi is the instant measured frequency, Ff is the fundamental frequency of the coated crystal, and ΔFT, ΔFP, ΔFη, ΔFm, and ΔFr are the contributions of the frequency shifts of temperature, pressure, viscosity, and density of the fluid and the mass loading and surface roughness of the crystal, respectively. In each isothermal measurement, ΔFT can be neglected. ΔFP, ΔFη, and ΔFm are all described by empirical formulas and they are used in QCM determination widely, written as follows: ΔFP = 1.095 × 10−5 − 2 × 10−8TF0P

(2)

⎛ C ⎞⎛ ρ η ⎞ ΔFη = −⎜ m ⎟⎜ f f ⎟ ⎝ 2 ⎠⎝ πF0 ⎠

(3)

1/2

ΔFm = −

2nF0 2 Δm = −CmΔm ρq μq

ΔF ′ = Fi − Ff − ΔFT − ΔFP − ΔFη = ΔFm + ΔFr

(5)

and then we can obtain ΔF ′ = −Cm(mA + Smp) + ΔFr

(4)

(6)

which suggests that the solubility of CO2 into the polymer film can be obtained from the slope of the plot of −ΔF′/Cm with the mass of polymer film (mp) without estimating the roughness effect. By this method, the solubility of CO2/drug compound in the polymer film also can be obtained. As an accurate and sensitive in situ analytical technique, it is not recommended to obtain the relation between mass and frequency with the Sauerbrey equation only; all four important

where P and T are the experimental pressure (MPa) and temperature (°C) respectively, F0 is the fundamental frequency of bare crystal, Cm is the mass sensitivity of QCM and is equal to 56.6 Hz·μg−1·cm2 for a 5 MHz crystal, and ηf and ρf are the shear viscosity (Pa·s) and density (kg·m−3) of the surrounding fluid at the experimental condition, which can be obtained from the NIST Web database.32 Crystals used in this work all have two faces; then n = 2, ρq (=2.648 g·cm−3) and μq = (=2.947 × 5875



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factors (temperature, pressure, viscoelasticity of fluid, and surface roughness) should be considered. High-Pressure Visual Cell Determination. As early as in the 1950s, Fox and Flory had established the free volume theory, which could be used to explain the glass transition temperatures of polymers.34 Along with the increment of temperature, the free volume of a polymer will be changed by the swelling of CO2; thus the Tg can be determined by analyzing the relationship between the ratio of volume change and temperature under isopiestic condition. The volume change ratio is defined as the ratio of the volume change (ΔVT) under isopiestic condition with different ambient temperatures to the initial volume (V0) of the polymer sample. Here we assume that the polymer sample is a cuboid (length (a0), width (b0), and height (c0)), and the length is equal to width; then the sample volume can be calculated by

V0 = a0b0c0 = a0 2c0

(7)

VT = aT bT cT = aT 2cT

(8)

high-pressure circulation device. The quartz window (S1) was used to observe the dissolution of IBU in CO2. Another horizontal high-pressure visual cell was used to record the volume change of the polymer sample via a CCD camera (OLYMPUS Model SP-350) through another quartz window (S2) when the Tg of the polymer was investigated. A backpressure valve (AMFLO Model R71) was connected to the visual cell to keep the CO2 pressure from changing with increasing temperature to maintain a pressure accuracy of ±0.01 MPa. The elastic filter (HAMLET Model H600) was installed to prevent the impurities from being carried to the back-pressure valve. A custom-made buffer tank with heater was connected after the cylinder to supply high-pressure CO2 to the three high-pressure cells. The crystal holder was connected to the oscillator circuit (Maxtek Model PLO-10i) with a high-pressure electrical feedthrough, and then a 225 MHz universal frequency counter (Agilent Model 5313A) was connected to the frequency output of the oscillator circuit to monitor the frequency of the vibrating crystal. The in situ data of frequency versus time were written to a computer by Agilent Ituilink Connectivity software. Experimental Methods and Procedures. Preparation of Polymer Film. PMMA films was prepared by dipping clean quartz crystals into 2−10 wt % PMMA−acetone solution for 30 min to ensure the two crystal faces were wetted completely. The solution was aspirated out slowly to leave the level of the solution at a speed of 1−5 mL/min so as to obtain a desired and uniform wet film. Most of the residual solvent could be evaporated at room temperature. The coated crystals were then dried under vacuum at 50 °C for 12 h to remove any residual solvent and obtain the applicable thin polymer film. The masses of different polymer films could be calculated with the Sauerbrey equation from the difference of frequencies between uncoated (F0) and coated crystals (Ff) at the experimental temperature in the vacuum. Determination of the Sorption of CO2 into Polymer. By isolating the QCM measurement cell from the vertical highpressure visual cell, a coated crystal was placed into the measurement cell to determine the initial frequency (Ff) in the vacuum (−0.1 MPa) at the experimental temperature until the frequency shift was stabilized to ±1 Hz for 30 min. The CO2 was supplied to the pressure cell at a given pressure, for a long enough time that the frequency shift value was steady again, and then a new value of the frequency (F1) was recorded. After that, the pressure inside the cell was supplied to the next given pressure to record a new steady frequency (F2). At last, a series of Fi values at different pressures for each coated crystal were recorded, and then the ΔFi′ values were calculated by eq 5. After determination of the ΔFi′ values with other coated crystals, the isothermal solubility of CO2 in the polymer could be obtained from the slope of a plot of −ΔFi′/Cm versus the different masses of the polymer film at each pressure. Determination of the Solubility of IBU in SCCO2. The cloud-point method was used to determine the solubility of IBU in SCCO2 with the vertical high-pressure visual cell. This technique used to obtain cloud-point curves has been described in detail elsewhere.35 A given mount of IBU was placed on the bottom of the visual cell where it could be observed through the quartz window (S1). After heating of the visual cell to the experimental temperature in the vacuum, CO2 was transferred into the cell to increase the pressure and to dissolve IBU until the cloud point was obtained, which indicated that the fluid phase was equal to the saturated solution. Each cloud-point

