Measurement and Correlation of Solubility and Thermodynamic

Article pubs.acs.org/jced

Cite This: J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Measurement and Correlation of Solubility and Thermodynamic Properties of Vinpocetine in Nine Pure Solvents and (Ethanol + Water) Binary Solvent Zengrui Yu,†,‡ Yongli Wang,†,‡ Manli Zhu,†,‡ and Lina Zhou*,†,‡ †

School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, China ‡ National Industrial Crystallization Engineering Technology Research Center, Tianjin 300072, China

J. Chem. Eng. Data Downloaded from pubs.acs.org by RICE UNIV on 12/31/18. For personal use only.

S Supporting Information *

ABSTRACT: The solid−liquid equilibrium data of vinpocetine in nine pure solvents and ethanol−water binary system at temperatures ranging from 283.15 to 323.15 K was experimentally measured by gravimetric method under atmospheric pressure. For the different types of investigated solvent, the solid−liquid equilibrium solubility of vinpocetine increased with augmented temperature. Experimental solubility was fitted with several thermodynamic models including the modified Apelblat model, λh model, and nonrandom two-liquid (NRTL) model, as well as the combined nearly ideal binary solvent/Redlich− Kister model. All the fitted values were in satisfactory agreement with the experimental results. The thermodynamic parameters were calculated by the activity coefficients of vinpocetine in different solvents, which were obtained by NRTL model. The results demonstrated that the mixing process of vinpocetine with experimental solvents was spontaneous and entropy-driven.

1. INTRODUCTION Pharmaceutical preparation and utilization require the selection of solvents and corresponding solubility data, such as the crystallization, formulation process, purification, and liquid drug product.1 Considering a drug has unique solubility data and physicochemical properties in different solvents, it is extremely important to select the appropriate solvent and operating conditions for crystallization and formulation.2 Particularly, in the previous literature, the solubility data and thermodynamic parameters have usually been determined by experiment and data fitting, which were applied to crystallization processes, screen potential crystal forms, and so on.3−5 Vinpocetine (14-ethoxycarbonyl-(3α,16α-ethyl)-14,15-eburnamenine, C22H26N2O2, CAS Reg. No. 42971-09-5) as a drug has poor aqueous solubility and low bioavailability after oral administration, which has been confirmed to enhance cerebral circulation and improve metabolism in the treatment of cerebrovascular circulatory disorder.6,7 The molecular structure of vinpocetine is illustrated in Figure 1. Vinpocetine (trade name Cavinton) was originally marketed in the late 20th century in Hungary and has been served in many European © XXXX American Chemical Society

Figure 1. Molecular structure of vinpocetine.

and Asian countries for treating cognitive disorders. Currently, different types of vinpocetine-containing memory pills such as Memolead (Kao Kabushiki Kaisha, Tokyo, Japan) and Intelectol (Memory Secret, Miami, FL) have been used worldwide as dietary supplements.8,9 Obviously, the thermodynamic properties of vinpocetine are critically important both in industrial production and clinical therapy. However, the research about thermodynamic properties of vinpocetine is Received: July 27, 2018 Accepted: December 14, 2018

A

DOI: 10.1021/acs.jced.8b00663 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

ray diffraction (PXRD) device. The PXRD measurement was employed on Rigaku D/MAX 2500 equipment (Cu Kα radiation, 1.5418 Å) at 40 kV and 100 mA; the scanning region was 2° to 40° with a rate of 8° min−1. 2.3. Characterization by TGA/DSC. The decomposition temperature, melting temperature, and enthalpy of fusion of vinpocetine were characterized by Mettler-Toledo TGA/DSC apparatus under protection of nitrogen. Thermogravimetric variation in the heating process of 25−300 °C was recorded by Mettler-Toledo TGA 1/SF at a rate of 10 K/min under 25 mL/min nitrogen purge. The DSC curve was acquired by a Mettler Toledo DSC 1/500 at 10 K/min heating rate with nitrogen as protection gas. The DSC apparatus was calibrated by using the melting temperature and melting enthalpy reference materials before the operation of measurements. The onset temperature of the melting process was selected as the melting temperature. Calibrated by indium, ΔfusH = 3266.58 J·mol−1 and Tm = 429.75 K; calibrated by zinc, ΔfusH = 7028.36 J·mol−1 and Tm = 692.65 K. The amount of sample used was about 5−10 mg. 2.4. Solubility Measurements. In this research, the solubility of vinpocetine in pure and binary solvents was determined by the gravimetric method. The method and principle of measurement were the same as that described in previous literature,11,12 and the experimental equipment mainly included a jacketed glass vessel (50 mL), a thermostat (Julabo CF41, Germany), and a magnetic stirrer. For each measurement, a certain amount of solvent was added to the jacketed glass vessel and the thermostat (with uncertainty of ±0.01 K) was used to control the temperature to the desired temperature. Excess vinpocetine powder was interfused to a rubber stopper sealed crystallizer. The solution was stirred for at least 12 h, and the temperature had to be kept constant to completely establish the equilibrium between solid and liquid. After agitation was stopped, the solution was left standing for at least 2 h to ensure complete settlement of undissolved suspended substance. A syringe was used to remove the supernatant fluid, approximately 5−6 mL, and it was quickly filtered with an organic membrane (0.22 μm) and injected into a preweighed beaker. Syringe and organic membrane have been preheated. Then, the beaker containing solution obtained from the previous step was weighed using an analytical balance (Mettler Toledo ML204, Switzerland) with accuracy of ±0.0001 g. The entire saturated solution was obtained and placed in a vacuum drying oven at 323.15 K until constant sample weight. All the experiments were repeated three times, and the average value was used to calculate the solubility of vinpocetine. The mole fraction solubility can be calculated as

