Article Cite This: J. Chem. Eng. Data XXXX, XXX, XXX-XXX
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Solid−Liquid Phase Equilibrium and Thermodynamic Properties of Olaparib in Selected Organic Solvents and (Tetrahydrofuran + MTBE, Acetonitrile + Isopropyl Alcohol) Binary Solvent Mixtures Wangdan Zhao,† Wenge Yang,*,† Jian Zhang,† Huace Sheng,† Xinxin Zhao,† and Yonghong Hu‡ †
School of Pharmaceutical Sciences, and ‡Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing Technical University, No. 30, South Puzhu Road, Nanjing 211816, China ABSTRACT: We focused on the solubility of olaparib under atmospheric pressure in isopropyl alcohol, MTBE, acetonitrile, and tetrahydrofuran as well as in the (tetrahydrofuran + MTBE, acetonitrile + isopropyl alcohol) mixtures from 280.35− 319.35 K. It is found that the solubility of olaparib and temperature were positively correlated in the range of our study. We chose the modified Apelblat equation, the Buchowski−Ksiazaczak λh equation, CNIBS/R-K equation, and the Jouyban−Acree equation to verify the thermodynamic properties of olaparib. Computational results showed that all selected equations agreed well with the experimental data, and the modified Apelblat equation gives the best correlation. We also selected two binary solvent dissolution systems, and the test found that (tetrahydrofuran + MTBE) mixtures may be a good recrystallization system. This study provides valuable data for olaparib’s production process purification.
1. INTRODUCTION Ovarian cancer is among the most common gynecological malignant tumors in women,1 and its mortality rate is at the top of the list. The incidence rate has increased year by year. The European Commission approved olaparib (1-(cyclopropylcarbonyl)-4-[5-[(3,4-dihydro-4-oxo-1-phthala-zinyl)methyl]-2fluorobenzoyl]piperazine) (Lynparza, structure shown in Figure 1, C24H23FN4O3, CASRN 763113-22-0) as a single
that the solubility properties of olaparib in different solvents are very important for its synthesis in the process, which is also the significance of our research for this article.3,4 A good recrystallization system is essential for improving the purity of the product. Up to now, no solubility data of olaparib have been reported in the literature especially in the (tetrahydrofuran + MTBE, acetonitrile + isopropyl alcohol) mixtures. In our paper, the solubility of olaparib in isopropyl alcohol, methyl tert-butyl ether (MTBE), acetonitrile, tetrahydrofuran, and (tetrahydrofuran+MTBE, acetonitrile+ isopropyl alcohol) mixtures at temperatures ranging from 280.35 K to 319.35 K was measured under atmospheric pressure by the gravimetric method.5 Acetonitrile and MTBE are the commonly used solvent, and isopropyl alcohol is an important chemical raw material and a relatively cheap solvent. Tetrahydrofuran is the universal solvent to be used during the crystallization process. We found that the solubility of olaparib in tetrahydrofuran was much higher than that in MTBE. Similarly, the solubility of olaparib is also greatly different in acetonitrile and isopropyl alcohol. Although a method for refining olaparib by recrystallization from aqueous ethanol was reported,6 the effect of removing impurities is not enough. From this we hypothesize that the (tetrahydrofuran + MTBE, acetonitrile + isopropyl alcohol) mixtures may be a good recrystallization system. In the single solution system, we used the modified Apelblat equation and the Buchowski−Ksiazaczak λh equation. In the miscible system, we used the CNIBS/R-K equation and the
Figure 1. Chemical structure of olaparib.
drug therapy for the treatment of platinum sensitive recurrent BRCA mutations in ovarian cancer on December 18th, 2014, and it has become the first PARP (poly(ADP-ribose) polymerase) inhibitor for the treatment of platinum sensitive recurrent ovarian cancer with BRCA mutations.2 The FDA also approved that on December 19th, 2014. Treating 2carboxybenzaldehybe (II) with dimethyl phosphate, followed by Wittig−Horner reaction, hydrolyzation, cyclization, acidification, and then amidation we can obtain the objective product olaparib(I). The synthetic route of olaparib was shown in (Figure 2). Figure 3 is the HRESIMS spectrum for olaparib and the peaks are located at m/z 433.2(M − H)− and 434.2(M). This is only part of our work, and we have found © XXXX American Chemical Society
Received: May 31, 2017 Accepted: October 12, 2017
A
DOI: 10.1021/acs.jced.7b00489 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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Figure 2. Synthesis method of olaparib.
Figure 3. HRESIMS spectrum for olaparib.