and the volume change ratio can be written as ΔVT a 2c = T2 T − 1 V0 a0 c0

(9)

The Tg data in this work can be obtained by finding the turning point in the plot of the ΔVT/V0 versus increasing temperature under atmospheric pressure and CO2 isopiestic condition, respectively.

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EXPERIMENTAL SECTION Materials. Nitrogen (UHP grade, 99.99%), and carbon dioxide (purity >99.9%) were purchased from Wugang Gas Co. Ltd. Acetone (AR grade) was obtained from Sinopharm Chemical Reagent Co. Ltd., and deionized water was supplied by our lab. Commercially available PMMA (Mw = 1.87 × 106 g/ mol, Tg = 108−113 °C) used in this study was purchased from Taiwan Chimei Co. Ibuprofen (racemic grade, purity >98%) was supplied by Juhua Group Corp. Pharmaceutical Factory. The 5 MHz AT-cut quartz crystals used in QCM measurements with gold electrodes sputtered centrally on both sides were purchased from Beijing Chenjing Electronic Co. Ltd. The crystals have a blank diameter of 12 mm, electrode diameter of 6 mm, and electrode thickness of 0.1 μm. To ensure the polymer films could be coated on both sides of the quartz crystals evenly, all the crystals were unpolished (slightly rough). Apparatus and Operation. A schematic illustration of the pressure cells and apparatus is shown in Figure 1. The QCM measurement cell was a thick-walled stainless steel cylinder (internal volume was equal to 50 mL) with a maximum working pressure of 30 MPa. A thermocouple was placed in the cell to measure the temperature of CO2, and a pressure transducer (LEEG Model SMP131, 0.2% full scale accuracy) was used to monitor the CO2 pressure. The quartz crystal was mounted vertically in the middle of the cell by a homemade crystal holder. The entire assembly was placed in a temperature-controlled air bath (HUSAC Model DHG9140A) to maintain a temperature accuracy of ±0.1 °C. The vertical highpressure visual cell was also an thick-walled stainless steel cylinder (the volume of the internal room was equal to 35 mL) with a maximum working pressure of 25 MPa, which was connected to the QCM measurement cell by a custom-made 5876



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Table 1. Solubility Data of Different Systems and the Partitioning Coefficient Data at Different Temperatures and Pressures P, MPa

SCO2/PMMA,33 g(CO2)/g(PMMA)

S(CO2+IBU)/PMMA, g(CO2+IBU)/g(PMMA)

7.5 8.0 8.5 9.0 10.0 11.0 12.0 13.0 14.0 15.0

0.2915 0.2957 0.2971 0.2998 0.3046 0.3087 0.3141 0.3196 0.3250 0.3281

0.3213 0.4034 0.4430 0.4498 0.4930 0.5103 0.5245 0.5314 0.5473 0.5597

7.5 8.0 8.5 9.0 10.0 11.0 12.0 13.0 14.0 15.0

0.1549 0.1634 0.1683 0.1694 0.1707 0.1722 0.1753 0.1782 0.1812 0.1832

0.1936 0.3036 0.5227 0.5961 0.6386 0.6723 0.6961 0.6833 0.6987 0.7057

7.5 8.0 8.5 9.0 10.0 11.0 12.0 13.0 14.0 15.0

0.1112 0.1245 0.1275 0.1352 0.1381 0.1406 0.1413 0.1425 0.1434 0.1452

0.1727 0.5280 0.7275 0.7475 0.8219 0.8423 0.8450 0.8563 0.8600 0.8636

SIBU/PMMA, g(IBU)/g(PMMA)

SIBU/CO2(×10−3), g(IBU)/g(CO2)

