Article pubs.acs.org/jced
Measurement and Correlation of Solubility of Loratadine in Different Pure Solvents and Binary Mixtures Xiujuan Yang,† Shui Wang,† and Jidong Wang*,† †
Beijing Key Laboratory of Membrane Science and Technology, College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China S Supporting Information *
ABSTRACT: The solubility of loratadine in pure solvents and binary mixed solvents is measured at the temperature range from 283.15 to 323.15 K using a laser technique. The results indicate that the solubility of loratadine increases with the increasing temperature in all these selected solvents. The solubility of loratadine reaches the maximum value when the mole fraction of methanol is 0.7 in the binary solvent mixtures of methanol + acetonitrile. Also, in the system of n-pentanol + acetonitrile mixed solvent the solubility reaches the maximum value when the mole fraction of n-pentanol is 0.6. The modified Apelblat equation and three parameters van’t Hoff equation are applied to correlate the experimental solubility in pure solvents. In binary mixed solvents, the modified Apelblat equation and Jouyban-Acree model are used to correlate the solubility data.
1. INTRODUCTION Loratadine is a white crystalline powder with its chemical name ethyl 4-(8-chloro-5,6-dihydro-11H-benzo [5,6]-cyclohepta [1,2-b] pyridin-11-ylidine)-1-piperidine carboxylate. The chemical structure is shown in Figure 1. Loratadine is one of a group of
2. EXPERIMENTAL SECTION Materials. Loratadine (purity >0.995), which used without purification in the experiments, was purchased from Yichang Yongnuo Pharmaceutical Co., Ltd. All the solvents used in the experiments are analytical grade. The detailed information is listed in Table 1. Table 1. Sources and Purity of the Materials materials
Figure 1. Chemical structure of loratadine.
second-generation antihistamines which is a long-acting tricyclic antihistamine with selective peripheral histamine H1-receptor antagonistic activity.1 In industry, the crystallization process is very important in the purification step, so it is necessary to know the solubility of loratadine in common solvents. But the lack of solubility data for loratadine hinders the design and optimization of crystallization process and crystallizer. Therefore, it is essential to do some research and acquire such information. In this work, the solubility of loratadine in different pure solvents and two binary solvent mixtures from about T = 283.15− 323.15 K is presented. Moreover, different models are used to correlate experimental data and some thermodynamic functions are calculated. © XXXX American Chemical Society
mass fraction purity (%)
loratadine
≥99.5
methanol ethanol i-propanol n-propanol n-butanol n-pentanol acetonitrile
≥99.5 ≥99.7 ≥99.5 ≥99.5 ≥99.5 ≥99.5 ≥99.5
acetone ethyl acetate DMF
≥99.5 ≥99.5 ≥99.5
sources Yichang Yongnuo Pharmaceutical Co., Ltd. Beijing Chemical Works Beijing Chemical Works Beijing Chemical Works Beijing HWRK Chemical Co., Ltd. Beijing Chemical Works Beijing HWRK Chemical Co., Ltd. Tianjin Fuchen Chemical Reagents Factory Beijing Chemical Works Beijing Chemical Works Beijing Chemical Works