Figure 4. DSC Figure of olaparib
Industrial Co., Ltd. And its mass fraction was higher than 98%. Its purity was measured by HPLC (type Agilent 1260 Infinity LC, Agilent Technologies). The melting temperature was 471.65 K (Standard uncertainties u is u(T) = 0.85K) determined by DSC (Netzsch DSC 204, DSC Instruments, Figure 4). The calibration was performed using pure indium, and DSC thermograms of pure and recovered olaparib were obtained under a nitrogen purge of 40 mL min−1 at a heating rate of 10 K min−1. All solvents used in the experiments were
Jouyban−Acree equation. All the equation results were closely related to the experimental data. We analyzed the solubility data by STATISTIC. STATISTIC is a ministatistical software, and you can calculate the average, variance, standard deviation, and coefficient of variation, etc.
2. EXPERIMENTAL 2.1. Materials and Apparatus. Olaparib is a white crystalline powder supplied by Nanjing Chemlin Chemical B
DOI: 10.1021/acs.jced.7b00489 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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acetonitrile + isopropyl alcohol) binary solvent mixtures, and achieve further application for the obtained solubility data, in this article, four models are chosen to correlate the experimental solubility, which correspond to the modified Apelblat equation, λh equation, CNIBS/R-K models, and Jouyban−Acree model. 3.1.1. Solubility in Monosolvents. 3.1.1.1. Modified Apelblat Equation. The saturated mole fraction solubility (x1) in tetrahydrofuran, isopropyl alcohol, acetonitrile, and MTBE at 280.35−319.35 K was presented in Table 2.
analytical reagents with a mass fraction of more than 99% purity. See Table 1 for details. Table 1. Provenance and Purity of the Materials Useda solvent olaparib tetrahydrofuran acetonitrile methyl tert-butyl ether isopropyl alcohol
source Nanjing Chemlin Chemical Industrial Shenbo Chemicals Shenbo Chemicals Shenbo Chemicals Shenbo Chemicals
mass fraction purity
molar mass (g/mol)
CASRN
≥0.980
434.21
763113-22-0
≥0.990
72.11
109-99-9
≥0.995
41.05
75-05-8
≥0.995
88.15
1634-04-4
≥0.990
60.06
67-63-0
Table 2. Mole Fraction Solubility (x 1) of Olaparib in Four Monosolvents at the Temperature Range from (280.35 to 319.35) K under Pressure p = 0.1 MPaa 100RD T/K
a
The sample purities were stated by the suppliers and no purification was applied to the chemicals.
280.35 284.35 288.35 292.35 296.35 300.35 303.35 307.35 311.35 315.35 319.35
2.2. Methods. The solubility of olaparib was determined by isothermal dissolution equilibrium method. Detailed measurements of the solubility are similar that in the literature,5 and the method verification was performed in our previous publication.7 The selected organic solvent and an excess of olaparib were added to a glass tube having a stopper to form a supersaturated solution. The glass tube was continuously agitated on a magnetic stirrer and held at a desired temperature in a thermostatic bath (280.35 K to 319.35 K) with a standard uncertainty of 0.02 K and then awaiting supersaturation. The stirrer was turned off during seven hours at constant temperature to precipitate the undissolved solid. A 1 mL aliquot of the clear saturated solution was removed by a 5 mL preheated syringe with a filter, and this sample was quickly transfer to a previously weighed 5 mL beaker with a cover. The analytical balance for weighing had an accuracy of 0.0001 g. Next, the total weight was measured quickly, and the beaker was placed in the dryer. The sample was repeatly weighed until a constant weight was obtained. In order to test the reproducibility of the experimental results, each experiment was repeated at least three times. The mole fractional solubility was calculated using the average of the three samples at each temperature for each solvent. The experimental solubilities of olaparib (x1) in mole fraction were determined using eq 1 and the composition of solvent mixtures (x2) is defined using eq 2. x1 =
m1/M1 m1/M1 + ∑ mi /Mi
x2 =
m2 /M 2 , m2 /M 2 + m3 /M3
280.35 284.35 288.35 292.35 296.35 300.35 303.35 307.35 311.35 315.35 319.35
m3 /M3 m2 /M 2 + m3 /M3
eq 4
MTBE 0.772 11.673 1.029 9.798 1.341 6.694 1.770 5.562 2.362 6.310 2.969 2.241 3.553 0.487 4.657 2.016 5.709 −2.190 7.151 −3.278 9.127 −1.425 Acetonitrile 1.349 7.400 1.831 6.102 2.424 3.455 3.250 2.968 4.399 4.465 5.584 0.809 6.726 −0.540 8.879 1.642 10.913 −2.064 13.667 −2.598 17.354 −0.334
eq 3 −1.992 −1.202 −1.932 −0.684 2.277 −0.028 −0.564 2.329 −0.849 −1.327 0.610 −0.987 −0.890 −2.181 −0.958 2.240 −0.288 −0.726 2.385 −0.758 −1.183 0.530
100x1
eq 4
eq 3
Isopropyl Alcohol 0.976 3.060 −1.696 1.311 2.420 −1.114 1.721 0.428 −2.006 2.287 0.594 −0.795 3.072 2.718 2.222 3.880 −0.291 −0.109 4.659 −1.175 −0.618 6.131 1.576 2.366 7.532 −1.555 −0.809 9.446 −1.574 −1.284 12.051 1.190 0.581 Tetrahydrofuran 2.024 8.009 −0.989 2.746 6.070 −0.846 3.637 2.865 −2.056 4.874 1.951 −0.959 6.598 3.211 2.095 8.376 −0.549 −0.259 10.089 −1.801 −0.718 13.318 0.793 2.384 16.370 −2.242 −0.736 20.501 −1.745 −1.193 26.030 1.831 0.530
a
The standard uncertainties u are u(T) = 0.3 K, ur(p) = 0.05, u(x1) = 0.0015.
