Heat Capacity for the Binary System of Quercetin + Poly(ethylene

Article pubs.acs.org/jced

Heat Capacity for the Binary System of Quercetin + Poly(ethylene glycol) 6000 Yuan Gao and Tong-Chun Bai* College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China ABSTRACT: The phase transition state and the heat capacity (cp) of the binary system of [quercetin (1) + poly(ethylene glycol) 6000 (2)] were measured by a differential scanning calorimeter (DSC). The effect of the mass fraction of quercetin (w1) on the melting temperature (Tfus) and enthalpy (Δfush) were discussed. Experimental results indicate that, for T > 353 K, a molten polymer dispersion is found in the region of w1 < 0.3; in the region of w1 > 0.6, the system is of the character of a mixture of solid quercetin + poly(ethylene glycol) (PEG) 6000 dispersion; in the composition region of w1 from (0.301 to 0.601), a special complex composed of molten PEG dispersion and solid quercetin is found. A polynomial equation with temperature and composition as variables is used to correlate the cp data. The mixing functions of enthalpy, entropy, and Gibbs function were calculated from the data of cp.

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the phase diagram for systems of (silybin + PEG 6000)12 and (silybin + Poloxamer 188)13 were constructed by DSC measurement. For systems such as [silybin + poly(vinylpyrrolidone) (PVP)]14 and (quercetin + PVP),15 the phase transition temperature of PVP is not observable in the temperature range above ambient temperature. With temperature increases, the polymer changes from a glassy state to a rubbery state and no apparent phase transition is observable until decomposition takes place. To characterize the phase state of these systems, the relationships of heat capacity with temperature and composition were constructed to cover the shortage of T−composition phase diagrams. Poly(ethylene glycol) (PEG) is one commonly used excipient in many pharmaceutical products. Its solid variants with higher molecular weight are used as ointment bases, film coatings, tablet binders, and lubricants, whereas the variants with lower molecular weight are used as solvents in oral liquids and soft capsules. Therefore, the mixing state of rubbery/or liquid PEG with solid drugs is of interest to pharmaceutical applications. In this work, binary mixture of quercetin and PEG 6000 was prepared by a solvent evaporation method. The variation of phase transition state and the heat capacity with temperature and composition were measured by a DSC method. The mixing state was analyzed from the variation of physical properties with composition and temperature.

INTRODUCTION Quercetin is one of flavonols present in nature. Its molecular structure is shown in Figure 1. It gained much attention by

Figure 1. Chemical structure of quercetin. The IUPAC name is 2-(3,4dihydroxyphenyl)-3,5,7- trihydroxy-4H-1-benzopyran-4-one.

many researchers for its biological and medicinal applications.1−4 However, a problem is the hydrophobic property that limits its dissolution rate and bioavailability when administered orally. To improve the dissolution rate and solubility of hydrophobic drug in water, a variety of methods have been developed; one of them is the solid dispersion.4,5 Solid dispersion improves the drug wetability and bioavailability by reducing the drug particle size.5 Its efficiency depends on the crystalline state and the mixing state in the preparation process. An amorphous drug generally has higher solubility in water than a crystalline drug.6,7 Physical properties, such as heat capacity, phase transition, and glass transition state, play a crucial role to characterize the mixing state of drugs and have gained extensive applications in biomaterials and pharmaceutics.8−11 For mixtures composed of drug and polymer, the phase diagram can be constructed by measuring the phase transition temperature and its variation with composition. For example, © 2013 American Chemical Society

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EXPERIMENTAL SECTION Materials. Polyethylene glycol with a purity of mass fraction of 0.98 was purchased from SinoPharm Chemical Reagents Co. Received: October 3, 2012 Accepted: March 29, 2013 Published: April 5, 2013 1122

dx.doi.org/10.1021/je301114z | J. Chem. Eng. Data 2013, 58, 1122−1132

Journal of Chemical & Engineering Data

Article

Ltd., China. Its CAS number is 25322-68-3, and the IUPAC name is poly(oxyethylene), given the acronym PEG. The molecular weight of PEG 6000 is in the region from (5500 to 6500) g·mol−1. The main impurity in PEG is water. Quercetin was purchased from SinoPharm Chemical Reagents Co. Ltd. Its CAS number is 117-39-5, and the IUPAC name is 2-(3,4dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one. Its purity is 0.9965 (mass fraction) as checked by HPLC. Materials were dried under vacuum (p < 10 kPa) at 333 K over 48 h and stored over P2O5 in a desiccator before use. The sample information is summarized in Table 1.

c p,sam = c p,std

chemical name

source

quercetina

SinoPharm

0.98

PEG 6000b

SinoPharm

0.98

purification method vacuum drying vacuum drying

final mass fraction purity 0.996 0.99

(1)

Where, cp,std/J·(K·g)−1 and cp,sam/J·(K·g)−1 are the heat capacity of the standard substance (sapphire) and the samples, respectively. Fbsl, Fstd, and Fsam are the heat flows of DSC runs of baseline, sapphire, and samples, respectively. And mstd and msam are the masses of the sapphire and sample, respectively. According to eq 1, the measurement of heat capacity included three DSC runs as described in our previous work.15,16 A thin disk of sapphire was used as the heat capacity standard. The first DSC run was performed to obtain the baseline for an empty Al pan with a lid. The second and third runs were performed on sapphire and (quercetin + PEG 6000) samples, respectively. One empty Al pan was used throughout three runs. To get better thermal data, the sapphire and sample run was performed with baseline subtraction. The heat flow curves of sapphire and the samples were recorded under the same temperature program (heating rate, 5 K·min−1). Other experimental details can be seen from our previous work.15,16 Another source of uncertainty in cp measurement comes from the weighing process. In our experiments, most samples were weighted to (5 ± 0.01) mg. Under these measurement conditions, the combined relative uncertainty of cp was estimated to be ur(cp) = 0.02. Thermogravimetric Analysis. A thermogravimetric (TG) analyzer, (model SDT 2960, TA Instruments), was used to measure the mass loss of samples during a process of temperature programming. Determination parameters are sample mass: 5 mg; heating rate, 10 K·min−1; protection gas, nitrogen; and gas flow rate, 100 cm3·min−1. Infrared Spectroscopy. A Magna 550 FT-IR system (Nicolet) with the KBr disk method was used to measure the Fourier transform infrared (FT-IR) spectra. The scanning range was (400 to 4000) cm−1 with a resolution of 2 cm−1. X-ray Powder Diffraction. A diffractometer, (model X’Pert PRO MPD, PANalytical Company), was used to obtain the X-ray powder diffraction (XRD) patterns. Operation parameters are, Cu−Kα, λ = 0.15406 nm; angular range, 5° < 2θ < 60°; and step width, 0.03. High Performance Liquid Chromatography (HPLC). Quercetin was analyzed by HPLC, model ProStar LC240, Varian, USA, with a Hypersil ODS-C18 column, (250 mm × 4.6 mm; i.d. 5 μm); UV, 370 nm detector; (0.2% phosphoric acid + methanol) (50:50, v/v) mobile phase, with a flow rate of 1.0 cm3·min−1. The column temperature was maintained at 303 K; the injection volume was 10 μL.