Apparatus and Procedures. The solubility of a solid was measured by laser technique at atmospheric pressure. A laser generator, a photoelectric transformer, and a light-intensity display constitute this laser monitoring observation system which Received: August 11, 2016 Accepted: December 21, 2016
A
DOI: 10.1021/acs.jced.6b00721 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Table 2. Experimental and Correlated Mole Fraction Solubility of Loratadine in Different Pure Solvents (0.1 MPa)a ABC T/K
3 exp
10 x
283.14 288.15 293.15 298.14 303.15 308.15 313.15 318.75 323.20
15.35 19.60 25.45 33.89 45.48 59.83 77.26 98.38 117.8
283.15 288.45 293.44 298.15 303.15 308.15 313.54 318.37 323.15
11.90 15.05 18.57 23.19 29.17 37.63 48.95 63.60 81.96
283.17 288.15 293.16 298.15 303.15 308.15 313.14 318.20 323.15
6.879 8.787 11.31 15.18 20.52 27.37 35.98 48.30 66.87
283.16 288.12 293.15 298.17 303.15 308.16 313.13 318.15 323.17
18.06 23.87 31.08 38.79 47.39 57.80 72.48 91.19 111.92
283.15 288.13 293.15 298.17 303.15 308.15 313.15 318.12 323.15
21.31 26.88 33.27 41.60 52.50 65.34 79.77 96.15 115.5
3 cal
10 x
ABC
abc RD%
Methanol 13.79 10.15 19.21 2.02 26.21 −3.00 35.08 −3.50 46.17 −1.51 59.74 0.15 76.08 1.53 98.00 0.39 118.3 −0.50 Ethanol 12.00 −0.86 14.96 0.63 18.61 −0.20 23.08 0.48 29.27 −0.33 37.44 0.50 49.26 −0.62 63.43 0.26 81.98 −0.03 i-Propanol 6.920 −0.60 8.901 −1.30 11.58 −2.41 15.20 −0.11 20.13 1.92 26.86 1.85 36.09 −0.31 49.02 −1.49 66.54 0.50 n-Propanol 19.04 −5.42 23.97 −0.41 30.17 2.95 37.84 2.46 47.23 0.34 58.87 −1.85 73.03 −0.76 90.55 0.70 111.96 −0.04 n-Butanol 20.76 2.59 26.58 1.13 33.73 −1.39 42.39 −1.89 52.67 −0.34 64.93 0.63 79.36 0.52 96.10 0.05 115.8 −0.19
3 cal
10 x
T/K
RD%
3 exp
10 x
13.78 19.22 26.24 35.10 46.18 59.72 76.03 97.96 118.4
10.20 1.94 −3.11 −3.58 −1.54 0.18 1.59 0.43 −0.54
283.12 288.15 293.13 298.15 303.15 308.13 313.15 318.17 323.15
22.45 28.55 35.76 44.67 55.95 68.30 82.72 102.21 122.21
12.06 14.96 18.58 23.04 29.24 37.44 49.29 63.48 81.95
−1.31 0.62 −0.04 0.65 −0.23 0.50 −0.69 0.19 0.01
283.20 288.25 293.15 298.15 303.15 308.75 313.15 318.15 323.19
3.001 3.843 4.769 5.847 7.475 9.567 12.09 15.56 20.50
6.951 8.902 11.56 15.17 20.10 26.86 36.12 49.06 66.51
−1.06 −1.32 −2.24 0.07 2.03 1.85 −0.38 −1.56 0.54
283.15 288.13 293.15 298.15 303.15 308.15 313.15 318.17 323.15
12.70 15.36 18.76 22.91 28.03 34.88 43.79 55.08 68.91
19.05 23.96 30.15 37.82 47.23 58.88 73.06 90.57 111.94
−5.46 −0.37 3.00 2.50 0.35 −1.87 −0.79 0.68 −0.02
283.15 288.15 293.15 298.15 303.12 308.15 313.15 318.15 323.20
17.55 20.81 24.65 29.33 35.63 43.02 52.32 63.41 77.05
20.76 26.58 33.74 42.40 52.67 64.92 79.34 96.09 115.8
2.57 1.10 −1.42 −1.91 −0.33 0.64 0.54 0.06 −0.20
283.11 288.15 293.15 298.15 303.15 308.19 313.15 318.17 323.15
20.89 26.04 31.20 38.87 47.37 56.63 68.40 82.52 99.91
3 cal
10 x
abc RD%
n-Pentanol 22.44 0.04 28.51 0.11 35. 85 −0.25 44.80 −0.31 55.53 0.76 68.27 0.05 83.51 −0.96 101.49 0.70 122.41 −0.16 Acetonitrile 3.121 −4.01 3.811 0.83 4.683 1.82 5.844 0.04 7.371 1.39 9.670 −1.08 12.06 0.18 15.63 −0.45 20.46 0.21 Acetone 12.70 −0.03 15.33 0.23 18.67 0.48 22.88 0.13 28.22 −0.69 35.02 −0.42 43.70 0.20 54.85 0.42 69.04 −0.19 Ethyl Acetate 17.42 0.73 20.71 0.51 24.73 −0.31 29.64 −1.06 35.62 0.03 43.05 −0.08 52.13 0.36 63.29 0.20 77.18 −0.17 DMF 21.10 −1.02 25.88 0.59 31.61 −1.34 38.51 0.92 46.80 1.21 56.82 −0.34 68.61 −0.31 82.84 −0.39 99.65 0.26