K

0.0297 0.1078 0.1355 0.1500 0.1884 0.2046 0.2105 0.2117 0.2223 0.2316

0.6215 1.8086 3.2116 4.3338 7.2780 8.7363 9.9130 10.2426 10.9490 11.4200

47.8394 59.5780 42.1943 34.6023 25.8891 23.4196 21.2308 20.6706 20.3014 20.2758

0.0387 0.1402 0.3544 0.4268 0.4679 0.5001 0.5209 0.5050 0.5175 0.5225

0.9895 2.9009 6.4374 10.2536 16.2404 20.1295 23.4436 23.8003 24.4697 24.9733

39.1406 48.3027 55.0529 41.6194 28.8091 24.8431 22.2183 21.2191 21.1470 20.9211

0.0615 0.4035 0.5740 0.6123 0.6838 0.7017 0.7037 0.7137 0.7166 0.7183

1.7411 10.0508 12.5481 18.6327 24.4228 27.0166 29.5180 30.7644 31.4084 31.8714

35.2940 40.1375 45.7403 32.8594 27.9992 25.9726 23.8390 23.1995 22.8165 22.5384

T = 35 °C

T = 50 °C

T = 60 °C

measurement was repeated at least twice at a fixed temperature, and the cloud-point pressures are reproducible to within ±0.1 MPa. Due to the different amounts of IBU, a series of cloudpoint pressures could be obtained at a given temperature. The consumption of CO2 used to dissolve a certain amount of IBU could be calculated by the fixed volume of the visual cell and the density of CO2 at the cloud-point pressure. By this method, we could obtain the saturated solubility of IBU in SCCO2 at different temperatures and pressures. Determination of the Solubility of IBU in Polymer. How to use the dual cell QCM device to investigate intermittently the impregnation process has been described in detail elsewhere.22 In this work, we tried to continuously determine the solubility of CO2/IBU compound in PMMA film. In order to obtain the solubility instead of the concentration of IBU in PMMA, the fluid in dual cell must be the saturated SCCO2/IBU solution with the experimental temperature and pressure. To ensure the IBU dissolved in SCCO2 was saturated, excessive IBU was loaded in the vertical visual cell while the coated crystal was put into the measurement cell, after the Ff of the coated crystal was recorded in the vacuum at the given temperature. CO2 was supplied to both pressure cells at a given pressure, maintaining the pressure within ±0.1 MPa, and then CO2 was only circulated through the QCM measurement cell until the F1,S was obtained. Then the valves were switched to allow the

saturated SCCO2/IBU solution to circulate through both cells for a long enough time until the new stable frequency (F1,D) was obtained, which indicated that the CO2/IBU compound absorbed completely into the PMMA film at this given pressure. The next given pressure was then supplied to both cells to obtain the new stable frequency (F2,S and F2,D). By this method, a series of Fi,S and Fi,D values at different pressures and fixed temperatures were obtained. The isothermal solubility of CO2/IBU compound in PMMA could be calculated from the slope of a plot of −ΔFi,D′/Cm versus the different masses of polymer film at each pressure. All experiments were operated in the homogeneous saturated (SCCO2−IBU) phase. According to the hypothesis of infinite dilute solution,36 the density and viscosity of SCCO2/IBU solution could be maintained the same as those of pure SCCO2 fluid.23 Therefore, the solubility of IBU in PMMA will be calculated by subtracting the solubility of CO2 in PMMA from the solubility of CO2/IBU compound in PMMA. Determination of the Glass Transition Temperature. As described above, the Tg of a polymer would be determined by the relationship between the volume change ratio and increasing temperature. The plate PMMA samples (10 mm × 10 mm × 1 mm) were prepared by enclosing the polymer pellets in a custom-made mold, which was placed in a tablet pressing machine. The mold was heated by a heating module 5877



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°C. The results are presented in Figure 2. Because the specific interaction between IBU and CO2 increased as the pressure

until the PMMA pellets were softened, and then the mold was compressed by the tablet pressing machine at a pressure of 15 MPa for a certain period of time (1−2 h) to keep the polymer sample from deformation while the mold was cooled to room temperature to obtain the desired samples. A sample was placed in the calibration holder and exposed to the CO2 atmosphere at an given experimental pressure for a certain time (∼12 h) to make the polymer sample swollen completely by CO2. Before increasing the temperature of the system, a initial morphology was recorded to determine the initial volume of the polymer sample by a CCD camera through the quartz window (S2). Then the temperature was increased from 25 to 120 °C at a speed of 0.5 °C/min with a simultaneous record of the morphology change of the polymer sample in the CO2 atmosphere every 10 min. After determination, the images of the morphology change of the polymer sample were treated by Image Pro Plus software to obtain the relationship between the volume change ratio and increasing temperature. When we determined the Tg reduction in the CO2−IBU−PMMA ternary system, the PMMA pellets were crushed into powder, with different mass proportions. IBU was uniformly mixed with PMMA powder in several sealed glass bottles, and then these sealed bottles were heated until both IBU and PMMA were melted to form the blends, which then were transferred to the heated mold. The other steps were the same as those in the preparation of the PMMA samples.

Figure 2. Solubility of IBU in SCCO2 at different temperatures and pressures up to 15 MPa. The data by Chan et al.40 were obtained by a dynamic solubility measurement technique at 35 and 45 °C for racemic IBU sample.