Table 1. Sample Information initial mass fraction purity

(Fsam − Fbsl)mstd (Fstd − Fbsl)msam

analysis method TGc and HPLCd TGc

a

Quercetin = 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one. bPEG 6000 = poly(oxyethylene) 6000. cTG = thermogravimetric analysis. dHPLC = high performance liquid chromatography.

Sample Preparation. A group of [quercetin (1) + PEG 6000 (2)] binary mixtures were accurately weighed and mixed. The mass fractions of quercetin (w1) are (0.100, 0.204, 0.301, 0.401, 0.499, 0.601, 0.700, 0.798 and 0.900), respectively. These premixed solid mixtures were dissolved in a desired amount of ethanol. After full dissolution, the solvent was evaporated in a rotary evaporator at about 313 K under reduced pressure. The samples were then fully dried under vacuum at 333 K over 48 h. The pressure in the rotary evaporator and vacuum drying oven was controlled to be less than 10 kPa. The prepared fully mixed binary samples were stored over P2O5 in a desiccator before use. DSC Analysis and Heat Capacity Measurements. A differential scanning calorimeter (DSC), (model DSC-204F1, NETSCH, Germany), was used to measure the phase transition temperature, enthalpy of fusion, and the heat capacity. Certified indium wire encapsulated in an aluminum crucible was used for temperature and heat flow calibration, as described in our previous work.15,16 A thin disk of sapphire was used as the heat capacity standard. The reference was an empty aluminum pan with a perforated lid. About 5 mg of samples was weighed to 0.01 mg by using an accurate balance, (model BT25S, Sartorius AG, Beijing). Nitrogen gas, with a purity of 0.99999 volume fraction, was used as the purge gas (at a rate of 20 cm3·min−1) and protective gas (at 70 cm3·min−1) in DSC operation. A heating rate of 5 K·min−1 is performed in the DSC measurements. The temperature and the enthalpy of fusion were measured from the peak temperature (Tfus/K) and peak area (Δfush/ J·g−1), and calculated by using the analysis software attached to the DSC instrument. The uncertainty in the melting temperature measurements with same operation parameters is ± 0.8 K, while the uncertainty associated with specific melting enthalpy was estimated to be ± 6.0 J·g−1. The measurement of heat capacity by DSC is based on eq 1.

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RESULTS AND DISCUSSIONS Thermal Analysis for Pure Quercetin and PEG 6000. The TG trail of pure quercetin shows dehydration below 393 K. Molecular decomposition is found at 493 K. The TG trail of PEG 6000 shows dehydration below 393 K too, and molecule decomposition starts at 633 K. In our experiment, all samples were dried carefully. The mass loss due to dehydration is less than 2%. The endothermic peak below 393 K due to dehydration was found in the DSC trails of pure quercetin and PEG 6000, respectively. For PEG 6000, a melting endoderm is observed at 335 K with a melting enthalpy of 201 J·g−1. The decomposition is found starting at 633 K. In the region from (337 to 612) K, the molten PEG is stable. For quercetin, the DSC curve shows no apparent endothermic peak until its decomposition take 1123



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place at 573 K. Moreover, an inflection point is found at 481 K. Some characteristic temperatures of TG and DSC trails of PEG 6000 and quercetin are summarized in Table 2. Table 2. The Characteristic Temperatures of Pure Quercetin and PEG 6000 from the TG and DSC Trailsa T/K TG melting water loss end inflection point decomposition a

DSC

quercetin

PEG 6000

393

393

493

633

quercetin

PEG 6000 335

481 573

612

Standard uncertainty of T is u(T) = 0.8 K.

Figure 2. The effect of the mass fraction of quercetin w1 on the melting temperature Tfus/K. The theoretical fit is shown as a line.

In the process of DSC operations, moisture absorption by samples is unavoidable because of the hygroscopicity. To measure the heat capacity, the moisture effect must be removed before the determination runs. Therefore, at the time interval after the sample has been loaded into the DSC oven and the cp measurement has not run, moisture removal was performed in the oven by three repeated DSC scans within the temperature region from room temperature to 393 K under the protection of nitrogen gas. By checking the sample mass at the start and the end of the fourth run, it was confirmed that the mass loss was less than 0.2% and that the moisture effect was eliminated by three repeated DSC scans.15,16 Therefore, the measurements of phase transition and cp were performed at the fourth run. Phase Transition. For a binary system of [quercetin (1) + PEG 6000 (2)], the thermal behavior was measured in the temperature range from (298 to 533) K by DSC. In the analysis process, the DSC curve was divided into two sections to separate the effect of PEG melting on cp. In the first section from (298 to 353) K, the variation of the melting temperature with composition is addressed. In the second section from (353 to 533) K, the variation of heat capacity with composition and temperature is addressed. In the temperature range from (298 to 353) K, an endothermic peak attributed to the melting of PEG 6000 is observed. From the peak temperature, we estimated the melting temperature Tfus = 335 K, and specific melting enthalpy Δfush = 201 J·g−1. These values agree fairly with the literature values of 333.9 K and 209 J·g−1.12 The deviations of melting temperature and enthalpy from literature are 1.1 K and 8 J·g−1, respectively. They are slightly larger than the experimental uncertainty, (0.8 K and 6 J·g−1). These deviations arise from the difference in sample source and instrument model. As shown in Figures 2 and 3, with the increase in the mass fraction of quercetin (w1) the temperature (Tfus/K) and the enthalpy (Δfush/J·g−1) of fusion are decreased. This information indicates that the binary system is of the character of solid mixture/or solid dispersion in this temperature range. To fit the relation ship between Tfus and w1 theoretically, equilibrium between a pure solid phase and a liquid mixture is assumed. Neglecting the influence of the heat capacities as well as of pressure, the solubility of a component i at atmospheric pressure can be expressed as13 *i⎛ −ΔfusHm, T ⎞ ⎜⎜1 − fus ⎟⎟ ln xiγi = * i⎠ RT Tfus, ⎝

Figure 3. The effect of the mass fraction of quercetin (w1) on the specific melting enthalpy (Δfush/J·g−1). Line is the result fitted by eq 6.