3 cal
10 x
RD%
22.44 28.52 35.85 44.80 55.53 68.27 83.51 101.49 122.41
0.04 0.11 −0.25 −0.31 0.76 0.05 −0.96 0.70 −0.16
3.133 3.810 4.674 5.833 7.363 9.672 12.07 15.65 20.45
−4.41 0.86 2.00 0.23 1.49 −1.10 0.10 −0.53 0.26
12.73 15.33 18.64 22.85 28.20 35.02 43.73 54.88 69.01
−0.36 0.22 0.60 0.27 −0.61 −0.42 0.14 0.37 −0.15
17.46 20.71 24.70 29.61 35.60 43.05 52.15 63.31 77.16
0.49 0.50 −0.22 −0.96 0.08 −0.09 0.32 0.16 −0.14
21.12 25.88 31.60 38.50 46.80 56.83 68.63 82.86 99.63
−1.08 0.61 −1.29 0.95 1.22 −0.35 −0.34 −0.41 0.28
a
ABC is the modified Apelblat equation. abc refers to three-parameter Van’t Hoff equation. xexp is experimental solubility data of loratadine. xcal represents the calculated solubility data of loratadine. RD refers to the corresponding relative deviation. The standard uncertainties are u(T) = 0.05 K, u(P) = 5 KPa. The relative standard uncertainty u is ur(x) = 0.05.
has already been described in other literature.2 The apparatuses consisted of a jacketed glass vessel, a constant-temperature bath with a thermoelectric controller (type 501, china), a mercuryin-glass thermometer, and a magnetic stirrer. The constanttemperature bath was used to help the jacketed glass vessel maintain a desired temperature with circulating water. The magnetic
stirrer provided continuous stirring to mix the solution. The mercury-in-glass thermometer was always inserted into the glass vessel to measure the temperature of the solution with uncertainty of ±0.05 K. The detailed procedure of solubility measurement was just like the introduction in the literature.3 First, a specified amount of loratadine and solvent were placed in B
DOI: 10.1021/acs.jced.6b00721 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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the glass vessel. When the solute dissolved completely under the action of stirring, the laser intensity reached the maximum. A small amount of solute was added into the vessel to see if the laser intensity returned to the maximum within a certain amount of time (usually 30 min). This procedure was repeated until the laser intensity could not return to the maximum, which meant loratadine did not dissolve completely. So the solubility range was determined. The measurement experiment should be conducted three times for a more accurate result. The solute and solvents were both weighed by an electric analytical balance (Sartorious CP224S, Germany) with accuracy of ±0.0001 g. The same solubility experiment was conducted three times and the mean value was used to calculate the mole fraction solubility x1 based on eq 1. The initial mole fraction concentration of binary mixed solvent x2 was calculated by eq 2. Figure 2. Solubility of loratadine in different pure solvents. ■, acetonitrile; ▼, i-propanol; ☆, acetone; ⧫, ethanol; ●, ethyl acetate; △, DMF; ▲, methanol; □, n-propanol; ◊, n-butanol; ★, n-pentanol.