relatively insufficient, and the solubility of vinpocetine has not been researched so far. Vinpocetine is sparingly soluble in water, but in the industry, organic solvents including C1−C4 alcohols, methyl acetate, ethyl acetate, alkyl ketones, or a mixture of them are preferred to obtain a solution of vinpocetine.10 In this article, the solubility of vinpocetine in nine pure organic solvents and ethanol−water binary solvent at 283.15−323.15 K was experimentally measured by gravimetric method under ambient pressure. The modified Apelblat model, λh model, nonrandom two-liquid (NRTL) model, and combined nearly ideal binary solvent/Redlich−Kister (CNIBS/R−K) model were employed to correlate the measured solubility data, which enable us to analyze the inter-relation between solubility and temperature, to predict the dissolution state for a wider temperature interval. Furthermore, thermodynamic properties related to the dissolution and mixing process were calculated on the basis of NRTL model.

2. EXPERIMENTAL SECTION 2.1. Materials. The vinpocetine powder, with mass fraction purity higher than 0.99, was purchased by Shanghai Bide Pharmaceutical Technology Co., Ltd. (Shanghai, China). All the organic solvents were Analytical Reagents including methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, ethyl acetate, methyl acetate, cyclohexane, and 2-butanone and were purchased from Tianjin Yuanli Chemical Technology Co., Ltd. All materials were used without further purification. The particular information on materials used in this research was listed in Table 1. 2.2. Powder X-ray Diffraction Analysis. To ensure that vinpocetine has the coincident crystal form in each saturated solution, the dried solute in beaker and undissolved substance suspended in saturated solution were detected by a powder XTable 1. Characteristics of Materials Used in This Research molecular mass (g mol−1)

mass fraction purity (%)

350.45

≥99.0

methanol

32.05

≥99.8

ethanol

46.07

≥99.7

1-propanol

60.10

≥99.8

2-propanol

60.1

≥99.7

1-butanol

74.12

≥99.5

ethyl acetate

88.11

≥99.5

methyl acetate

74.08

≥98.0

cyclohexane

84.16

≥99.5

2-butanone

72.11

≥99.5

water

18.02

material name vinpocetine

source Shanghai Bide Pharmatech Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. Tianjin Yuanli Chemiacl Co., Ltd. double-distilled water prepared by laboratory

analysis method HPLCa GCb GCb GCb GCb GCb GCb

x1 =

GCb

m1/M1 m1/M1 + m2 /M 2

(1)

where x1 is the mole fraction solubility of vinpocetine in the pure solvents and m1 and m2 are the masses of the solute and solvent. M1 is the molar weight of vinpocetine (M1 = 350.45 g· mol−1), and M2 represents the molar mass of different solvents, respectively. The ethanol−water binary solvent was prepared with calculated molar ratio and converted into the mass ratio, weighed using an analytical balance (Mettler Toledo ML204) with accuracy of ±0.0001 g. The molar fraction of the solute in the binary solvent can be calculated as

GCb GCb

a High performance liquid chromatography. bGas liquid chromatography. Both the analysis method and the mass fraction purity were provided by the suppliers.

B


Journal of Chemical & Engineering Data x=

m1/M1 m1/M1 + wm2 /ME + (1 − w)m2 /MW

(2)

where x is the mole fraction solubility of vinpocetine in binary solvent and m1 and m2 are the masses of the solute and solvent. M1, ME, and MW represent the relative molecular masses of solute, ethanol, and water; w is the mass fraction of ethanol in the binary solvent, respectively.

+

B + C ln T T

ln xi =

ln γi =

ΔCp1

T

T

m

ΔCp1 dT

m

dT

(7)

ΔfusH jij 1 1 zy − zzz − ln γi jjj R k Tm T z{

(8)

(Gjixj + Gkixk)(τjiGjixi + τkiGkixk) (xi + xjGji + xkGki)2 +

where λ and h are two adjustable parameters, both having their thermodynamic significance. xi is mole fraction solubility; Tm is the melting temperature of the vinpocetine under DSC test. The value of λ is defined as the average relative amount of solute molecules, which represents the nonideality of the solution system. Parameter h reflects the enthalpy of the solution. 3.1.3. Local Composition Models. In a system of solid− liquid phase equilibrium, under conditions of constant temperature and pressure, the fugacity is adopted to express the changes in thermodynamic properties of real solution. Moreover, the fugacity of the compounds in the two phases of solid and liquid must be the identical value. It can be expressed as follows:

+

[τijGijxj 2 + GijGkjxjxk(τij + τkj)] xj + xiGij + xkGkj 2 [τijGik xk 2 + Gik Gjk xjxk(τik + τjk)] (xk + xiGik + xjGjk )2

(9)

where Gij = exp( −αijτij) αij =

(gij − gjj) RT

=

(10) Δgij

(11)

RT

The parameters Gij, Gji, Gik, Gki, Gjk, Gjk, τij, τji, τik, τki, τjk, and τjk are all proposed by NRTL model, where Δgij stands for the intermolecular interaction energy parameters and αij is the coefficient of the nonrandomness of the solution, which is an adjustable empirical coefficient between 0 and 1. 3.1.5. CNIBS/Redlich−Kister Model. : To calculate the solid−liquid equilibrium data in binary solvents, the combined nearly ideal binary solvent/Redlich− Kister (CNIBS/R-K) model as an illustrious model was proposed by Arcee and Zvaigzne and can be presented as follows,18