where, ΔfusHm,i * and Tfus,i * are the molar enthalpy and temperature of fusion of pure component i, respectively. The xi represents the mole fraction in the liquid phase. In theoretical calculations, the calculation of mole fraction will introduce the molar mass Mi, (M1 = 302.23 g·mol−1, M2 = 6000 g·mol−1). For PEG 6000, the molecular mass is an average one, which is distributed from 5500 to 6500. The uncertainty of xi (dx2) arising from molecular mass distribution (dM2 = 500) can be estimated from the uncertainty transformation, which leads to an uncertainty of dx2 = 0.0058. Moreover, it was found from uncertainty analysis that dx2 decreases with a decrease in w2. Equation 2 is suitable for solution. For estimating the phase transition equilibrium, we assume this equation is acceptable. This assumption is based on our experimental conditions. In this work, the solid mixture was prepared by a solution method, and then the solvent was evaporated. Therefore, the mixing state of the solid binary mixture is assumed to be homogeneous. As temperature rises to the melting temperature, the mixture transforms to the liquid state. The assumption of the homogeneous mixing state for both liquid and solid is acceptable. For the binary system, the Flory- Huggins model was used to calculate the activity coefficient γ2. ln γ2 = ln[ϕ2 /x 2] + (1 − Vm,2/Vm,1)ϕ1 + ϕ12χ /RT

(3)

where, the χ is a theoretical interaction parameter. The volume fraction ϕ was calculated by the van der Waals mole volume

(2) 1124



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Vm,i, which can be estimated by the group contribution method as described by Bondi.17 ϕi =

from DSC trails. In this range, PEG 6000 is in a molten state. The mixing state of molten PEG 6000 with solid quercetin determines the variation behavior of cp with temperature and composition. The data of cp are provided in Table 4. As shown in Figures 4 to 6, the curves of cp vs T can be classified into three groups according to their curve features. Figure 4 shows the variation behavior of cp with T for mixtures with w1= (0, 0.100, and 0.204) in the temperature range from (353 to 533) K. As the temperature is raised up to 353 K, the endothermic melting peak disappears, and the baseline is determined by the heat capacity of the molten polymer. The cp curves of this group have a shape similar to pure PEG 6000. With the increase in w1, the cp curve downward. With temperature increase, the cp increases slowly. This feature is a character of molten polymer dispersion. Figure 5 shows the variation of cp with T for samples of w1 = (0.301, 0.401, 0.499 and 0.601) in the temperature range from (353 to 533) K. Two curve features in Figure 5 are worthy of notice. (1) In the temperature range from (373 to 403) K, there is a small peak. With the increase in w1, the peak top shifts to higher temperature direction, decreases in size, and disappears at w1 = 0.601. To examine this peak further, a repeated cooling and thawing operation was performed. Testing results indicate that this small peak is neither a dehydration peak nor a melting peak. It may be attributed to some special interaction between PEG and quercetin. (2) The molten PEG has a higher cp value and lower curve slope against temperature. For solid quercetin, there is a lower cp value and a higher curve slope. In this group, with a w1 increase, the cp decreases and the slope increases. This observation indicates a mixing effect of molten PEG dispersion with solid quercetin. In this composition region, w1 = (0.301 to 0.601), the system undergoes a transition process, from a molten PEG dispersion to a phase equilibrium state. In another word, the system is in an equilibrium state between the molten PEG dispersion and solid quercetin. The third group is the mixtures with w1 = (0.700, 0.798, 0.900 and 1). The curve of cp against T is shown in Figure 6. For this group, the curve shape is of the feature similar to quercetin. As PEG is mixed with quercetin (w1 decreases), a melting peak attribute to PEG 6000 appears in the lower temperature region, and the value of cp increases. Apparently, solid quercetin determines the curve shape of cp. The values of cp in the range from T = (353 to 533) K are provided in Table 4. Fitting Experimental cp. Empirical equations have been used to correlate the data of cp. In the range from an initial temperature Ti to a final temperature Tf, the dependence of cp on T can be expressed by eq 7.

(wi /Mi)Vm, i (w1/M1)Vm,1 + (w2 /M 2)Vm,2

(4)

In the PEG 6000-rich region, we have Tfus/K =

* + χϕ 2 ΔfusHm,2 1 * /Tfus,2 * − R[ln φ + ϕ (1 − Vm,2/Vm,1)] ΔfusHm,2 2 1 (5)

By using a nonlinear least-squares method, parameter χ was obtained by fitting experimental data. The fitting result is shown in Figure 2 in a line. The theoretical parameter was obtained, χ = −40.6 kJ·mol−1, with a fitting correlation coefficient r = 0.9927 and standard deviation u(Tfus) = 0.8 K. From eq 5 it was found that the melting parameter of the binary mixtures is associated with the melting parameters of pure substances (Tfus,2 * and ΔfusHm,2 * ). By an uncertainty transformation analysis from d(T*fus,2) and d(ΔfusH*m,2), we estimated that the deviation of d(Tfus/Tfus * ) is 5.41·10−4 over the whole binary composition region, and it is not larger than the experimental error. The interaction parameter for the system of (PEG 6000 + silybin)12 is χ = −369 kJ·mol−1, and for (Poloxamer 188 + silybin)13 it is χ = −21 kJ·mol−1. A comparison of the result of this work with that of our previous work indicates that the interaction between quercetin and PEG 6000 is weaker than that of silybin and PEG 6000, and stronger than that of silybin and Poloxamer 188. Figure 3 shows the dependence of enthalpy of fusion on composition. Clearly, it decreases with the increase in w1. If a polynomial relation is assumed, Δfush/J·g −1 = A + Bw1 + Cw12

(6)

we have a better fitting result as shown in Figure 3 in line, with parameters A = 199.7 J·g−1, B = −341 J·g−1, C = 109 J·g−1, standard uncertainty u(Δfush) = 7 J.g−1, and correlation coefficient r = 0.9903. The values of the temperature (Tfus/ K), the enthalpy (Δfush/J·g−1) of fusion, and the activity coefficients of the components are provided in Table 3. Heat Capacity. The specific heat capacities cp were evaluated in the temperature range from (353 to 533) K Table 3. The Temperature Tfus/K, Specific Enthalpy Δfush/ J·g−1 of Fusion, and the Activity Coefficients γ1, for Binary Systems of [Quercetin (1) + PEG 6000 (2)] at Mass Fraction w1a w1

Tfus/K

Δfush/J·g−1

γ1

0 0.100 0.204 0.301 0.401 0.499 0.601 0.700 0.798

335 333 330 329 327 324 323 318 314

201 160 142 101 89 58 30 5 4

0.304 0.474 0.607 0.721 0.812 0.885 0.937 0.973

c p/J· (K·g)−1 = a1 + a 2x + a3x 2 + a4x 3

(7)

x = (T − Ti)/(Tf − Ti)

(8)

Where, ai is the coefficient of the polynomial equation. For a binary system, coefficient ai depends on the composition to some extent. As a simple approximation, a linear relationship between ai and composition w1 is supposed. For the data in figure 4, the cp behaves like that of PEG. If we suppose Ti = 353 K and Tf = 533 K, the relations between ai and w1 should be eqs 9.1 and 9.2.