Apelblat first uses the modified Apelblat equation, which is often used to describe the relationship between solubility and temperature in a single solution system:8,9 B ln x = A + + C ln(T /K) (3) T /K
(1)
x3 =
100x1
100RD
where x and T represent the mole fraction solubility of the olaparib and test temperature in K, respectively. In addition, regression curve parameters for A, B, and C are listed in Table 3. 3.1.1.2. Buchowski−Ksiazaczak λh Equation. The Buchowski−Ksiazaczak λh equation is also used in this study:10
(2)
where m1 represents the mass of the solute, m2 represents the mass of tetrahydrofuran and acetonitrile, and m3 represents the mass of MTBE and isopropyl alcohol. M1, M2, and M3 represent the molecular weight of the solute, and different solvents, respectively.
⎡ 1 ⎛ λ(1 − x) ⎞ 1 ⎤ ln⎜1 + ⎟ = λh⎢ − ⎥ ⎝ ⎠ x (Tm/K) ⎦ ⎣ (T /K)
3. RESULTS AND DISCUSSION 3.1. Solubility Data and Correlation Models. To find suitable models to describe the solubility behavior of olaparib in selected organic solvents and (tetrahydrofuran + MTBE,
(4)
where Tm represents the melting point of the olaparib in Kelvin; λ and h are the two parameters of the equation. C
DOI: 10.1021/acs.jced.7b00489 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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in Table 5 and Table 6. Figures 5 and 6 show us more intuitively the relationship between the solubility and temperature of olaparib in the miscible system. It can be noted that the solubility in the (tetrahydrofuran + MTBE) mixtures increases with an increase in temperature and mole fraction of tetrahydrofuran from Table 5 and Figure 5. It can be also noted that the solubility in (acetonitrile+ isopropyl alcohol) mixtures increases with an increase in temperature and mole fraction of acetonitrile from Table 6 and Figure 6. The solubility of olaparib in (acetonitrile+ isopropyl alcohol) solvent mixtures is lower than that in (tetrahydrofuran + MTBE). 3.1.2.1. CNIBS/R-K Models. We know that the solubility of olaparib at the fixed temperature is related to the composition of the solvent. Equation 6 is the combined nearly ideal binary Solvent/Redlich−Kister (CNIBS/R-K) model used to describe the relationship between the isothermal mole fraction solubility and the binary solvent composition.15−17
Table 3. Parameters of the Modified Apelblat Equation for Olaparib in the Monosolvents solvent
A
B/100
C
MD
MTBE isopropyl alcohol acetonitrile tetrahydrofuran average MD =
−1.78 35.52 106.87 107.77
−48.54 −65.98 −98.59 −98.83
2.53 −2.95 −13.48 −13.56
0.021 0.023 0.019 0.017 0.0195
According to the data in Table 2, the three parameters of equation 3 in Table 3 include A, B, and C, and Table 4 gives the Table 4. Parameters of Buchowski−Ksiazaczak λh Equation for Olaparib in the Monosolvents solvent
λ
h
MD
MTBE isopropyl alcohol acetonitrile tetrahydrofuran average MD =
37.94 62.94 143.84 283.75
155.07 96.56 44.88 23.42
0.341 0.030 0.134 0.126 0.158
N
ln x1 = x 2 ln(x1)2 + x3 ln(x1)3 + x 2x3 ∑ Si(x 2 − x3)i i=0
(6)
where Si is the model constant and N can be equal to 0, 1, 2, and 3. x2 and x3 represent the initial mole fraction composition of the binary solvent when the solute was not added. (x1)i is the saturated mole fraction solubility of the solute in monosolvent i. When N = 2 and substitution of (1 − x2) for x3, eq 4 can be written as eq 7.