x1 =
mA MA mA MA
n
+ ∑i = 2
mi Mi
(1)
Table 3. Mole Fraction Solubility of Loratadine in Methanol (2) + Acetonitrile (3) Binary Solvent Mixtures (0.1 MPa)a RD% T/K 283.20 288.25 293.15 298.15 303.15 308.75 313.15 318.15 323.19 283.15 288.15 293.15 298.15 303.15 308.35 313.15 318.15 323.16 283.15 288.15 293.20 298.15 303.15 308.20 313.15 318.17 323.15 283.15 288.20 293.15 298.15 303.15 308.19 313.15
103xexp x2 3.001 3.843 4.769 5.847 7.475 9.567 12.09 15.56 20.50 x2 6.064 7.383 8.973 11.04 14.07 18.18 23.10 30.14 40.83 x2 10.46 12.80 15.75 19.43 24.38 31.31 40.43 52.22 68.63 x2 15.48 19.19 23.47 29.98 37.86 48.77 62.13
eq 3
RD% T/K
eq 9
103xexp
eq 3
eq 9
1.19 −0.19 −1.78 −1.16 0.47 0.96 1.35 0.61 −1.51
3.43 1.79 −0.14 −0.05 0.94 0.70 0.27 −1.42 −4.63
2.33 −1.22 −2.57 −1.57 0.67 1.68 1.93 1.07 −2.48
0.18 −0.88 −0.66 0.93 2.88 2.78 1.34 −2.12 −9.13
1.64 −1.32 −1.15 −0.81 0.16 0.91 1.51 0.49 −1.48
3.63 1.41 1.62 1.41 1.25 0.36 −1.18 −4.92 −10.29
2.18 −1.71 −1.64 −1.24 0.18 1.99 1.61
7.63 2.62 1.14 −0.25 −0.81 −1.13 −3.90
x2 = 0.4005
= 0.0000 −1.85 1.64 1.75 −0.60 0.51 −1.91 −0.34 −0.38 1.11
−1.23 3.30 4.02 1.97 2.90 −0.05 0.74 −0.47 −0.45
283.15 288.55 293.15 298.15 303.15 308.15 313.13 318.15 323.15
20.99 26.20 31.48 39.26 49.39 61.34 75.90 92.85 111.8
−0.65 0.80 0.30 −0.59 0.41 0.43 −0.55 −0.11 0.93
−2.93 −3.30 −4.91 −6.16 −4.71 −3.56 −2.94 −1.27 3.42
283.15 288.13 293.15 298.14 303.15 308.40 313.15 318.25 323.15
24.46 30.49 38.39 48.76 62.01 77.75 93.78 112.2 128.5
−0.45 0.51 0.50 −0.21 −0.63 −0.06 0.49 −0.25 0.09
−0.92 −1.27 −1.86 −2.45 −2.07 −0.06 2.41 4.13 7.28
283.13 288.12 293.15 298.15 303.15 308.15 313.15 318.15 323.15
28.14 35.06 44.52 55.82 69.55 85.47 103.7 122.6 142.1
1.00 0.19 −2.02 −0.49 −0.50 0.98 1.39
−1.54 −1.49 −2.71 −0.01 1.27 4.10 5.95
283.15 288.15 293.14 298.15 303.15 308.15 313.17
30.33 37.15 46.72 58.26 72.51 89.62 107.3
x2 = 0.5020
= 0.1002
x2 = 0.5999
= 0.2000
x2 = 0.6989
= 0.3055
C
DOI: 10.1021/acs.jced.6b00721 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
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Table 3. continued RD% 3 exp
T/K
10 x
eq 3
RD% 3 exp
T/K
eq 9
10 x
318.15 323.15
79.10 97.89
283.15 288.13 293.15 298.17 303.15 308.21 313.15 318.20 323.15
28.52 35.36 44.82 57.08 72.29 90.19 108.3 127.4 146.7
283.18 288.12 293.15 298.15 303.12 308.15 313.15 318.15 323.15
21.81 29.01 38.44 50.02 64.78 82.55 100.5 119.6 139.7
eq 3
eq 9
0.14 −1.62
−8.07 −12.85
3.07 −1.51 −3.61 −2.13 0.80 2.50 3.12 0.24 −2.75
−2.41 −9.02 −11.60 −8.97 −3.62 1.37 6.06 8.78 11.03
x2 = 0.6989
x2 = 0.3055 1.28 −1.91
7.39 6.06
318.15 323.15
125.6 145.4
2.67 −1.75 −2.67 −1.50 0.66 2.33 1.90 0.29 −2.08
7.46 2.32 0.35 0.27 1.11 1.36 −0.56 −3.88 −8.14
283.14 288.15 293.15 298.14 303.15 308.15 313.15 318.75 323.20
15.35 19.60 25.45 33.89 45.48 59.83 77.26 98.38 117.8
1.49 −0.71 −1.44 −1.54 0.17 1.96 1.23 0.09 −1.32