a

w1 is the mass fraction of quercetin in the [quercetin (1) + PEG 6000 (2)] mixture. Standard uncertainties of u are u(w1) = 0.002, u(Tfus) = 0.8 K, u(ΔfusH) = 6 J·g−1.

a1 = a11 + a12w1 1125

(9.1)



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Table 4. The Specific Heat Capacity, cp/J·(K·g)−1, for Systems of [Quercetin (1) + PEG 6000 (2)] with Mass Fraction w1 at Temperature Ta w1 T/K

0

0.100

0.204

0.301

0.401

0.499

0.601

0.700

0.798

0.900

1

353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410

2.27 2.28 2.27 2.27 2.27 2.27 2.27 2.28 2.27 2.28 2.28 2.27 2.26 2.27 2.27 2.28 2.27 2.27 2.27 2.28 2.28 2.28 2.28 2.28 2.29 2.29 2.28 2.28 2.29 2.28 2.28 2.29 2.28 2.29 2.29 2.29 2.29 2.29 2.29 2.29 2.29 2.30 2.29 2.30 2.29 2.31 2.31 2.30 2.30 2.31 2.31 2.31 2.31 2.32 2.32 2.33 2.32 2.33

2.06 2.06 2.06 2.06 2.07 2.06 2.06 2.06 2.06 2.07 2.07 2.07 2.06 2.07 2.07 2.07 2.08 2.07 2.07 2.08 2.08 2.08 2.08 2.08 2.08 2.09 2.09 2.09 2.09 2.09 2.10 2.09 2.10 2.10 2.10 2.11 2.11 2.11 2.12 2.11 2.12 2.12 2.12 2.12 2.13 2.12 2.13 2.13 2.13 2.13 2.14 2.13 2.14 2.14 2.14 2.16 2.15 2.15

1.94 1.94 1.94 1.94 1.94 1.93 1.94 1.94 1.94 1.94 1.94 1.94 1.95 1.94 1.95 1.95 1.94 1.94 1.95 1.95 1.95 1.95 1.96 1.95 1.95 1.95 1.96 1.96 1.96 1.96 1.96 1.97 1.96 1.97 1.96 1.97 1.97 1.97 1.97 1.98 1.98 1.98 1.98 1.98 1.98 1.98 1.99 1.99 1.99 1.99 2.00 2.000 1.99 1.99 1.99 2.00 2.00 2.00

2.06 2.06 2.06 2.06 2.06 2.06 2.06 2.06 2.07 2.06 2.07 2.07 2.07 2.07 2.08 2.07 2.07 2.08 2.08 2.08 2.09 2.08 2.09 2.09 2.09 2.10 2.10 2.10 2.11 2.11 2.11 2.11 2.11 2.11 2.12 2.12 2.12 2.12 2.13 2.13 2.13 2.13 2.13 2.13 2.13 2.12 2.12 2.11 2.10 2.10 2.09 2.10 2.09 2.10 2.10 2.10 2.10 2.10

1.87 1.87 1.86 1.87 1.87 1.88 1.88 1.88 1.88 1.89 1.90 1.90 1.90 1.90 1.92 1.91 1.91 1.92 1.92 1.92 1.93 1.93 1.95 1.94 1.94 1.94 1.96 1.96 1.96 1.97 1.98 1.97 1.98 1.99 1.99 1.99 2.00 2.01 2.01 2.02 2.03 2.03 2.03 2.04 2.04 2.05 2.05 2.06 2.06 2.07 2.08 2.08 2.09 2.09 2.10 2.10 2.09 2.11

1.8 1.79 1.79 1.79 1.78 1.78 1.79 1.78 1.79 1.78 1.79 1.79 1.79 1.80 1.79 1.80 1.80 1.80 1.81 1.81 1.81 1.82 1.82 1.83 1.82 1.83 1.85 1.85 1.86 1.86 1.87 1.88 1.9 1.88 1.88 1.90 1.90 1.91 1.91 1.92 1.93 1.92 1.93 1.94 1.94 1.94 1.95 1.95 1.96 1.97 1.98 1.98 1.99 1.99 2.00 2.00 2.01 2.02

1.75 1.75 1.76 1.75 1.75 1.76 1.75 1.76 1.76 1.76 1.76 1.76 1.76 1.77 1.77 1.77 1.78 1.78 1.78 1.79 1.78 1.79 1.79 1.80 1.79 1.80 1.80 1.82 1.82 1.83 1.83 1.84 1.84 1.84 1.85 1.85 1.86 1.87 1.87 1.88 1.89 1.89 1.9 1.91 1.91 1.91 1.92 1.93 1.93 1.93 1.94 1.94 1.95 1.94 1.95 1.95 1.94 1.95

1.98 1.97 1.98 1.98 1.97 1.97 1.98 1.97 1.98 1.98 1.99 1.99 1.99 1.99 1.98 1.99 1.99 2.00 2.00 2.01 2.01 2.01 2.01 2.02 2.02 2.02 2.03 2.03 2.04 2.05 2.05 2.06 2.05 2.06 2.06 2.07 2.07 2.08 2.09 2.09 2.10 2.10 2.10 2.11 2.11 2.12 2.13 2.12 2.13 2.14 2.14 2.15 2.14 2.15 2.14 2.15 2.16 2.16

1.79 1.79 1.79 1.79 1.80 1.79 1.80 1.80 1.80 1.81 1.80 1.80 1.81 1.81 1.81 1.82 1.82 1.83 1.81 1.82 1.83 1.83 1.83 1.83 1.84 1.84 1.85 1.85 1.86 1.85 1.86 1.86 1.86 1.86 1.87 1.88 1.88 1.88 1.89 1.89 1.89 1.9 1.9 1.91 1.91 1.92 1.91 1.92 1.92 1.93 1.93 1.94 1.94 1.94 1.95 1.95 1.96 1.96

1.51 1.51 1.51 1.51 1.52 1.51 1.52 1.52 1.52 1.52 1.52 1.52 1.52 1.52 1.53 1.53 1.53 1.53 1.52 1.53 1.53 1.54 1.54 1.54 1.54 1.55 1.55 1.55 1.56 1.56 1.57 1.57 1.57 1.57 1.58 1.58 1.59 1.59 1.59 1.59 1.60 1.61 1.61 1.61 1.62 1.62 1.63 1.63 1.63 1.64 1.64 1.65 1.66 1.66 1.66 1.67 1.67 1.67

1.23 1.24 1.23 1.23 1.23 1.23 1.24 1.25 1.24 1.24 1.23 1.24 1.24 1.24 1.25 1.25 1.24 1.24 1.23 1.23 1.24 1.24 1.26 1.25 1.24 1.25 1.26 1.26 1.27 1.26 1.27 1.27 1.27 1.28 1.27 1.27 1.27 1.29 1.29 1.28 1.29 1.28 1.29 1.29 1.30 1.30 1.31 1.31 1.32 1.32 1.32 1.33 1.33 1.33 1.34 1.34 1.34 1.34