(5)

Generally speaking, the fugacity of compounds in the liquid phase (f Li (T,P,xi)) in solid−liquid equilibrium can be signified by the solution composition xi, the activity coefficient γi, and the fugacity of the pure liquid phase (f Li (T,P,)). xiγi(T , P , xi) fiL (T , P) = f iS (T , P)

∫T

T

The simplified equation has been widely used in predictive solubility calculations. The activity coefficient, melting temperature, and fusion enthalpy of the solute are essential for this model. Therefore, the NRTL model will be used in this work as an appropriate model to calculate the solute activity coefficient in the liquid phase. In addition, the thermodynamic data of the solute will be obtained by thermogravimetric analysis. 3.1.4. NRTL Model. Based on an assumption similar to that of the quasichemical theory of Guggenheim, Renon and Prausnitz have proposed that the NRTL equation can be used to calculate the thermodynamic properties of composition models.17 It can calculate the activity coefficient as follows:

(3)

Where A, B, and C are semiempirical constants, xi represents the molar fraction solubility of the solute, and T is the absolute temperature. The effect of temperature on the enthalpy of fusion is expressed by the value of parameter C. Parameters A and B represent the variation of the activity coefficient in the solution, which can be reflected as an indication of the incidence of nonideal solution on the solubility of the solute. 3.1.2. λh Model. The λh model,15 as a universal model, is based on two parameters, λ and h. From another perspective, it can provide theoretical assumptions for the solubility of drugs in different solvents with temperature changes. It can be expressed as follows: ÅÄÅ ÑÉ i1 λ(1 − xi) ÑÑÑ Å 1 yzz ÑÑ = λhjjjj − lnÅÅÅÅ1 + z Ñ jT ÅÅÇ ÑÑÖ xi Tm zz{ (4) k

fiL (T , P , xi) = f iS (T , P)

1 R

∫T

where xi and γi represent the molar solubility and the activity coefficient of solute. R is the gas constant. Tm is the melting point of the solute, and ΔfusH and ΔCp1 are the fusion enthalpy and the difference between the molar heat capacity of the melting and solid states of the solute, respectively. In the previous literature, after appropriate simplification of the model, the local composition models can be simplified as.17

3. THEORETICAL BASIS 3.1. Thermodynamic Models. 3.1.1. Modified Apelblat Model. Semiempirical modified Apelblat model13,14 was used to correlate the mole fraction of vinpocetine with temperature, which can be presented as follows: ln xi = A +

ΔfusH jij 1 1 zy 1 − zzz − jjj z R k Tm T { RT

ln xi = − ln γi +

Article

(6)

N

ln xi = x 2 ln X 2 + x3 ln X3 + x 2x3 ∑ Si(x 2 − x3)i

The local composition model explains the correlation between solubility and temperature in nonideal solution; the solubility of solute in the solid−liquid equilibrium can be described as16

i=0

(12)

where xi is the mole fraction solubility of vinpocetine, x2 and x3 are the initial molar fractions of the ethanol−water binary C



Article

4. RESULTS AND DISCUSSION 4.1. PXRD Characterization of Vinpocetine. Through comparative analysis, PXRD spectra have been determined to

solvent, and X2 and X3 refer to the solubility of vinpocetine in pure solvents 2 and 3, respectively. Si is a model parameter, the value of N is 2 and stands for binary solvent systems, and x2 = 1 − x3. Substituting the above parameters into eq 8 is simplified to eq 9, which is called the deformation of CNIBS/ R−K model. It can be shown as19 ln xi = b0 + b1x 2 + b2x 2 2 + b3x 2 3 + b4x 2 4

(13)

b0, b1, b2, b3, and b4 are the parameters of the CNIBS/R−K model, and x2 is the initial molar fraction of ethanol in the binary solvent. 3.2. Solution Mixing Thermodynamics. The dissolution process of solutes can be regarded as a hypothetical stage, which is accompanied by a thermodynamic phase transition from the solid phase to the liquid phase. This process includes solute dissolution, cooling the solute to harmonic mean temperature, and the mixing of supercooled solution. The ideal solution mixing thermodynamic properties can be calculated by the following formulas:20 n

Δmix Gid = RT ∑ xi ln xi

Figure 2. Powder X-ray diffraction patterns of vinpocetine: (a) raw material; (b) dried solute in beaker; (c) undissolved substance suspended in saturated solution.

(14)

i

Δmix H id = 0

(15) n

Δmix S id = −R ∑ xi ln xi

(16)

i

where xi refer to the mole fractions of vinpocetine and solvents, respectively. ΔmixGid, ΔmixSid and ΔmixHid represent the mixed Gibbs energy, the mixture entropy, and the mixing enthalpy of the ideal solution. For a pure solvent solution, n = 2. For a binary solvent solution, n = 3. For a real solution, the mixed thermodynamic properties need to be calculated by considering the activity coefficient as follows, and the activity coefficient is calculated by the NRTL model.21 Δmix G = GE + Δmix Gid

(17)

Δmix H = HE + Δmix H id

(18)

Δmix S = S E + Δmix S id

(19)

Figure 3. Thermal analysis (TGA/DSC) of vinpocetine.