increased,39 the SIBU/CO2 continued increasing over the entire pressure range. Especially in the pressure range below 11 MPa, SIBU/CO2 increased sharply. All the solubility data increased generally in the range from 10−5 to 10−3 mole fraction with increasing pressure over the entire experimental condition. When IBU was presented in the CO2 atmosphere, the melting point of IBU was reduced;40 therefore, SIBU/CO2 increased obviously with increasing temperature at a given pressure, especially for the temperatures of 50 and 60 °C in this work. The solubility values for the temperatures of 35 and 45 °C were in agreement with those of Chan et al.,40 which further validated our experimental system and procedures. It can also be seen in Figure 2 that SIBU/CO2was dominantly affected by CO2 pressure in the pressure range below 11 MPa, while it was affected by temperature at higher pressure. The ΔFi,D′ values, caused by the sorption of CO2/IBU compound in PMMA film, with different thicknesses of PMMA film were determined using the dual cell QCM (DCQ) technique. A set of ΔFi,D′ values as a function of pressure for different thicknesses (or masses) of PMMA film at the temperature of 35 °C are shown in Figure 3. The plot displays that the ΔFi,D′ values decreased with increasing pressure and film thickness (or mass). According to eq 6, S(CO2+IBU)/PMMA

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RESULTS AND DISCUSSION Solubility of CO2 in PMMA. In our recent work, we obtained the solubility of CO2 in PMMA (SCO2/PMMA) at different temperatures (35, 50, and 60 °C) as the CO2 pressure was increased to 15 MPa,33 and the results are shown in Table 1 for comparison. As we know, as the pressure increased, the density of CO2 increased, causing more CO2 molecules to absorb into the polymer, especially in the vicinity of critical pressure; therefore, SCO2/PMMA increased with increasing pressure. As the temperature increased, the chain flexibility of the polymer increased, but the intermolecular interaction between CO2 and PMMA decreased,37 causing SCO2/PMMA to decrease. On the other hand, when the polymer state is glassy, the molecular kinetic energy is too low to rotate the main chain of the polymer, which cannot inspire the motion of polymer segments, and the segments are in a frozen state. The free volume of the polymer is fixed; therefore, SCO2/PMMA increases sharply with increasing pressure. The sorption behavior is fitted for a dual-sorption model which would take into account the nonequilibrium nature of the glassy polymer.38 When the polymer state changes from glassy to rubbery, the free volume of polymer begins to expand, and the molecular kinetic energy is sufficient for rotating the main chain of the polymer to make the polymer segments relax; besides, in high-density CO2, the sorption of CO2 into the polymer gradually tends to achieve saturation due to the equilibrium nature of rubbery polymer. Solubility of IBU in PMMA. Before calculating the solubility of IBU in PMMA (SIBU/PMMA), the solubility of CO2/IBU compound in PMMA (S(CO2+IBU)/PMMA) should be determined. To calculate the partition coefficient of IBU between PMMA and CO2, the solubility of IBU in SCCO2 (SIBU/CO2) is also needed. SIBU/CO2 was measured at pressures in the range 7.5−15 MPa and temperatures of 35, 45, 50, and 60

Figure 3. Plot of ΔFi,D′ as a function of pressure for differing thickness (or mass) of PMMA film at 35 °C. 5878



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was obtained from the slope of the linear plot of −ΔFi,D′/Cm versus film mass. Taking the ΔFi,D′ values at 35 °C and 11 MPa, for example, which are shown by the dashed line in Figure 3, then the linear relation between −ΔFi,D′/Cm and the film mass is shown in Figure 4. The slope obtained by linear fitting is the

being transported by SCCO2 and dissolved in PMMA; therefore, the faster dissolution occurred at the higher temperature where the mass transfer in SCCO2 is greater, which could be attributed to the lower kinematic viscosity. To verify the feasibility of the calculation for the solubility of IBU in PMMA, a series of experiments for comparison were carried out by the weighting technique. A given mass of PMMA sample was exposed to the saturated SCCO2/IBU solution at each temperature and pressure for 12 h, followed by fast depressurization (typically 8−10 s). IBU became entrapped inside the deplasticized PMMA, and after all the CO2 absorbed in PMMA released from PMMA matrix, the difference in the mass of the PMMA sample was the solubility of IBU in PMMA. The results are shown in Figure 5b. All the data measured by the weighting technique were almost lower than those of the DCQ technique, which could be attributed to the mass loss carried by SCCO2 with fast depressurization or the deviation of a different estimated method; however, these experimental results could still be reliable. The partitioning coefficient (K) of IBU between PMMA and CO2 can be defined as follows:

Figure 4. Plot of −ΔFi,D′/Cm as a function of PMMA film mass at 35 °C and 11 MPa.

K=

solubility of CO2/IBU compound in PMMA, S(CO2+IBU)/PMMA = 0.5103 ± 0.0097 g/g, with a correlation coefficient of 0.998. The relative deviation ranged from 0.9 to 2.5%. With this method, the effect of roughness could be canceled out completely,33 and all the available S(CO2+IBU)/PMMA data would be obtained using this correction method. The S(CO2+IBU)/PMMA values are presented in Figure 5a and Table 1. The solubility of IBU in PMMA (SIBU/PMMA) could be calculated by subtracting SCO2/PMMA from S(CO2+IBU)/PMMA, and the results are presented in Figure 5b and Table 1. Both the isothermal S(CO2+IBU)/PMMA and SIBU/PMMA increased sharply as the pressure increased from 7.5 to 9 MPa, and then leveled off at 11 MPa, while in the pressure range above 8.5 MPa, S(CO2+IBU)/PMMA and SIBU/PMMA increased with increasing temperature. IBU hardly dissolved in gaseous CO2, while it could easily dissolve in SCCO2, and then dissolve in PMMA with the assistance of SCCO2. When the pressure increased above 11 MPa, the solubility of CO2 in PMMA as well as swelling of PMMA gradually tended to achieve saturation. As described above, the increasing temperature enhanced the solubility of IBU in SCCO2, which led to much more IBU

SIBU/PMMA SIBU/CO2

(10)

The results are shown in Figure 6. It can be seen that the isothermal partitioning coefficient increased as the pressure

Figure 6. Partitioning coefficient of IBU between PMMA and CO2 at different temperatures and pressures in the range 7.5−15 MPa.