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Table 4. continued w1 T/K

0

0.100

0.204

0.301

0.401

0.499

0.601

0.700

0.798

0.900

1

411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469

2.33 2.34 2.34 2.34 2.34 2.35 2.35 2.35 2.35 2.36 2.36 2.36 2.36 2.36 2.36 2.37 2.37 2.38 2.37 2.37 2.38 2.38 2.38 2.39 2.38 2.38 2.39 2.39 2.40 2.40 2.40 2.40 2.41 2.41 2.42 2.42 2.42 2.42 2.43 2.42 2.42 2.43 2.44 2.43 2.44 2.44 2.44 2.45 2.44 2.45 2.46 2.46 2.45 2.45 2.46 2.46 2.46 2.46 2.47

2.15 2.15 2.15 2.15 2.16 2.15 2.16 2.15 2.16 2.17 2.16 2.17 2.16 2.17 2.18 2.17 2.17 2.18 2.18 2.18 2.19 2.19 2.20 2.19 2.20 2.20 2.20 2.20 2.20 2.21 2.21 2.2 2.21 2.21 2.22 2.21 2.22 2.21 2.22 2.23 2.22 2.22 2.22 2.23 2.23 2.23 2.23 2.23 2.23 2.23 2.24 2.25 2.24 2.25 2.24 2.25 2.24 2.25 2.25

2.00 2.01 2.01 2.01 2.01 2.01 2.02 2.01 2.03 2.02 2.02 2.03 2.03 2.03 2.04 2.03 2.04 2.04 2.03 2.04 2.04 2.04 2.04 2.04 2.04 2.05 2.05 2.05 2.05 2.05 2.05 2.06 2.06 2.06 2.06 2.06 2.06 2.07 2.07 2.07 2.06 2.07 2.07 2.07 2.08 2.07 2.08 2.08 2.08 2.08 2.08 2.08 2.09 2.09 2.09 2.09 2.09 2.10 2.09

2.10 2.10 2.10 2.10 2.11 2.09 2.10 2.10 2.10 2.10 2.10 2.11 2.11 2.11 2.11 2.11 2.12 2.12 2.11 2.12 2.12 2.12 2.12 2.13 2.13 2.13 2.13 2.13 2.13 2.13 2.13 2.13 2.13 2.14 2.14 2.14 2.14 2.14 2.14 2.14 2.14 2.14 2.15 2.15 2.15 2.15 2.15 2.15 2.15 2.16 2.16 2.15 2.16 2.16 2.17 2.16 2.17 2.17 2.17

2.11 2.11 2.13 2.12 2.12 2.12 2.12 2.11 2.11 2.10 2.10 2.09 2.08 2.07 2.08 2.08 2.08 2.08 2.09 2.10 2.10 2.09 2.11 2.11 2.11 2.12 2.12 2.12 2.13 2.13 2.13 2.14 2.14 2.14 2.15 2.14 2.14 2.15 2.14 2.16 2.16 2.15 2.16 2.15 2.16 2.15 2.15 2.16 2.15 2.16 2.16 2.16 2.15 2.16 2.16 2.16 2.16 2.16 2.16

2.02 2.03 2.03 2.04 2.04 2.04 2.04 2.05 2.06 2.07 2.06 2.07 2.07 2.06 2.06 2.06 2.05 2.05 2.04 2.03 2.02 2.01 2.01 2.01 2.01 2.02 2.03 2.03 2.04 2.04 2.04 2.04 2.06 2.06 2.06 2.06 2.10 2.09 2.09 2.10 2.10 2.10 2.11 2.12 2.12 2.12 2.13 2.12 2.13 2.13 2.14 2.14 2.15 2.14 2.15 2.15 2.15 2.16 2.15

1.96 1.96 1.97 1.96 1.97 1.97 1.98 1.97 1.97 1.98 1.97 1.98 1.98 1.98 1.98 1.98 1.99 1.99 1.99 2.00 2.00 2.00 2.01 2.02 2.02 2.02 2.03 2.03 2.04 2.04 2.04 2.05 2.05 2.06 2.06 2.06 2.08 2.08 2.08 2.08 2.09 2.09 2.1 2.11 2.12 2.12 2.13 2.13 2.13 2.14 2.14 2.15 2.17 2.16 2.16 2.17 2.18 2.20 2.19

2.17 2.16 2.16 2.17 2.17 2.16 2.18 2.18 2.19 2.19 2.19 2.2 2.19 2.19 2.2 2.2 2.2 2.21 2.21 2.21 2.22 2.22 2.22 2.23 2.24 2.25 2.24 2.25 2.26 2.26 2.27 2.26 2.26 2.27 2.28 2.29 2.29 2.29 2.30 2.30 2.30 2.31 2.32 2.32 2.33 2.33 2.33 2.34 2.36 2.35 2.37 2.37 2.36 2.38 2.38 2.38 2.39 2.40 2.41

1.96 1.97 1.97 1.97 1.98 1.98 1.99 2.00 2.00 2.00 2.01 2.02 2.02 2.02 2.03 2.02 2.03 2.04 2.04 2.05 2.05 2.06 2.06 2.07 2.06 2.07 2.08 2.08 2.09 2.09 2.10 2.10 2.11 2.10 2.11 2.12 2.13 2.13 2.13 2.14 2.15 2.15 2.15 2.16 2.16 2.17 2.18 2.19 2.19 2.2 2.21 2.21 2.23 2.23 2.24 2.24 2.25 2.26 2.27

1.68 1.69 1.69 1.69 1.70 1.71 1.71 1.71 1.72 1.72 1.73 1.73 1.74 1.75 1.75 1.75 1.75 1.77 1.77 1.77 1.78 1.78 1.79 1.79 1.80 1.81 1.81 1.81 1.81 1.81 1.82 1.83 1.83 1.84 1.84 1.85 1.85 1.85 1.86 1.86 1.87 1.88 1.88 1.89 1.89 1.89 1.90 1.90 1.91 1.91 1.92 1.93 1.93 1.93 1.94 1.94 1.95 1.95 1.96

1.35 1.35 1.35 1.36 1.36 1.36 1.36 1.37 1.37 1.37 1.36 1.37 1.37 1.37 1.38 1.38 1.38 1.39 1.39 1.39 1.40 1.40 1.40 1.41 1.41 1.42 1.42 1.42 1.42 1.43 1.43 1.45 1.44 1.45 1.45 1.45 1.47 1.47 1.48 1.48 1.49 1.49 1.49 1.5 1.51 1.52 1.52 1.53 1.55 1.54 1.55 1.56 1.56 1.56 1.58 1.57 1.59 1.59 1.59