identify the consistent crystal forms of material during the whole dissolution and drying process. Figure 2 reveals the powder X-ray diffraction results of the raw material, the dried solute in beaker, and undissolved substance suspended in saturated solution. Obviously, the experimental results of PXRD indicated that there is no polymorphic transformation during the measurement. Vinpocetine always maintains the stability of the crystal forms in pure solvent or mixed solvent. The results of PXRD characterization indirectly verify the reliability of solubility measurement, so all the PXRD patterns were not listed there. 4.2. TGA/DSC. The TGA/DSC results are shown in Figure 3. The experimental data measured by the calibrated instrument in this experiment should be reliable. The DSC experiment showed that vinpocetine only exhibited a steep peak, corresponding to the temperature of 422.15 K (standard uncertainty of Tm was estimated to be 0.5 K). TGA experiments confirmed that the weight loss of vinpocetine samples occurred after 493.15 K. Compared with the corresponding enthalpy changes, it can be determined that

where G , H , and S refer to the excess properties and ΔmixG , ΔmixSid, and ΔmixHid are the mixing properties of ideal systems. Based on the NRTL model, the excess mixing properties GE, E H , and SE can be calculated by the following equations:20 E

E

E

id

n E

G = RT ∑ xi ln γi

n i ∂ ln γi yz zz HE = −RT 2 ∑ xijjjj z k ∂T { p , x i

(20)

i

SE =

HE − GE T

(21)

(22)

xi represents the molar fraction of the composition i, and γi is the activity coefficient of the composition i in real solution calculated by the NRTL model. For a pure solvent system, n = 2. For a binary solvent system, n = 3. D



Article

Table 2. Mole Fraction Solubilities (xexp) of Vinpocetine in Nine Pure Solvents at Temperature (T) and Pressure (P = 101.3 kPa)a 103xcal 3 exp

T (K)

10 x

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.3783 0.4755 0.6076 0.7365 0.8899 1.0989 1.3599 1.6592 2.0372

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.4919 0.6407 0.8204 1.0134 1.2637 1.5808 1.9711 2.4458 3.0239

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.7266 0.9796 1.2636 1.6386 2.0846 2.6809 3.4291 4.3483 5.2778

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.3447 0.4736 0.6429 0.8341 1.0840 1.3737 1.8399 2.4499 3.2311

283.15 288.15 293.15 298.15 303.15 308.15 313.15

0.9356 1.2655 1.7022 2.2020 2.8501 3.7399 4.8003

Apelblat Methanol 0.3873 0.4790 0.5915 0.7294 0.8982 1.1045 1.3561 1.6625 2.0351 Ethanol 0.5036 0.6381 0.8053 1.0126 1.2688 1.5842 1.9714 2.4452 3.0232 1-Propanol 0.7168 0.9568 1.2618 1.6448 2.1209 2.7066 3.4202 4.2819 5.3134 2-Propanol 0.3689 0.4785 0.6232 0.8143 1.0675 1.4032 1.8490 2.4416 3.2302 1-Butanol 0.9553 1.2656 1.6694 2.1926 2.8679 3.7361 4.8483

103xcal

λh

NRTL

T (K)

10 x

0.3781 0.4756 0.5940 0.7372 0.9094 1.1158 1.3621 1.6554 2.0039

0.3770 0.4753 0.5944 0.7388 0.9110 1.1181 1.3642 1.6551 1.9983

318.15 323.15

6.3232 8.0564

0.4949 0.6346 0.8074 1.0199 1.2795 1.5953 1.9776 2.4388 2.9934

0.4951 0.6342 0.8074 1.0201 1.2803 1.5962 1.9793 2.4392 2.9911

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

3.8971 4.8064 5.8528 7.1846 8.7908 10.6196 12.7494 15.3509 18.5256

0.7338 0.9673 1.2636 1.6368 2.1036 2.6839 3.4010 4.2826 5.3619

0.6901 0.9252 1.2283 1.6163 2.1082 2.7283 3.5054 4.4722 5.6631

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.6245 3.2931 4.1581 5.1682 6.4589 7.9443 9.7327 12.1088 14.8049

0.3439 0.4670 0.6278 0.8360 1.1033 1.4438 1.8746 2.4162 3.0934

0.3442 0.4671 0.6281 0.8363 1.1032 1.4431 1.8743 2.4174 3.0959

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

1.3289 1.6960 2.1590 2.7439 3.4599 4.3274 5.3664 6.5604 8.0228

0.9331 1.2573 1.6776 2.2175 2.9058 3.7765 4.8706

0.9341 1.2572 1.6773 2.2162 2.9041 3.7753 4.8691

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

5.2639 6.4916 7.9349 9.6199 11.7504 14.1567 16.9744 20.2769 23.8834

3 exp

Apelblat 1-Butanol 6.2678 8.0731 Ethyl Acetate 3.9064 4.8035 5.8842 7.1817 8.7345 10.5868 12.7897 15.4019 18.4906 Methyl Acetate 2.6366 3.3106 4.1417 5.1635 6.4154 7.9447 9.8072 12.0687 14.8071 Cyclohexane 1.3133 1.6967 2.1713 2.7540 3.4635 4.3206 5.3487 6.5731 8.0219 Butanone 5.2279 6.4686 7.9465 9.6957 11.7535 14.1606 16.9607 20.2012 23.9327