Figure 5. Corrected solubility of (a) CO2/IBU compound and (b) IBU in PMMA at different temperatures and pressures in the range 7.5−15 MPa. 5879



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Figure 7. Isopiestic volume change ratios of different samples as a function of temperature under atmospheric pressure and various CO2 pressures.

Greenhalgh et al.43 suggested that the smaller the Δδ was, the stronger the miscibility (or molecular interaction) between two components was. Although both Δδ CO 2 −IBU and ΔδCO2−PMMA decreased as the CO2 density increased (i.e., increasing pressure or decreasing temperature), ΔδIBU−PMMA, which was independent of the temperature and pressure, was much smaller than ΔδCO2−IBU.22 Therefore, the interaction between IBU and PMMA was much stronger than that between IBU and CO2. However, the latter as well as the interaction between CO2 and PMMA increased as the density of CO2 increased, which negatively affected the interaction between IBU and PMMA. On the other hand, according to the Flory− Huggins close-packed lattice theory44,45 and the Sanchez− Lacombe lattice theory,46 the amorphous zone of the polymer could be considered as empty sites, and small molecules dissolved into the polymer would occupy these empty sites.

increased from 7.5 to 8.5 MPa, and then decreased at the pressure range above 8.5 MPa; i.e., peaks of the partitioning coefficient appeared at certain pressures. The K values decreased as temperature increased in the pressure range below 8.5 MPa, and then increased with increasing temperature in the pressure range above 11 MPa. To the best of our knowledge, what caused the partitioning coefficient to change at different temperatures and pressures can be attributed to two reasons: one is the molecular interactions between the three components; the other is the structural characteristics of the polymer. The strength of molecular interactions between two components could be determined by the difference between the corresponding solubility parameters of different components,41,42 and the difference of solubility parameters (Δδ) between CO2, PMMA, and IBU could be defined in the study of Hussain and Grant.22 5880



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When most of these empty sites were occupied by CO2 and IBU, the solubility of both IBU and CO2 in PMMA would increase slightly with increasing pressure at a certain temperature, while in the SCCO2 phase, increasing pressure could significantly increase the density of SCCO2, leading to the increment of the solubility of IBU in SCCO2. In summary, due to the stronger interaction of IBU with PMMA and enough amorphous zone of PMMA, the solubility of IBU in PMMA increased sharply with increasing pressure until saturation was achieved, while the solubility of IBU in SCCO2 increased as the density of CO2 increased continually. Therefore, the peaks of plots of the partitioning coefficient versus pressure appeared at certain pressures for different temperatures. It has been demonstrated that the mechanism for the impregnation of IBU into polymer using SCCO2 could be defined in two ways: kinetically and thermodynamically driven.22,31,47 For the CO2−IBU−PMMA system, it has been investigated that the solubility of IBU in SCCO2 was higher than that of most other drug additives;48 therefore, the kinetically driven mechanism should be considered to describe the impregnation of IBU into PMMA with SCCO2. On the other hand, once the IBU molecule was impregnated into PMMA by SCCO2, CO2 acted as an electron acceptor and would form an electron acceptor−donor complex with the oxygen atom on the carbonyl group of PMMA.37 However, this oxygen atom would also form an hydrogen bond with the hydroxyl group in IBU, and the interaction of the hydrogen bond was stronger than that of the electron acceptor−donor complex at low CO2 density, which became weaker at high CO2 density.37 This result could also explain why the K values increased with the increment of pressure when the pressure was below 8.5 MPa and then decreased in the pressure range above 8.5 MPa. Therefore, the impregnation of IBU into polymer using SCCO 2 should be driven by both kinetic and thermodynamic mechanisms. Glass Transition Temperature. The volume change ratios of PMMA and IBU/PMMA blend samples as the temperature increased up to 120 °C with different CO2 pressures are presented in Figure 7a and b−f, respectively. For the PMMA samples, at each pressure except for 8 MPa, the increment of ΔVT/V0 values with increasing temperature was composed of two parts by different rates of increment; then an intersection, i.e., the turning point, could be obtained by fitting the linear data in each part, respectively. The detail of an example is expressed in Figure 8; this turning point was the glass transition point. The glass transition point of PMMA samples moved toward the low temperature as the CO2 pressure increased. At the pressure of 8 MPa, the ΔVT/V0 increased continually with increasing temperature at a steady increment rate; therefore, the glass transition point could not be found. For the IBU/ PMMA blend samples, it was shown that there was little difference in ΔVT/V0 changing with increasing temperature among different samples, while the initial glass transition point of different samples gradually moved toward the low temperature as the amount of IBU incorporated in PMMA increased under atmospheric pressure. When each sample was immersed in CO2, the isothermal ΔVT/V0 increased as CO2 pressure increased, and the isopiestic ΔVT/V0 increased with the increment of temperature as well as the proportion of IBU in PMMA. The glass transition point of IBU/PMMA blend samples also moved toward the low temperature as the CO2 pressure increased; also, the higher the proportion of IBU in

Figure 8. Isopiestic volume change ratio of PMMA sample as a function of temperature under atmospheric pressure.