1127



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0

0.100

0.204

0.301

0.401

0.499

0.601

0.700

0.798

0.900

1

470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528

2.48 2.47 2.47 2.48 2.48 2.48 2.48 2.48 2.48 2.48 2.50 2.49 2.50 2.50 2.50 2.50 2.50 2.52 2.50 2.52 2.50 2.51 2.51 2.53 2.52 2.51 2.51 2.52 2.53 2.53 2.54 2.54 2.53 2.53 2.53 2.54 2.54 2.54 2.55 2.54 2.54 2.56 2.55 2.56 2.56 2.55 2.55 2.55 2.55 2.56 2.56 2.56 2.56 2.56 2.57 2.57 2.56 2.57 2.57

2.26 2.25 2.26 2.26 2.26 2.27 2.26 2.27 2.25 2.27 2.27 2.27 2.27 2.27 2.27 2.27 2.27 2.28 2.28 2.29 2.28 2.29 2.28 2.29 2.29 2.29 2.29 2.29 2.3 2.29 2.31 2.29 2.3 2.3 2.3 2.31 2.31 2.31 2.31 2.31 2.31 2.31 2.31 2.31 2.31 2.32 2.31 2.32 2.32 2.32 2.32 2.32 2.31 2.32 2.33 2.32 2.32 2.33 2.33

2.10 2.09 2.09 2.10 2.09 2.10 2.11 2.11 2.11 2.11 2.11 2.11 2.12 2.12 2.11 2.12 2.13 2.12 2.12 2.13 2.13 2.13 2.13 2.13 2.14 2.14 2.14 2.15 2.16 2.16 2.15 2.15 2.14 2.14 2.14 2.14 2.14 2.14 2.14 2.14 2.14 2.14 2.15 2.14 2.15 2.15 2.14 2.15 2.15 2.15 2.15 2.15 2.15 2.15 2.15 2.16 2.15 2.16 2.16

2.17 2.17 2.16 2.17 2.17 2.16 2.17 2.17 2.16 2.17 2.17 2.17 2.17 2.16 2.16 2.17 2.17 2.16 2.17 2.16 2.16 2.16 2.16 2.16 2.17 2.17 2.17 2.17 2.17 2.16 2.17 2.16 2.16 2.17 2.16 2.16 2.17 2.16 2.16 2.16 2.16 2.16 2.16 2.16 2.16 2.16 2.16 2.17 2.17 2.17 2.16 2.16 2.16 2.16 2.16 2.16 2.16 2.16 2.16

2.17 2.16 2.17 2.17 2.17 2.17 2.16 2.17 2.19 2.18 2.18 2.19 2.18 2.19 2.19 2.20 2.19 2.20 2.20 2.21 2.21 2.21 2.21 2.21 2.22 2.21 2.21 2.22 2.23 2.21 2.23 2.23 2.23 2.23 2.23 2.23 2.23 2.23 2.23 2.23 2.23 2.23 2.22 2.21 2.21 2.21 2.22 2.22 2.21 2.23 2.21 2.22 2.21 2.21 2.21 2.21 2.21 2.21 2.2

2.16 2.15 2.15 2.16 2.15 2.16 2.16 2.17 2.16 2.15 2.16 2.17 2.16 2.16 2.16 2.16 2.16 2.16 2.17 2.16 2.18 2.18 2.17 2.17 2.18 2.18 2.18 2.19 2.19 2.17 2.19 2.19 2.19 2.19 2.19 2.18 2.19 2.19 2.2 2.19 2.20 2.21 2.20 2.20 2.21 2.21 2.22 2.21 2.22 2.22 2.21 2.21 2.22 2.23 2.21 2.2 2.21 2.19 2.18

2.19 2.20 2.20 2.20 2.21 2.22 2.22 2.22 2.23 2.24 2.25 2.25 2.25 2.25 2.26 2.26 2.25 2.26 2.27 2.27 2.28 2.28 2.28 2.28 2.29 2.29 2.29 2.29 2.3 2.3 2.3 2.31 2.31 2.32 2.31 2.31 2.32 2.33 2.33 2.33 2.33 2.33 2.34 2.34 2.34 2.34 2.34 2.34 2.35 2.35 2.35 2.35 2.34 2.34 2.35 2.35 2.34 2.34 2.34

2.41 2.42 2.42 2.44 2.44 2.45 2.45 2.46 2.47 2.47 2.47 2.48 2.49 2.49 2.5 2.5 2.51 2.51 2.51 2.51 2.53 2.53 2.53 2.55 2.56 2.56 2.56 2.57 2.57 2.58 2.59 2.60 2.60 2.61 2.62 2.63 2.63 2.64 2.64 2.65 2.66 2.67 2.68 2.68 2.69 2.70 2.71 2.71 2.72 2.73 2.74 2.75 2.75 2.76 2.77 2.78 2.78 2.79 2.81

2.28 2.29 2.29 2.30 2.30 2.30 2.31 2.32 2.33 2.33 2.34 2.35 2.36 2.36 2.37 2.38 2.38 2.38 2.39 2.4 2.41 2.4 2.4 2.41 2.43 2.43 2.43 2.48 2.49 2.49 2.5 2.51 2.52 2.54 2.55 2.56 2.56 2.58 2.6 2.61 2.62 2.63 2.65 2.67 2.68 2.70 2.71 2.72 2.75 2.76 2.77 2.79 2.81 2.84 2.85 2.87 2.89 2.91 2.94

1.96 1.96 1.97 1.97 1.98 1.98 1.98 1.98 1.98 1.99 1.98 1.98 1.98 1.99 1.99 1.99 1.99 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00 1.99 1.99 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.01 2.01 2.02 2.02 2.02 2.03 2.03 2.04 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.15 2.16 2.19 2.23

1.6 1.62 1.63 1.64 1.63 1.65 1.66 1.65 1.66 1.64 1.64 1.64 1.66 1.66 1.66 1.66 1.67 1.68 1.67 1.68 1.68 1.68 1.67 1.68 1.69 1.69 1.68 1.69 1.69 1.69 1.69 1.69 1.69 1.69 1.69 1.70 1.70 1.70 1.70 1.70 1.70 1.70 1.71 1.71 1.71 1.71 1.73 1.73 1.73 1.73 1.74 1.73 1.75 1.75 1.76 1.76 1.77 1.77 1.79

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0

0.100

0.204

0.301

0.401

0.499

0.601

0.700

0.798

0.900

1

529 530 531 532 533

2.57 2.57 2.57 2.58 2.57

2.32 2.32 2.32 2.33 2.33

2.16 2.16 2.16 2.17 2.17

2.16 2.17 2.16 2.16 2.16

2.21 2.21 2.21 2.21 2.21

2.17 2.17 2.17 2.16 2.17

2.33 2.34 2.34 2.33 2.34

2.81 2.82 2.82 2.81 2.83

2.96 2.97 2.99 2.99 3.00

2.28 2.34 2.38 2.42 2.43

1.80 1.81 1.86 1.94 2.09

a w1 is the mass fraction of quercetin in the [quercetin (1) + PEG 6000 (2)] mixture. Standard uncertainties u are u(T) = 0.8 K, u(w1) = 0.002, and the combined relative uncertainty of ur(cp) = 0.02 (level of confidence = 0.95).