−1.43 −1.27 −0.13 1.08 3.53 5.61 4.84 3.29 1.09
x2 = 0.7994
x2 = 1.000
x2 = 0.8993
a
Equation 3 pertains to the modified Apelblat equation. Equation 9 refers to the Jouyban-Acree model. xexp is experimental solubility data of loratadine. x2 represents the initial mole fraction of methanol in binary methanol (2) + acetonitrile (3). RD refers to the corresponding relative deviation. The standard uncertainties are u(T) = 0.05 K, u(P) = 5 KPa. The relative standard uncertainty u is ur(x) = 0.05. The relative standard uncertainty u is ur(x2) = 0.05.
x2 =
m2 M2 m2 M2
+
m3 M3
Jouyban-Acree Model. The Jouyban-Acree model7 describes the solubility of a solute not only with the temperature but also with the initial composition of binary solvent mixtures,8 which is represented by
(2)
In eq 1, mA and mi represent the mass of the solute loratadine and the solvents, respectively. MA and Mi are the molecular mass of loratadine and the solvents, respectively. In this work, n = 2 means that it is in pure solvent while n = 3 means that it is in binary mixed solvent. In eq 2, 2 and 3 represent two different solvents. M and m stand for the molecular mass and mass of the solvents, respectively.
N
ln x1 = x 2 ln(x1)2 + x3 ln(x1)3 + x 2x3 ∑ i=0
ln(x1)2 = a1 +
b1 + c1 ln T T
ln(x1)3 = a 2 +
(5)
b2 + c 2 ln T T
(6)
(7)
In binary solvent mixtures, N is equivalent to 2 and x3 can be replaced by (1 − x2). Then a new equation used in binary solvent mixtures can be obtained
where x1 is the mole fraction solubility of solute at the temperature T and A, B, and C are model parameters. Three-Parameter Van’t Hoff Equation. The relationship between solubility and absolute temperature is often correlated by van’t Hoff equation.6 So the three-parameter van’t Hoff equation is introduced to correlate the nature logarithm of mole fraction solubility x1 against the absolute temperature T, just as the following equation shows b c + 2 T T
(x 2 − x3)i
in which T is the absolute temperature and (x1)i represents the saturated mole fraction solubility of solute in pure solvent i. Meanwhile, N is equal to 0, 1, 2, 3 and Ji is the model constant. The modified Apelblat equation can be used to determine x2 and x3, represented by
3. THERMODYNAMIC MODELS Modified Apelblat Equation. The modified Apelblat equation is a semiempirical model and deduced from the Clausius− Clapeyron equation, which is widely used to correlate the mole fraction solubility against temperature.4,5 It is described as eq 3 B ln x1 = A + + C ln(T /K ) (3) T /K
ln x1 = a +
Ji T
b1 x + c1 ln T + (a1 − a 2)x 2 + (b1 − b2 + J0 − J1 + J2 ) 2 T T x 22 x 23 x 24 + (3J1 − J0 − 5J2 ) + (8J2 − 2J1) + (− 4J2 ) T T T
ln x1 = a1 +
+ (c1 − c 2)x 2 ln T
(8)
By introducing a constant term to eq 8, it can be further simplified as ln x1 = A1 +
(4)
A2 x x2 x3 x4 + A3 ln T + A4 x 2 + A5 2 + A 6 2 + A 7 2 + A8 2 T T T T T
+ A 9x 2 ln T
where a, b, and c are model parameters. D