PMMA was, the more significant the glass transition temperature of PMMA reduced. For instance, when IBU (19.8 wt %) was blended with PMMA (80.2 wt %), the glass transition of PMMA would occur at the temperature of 40 °C, which was much lower than that of any other samples at the given CO2 pressure of 2 MPa. One way of verifying the reliability of the method for Tg determination in this work is to compare the experimental data with the results obtained by DSC technique. Duplicate experiments were done to obtain the average Tg of PMMA sample under atmospheric pressure, and the result was 111 °C, which was quite close to that determined by DSC (NETZSCH DSC-204), 110.3 °C. The relative deviation ranged from 0.64 to 4.39%. Using this available method, all the Tg values of different samples could be obtained over the entire experimental pressure range, and they are shown in Figures 7 and 9.

Figure 9. Glass transition temperature (Tg) values of PMMA in CO2− PMMA, IBU−PMMA, and CO2−IBU−PMMA systems. The inset represents the relation between the Tg reduction of PMMA and the proportion of IBU in PMMA. For comparison, several literature data are shown from Handa et al.,49 Liu et al.,50 Kikic et al.,51 Condo et al.,52 and Velasco et al.24 5881



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For the CO2−polymer binary system, the Tg of plasticized polymer is usually lower than that of pure polymer, which can be attributed to the presence of CO2 molecules that can increase the free volume and enhance the chain mobility, i.e., the plasticizing effect of CO. This effect directly depends on the concentration of CO2 in the polymer matrix. Due to the interaction between CO2 and the carbonyl groups of PMMA,37 the Tg reduction of PMMA caused by the CO2 plasticization is greater than that of other polymers without carbonyl groups. To compare the result of this work, Figure 9 represents several literature results of the Tg reduction behavior of PMMA as a function of CO2 pressure. It was found that different types of Tg reduction behavior could be obtained by different determination techniques, different apparatus, and differences in the PMMA material, including the molecular weight and the concentration of isomer. Handa et al.49 obtained retrograde vitrification behavior with high-pressure DSC (Setaram DSC121). By using high-pressure DSC (TA2920), Liu et al.50 obtained positive behavior (concave up), which was similar to that determined in this work, while Kikic et al.51 used an in situ gas chromatographic technique to obtain negative behavior (concave down). Condo et al.52 also found the retrograde vitrification behavior with a creep compliance technique. Furthermore, four different types of behavior had been predicted by the thermodynamic model which asserted that the total entropy of the CO2−polymer system was equal to zero at the glass transition point51,53,54 and different CO2-induced Tg reduction behavior would be predicted only by adjusting the binary interaction parameter; therefore, the interaction between CO2 and polymer could seriously affect the glass transition behavior of polymer. What we should consider is the retrograde vitrification behavior in the CO2−PMMA system, which represents that PMMA is glassy within the Tg−Pg phase envelope while it is rubbery outside this envelope. Due to the high value of the interaction parameter, the significant solubility of CO2 in PMMA at low temperature can also result in improved chain mobility as increased temperature can; then PMMA changes from glassy to rubbery.50,51 The thinner the polymer sample is, the more significant retrograde vitrification behavior exhibits.54 For the IBU−PMMA binary system, the inset in Figure 9 illustrates that the Tg of IBU−PMMA blends was composition dependent; i.e., increasing the proportion of IBU in PMMA would result in the reduction of Tg. Gordon and Taylor proposed an empirical equation which can predict the Tg of the drug−polymer blends.55 This equation is based on the individual components characteristic of ideal mixing and is given by the expression Tg,12 =