Figure 4. The dependence of cp on T for [quercetin (1) + PEG 6000 (2)] with mass fraction w1 = 0, 0.100, and 0.204, (from top to bottom), in the temperature range from (353 to 533) K, respectively.

Figure 6. The curves of cp against T for binary system of [quercetin (1) + PEG 6000 (2)] with mass fraction w1 = 0.700, 0.798, 0.900 and 1, respectively (from top to bottom). In the range of T < 353 K, the effect of PEG melting on cp is observable, but its effect is decreased with a w1 increase. In the range of T > 353 K, cp decreases with w1 increase.

By using a nonlinear fitting method, the cp curve can be satisfactorily correlated with the fitting parameters provided in Table 5. Because the existence of small peak in Figure 5, it is difficult to use empirical equations to fit the cp data for this group of samples. Thermodynamic Functions. From the initial temperature Ti to a final temperature T, the change in thermodynamic functions can be calculated from the data of cp by eqs 11 to 13.

Δh =

∫T

T

c p dT

(11)

i

Figure 5. The dependence of cp on T for systems of [quercetin (1) + PEG 6000 (2)] with mass fraction w1 = 0.301 (solid line), 0.401 (dash line), 0.499 (short dash line), and 0.601 (dash dot line), in the temperature range from (353 to 533) K, respectively.

a 2 = a 21 + a 22w1

Δs =

a 2 = a 21 + a 22w2

(10.2)

(c p / T ) d T

(12)

Δg = Δh − T Δs −1

(13) −1

−1

Where, the h/J·g , s/J·K·g , and g/J·g are the specific enthalpy, entropy, and Gibbs function, respectively. The functions of Δh, Δs, and Δg are the specific enthalpy change, specific entropy change, and specific Gibbs function change from the initial temperature Ti to a final temperature T (where T varies from (353 to 500) K). The mixing function, for example, the mixing specific enthalpy, is defined by eq 14.

By using a nonlinear fitting method, the cp curve can be satisfactorily correlated. The fitting parameters are provided in Table 5. For the data in Figure 6, the curve shape of cp is like that of quercetin. To exclude the effect of melting and decomposition, Ti = 353 K and Tf = 500 K were supposed. The relations between ai and composition w2 were supposed to be eqs 10.1 and 10.2. (10.1)

T

i

(9.2)

a1 = a11 + a12w2

∫T

Δmix h = Δh − (w1Δh1 + w2Δh2)

(14)

Where, Δh1 and Δh2 are the specific enthalpy change of pure quercetin and PEG 6000, respectively. The changes of specific mixing functions of Δmixh, Δmixs, and Δmixg with the final temperature T (it varies from (353 to 500) K) and composition w1 are graphically shown in Figures 7, 8, and 9, respectively. 1129



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Table 5. The Fitting Parameters aij of eqs 7 to 10 for System of [Quercetin (1)+PEG 6000 (2)] in Two Composition Ranges with w1 = (0 to 0.204) and (0.700 to 1), respectively. Where u(cp) is the Standard Deviation of the Fits and the R is the Correlation Coefficientsa w1

a11

a12

a21

a22

a3

a4

u(cp)/J·(g·K)−1

R

0 to 0.204 0.700 to 1

2.24 1.24

−1.50 2.53

0.157 0.127

−0.488 0.389

0.513 −0.354

0.663 −0.268

0.01 0.04

0.995 0.991

Figure 7. The dependence of specific mixing enthalpy Δmixh on temperature T and composition w1 (mass fraction) for binary system of [quercetin (1) + PEG 6000 (2)].

Figure 9. The dependence of specific mixing Gibbs function Δmixg on temperature T and composition w1 (mass fraction) for binary system of [quercetin (1) + PEG 6000 (2)].

leads the mixing Gibbs function changes toward two different directions. FT-IR Spectroscopy. The infrared spectra of quercetin, PEG 6000, and some of their mixtures with w1= (0.204, 0.499, 0.798, and 0.900), are provided in Figure 10. For quercetin, the bands attribution is given as follows: 3400 cm−1, the vibration of free −OH; 1653 cm−1 and 1611 cm−1, the stretching vibration of the CO group that appears as a

Figure 8. The dependence of specific mixing entropy Δmixs on temperature T and composition w1 (mass fraction) for binary system of [quercetin (1) + PEG 6000 (2)].

In Figure 5, a small peak is observed, and it may be attributed to some special intermolecular interaction. This interaction can be confirmed by the mixing Gibbs function. In Figure 9, as 0.3 < w1 < 0.6, Δmixg changes little with w1. In the composition region of w1 < 0.3, a maximum value of Δmixg is found. Meanwhile, in the composition region of w1 > 0.7, a minimum value of Δmixg is found. Therefore, in the composition region of w1 = (0.3 to 0.6), an intermolecular compound may exist. It

Figure 10. FT-IR spectra (transmittance Tr vs wavenumber ν) of mixtures of [quercetin (1) + PEG 6000 (2)] with mass fractions of w1 = 0, (a); w1 = 0.204, (b); w1 = 0.499, (c); w1 = 0.798, (d); w1= 0.900, (e); and w1= 1, (f) (in the order from top to bottom). 1130



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doublet; 1510 cm−1, attribute to aromatic group; 1166 cm−1 and 1096 cm−1, vibration of C−O−C group; 929 cm−1, bending vibration of aromatic C−H group. For PEG 6000, the bands attribution is given as follows: 2882 cm−1 and 1639 cm−1, vibration of −CH2− group; 1112 cm−1, vibration of C−O−C group; 957 cm−1, vibration of C−H group; a broad band at 3438 cm−1, presence of water. For samples of w1 = (0, 0.204 and 0.499), the spectrum is almost the same as pure PEG, the characteristic peak of quercetin is covered by PEG. This phenomenon can be attributed to the formation of solid dispersion of queretin in PEG. For samples of w1 = (0.798, 0.900 and 1), the characteristic peak is almost the same as quercetin, and no band shift was observed. This is an indication that a chemical reaction is not present between PEG and quercetin. In this composition region, the equilibrium between solid quercetin and PEG dispersion is expected. X-ray Powder Diffraction. The XRD patterns of quercetin, PEG 6000, and their mixtures with w1 = (0.100, 0.301, 0.499, and 0.798), are shown in Figure 11. Figure 11 top curve is the

variation of the melting properties with composition was concerned. With the increase in w1, the temperature (Tfus/K) and enthalpy (Δfush/J·g−1) of fusion are decreased. This indicates that the binary system is of the character of solid mixture/or solid dispersion in this temperature range. In the second section from (353 to 533) K, the variation of heat capacity with composition and temperature was concerned. The molten polymer dispersion is formed in the region of w1 < 0.301. In this region, the cp increases slowly with the increase in temperature, the curve shape of samples are similar to the shape of PEG, and cp decreases slightly with the increase in w1. In the region of w1 > 0.601, a mixture of solid quercetin and PEG dispersion is formed. However, in the composition region from w1 = (0.301 to 0.601), the character of a molten PEG dispersion equilibrating with solid quercetin is observed. By using empirical equations, cp, T, and w1 are correlated. The changes in mixing enthalpy, entropy, and Gibbs function with temperature were calculated from cp.