(9) DOI: 10.1021/acs.jced.6b00721 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Table 4. Mole Fraction Solubility of Loratadine in n-Pentanol (2) + Acetonitrile (3) Binary Solvent Mixtures (0.1 MPa)a RD% T/K
3 exp
10 x
eq 3
RD% T/K
eq 9
3 exp
10 x
283.20 288.25 293.15 298.15 303.15 308.75 313.15 318.15 323.19
3.001 3.843 4.769 5.847 7.475 9.567 12.09 15.56 20.50
283.16 288.18 293.15 298.18 303.16 308.13 313.15 318.18 323.15
11.51 13.85 16.97 20.76 25.83 31.93 40.92 53.69 69.28
283.16 288.15 293.15 298.14 303.13 308.15 313.16 318.15 323.15
24.95 28.61 34.54 41.19 49.55 60.34 73.07 88.06 105.99
283.15 288.17 293.13 298.15 303.18 308.19 313.15 318.15 323.17
37.67 44.02 50.99 59.88 70.27 81.79 96.11 112.26 130.28
283.15 288.13 293.18 298.15 303.16 308.15 313.12 318.17 323.15
47.45 56.11 64.88 74.86 86.79 100.48 116.18 133.27 151.77
283.18 288.17 293.17 298.15 303.12 308.15 313.15 318.15
39.48 47.08 55.05 64.44 74.95 88.07 103.79 121.11
eq 3
eq 9
−0.63 1.09 0.18 −0.66 −0.32 0.03 0.31 0.10 −0.11
5.54 5.69 3.11 0.29 −1.60 −3.70 −6.10 −9.27 −12.74
0.49 −0.25 −0.23 −0.78 −0.11 0.78 0.48 0.21 −0.60
10.52 8.43 6.61 3.85 1.89 −0.22 −3.93 −8.02 −13.21
0.24 0.19 −0.40 −0.63 −0.05 0.21 0.76 0.31 −0.64
11.21 9.24 6.65 4.23 2.45 0.28 −1.75 −4.92 −8.81
−0.28 0.51 0.04 −0.23 −0.15 −0.13 −0.01 0.56 −0.31
8.39 7.31 4.97 2.72 0.71 −1.41 −3.56 −5.30 −8.66
0.02 0.10 −0.25 −0.30 0.77 0.06 −0.95 0.70 −0.17
−26.30 −16.71 −9.18 −2.48 4.26 8.36 11.58 16.47 18.64
x2 = 0.3997
x2 = 0.0000 −1.85 1.64 1.75 −0.60 0.51 −1.91 −0.34 −0.38 1.11
−10.60 −6.56 −5.52 −6.46 −3.16 −2.64 1.64 5.00 10.05
283.15 288.15 293.13 298.17 303.15 308.15 313.13 318.12 323.18
47.01 55.19 63.06 72.19 83.45 96.48 111.35 127.84 146.99
−0.60 −0.02 1.08 0.45 0.38 −1.42 −0.96 0.80 0.26
−3.14 −3.22 −1.51 −0.41 2.26 4.17 9.01 15.48 20.25
283.15 288.16 293.17 298.18 303.15 308.15 313.15 318.13 323.14
53.52 61.18 70.29 80.11 92.11 106.01 120.30 136.21 153.20
1.40 −1.71 −0.22 −0.39 −0.15 0.82 0.89 0.23 −0.90
−0.62 −4.06 −2.53 −2.45 −1.71 −0.02 0.95 1.37 1.51
283.15 288.17 293.15 298.15 303.17 308.12 313.15 318.13 323.16
55.63 63.58 72.21 82.36 94.75 108.45 124.74 141.83 160.64
0.15 0.17 −0.54 −0.10 0.22 −0.25 0.42 0.34 −0.42
1.87 1.07 −0.63 −1.39 −2.46 −4.50 −5.53 −7.51 −10.43
283.15 288.15 293.18 298.15 303.17 308.11 313.15 318.15 323.15
54.14 62.40 71.10 81.03 92.81 105.99 121.47 139.67 158.24
−0.43 0.87 0.02 −0.49 −0.36 −0.04 0.48 0.24 −0.29
−0.24 1.23 0.23 −0.75 −1.39 −2.11 −2.89 −4.73 −7.13
283.12 288.15 293.13 298.15 303.15 308.13 313.15 318.17 323.15
22.45 28.55 35.76 44.67 55.95 68.30 82.72 102.21 122.21
−0.56 0.78 0.25 0.03 −0.67 −0.40 0.44 0.30
−4.09 −1.90 −1.74 −1.36 −1.55 −0.84 0.37 0.52
x2 = 0.0998
x2 = 0.4983
x2 = 0.2006
x2 = 0.5999
x2 = 0.2996
x2 = 0.7005
x2 = 0.7989
x2 = 1.0000
x2 = 0.8975
E
DOI: 10.1021/acs.jced.6b00721 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Table 4. continued RD% 3 exp