parameters λ and h of equation 4. We introduce equation 5 using the mean deviation (MD)11,12 to understand the validity of the model: ∑ MD = 100
|x1 − x1cal| x1
(5) N cal where x1 is the solubility of olaparib, x1 is the calculated value of solubility, and N is the number of experiments. The solubility of olaparib in pure acetonitrile, MTBE, isopropyl alcohol, and tetrahydrofuran, measured at temperatures from 280.35 to 319.35 K, is presented in Table 2. From Table 2, it can be found that the solubility of olaparib in acetonitrile, MTBE, isopropyl alcohol, and tetrahydrofuran is a function of temperature. There is a positive correlation between the solubility of the olaparib and temperature. The solubility order shows the following trend: tetrahydrofuran > acetonitrile > isopropyl alcohol > MTBE. The reason for this discrepancy may be due to the hydrogen bonding interaction and bonding between the solute molecules and the solvent molecules. Oxygen atoms of tetrahydrofuran can provide a lone pair of electrons to combine with the carboxyl proton of olaparib. So it can dissolve the largest amount of solute. The solubility of olaparib in the remaining three solvents conformed to the “like dissolves like” principle.13,14 The temperature dependence of olaparib solubility can be described by equation 3 and equation 4. Table 3 and Table 4 show the fitting parameters. The small MD showed that the calculated data of olaparib in four monosolvents were in good agreement with the experimental data. The mean deviation (MD) calculated by eq 3 is 0.021, 0.020, 0.019, and 0.018, respectively, and values calculated by eq 4 are 0.341, 0.030, 0.134, and 0.126, respectively. Meanwhile, from Tables 3 and 4, for the modified Apelblat equation and the λh equation, the average MDs are 0.0195 and 0.158, respectively. It is obvious that the solubility of olaparib can be calculated by eq 3 and eq 4, but eq 3 is more accurate than eq 4 in the study. 3.1.2. Solubility in the Two Binary Solvent Mixtures. The solubility of olaparib in (tetrahydrofuran + MTBE, acetonitrile + isopropyl alcohol) mixtures at different temperatures is listed
ln x1 = ln(x1)3 + (ln(x1)2 − ln(x1)3 + S0 − S1 + S2)x 2 + ( −S0 + 3S1 − 5S2)x 22 + ( −2S1 + 8S2)x 23 + ( −4S2)x 24
(7)
which can be further simplified as ln x1 = B0 + B1x 2 + B2 x 22 + B3x 23 + B4 x 24
(8) 18,19
here B0, B1, B2, B3, and B4 are equation constants. Equation 8 is another form of the CNIBS/R-K model. When N = 2 and (1 − x2) is substituted into x3, eq 6 can be rearranged to cause eq 9. ln x1 − (1 − x 2) ln(x1)3 − x 2 ln(x1)2 = (1 − x 2)x 2[S0 + S1(2x 2 − 1) + S2(2x 2 − 1)2 ]
(9)
15
This is the second variant of CNIBS/R-K model. The parameters Si would be acquired by regressing {ln x1 − (1 − x2) ln(x1)3 − x2 ln(x1)2} versus {(1 − x 2)x 2[S0 + S1(2x 2 − 1) + S2(2x 2 − 1)2 ]}.