and the results determined by Velasco et al.24 using DSC (Perkin-Elmer DSC-7) also showed this phenomenon. The deviation from ideal behavior could indicate the intermolecular interactions between the drug molecules themselves or between the drug and the polymer.16 If the drug−polymer interaction was stronger than that of the drug−drug interaction, the Tg would be higher than expected. In contrast, if the interaction between the drugs themselves was stronger than that of drug− polymer, self-association of drug molecules would generate, and the Tg was usually lower than expected. Therefore, the plasticizing effect of IBU could induce the PMMA chains to relax from its “frozen” nonequilibrium state, and then reduce the Tg of PMMA. The stronger interaction of H-bond constituted by the oxygen of the CO group in PMMA and the OH group in IBU would somewhat interfere with the chain mobility. The Tg reduction behavior also represented an obvious positive deviation from ideal behavior. In summary, like other drug−polymer binary systems,16,24,57,58 IBU also can have a plasticizing effect on PMMA. For the CO2−IBU−PMMA ternary system, it was found that the Tg of PMMA decreased as the CO2 pressure increased at a fixed proportion of IBU, and decreased as the proportion of IBU increased at a given CO2 pressure. When IBU was incorporated in PMMA, it was initially crystallized; after melting, IBU molecules diffused into the amorphous zone of PMMA to weaken the interaction between PMMA chains, i.e., had a plasticizing effect.25 In addition, melted IBU also acted as a porogen: after swelling by CO2, the samples with IBU would exhibit more porosity than those without IBU.24 On the other hand, once CO2 dissolved in IBU/PMMA blend, there would be three dominant effects that CO2 could make: (i) depressing the Tm of IBU to make IBU melt at relatively lower temperature, and then the IBU molecules could conveniently diffuse into PMMA; (ii) swelling the PMMA to increase the free volume, accelerate the diffusion of IBU, decrease the chain entanglement, and enhance the chain mobility; (iii) acting as a molecular lubricant that reduced the melted viscosity, and this viscosity reduction effect also corresponded to the reduction of Tg of PMMA. In summary, due to the significant interactions between CO2, IBU, and PMMA, when both CO2 and IBU dissolved into the PMMA matrix, a synergistic plasticizing effect would accelerate the Tg reduction of PMMA, which was more significant than the individual plasticizing effect of CO2 or IBU. Also, this synergistic plasticizing effect was proportional to the CO2 pressure and the proportion of IBU blended with PMMA. It is well-known that the retrograde vitrification behavior of PMMA caused by CO2 can be attributed to the significant dissolution of CO2 into PMMA at low temperature, i.e., significant interaction in this binary system, which can result in similar improved mobility similar to that of thermal contribution.50,54 However, in the CO2−IBU−PMMA ternary system, whether the retrograde vitrification behavior still exists has not been unknown. It was suggested that the long-range interactions, such as polar, hydrogen bonding, and electron acceptor−donor structure, might be more important than short-range dispersion forces in the plasticizing effect of solute on the glass transition of polymer.59 Therefore, as the results described in this work, both CO2 and IBU have significant interactions with PMMA, and the retrograde vitrification behavior is likely to occur at very low temperature region; i.e., it might below 0 °C. Due to the limit of the apparatus used in this work, at present, the glass transition behavior cannot be determined below 25 °C, even if this apparatus is suitable for

ω1Tg0,1 + Kω2Tg0,2 ω1 + Kω2

(11)

where Tg,12 is the glass transition temperature of the drug− polymer blend. ω1, ω2, Tg0,1 (=223 K obtained from DSC determination56), and Tg0,2 (=383 K) are the weight fractions and glass transition temperatures of the pure IBU and PMMA, respectively. The constant K, which represents the interaction between the components, can be approximated using the equation K ≈ ρ1Tg0,1/ρ2Tg0,2, where ρ1 (=1.28 g/cm3 obtained using a pycnometer) and ρ2 (=1.18 g/cm3) refer to the densities of pure components. The measured Tg values of the IBU−PMMA blend were higher than that predicted by the Gordon−Taylor equation, 5882



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experimental study exhibited that the synergistic plasticizing effect would accelerate the Tg reduction of PMMA, which was more significant than the individual plasticizing effect of CO2 or IBU.

the determination in the high-pressure region. In conclusion, it still be worth investigating the retrograde vitrification behavior of PMMA caused by the synergistic plasticizing effect of CO2/ IBU, even if it might exist in other CO2−drug−polymer ternary systems. Furthermore, Kamiya et al.60 assumed that each microvoid of PMMA could accommodate only a CO2 molecule. When the number of microvoids decreased to zero, the CO2 concentration would increase to the glass transition concentration, and then PMMA began to change from glassy to rubbery. But what we should notice is that, in the CO2−IBU−PMMA ternary system, the competition relation between IBU and CO2 dissolved in the PMMA; i.e., the CO2 absorbed into PMMA will be driven away from PMMA by IBU due to the different partitioning coefficients of IBU between PMMA and CO2. Therefore, to obtain the more accurate solubility of IBU in PMMA, even the synergistic plasticizing effect of CO2/IBU on the Tg of PMMA, it is vital to adopt a series of thermodynamic simulations, which are based on a lattice fluid model, such as the Sanchez−Lacombe equation of state, Tait equation, Chow equation, Gibbs−Dimarzio criterion, and so on, and these predictive attempts will be carried out in our future work.

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AUTHOR INFORMATION

Corresponding Author

*Tel.: +86-21-64253934. E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is supported by the National Natural Science Foundation of China (NSFC), Grants 20676031 and 20876051.