λh

NRTL

6.2369 7.9337

6.2392 7.9401

3.8681 4.7929 5.9002 7.2193 8.7839 10.6323 12.8089 15.3648 18.3594

3.8601 4.7882 5.9012 7.2271 8.7983 10.6511 12.8252 15.3623 18.3071

2.5965 3.2983 4.1582 5.2054 6.4734 8.0014 9.8342 12.0244 14.6331

2.5962 3.2971 4.1572 5.2053 6.4762 8.0071 9.8411 12.0272 14.6201

1.3263 1.7031 2.1696 2.7435 3.4454 4.2992 5.3329 6.5795 8.0778

1.3272 1.7033 2.1693 2.7434 3.4452 4.3014 5.3352 6.5811 8.0731

5.2631 6.4872 7.9452 9.6736 11.7135 14.1121 16.9231 20.2085 24.0399

5.2521 6.4822 7.9483 9.6881 11.7363 14.1394 16.9425 20.1962 23.9641

a Standard uncertainty of T is u(T) = 0.02 K, the relative standard uncertainty of the solubility measurement is ur(xexp) = 0.03, and the standard uncertainty of pressure is u(P) = 0.3 kPa.

the endothermic peak at 422.15 K indicates the decom-

ΔfusS =

position-free melting of the sample. The thermal analysis of vinpocetine, which characterizes the melting point (Tm) of

ΔfusH Tm

(23)

The melting entropy is solved by substituting the DSC data into the above equation, ΔfusS = 88.5 J·mol−1·K−1. 4.3. Solubility Data. The solubility data of vinpocetine in binary solvents of pure methanol, ethanol, 1-propanol, 2propanol, 1-butanol, ethyl acetate, methyl acetate, cyclohexane, 2-butanone, and ethanol−water binary solvent were deter-

vinpocetine is 422.15 K and the melting enthalpy ΔfusH = 37.359 kJ·mol−1, and the relative standard uncertainty of ΔfusH was estimated to be 0.02, respectively. The melting entropy of vinpocetine can be calculated by the following equation:22 E



Article

Table 3. Mole Fraction Solubilities (xexp) of Vinpocetine in Ethanol (w) + Water (1 − w) at Temperature (T) and Pressure (P = 101.3 kPa)a 103xcal T (K)

3 exp

10 x

Apelblat e

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.0039 0.0055 0.0076 0.0103 0.0140 0.0189 0.0253 0.0346 0.0461

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.0343 0.0446 0.0580 0.0720 0.0910 0.1154 0.1400 0.1799 0.2300

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.0883 0.1152 0.1485 0.1762 0.2318 0.2900 0.3530 0.4393 0.5613

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.1682 0.2154 0.2760 0.3398 0.4299 0.5390 0.6684 0.8499 1.0390

283.15 288.15

0.2561 0.3302

w 0.0042 0.0056 0.0076 0.0103 0.0139 0.0188 0.0254 0.0343 0.0463 we 0.0360 0.0451 0.0567 0.0713 0.0899 0.1134 0.1431 0.1809 0.2288 we 0.0917 0.1151 0.1445 0.1812 0.2272 0.2846 0.3564 0.4459 0.5574 we 0.1691 0.2147 0.2717 0.3426 0.4307 0.5397 0.6742 0.8397 1.0429 we 0.2625 0.3307

λh = 0.2 0.0039 0.0055 0.0076 0.0105 0.0143 0.0192 0.0257 0.0341 0.0449 = 0.3 0.0342 0.0443 0.0570 0.0726 0.0920 0.1157 0.1446 0.1797 0.2224 = 0.4 0.0883 0.1136 0.1450 0.1836 0.2310 0.2888 0.3589 0.4436 0.5457 = 0.5 0.1667 0.2143 0.2733 0.3461 0.4352 0.5439 0.6758 0.8352 1.0274 = 0.6 0.2568 0.3285

103xcal NRTL

T (K)

R−K

3 exp

10 x

Apelblat e

0.0040 0.0054 0.0073 0.0099 0.0133 0.0179 0.0240 0.0321 0.0428

0.0034 0.0049 0.0094 0.0128 0.0161 0.0189 0.0213 0.0297 0.0472

0.0310 0.0402 0.0522 0.0675 0.0870 0.1119 0.1434 0.1835 0.2340

0.0311 0.0411 0.0556 0.0686 0.0887 0.1107 0.1332 0.1709 0.2243

0.0896 0.1148 0.1466 0.1866 0.2371 0.3001 0.3787 0.4768 0.5996

0.0955 0.1231 0.1536 0.1849 0.2378 0.3014 0.3702 0.4641 0.5762

0.1696 0.2157 0.2736 0.3457 0.4361 0.5486 0.6882 0.8626 1.0769

0.1691 0.2174 0.2795 0.3376 0.4280 0.5411 0.6652 0.8350 1.0342

0.2579 0.3266

0.2469 0.3166

293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.4293 0.5195 0.6387 0.8258 0.9999 1.2573 1.5519

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.3609 0.4514 0.5896 0.7147 0.8996 1.1281 1.4091 1.7559 2.1501

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0. 4308 0.5553 0.7108 0.8798 1.0954 1.4133 1.7198 2.1924 2.6647

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.4501 0.5778 0.7554 0.9516 1.1836 1.5383 1.8743 2.4363 3.0155

w 0.4156 0.5209 0.6513 0.8122 1.0103 1.2537 1.5520 we 0.3593 0.4555 0.5751 0.7232 0.9062 1.1313 1.4074 1.7449 2.1561 we 0.4317 0.5513 0.7005 0.8858 1.1147 1.3964 1.7418 2.1633 2.6761 we 0.4523 0.5795 0.7401 0.9426 1.1971 1.5161 1.9147 2.4117 3.0197