The values of the parameters are listed in Table 7 and Table 8. 3.1.2.2. Jouyban−Acree Model. To investigate the interaction of solvent composition and temperature on the solubility of olaparib, we chose the model20−22 that is usually used to describe the solute solubility with the initial composition and temperature of the binary solvent mixture: N
ln x1 = x 2 ln(x1)2 + x3 ln(x1)3 + x 2x3 ∑ i=0
Ji (x 2 − x3)i T (10)
where Ji and T are model constants and absolute temperatures, respectively. The meanings of other symbols are given by eq 6. D
DOI: 10.1021/acs.jced.7b00489 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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Table 5. Mole Fraction Solubility (x1) of Olaparib in Tetrahydrofuran + MTBE Binary Solvent Mixtures at the Temperature Range from (280.35 to 319.35) K under Pressure p = 0.1 MPaa 100RD x2
100x1
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
0.772 0.812 0.884 0.971 1.091 1.242 1.785 2.024
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
1.341 1.434 1.561 1.715 1.927 2.194 3.153 3.637
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
2.362 2.531 2.773 3.097 3.469 3.924 5.638 6.598
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
3.553 3.768 4.140 4.589 5.203 5.978 8.666 10.089
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
5.709 6.055 6.674 7.377 8.317 9.660 14.760 16.370
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
9.127 9.627 10.612 11.729 13.225 15.360 23.468 26.030
eq 8 T −0.034 −0.118 0.427 −0.303 −0.073 0.141 −0.072 0.037 T −0.509 0.631 0.542 −0.676 −0.399 0.586 −0.300 0.151 T −0.435 0.578 0.264 −0.237 −0.585 0.592 −0.277 0.134 T −0.433 0.386 0.766 −0.603 −0.585 0.667 −0.314 0.154 T 0.658 −1.121 0.087 0.317 0.454 −0.528 0.241 −0.130 T 0.727 −1.265 0.116 0.374 0.458 −0.560 0.260 −0.141
eq 9
100RD eq 12
100x1
= 280.35 K
= 288.35
= 296.35
= 303.35
= 311.35
= 319.35
0.000 −0.097 0.429 −0.313 −0.081 0.152 −0.077 0.000 K 0.000 0.819 0.531 −0.758 −0.434 0.658 −0.341 0.000 K 0.000 0.742 0.257 −0.307 −0.615 0.654 −0.311 0.000 K 0.000 0.555 0.763 −0.676 −0.621 0.733 −0.349 0.000 K 0.000 −1.356 0.108 0.418 0.492 −0.606 0.282 0.000 K 0.000 −1.524 0.141 0.485 0.498 −0.646 0.304 0.000
−3.937 −5.191 −4.010 −3.183 −1.738 −2.268 −5.294 −4.099
1.029 1.091 1.188 1.305 1.467 1.670 2.400 2.746
−3.521 −3.294 −2.466 −2.033 −1.045 −2.067 −5.615 −2.646
1.770 1.887 2.076 2.281 2.563 2.909 4.194 4.874
1.262 1.442 2.568 4.221 4.454 2.382 −1.490 2.809
2.969 3.197 3.478 3.896 4.367 4.876 7.194 8.376
−1.026 −2.114 −0.939 −0.257 0.849 −0.111 −3.579 0.312
4.657 4.939 5.442 6.013 6.777 7.868 12.017 13.318
−0.519 −1.851 −0.615 −0.549 −0.356 −0.669 0.757 −0.245
7.151 7.580 8.356 9.235 10.413 12.094 18.479 20.501
eq 8
eq 9
T = 284.35 K −0.285 0.000 0.282 0.391 0.487 0.482 −0.502 −0.551 −0.247 −0.270 0.378 0.422 −0.194 −0.218 0.099 0.000 T = 292.35K −0.371 0.000 0.255 0.402 0.840 0.837 −0.700 −0.765 −0.453 −0.485 0.603 0.663 −0.295 −0.327 0.146 0.000 T = 300.35 K −0.214 0.000 0.564 0.627 −0.415 −0.427 −0.067 −0.092 0.214 0.213 −0.093 −0.078 0.016 0.007 −0.007 0.000 T = 307.35 K 0.664 0.000 −1.125 −1.363 0.076 0.098 0.322 0.424 0.469 0.507 −0.541 −0.620 0.247 0.288 −0.134 0.000 T = 315.35 K 0.661 0.000 −1.131 −1.366 0.093 0.115 0.319 0.420 0.449 0.487 −0.526 −0.604 0.241 0.281 −0.130 0.000
eq 12 −2.979 −3.428 −2.437 −1.816 −0.613 −1.387 −4.652 −2.526 −2.012 −2.205 −0.478 −0.232 0.530 −1.057 −4.462 −0.743 −0.748 −0.192 0.095 1.904 2.030 −1.622 −3.139 0.731 0.599 −1.092 0.127 0.338 0.440 −0.563 0.276 −0.151 −0.552 −2.063 −0.958 −1.047 −1.035 −1.553 −0.321 −1.298
1.832 −0.254 0.703 0.467 0.303 −0.404 0.614 −0.366
a
x2 represents the mole fraction of tetrahydrofuran in the binary solvent. Standard uncertainties u are u(T) = 0.3 K, u(x1) = 0.0015, u(x2) = 0.0001, u(P) = 0.05 MPa. The relative standard uncertainties: ur(x1) = 0.02. E