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REFERENCES

(1) Kemmere, M. F.; Meyer, T. Supercritical carbon dioxide for sustainable polymer processes. Supercritical Carbon Dioxide: In Polymer Reaction Engineering; Wiley-VCH: Weinheim, Germany, 2005; pp 1− 14. (2) DeSimone, J. M. Practical approaches to green solvents. Science 2002, 297, 799−803. (3) Wen, H. B.; Dai, J. J. Dyeing of polylactide fibers in supercritical carbon dioxide. J. Appl. Polym. Sci. 2007, 105, 1903−1907. (4) Villarroya, S.; Zhou, J.; Thurecht, K. J.; Howdle, S. M. Synthesis of graft copolymers by the combination of ATRP and enzymatic ROP in SC-CO2. Macromolecules 2006, 39, 9080−9086. (5) Zhai, W.; Wang, H.; Yu, J.; Dong, J. Y.; He, J. Foaming behavior of isotactic polypropylene in supercritical CO2 influenced by phase morphology via chain grafting. Polymer 2008, 49 (13−14), 3146− 3156. (6) Ema, Y.; Ikeya, M.; Okamoto, M. Foam processing and cellular structure of polylactide-based nanocomposites. Polymer 2006, 47, 5350−5359. (7) Zhang, R.-H.; Li, X.-K.; Cao, G.-P.; Shi, Y.-H.; Liu, H.-L.; Yuan, W.-K.; Roberts, G. W. Improved Kinetic Model of Crystallization for Isotactic Polypropylene Induced by Supercritical CO2: Introducing Pressure and Temperature Dependence into the Avrami Equation. Ind. Eng. Chem. Res. 2011, 50, 10509−10515. (8) Kikic, I.; Vecchione, F. Supercritical impregnation of polymers. Curr. Opin. Solid State Mater. Sci. 2003, 7, 399−405. (9) Kazarian, S. G. Supercritical Fluid Impregnation of Polymers for Drug Delivery; Marcel Dekker, Inc.: London, 2004. (10) Kawahara, Y.; Yoshioka, T.; Sugiura, K.; Ogawa, S.; Kikutani, T. Dyeing Behavior of High-Speed Spun Poly(ethylene terephthalate) Fibers in Supercritical Carbon Dioxide. J. Macromol. Sci., Part B 2001, 40, 189−197. (11) Sfiligoj, M. S.; Zipper, P. WAXS analysis of structural changes of poly(ethylene terephthalate) fibers induced by supercritical-fluid dyeing. Colloid Polym. Sci. 1998, 276, 144−151. (12) Beltrame, P. L.; Castelli, A.; Selli, E.; Villani, L.; Mossa, A.; Seves, A.; Testa, G. Morphological changes and dye uptake of poly(ethylene terephthalate) and 2,5-cellulose diacetate immersed in supercritical carbon dioxide. Dyes Pigm. 1998, 39, 35−47. (13) Lopez-Periago, A.; Argemi, A.; Andanson, J. M.; Fernandez, V.; Garcia-Gonzalez, C. A.; Kazarian, S. G.; Saurina, J.; Domingo, C. Impregnation of a biocompatible polymer aided by supercritical CO2: Evaluation of drug stability and drug-matrix interactions. J. Supercrit. Fluids 2009, 48, 56−63. (14) Zhang, Q.; Xanthos, M.; Dey, S. K. In-line Measurement of Gas Solubility in Polystyrene and Polyethylene Terephthalate Melts During Foam Extrusion. MD (Am. Soc. Mech. Eng.) 1998, 82, 75−83. (15) Chiou, J. S.; Barlow, J. W.; Paul, D. R. Plasticization of glassy polymers by CO2. J. Appl. Polym. Sci. 1985, 30, 2633−2642. (16) Nair, R.; Nyamweya, N.; Gonen, S.; Martinez-Miranda, L. J.; Hoag, S. W. Influence of various drugs on the glass transition

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CONCLUSIONS The solubility of CO2 in PMMA, which increased as the pressure increased up to 15 MPa, but decreased as the temperature increased from 35 to 60 °C, can be obtained by fitting the linear relation between −ΔF′/Cm and the film mass.33 The solubility of IBU in SCCO2 increased with both increasing pressure and temperature, and the solubility data changed in the range from 10−5 to 10−3 mole fraction, which could be assumed to an infinite dilute solution. The solubility of CO2/IBU compound in PMMA can also be obtained by fitting the linear relation between −ΔFi,D′/Cm and the film mass. The solubilities of both CO2/IBU compound and IBU in PMMA increased sharply as the pressure increased from 7.5 to 9 MPa and then leveled off at the pressure of 11 MPa, while in the pressure range above 8.5 MPa, all these two kinds of solubility data increased with increasing temperature. The partitioning coefficient of IBU between PMMA and CO2 could be calculated by the ratio of the solubility of IBU in PMMA to the solubility of IBU in SCCO2. The results illustrated that the isothermal partitioning coefficient increased as the pressure increased from 7.5 to 8.5 MPa, and then decreased in the pressure range above 8.5 MPa. It decreased with increasing temperature in the pressure range below 8.5 MPa, and then increased with increasing temperature in the pressure range above 11 MPa. The small difference of solubility parameters between PMMA and IBU suggested that IBU could be easily miscible with PMMA. For the CO2−PMMA system, the glass transition temperature of PMMA was reduced from 111 to 37 °C as the pressure of CO2 increased from 0.1 to 7 MPa, which could not be determined at 8 MPa. For the IBU−PMMA system, the glass transition temperature of PMMA was reduced from 107 to 87 °C as the proportion of IBU in PMMA increased from 4.3 to 19.8 wt % under atmospheric pressure. For the CO2−IBU− PMMA ternary system, the reduction of the glass transition temperature of PMMA was proportional to the CO2 pressure and the proportion of IBU in PMMA, i.e. the Tg reduced from 87 to 40 °C as the pressure increased from 0.1 to 2 MPa with the proportion of IBU in PMMA of 19.8 wt %. This 5883



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