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AUTHOR INFORMATION

Corresponding Author

*Tel.: 86-512-65880363. Fax: 86-512-65880089. E-mail: [email protected]. Funding

This project was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. Notes

The authors declare no competing financial interest.

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REFERENCES

(1) Needs, P. W.; Kroon, P. A. Convenient Syntheses of Metabolically Important Quercetin Glucuronides and Sulfates. Tetrahedron 2006, 62, 6862−6868. (2) Bergonzi, M. C.; Bilia, A. R.; Bari, L. D.; Mazzia, G.; Vincieri, F. F. Studies on the Interactions between Some Flavonols and Cyclodextrins. Bioorg. Med. Chem. Lett. 2007, 17, 5744−5748. (3) Jullian, C.; Moyano, L.; Yanez, C.; Olea-Azar, C. Complexation of Quercetin with Three Kinds of Cyclodextrins: An Antioxidant Study. Spectrochim. Acta, Part A 2007, 67, 230−234. (4) Zhu, J.; Yang, Z.-G.; Chen, X.-M.; Sun, J.-B.; Awuti, G.; Zhang, X.; Zhang, Q. Preparation and Physicochemical Characterization of Solid Dispersion of Quercetin and Polyvinylpyrrolidone. J. Chin. Pharm. Sci. 2007, 16, 51−56. (5) Vasconcelos, T.; Sarmento, B.; Costa, P. Solid Dispersions as Strategy to Improve Oral Bioavailability of Poor Water Soluble Drugs. Drug Discovery Today 2007, 12, 1068−1075. (6) Blagden, N.; de Matas, M.; Gavan, P. T.; York, P. Crystal Engineering of Active Pharmaceutical Ingredients To Improve Solubility and Dissolution Rates. Adv. Drug Delivery Rev. 2007, 59, 617−630. (7) Fini, A.; Cavallari, C.; Ospitali, F. Raman and Thermal Analysis of Indomethacin /PVP Solid Dispersion Enteric Microparticles. Eur. J. Pharm. Biopharm. 2008, 70, 409−420. (8) O’Neill, M. A.A.; Gaisford, S. Application and Use of Isothermal Calorimetry in Pharmaceutical Development. Int. J. Pharm. 2011, 417, 83−93. (9) Kanungo, I.; Chellappa, N.; Fathima, N. N.; Rao, J. R. Calorimetric Analysis of Gelatine−Glycosaminoglycans Blend System. Int. J. Biol. Macromol. 2011, 49, 289−296. (10) Signori, F.; Pelagaggi, M.; Bronco, S.; Righetti, M. C. Amorphous/Crystal and Polymer/Filler Interphases in Biocomposites from Poly(butylene succinate). Thermochim. Acta 2012, 543, 74−81. (11) Joseph, A.; Bernardes, C. E.S.; Minas da Piedade, M. E. Heat Capacity and Thermodynamics of Solid and Liquid Pyridine-3-

Figure 11. X-ray diffraction patterns of [quercetin (1) + PEG 6000 (2)] mixtures with mass fraction w1 = 0, (a); w1 = 0.100, (b); w1 = 0.301, (c); w1 = 0.499, (d); w1 = 0.798, (e) and w1= 1, (f). (in the order from top to bottom).

pattern of PEG 6000. The distinct sharp peaks indicate that PEG appears to be a crystalline material with characteristic diffraction peaks appearing at angles of 2θ = (19.04, 23.15, 26.20, 26.1 and 27.72)°. Figure 11 bottom curve is the pattern of quercetin. The characteristic diffraction peaks appear at angles of 2θ = (10.97, 13.10, 16.91, 22.09, and 26.35)°. For samples of (quercetin + PEG 6000), their XRD pattern can be viewed as a combination of two components. As w1 < 0.5, the pattern of quercetin is covered by PEG. While for w1 = 1 and 0.798, the intensity of the peak of quercetin is lowered by the addition of PEG. No new crystalline is found from XRD results. The results of XRD confirm our conclusion from cp analysis.

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CONCLUSIONS For a binary system of (quercetin + PEG 6000), the phase transition behavior and the heat capacity was measured in temperature range from (298 to 533) K by DSC. The DSC curve was divided into two sections to separate the effect of PEG melting on cp. In the first section from (298 to 353) K, the 1131



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carboxylic Acid (Nicotinic Acid) Over the Temperature Range 296 to 531 K. J. Chem. Thermodyn. 2012, 55, 23−28. (12) Yao, W. W.; Bai, T. C.; Sun, J. P.; Zhu, C. W.; Hu, J.; Zhang, H. L. Thermodynamic Properties for the System of Silybin and Poly(ethylene glycol) 6000. Thermochim. Acta 2005, 437, 17−20. (13) Han, W.; Bai, T. C.; Zhu, J. J. Thermodynamic Properties for the Solid−Liquid Phase Transition of Silybin + Poloxamer 188. J. Chem. Eng. Data 2009, 54, 1889−1893. (14) Li, Y. L.; Bai, T. C.; Yang, Y. Heat Capacity for the Binary System of Silybin and Poly(vinylpyrrolidone) K30. Thermochim. Acta 2011, 520, 99−104. (15) Li, Y. L.; Yang, Y.; Bai, T. C.; Zhu, J. J. Heat Capacity for the Binary System of Quercetin and Poly(vinylpyrrolidone) K30. J. Chem. Eng. Data 2010, 55, 5856−5861. (16) Wang, Y. Y.; Li, Y. L.; Bai, T. C.; Zhang, M. Heat Capacity for the Binary System of Silybin and Sodium Cholate. J. Chem. Eng. Data 2011, 56, 3426−3432. (17) Bondi, A. van der Waals Volumes and Radii. J. Phys. Chem. 1964, 68, 441−451.

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Heat Capacity for the Binary System of Quercetin + Poly(ethylene

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