DOI: 10.1021/acs.jced.7b00489 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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Table 6. Mole Fraction Solubility (x1) of Olaparib in Acetonitrile + Isopropyl Alcohol Binary Solvent Mixtures at the Temperature Range from (280.35 to 319.35) K under Pressure p = 0.1 MPaa 100RD x2
100x1
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
0.976 0.992 1.011 1.048 1.094 1.169 1.298 1.349
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
1.721 1.738 1.773 1.826 1.917 2.071 2.299 2.424
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
3.072 3.103 3.165 3.284 3.461 3.644 4.149 4.399
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
4.659 4.706 4.800 4.944 5.191 5.606 6.307 6.726
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
7.532 7.607 7.759 7.992 8.392 8.979 10.147 10.913
0.000 0.090 0.194 0.315 0.458 0.628 0.941 1.000
12.051 12.172 12.415 12.787 13.427 14.367 16.364 17.354
eq 8 T −0.256 0.458 −0.018 −0.061 −0.532 0.570 −0.444 0.274 T −0.433 0.614 0.473 −0.551 −0.874 1.084 −0.863 0.523 T −0.263 0.505 0.025 −0.412 −0.025 0.280 −0.277 0.167 T −0.483 0.697 0.507 −0.620 −0.935 1.181 −0.919 0.544 T −0.497 0.752 0.470 −0.710 −0.773 1.103 −0.878 0.512 T −0.341 0.508 0.340 −0.515 −0.509 0.745 −0.591 0.353
eq 9
100RD eq 12
100x1
= 280.35 K
= 288.35
= 296.35
= 303.35
= 311.35
= 319.35
0.000 0.573 −0.021 −0.128 −0.570 0.651 −0.517 0.000 K 0.000 0.821 0.473 −0.673 −0.949 1.235 −0.997 0.000 K 0.000 0.604 0.015 −0.466 −0.047 0.338 −0.330 0.000 K 0.000 0.922 0.504 −0.752 −1.013 1.342 −1.057 0.000 K 0.000 0.974 0.464 −0.838 −0.844 1.259 −1.012 0.000 K 0.000 0.661 0.335 −0.603 −0.559 0.852 −0.683 0.000
−4.235 −2.036 −2.004 −2.071 −2.532 −0.929 −4.575 −6.219
1.311 1.324 1.351 1.391 1.461 1.578 1.751 1.831
−3.590 −2.164 −2.119 −2.964 −2.880 −0.288 −4.011 −4.028
2.287 2.310 2.356 2.427 2.548 2.752 3.055 3.250
1.336 2.567 2.525 2.380 2.763 2.699 1.581 2.154
3.880 3.919 3.997 4.117 4.323 4.598 5.245 5.584
−1.155 −0.002 −0.116 −1.055 −1.084 1.302 −1.068 0.166
6.131 6.192 6.316 6.506 6.831 7.377 8.300 8.879
−1.134 −0.100 −0.293 −1.288 −1.373 0.016 −1.968 0.186
9.446 9.540 9.731 10.023 10.524 11.314 12.841 13.667
eq 8 T −0.358 0.496 0.413 −0.456 −0.753 0.919 −0.730 0.448 T −0.513 0.739 0.538 −0.651 −1.002 1.260 −1.004 0.598 T −0.342 0.531 0.312 −0.561 −0.398 0.676 −0.553 0.329 T −0.512 0.742 0.530 −0.656 −0.981 1.244 −0.968 0.570 T −0.409 0.599 0.419 −0.565 −0.713 0.954 −0.743 0.441
eq 9
eq 12
= 284.35 K
= 292.35
= 300.35
= 307.35
= 315.35
0.000 0.670 0.414 −0.559 −0.817 1.046 −0.844 0.000 K 0.000 0.981 0.536 −0.793 −1.087 1.435 −1.158 0.000 K 0.000 0.680 0.305 −0.646 −0.443 0.778 −0.642 0.000 K 0.000 0.979 0.527 −0.795 −1.062 1.413 −1.113 0.000 K 0.000 0.786 0.415 −0.674 −0.776 1.086 −0.857 0.000
−3.132 −1.642 −1.552 −2.361 −2.244 0.377 −3.301 −4.228 −2.012 −0.674 −0.674 −1.538 −1.486 1.026 −2.668 −1.741 −0.782 0.412 0.328 −0.585 −0.592 0.305 −0.678 0.363 1.968 3.027 2.877 1.940 1.884 4.162 1.843 3.375 −1.591 −0.610 −0.842 −1.868 −1.981 −0.155 −1.709 −0.580
0.261 1.169 0.905 −0.129 −0.265 1.033 −0.166 0.618
a
x2 represents the mole fraction of acetonitrile in the binary solvent. Standard uncertainties u are u(T) = 0.3 K, u(x1) = 0.0015, u(x2) = 0.0001, u(P) = 0.05 MPa. The relative standard uncertainties: ur(x1) = 0.02. F
DOI: 10.1021/acs.jced.7b00489 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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Table 7. Parameters of the Variant 1 of CNIBS/R-K Equation for Olaparib in the Binary Solvent T/K
Figure 5. Mole fraction solubility (x1) of olaparib versus temperature (T) in (tetrahydrofuran + MTBE) binary solvent mixtures: ■, x2 = 0; ●, x2 = 0.090; ▲, x2 = 0.194; ▼, x2 = 0.315; ◆, x2 = 0.458; ☆, x2 = 0.628; ◇, x2 = 0.941; ★, x2 = 1.