λh = 0.6 0.4171 0.5258 0.6584 0.8194 1.0140 1.2486 1.5303 = 0.7 0.3554 0.4551 0.5782 0.7294 0.9139 1.1381 1.4093 1.7362 2.1291 = 0.8 0.4287 0.5515 0.7038 0.8916 1.1216 1.4022 1.7426 2.1543 2.6505 = 0.9 0.4410 0.5747 0.7427 0.9522 1.2117 1.5315 1.9235 2.4018 2.9833

NRTL

R−K

0.4128 0.5192 0.6518 0.8184 1.0220 1.2769 1.5913

0.4193 0.5107 0.6392 0.8068 0.9895 1.2468 1.5469

0.3460 0.4366 0.5505 0.6907 0.8660 1.0837 1.3538 1.6891 2.1021

0.3476 0.4426 0.5787 0.7076 0.8805 1.1195 1.3744 1.7314 2.1212

0.4282 0.5395 0.6783 0.8498 1.0627 1.3301 1.6558 2.0678 2.5690

0.4322 0.5772 0.7309 0.8981 1.1181 1.4413 1.7717 2.2399 2.7070

0.5018 0.6308 0.7914 0.9897 1.2346 1.5420 1.9152 2.3907 2.9720

0.4534 0.5698 0.7483 0.9447 1.1763 1.5275 1.8561 2.4184 3.0105

a Standard uncertainty of T is u(T) = 0.02 K, the relative standard uncertainty of the solubility measurement is ur(xexp) = 0.03, and the standard uncertainty of pressure is u(P) = 0.3 kPa. w e denotes the mole fraction of ethanol in a binary solvent.

In the past literature, the polarity of the solvent has been frequently considered to explain the order of solubility, but according to the characteristics of vinpocetine, it is obviously not fully applicable to this pattern.23 When the solubility sequence is interpreted by the well-known rule “like dissolves like”,19 the characteristic functional groups (-OC−O- or -CO-) in acetates and ketones also exist in the molecular structure of vinpocetine. The dissolution process of the solute, due to the interaction of the same functional groups, may enhance the amount of positive charges in acetates and ketones and the highly negative charge in vinpocetine. When electrostatic attraction occurs between them, it is easier to overcome the energy barrier of solute−solvent bonding. In addition, polarity is also considered to be one factor in

mined. Each solvent was subjected to the temperature range of 283.15 to 323.15 K under ambient atmospheric pressure. Taking into account the boiling point limits of cyclohexane and methyl acetate, the measurement temperature range is controlled from 283.15 to 323.15 K. The solubility data are shown in Table 2 and Table 3. 4.3.1. Solubility Data in Nine Pure Solvents. The solubilities of vinpocetine in nine pure solvents are vividly described in Figure 4, from which it can be realized that the solubility data in all of the nine systems increases with the increasing temperature. Under ambient conditions, the solubility levels were 2-butanone > ethyl acetate > methyl acetate > cyclohexane > 2-propanol > 1-butanol > 1-propanol > ethanol or 2-propanol > methanol. F



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Table 4. Parameters of Modified Apelblat Model for Vinpocetine in Pure Solvents solvent

A

B

C

102ARDa

105RMSDb

methanol ethanol 1-propanol 2-propanol 1-butanol ethyl acetate methyl acetate cyclohexane butanone

−127.1 −89.6 61.7 −279.8 −107.6 −66.8 −86.1 24.0 5.0

2176.9 243.9 −6957.4 8066.2 424.9 −233.7 289.6 −4862.7 −3388.8

19.8 14.4 −7.9 43.1 17.6 11.0 14.0 −2.4 0.3

0.9715 0.5986 1.0396 2.0020 0.8090 0.2958 0.3631 0.3275 0.2985

0.7693 0.6758 3.0523 1.7266 2.8942 3.4619 3.2981 1.0715 4.2262

a

ARD is the average relative deviation. bRMSD is the root-meansquare deviation.

Table 5. Parameters of Modified Apelblat Model for Vinpocetine in Binary Solvent

Figure 4. Mole fraction solubility (x1) of vinpocetine in different pure organic solvents ranging from 283.15 to 323.15 K.

determining the order of dissolution. Referring to the molecular structure of vinpocetine, it can be analyzed that it has a small molecular polarity and is difficult to dissolve in a solvent having a large polarity, which is almost the same as the phenomena that are obtained by experiments. 4.3.2. Solubility Data in Binary Solvent. Ethanol is commonly used in the industry as the main solvent for separation of vinpocetine production, and vinpocetine is poorly soluble in water. Therefore, ethanol is used as a good solvent, and water is an antisolvent to prepare a binary solvent. Figure 5 shows the solubility of vinpocetine in pure ethanol and ethanol−water binary solvents. Solubility in ethanol− water binary solvents increases with the increasing temperature and mole fraction of ethanol. It is worth noting that the composition of water as an antisolvent in binary solvents has a decisive influence on the dissolution process of vinpocetine. The results show that the ethanol−water mixture is a suitable cosolvent for recrystallization or antisolvent crystallization of vinpocetine.

wea

A

B

C

102ARDb

105RMSDc

0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

−228.8 −213.9 −164.1 −101.1 −112.2 −85.8 −66.1 116.8

5115.2 5613.1 3498.4 659.3 1262.6 57.6 −881.9 1251.9

35.1 32.6 25.2 15.9 17.6 13.8 10.9 18.5

1.1782 1.7215 1.8257 0.6670 1.2299 0.7836 1.0028 1.3243

0.0146 0.1591 0.4368 0.4483 0.8795 0.7571 1.5883 1.9432

a e

w denotes the mole fraction of ethanol in binary solvent. bARD is the average relative deviation. cRMSD is the root-mean-square deviation.