T/K
10 x
eq 3
RD% T/K
eq 9
3 exp
10 x
eq 3
eq 9
x2 = 0.8975 323.15
140.59
−0.18
0.26
a
Equation 3 pertains to the modified Apelblat equation. Equation 9 refers to the Jouyban-Acree model. xexp is experimental solubility data of loratadine. x2 represents the initial mole fraction of methanol in binary methanol (2) + acetonitrile (3). RD refers to the corresponding relative deviation. The standard uncertainties are u(T) = 0.05 K, u(P) = 5 KPa. The relative standard uncertainty u is ur(x) = 0.05. The relative standard uncertainty u is ur(x2) = 0.05.
Solubility of Loratadine in Binary Mixed Solvents. The solubility data of loratadine in methanol + acetonitrile and n-pentanol + acetonitrile binary solvent mixtures are separately shown in Tables 3 and 4. The solubility curves of loratadine in these two binary mixed solvents are shown in Figures 3 and 4, respectively. From Figures 3 and 4, we can learn that the
While using this model, every term has corresponding P value. The associated P value indicates the importance of every term. If the P value is smaller than the significance level α, which is often 0.05,9 we take this term as statistically significant and cannot be ignored. However, while the P value is larger than the significance level, it means this term is unimportant and can be removed from the model. The parameters and the associated P values are obtained by the linear regression. According to the above statements, calculating process may need to be repeated until all associated P values of the final equation are smaller than 0.05.10
4. RESULTS AND DISCUSSION Solubility of Loratadine in Pure Solvents. The measured solubility data of loratadine in 10 pure solvents (methanol, ethanol, i-propanol, n-propanol, n-butanol, n-pentanol, acetonitrile, acetone, ethyl acetate, and DMF) at different temperature from 283.15 to 323.15 K are listed in Table 2 and graphically shown in Figure 2. From Figure 2, it can be learned that the solubility of loratadine in all of the solvents increases with the increase of temperature. And the solubility order is n-pentanol > n-butanol, methanol > n-propanol > DMF > ethanol, ethyl acetate > acetone > i-propanol > acetonitrile. The modified Apelblat equation and three-parameter van’t Hoff equation are used to correlate the solubility of loratadine in pure solvents. Three kinds of deviations are applied to evaluate the applicability of the models. The relative deviation (RD) between the experimental values (xexp) and calculated values (xcal) is calculated according to eq 10 RD =
x exp − x cal x exp
Figure 3. Solubility of loratadine (1) in methanol (2) + acetonitrile (3) binary solvent mixtures depending on temperature T and the mole fraction of methanol (x2). ○, 0.0000; ▽, 0.1002; □, 0.2000; △, 0.3055; ⧫, 0.4005; ■, 0.5020; ●, 0.5999; ▲, 0.6989; ★, 0.7994; ◊, 0.8993; ▼, 1.000.