Equation 11 is obtained when N = 2 in eq 10 and substituting (1 − x2) into x3.
+
( −J0 + 3J1 − 5J2 )x 22
+
( −4J2 )x 24
T
+
(J0 − J1 + J2 )x 2
T ( −2J1 + 8J2 )x 23
T Equation 11 can be further simplified as21 ⎛ A ⎞ ⎛ A⎞ ln x = x1⎜A 0 + 1 ⎟ + x 2⎜A 2 + 3 ⎟ ⎝ ⎝ T⎠ T⎠ ⎡x x 2 ⎤ + ⎢ 1 2 ∑ Ji (x1 − x 2)i ⎥ ⎢⎣ T i = 0 ⎥⎦
B1
B2
B3
280.35 284.35 288.35 292.35 296.35 300.35 303.35 307.35 311.35 315.35 319.35 average MD =
−4.863 −4.574 −4.306 −4.030 −3.741 −3.515 −3.333 −3.073 −2.870 −2.644 −2.401
Tetrahydrofuran + MTBE 0.413 1.945 −3.643 0.434 2.057 −4.023 0.452 2.158 −4.360 0.468 2.318 −4.826 0.453 2.708 −5.666 0.592 1.966 −4.505 0.336 2.972 −5.652 0.868 −0.223 0.165 0.864 −0.184 0.094 0.857 −0.155 0.052 0.813 −0.132 −0.104
280.35 284.35 288.35 292.35 296.35 300.35 303.35 307.35 311.35 315.35 319.35 average MD =
0.022 0.274 0.547 0.832 1.125 1.359 1.544 1.818 2.024 2.250 2.493
Acetonitrile + Isopropyl Alcohol −0.102 1.009 −1.376 −0.112 1.412 −1.840 −0.139 1.680 −2.360 −0.183 1.964 −2.909 −0.117 1.826 −2.936 −0.118 1.674 −2.608 −0.169 1.889 −2.803 −0.185 1.991 −2.999 −0.193 2.107 −3.350 −0.137 1.722 −2.560 −0.107 1.566 −2.323
B4
MD
2.248 2.509 2.740 3.047 3.527 2.982 3.382 0.249 0.287 0.308 0.370
0.151 0.309 0.474 0.458 0.388 0.199 0.489 0.447 0.442 0.444 0.487 0.390
0.667 0.852 1.152 1.469 1.582 1.408 1.440 1.553 1.796 1.336 1.222
0.326 0.572 0.677 0.788 0.244 0.463 0.736 0.775 0.712 0.605 0.488 0.581
where A0, A1, A2, A3, and Ji terms are the model constants and are listed in Table 9. Experimental solubility data of olaparib were bound up with eq 8, eq 9 and eq 12. The calculated solubility data (xcal 1 ) from these models are listed in Table 5 and Table 6. From the data listed in Tables 7−9, the average MD values of two variants of the CNIBS/R-K model and Jouyban−Acree model in (tetrahydrofuran + MTBE) are 0.390, 0.363, and 1.581 and in (acetonitrile + isopropyl alcohol) are 0.581, 0.550, and 1.730. So (tetrahydrofuran + MTBE) may be a better system than (acetonitrile + isopropyl alcohol). The results show that the experimental data are in good agreement with the calculated results of the three equations. In contrast, CNIBS/RK equations have lower MD. The CNIBS/R-K model can only be used to predict the solubility of mixed solvents of different components at fixed temperatures. However, when the temperature and composition need to be considered together, the Jouyban−Acree model can be used, supplemented by the modified Apelblat equation and the CNIBS/R-K model.