4.4. Data Correlation. To generalize the application of measured solubility, the solubility results were correlated using the modified Apelblat model, the λh model, the NRTL model, and the R−K model. The experimental value xexp and the correlation value xcal obtained by the above model are shown in Table 2 and Table 3. The formulas for calculating the average relative deviation (ARD) and the root-mean-square deviation (RMSD) are as follows:

Figure 5. Mole fraction solubility (x) of vinpocetine in the ethanol + water binary mixed solvent at different mole fractions of ethanol (w) from 0.2 to 1.0 (P = 0.1 MPa). G



Article

Table 6. Parameters of λh Model for Vinpocetine in Pure Solvents solvent

λ

h

102ARDa

105RMSDb

methanol ethanol 1-propanol 2-propanol 1-butanol ethyl acetate methyl acetate cyclohexane butanone

0.027 0.052 0.134 0.119 0.262 0.209 0.231 0.145 0.257

135788.9 76672.4 33442.4 42000.7 18488.3 16496.8 16754.5 27866.3 13078.4

0.9064 0.8416 0.8131 2.0651 1.1501 0.4412 0.6433 0.4212 0.2995

1.4836 1.3905 3.7641 5.4615 6.0381 6.3286 7.6452 2.5131 6.5115

ARD =

Table 7. Parameters of λh Model for Vinpocetine in Binary Solvent h

102ARDb

105RMSDc

0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

0.0025 0.0044 0.0104 0.0185 0.0259 0.0365 0.0483 0.0644

2232285.0 947843.8 391210.7 218928.1 153285.1 109331.2 84269.7 66673.9

1.4835 1.2686 1.5685 1.1502 1.3546 1.2142 1.1410 1.1920

0.0493 0.3006 0.6385 0.7497 1.2303 1.3016 1.8841 2.6663

a

w e denotes the mole fraction of ethanol in binary solvent. bARD is the average relative deviation. cRMSD is the root-mean-square deviation.

Table 8. Parameters of NRTL Model for Vinpocetine in Pure and Binary Solvents solvent

Δg12

Δg21

102ARDa

105RMSDb

methanol ethanol 1-propanol 2-propanol 1-butanol ethyl acetate methyl acetate cyclohexane butanone ethanol + water

38126.5 25448.3 9652.7 9246.5 5976.0 23711.6 18434.4 18986.1 23262.8 −12488.3

−1349.2 −3076.1 3544.5 172.1 −567.8 −7958.2 −6775.3 −5241.3 −8692.0 27672.4

1.0763 0.8734 3.3493 2.0358 1.1118 0.5506 0.6706 0.3987 0.2712 4.9733

0.0017 0.0015 0.0141 0.0054 0.0058 0.0082 0.0081 0.0023 0.0047 0.0340

i=1

xiexp − xical xiexp

(24)

∑i = 1 (xical − xiexp)2

(25)

N

where N is the number of experimental points, the superscript exp represents the experimental data, and cal stands for the calculated value. The relevant fitting parameters for all the above models, ARDs, and RMSDs are described in Tables 4−9. The values of ARD and RMSD indicate a slight deviation between the fitted and experimental values. The calculated points of the different equations are slightly scattered, but the ARD value of each point is not more than 5%. From the results, the solubility calculated based on the above models is basically consistent with the experimental value. Therefore, the Apelblat model, the λh model, the NRTL model, and the R−K model are all suitable for correlating and predicting the solubility of vinpocetine, and it also imply that the experimental values have satisfactory accuracy in the solvents measured. 4.5. Thermodynamic Properties of Solutions. The activity coefficients of vinpocetine in different pure solvents and binary solvent were calculated by the NRTL model. The logarithmic form of the activity coefficients ln γ1 are shown in Tables 10 and 11. The calculation results of the thermodynamic properties of the mixing process are also listed in Tables 10 and11. As shown in Tables 10 and 11, all the values of ΔmixG are negative, which can be inferred from the mixing of vinpocetine in pure solvents and binary solvent and is a spontaneous and favorable process. The entropy changes ΔmixS of all mixing processes are positive, indicating that the mixing process is an entropy increasing process. The positive or negative value of the enthalpy of each mixing process implies that the process is endothermic or exothermic.24 The positive or negative ΔmixH of each mixing process indicates that the process is endothermic or exothermic. From Tables 10 and 11, ΔmixH of vinpocetine in the mixing process of 1-propanol, 2propanol, and 1-butanol is positive, indicating that their mixing process is endothermic. Negative ΔmixH reflects that other mixing processes are exothermic.