(10)
The root-mean-square deviation (RMSD) and the average relative deviation (ARD%) are defined respectively as the following equations N
RMSD =
ARD% =
∑i = 1 (xiexp − xical)2
100 N
N
∑ i=1
N
(11)
xiexp − xical xiexp
(12)
where N refers to the number of experimental points, and xiexp and xical represent the experimental and calculated solubility values, respectively. The calculated solubility of loratadine is also listed in Table 2. The regressed parameters of the modified Apelblat equation and three-parameter van’t Hoff equation together with ARD% and RMSD are all listed in Tables S1 and S2 in the Supporting Information. It can be found that both the two models have satisfied results in correlating the solubility of loratadine in pure solvents from Tables S1 and S2.
Figure 4. Solubility of loratadine (1) in n-pentanol (2) + acetonitrile (3) binary solvent mixtures depending on temperature T and the mole fraction of n-pentanol (x2). ●, 0.0000; ▲, 0.0998; ■, 0.2006; ⧫, 0.2996; ▼, 0.3997; ○, 0.4983; △, 0.5999; □, 0.7005; ▽, 0.7989; ◊, 0.8975; ★, 1.000. F
DOI: 10.1021/acs.jced.6b00721 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
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solubility of loratadine in binary mixed solvents increases as the temperature increases. It can be found that the solubility of loratadine increases first and then decreases with the increasing mole fraction of methanol or n-pentanol separately in these two different binary solvent mixtures. The solubility in methanol + acetonitrile binary solvent mixtures reaches maximum value when the mole fraction of methanol is 0.7 and the solubility in n-pentanol + acetonitrile binary solvent mixtures reaches maximum value when the mole fraction of n-pentanol is 0.6. The modified Apelblat equation and Jouyban-Acree model are applied to correlate the solubility in binary solvent mixtures and the parameters are given in Tables S3−S6 in the Supporting Information. Also, ARD% and RMSD are used to evaluate the applicability of the models and their values are given in the corresponding parameter tables. We can find that both the two models fit well to the experimental solubility data in binary solvent mixtures from Tables S3−S6. In these two binary solvent systems, the solubility as a function of temperature is correlated better with the modified Apelblat equation. Moreover, the Jouyban-Acree model shows better correlation as a function of solvent composition in methanol + acetonitrile mixed solvent system than in n-pentanol + acetonitrile mixed solvent. While using Jouyban-Acree model, the solubility in n-pentanol + acetonitrile mixed solvent need to repeat the calculating process to get the right P values and appropriate parameters. The number of the parameters were reduced from nine to eight.
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5. CONCLUSION In this work, the solubility of loratadine in different pure solvents and binary mixed solvents of acetonitrile + (methanol, n-pentanol) is measured by a synthetic method from T = 283.15 to 323.15 K at atmosphere pressure (P = 0.1 MPa). The solubility of loratadine increases with the increasing temperature in all these selected solvents. In binary solvent mixtures, the experimental data indicates that the solubility increases first and then decreases with the increasing x2 but the maximum values appear at different value in different systems. In pure solvents, the modified Apelblat equation and threeparameter van’t Hoff equation investigate the dependency of the solubility on absolute temperature. Moreover, both the two models have satisfactory correlation results. The modified Apelblat equation and the Jouyban-Acree model are used to correlate the solubility data in binary mixed solvents. However, the modified Apelblat equation has better correlation results.
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Article
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.6b00721. Parameters of different models used in different systems (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Jidong Wang: 0000-0003-1726-4064 Author Contributions
All authors contributed equally. Notes
The authors declare no competing financial interest. G
DOI: 10.1021/acs.jced.6b00721 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