Figure 6. Mole fraction solubility (x1) of olaparib versus temperature (T) in (acetonitrile + isopropyl alcohol) binary solvent mixtures: ■, x2 = 0; ●, x2 = 0.090; △, x2 = 0.194; ▼, x2 = 0.315; ▲, x2 = 0.458; ○, x2 = 0.628; ⧫, x2 = 0.941; ★, x2 = 1.
ln x1 = ln(x1)3 + (ln(x1)2 − ln(x1)3 )x 2 +
B0
4. CONCLUSIONS This paper provides new research data for the solubility of olaparib in four monosolvents and (tetrahydrofuran + MTBE, acetonitrile + isopropyl alcohol) binary solvent mixtures at a temperature range from 280.35 to 319.35 K. The solubility is positively correlated with temperature according to the experimental data for a given solvent. The solubility values of olaparib in monosolvents comply with the following order: tetrahydrofuran > acetonitrile > isopropyl alcohol > MTBE. The solubility of olaparib in (tetrahydrofuran + MTBE, acetonitrile + isopropyl alcohol) binary solvent mixtures is
T (11)
(12) G
DOI: 10.1021/acs.jced.7b00489 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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positively correlated with the temperature, and the content of tetrahydrofuran and acetonitrile at constant temperature. In addition, the solubility data could be correlated well with the modified Apelblat equation, the Buchowski−Ksiazaczak λh equation, the CNIBS/R-K model, and Jouyban−Acree model, but the modified Apelblat equation and CNIBS/R-K equation were more accurate. The (tetrahydrofuran + MTBE) mixture may be a great recrystallization system.
Table 8. Parameters of the Variant 2 of CNIBS/R-K Equation for Olaparib in the Binary Solventa T/K 280.35 284.35 288.35 292.35 296.35 300.35 303.35 307.35 311.35 315.35 319.35 average MD = 280.35 284.35 288.35 292.35 296.35 300.35 303.35 307.35 311.35 315.35 319.35 average MD = a
S0
S1
Tetrahydrofuran + MTBE −0.414 −0.430 −0.410 −0.514 −0.407 −0.587 −0.407 −0.655 −0.375 −0.717 −0.423 −0.737 −0.406 −0.579 −0.471 −0.300 −0.471 −0.303 −0.472 −0.303 −0.481 −0.284
S2
MD
−0.565 −0.627 −0.682 −0.763 −0.879 −0.736 −0.846 −0.073 −0.083 −0.088 −0.105
0.144 0.292 0.443 0.435 0.361 0.180 0.462 0.413 0.408 0.409 0.450 0.363
Acetonitrile + Isopropyl Alcohol −0.113 −0.030 −0.179 −0.143 −0.031 −0.237 −0.157 −0.016 −0.315 −0.171 −0.065 −0.398 −0.188 −0.132 −0.398 −0.227 −0.134 −0.366 −0.205 −0.085 −0.387 −0.210 −0.103 −0.417 −0.225 −0.167 −0.473 −0.220 −0.094 −0.355 −0.220 −0.092 −0.322
■
*Tel: +86-25-58139393. Fax: +86-25-58139393. E-mail:
[email protected]. ORCID
Wenge Yang: 0000-0002-2501-3532 Funding
This research work was financially supported by National Key Research & Development (R&D) plan, 2016YFD0201000.
0.307 0.544 0.643 0.749 0.225 0.437 0.699 0.736 0.674 0.574 0.462 0.550
Notes
The authors declare no competing financial interest.
■
Table 9. Parameters of the Jouyban−Acree Equation for Olaparib in the Binary Solvent
280.35 284.35 288.35 292.35 296.35 300.35 303.35 307.35 311.35 315.35 319.35 average MD = 280.35 284.35 288.35 292.35 296.35 300.35 303.35 307.35 311.35 315.35 319.35 average MD =
MD Ttetrahydrofuran + MTBE 3.215 A0 2.480 A1 2.536 A2 1.465 A3 2.379 J0 1.308 J1 1.148 J2 0.448 0.695 1.103 0.618 1.581 Acetonitrile + Isopropyl Alcohol 3.775 A0 2.355 A1 2.755 A2 1.477 A3 2.251 J0 0.506 J1 0.743 J2 2.635 0.795 1.167 0.568 1.730
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0.95 level of confidence.
T/K
AUTHOR INFORMATION
Corresponding Author
Parameters −5538.61 14.93 1.83 −326.29 88.70 −240.50 236.85
−5668.73 15.63 0.49 −198.28 549.58 −830.04 436.11
H
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I
DOI: 10.1021/acs.jced.7b00489 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