λ

N

∑ N

RMSD =

a

wea

1 N

5. CONCLUSION The solubility data of vinpocetine in nine pure organic solvents and ethanol−water binary solvent were measured by the gravimetric method at wide temperature ranging from 283.15 to 323.15 K. Obviously, the experimental results demonstrate

a


Table 9. Parameters of RK Model for Vinpocetine in Binary Solvent T (K)

b0

b1

b2

b3

b4

102ARDa

105RMSDb

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

−23.54 −22.60 −19.34 −18.41 −18.39 −18.66 −18.97 −18.07 −16.36

86.35 81.33 58.87 53.55 55.57 59.28 62.86 58.01 47.28

−196.31 −182.83 −123.13 −109.34 −115.03 −124.82 −133.94 −121.14 −93.16

207.23 191.38 124.04 108.68 115.04 126.00 136.07 121.46 89.85

−82.27 −75.43 −48.07 −41.79 −44.27 −48.65 −52.73 −46.59 −33.60

4.3229 3.6133 2.2288 2.1100 1.3902 1.8961 2.3625 2.3438 1.2481

1.0597 1.0542 0.9462 0.8662 1.1046 1.3662 2.4188 2.2911 1.9873

a

ARD is the average relative deviation. bRMSD is the root-mean-square deviation. H



Article

Table 10. Mixing Thermodynamic Properties of Vinpocetine in Pure Solvents T (K)

ln γ1a

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.6333 2.6773 2.7192 2.7591 2.7969 2.8329 2.8669 2.8991 2.9296

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.3606 2.3878 2.4129 2.4361 2.4575 2.4771 2.4950 2.5113 2.5261

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.0287 2.0107 1.9932 1.9758 1.9585 1.9410 1.9233 1.9052 1.8876

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.7238 2.6939 2.6643 2.6352 2.6063 2.5779 2.5493 2.5207 2.4919

283.15 288.15 293.15 298.15 303.15 308.15

1.7258 1.7035 1.6815 1.6597 1.6381 1.6163

ΔmixG (J·mol−1)

ΔmixH (J·mol−1)

Methanol −5.5627 −2.2790 −6.8047 −2.8240 −8.4208 −3.5533 −9.9571 −4.2365 −11.7232 −5.0293 −14.0197 −6.0946 −16.7551 −7.3927 −19.7534 −8.8306 −23.3426 −10.6019 Ethanol −7.2448 −1.8558 −9.1554 −2.3194 −11.3818 −2.8441 −13.7097 −3.3573 −16.6107 −3.9915 −20.1342 −4.7484 −24.2863 −5.6150 −29.1117 −6.5869 −34.7097 −7.6726 1-Propanol −10.5977 1.6207 −13.8791 2.1808 −17.4806 2.8092 −22.0653 3.6389 −27.3604 4.6259 −34.1471 5.9447 −42.3269 7.5978 −51.9757 9.6261 −61.5427 11.6817 2-Propanol −5.0702 1.3659 −6.7624 1.9092 −8.9059 2.6347 −11.2725 3.4727 −14.2567 4.5821 −17.6291 5.8920 −22.7273 8.0027 −29.0664 10.7997 −36.7687 14.4277 1-Butanol −13.7588 2.7042 −18.0889 3.7024 −23.6117 5.0381 −29.7742 6.5903 −37.4778 8.6210 −47.5801 11.4270

ΔmixS (J·K−1·mol−1) 0.0116 0.0138 0.0166 0.0192 0.0221 0.0257 0.0299 0.0343 0.0394 0.0190 0.0237 0.0291 0.0347 0.0416 0.0499 0.0596 0.0708 0.0837 0.0432 0.0557 0.0692 0.0862 0.1055 0.1301 0.1594 0.1936 0.2266 0.0227 0.0301 0.0394 0.0495 0.0621 0.0763 0.0981 0.1253 0.1584 0.0581 0.0756 0.0977 0.1220 0.1521 0.1915

T (K)

ln γ1a

313.15 318.15 323.15

1.5946 1.5722 1.5498

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.3065 0.3664 0.4234 0.4778 0.5297 0.5791 0.6261 0.6712 0.7143

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

0.7033 0.7397 0.7739 0.8060 0.8362 0.8645 0.8910 0.9160 0.9392

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

1.3744 1.4004 1.4244 1.4467 1.4672 1.4860 1.5032 1.5189 1.5331

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

−0.0013 0.0636 0.1256 0.1847 0.2416 0.2958 0.3478 0.3976 0.4451

ΔmixG (J·mol−1)

ΔmixH (J·mol−1)

1-Butanol −59.1910 14.8085 −74.9372 19.6827 −92.1579 25.2922 Ethyl Acetate −57.2769 −31.1522 −68.7859 −37.6541 −81.5952 −44.9123 −97.2546 −53.9650 −115.3774 −64.5864 −135.1976 −76.2658 −157.3182 −89.4294 −183.0725 −105.0657 −212.8912 −123.5752 Methyl Acetate −38.5506 −12.9455 −47.1473 −15.7662 −57.8523 −19.3064 −69.9316 −23.2529 −84.7347 −28.1304 −101.1411 −33.4603 −120.0853 −39.5958 −143.9607 −47.5040 −169.8105 −55.9294 Cyclohexane −19.5480 −4.7760 −24.2910 −5.8487 −30.0608 −7.1332 −37.0721 −8.6711 −45.3253 −10.4387 −54.9293 −12.4398 −65.9655 −14.6658 −78.1563 −17.0037 −92.4125 −19.6640 Butanone −77.4707 −45.0224 −92.9631 −54.4729 −110.5320 −65.2892 −130.2983 −77.5692 −154.2319 −92.7793 −180.1724 −109.3842 −209.2358 −128.2416 −241.7395 −149.6504 −275.6624 −172.0578

ΔmixS (J·K−1·mol−1) 0.2363 0.2974 0.3635 0.0923 0.1080 0.1251 0.1452 0.1675 0.1912 0.2168 0.2452 0.2764 0.0904 0.1089 0.1315 0.1566 0.1867 0.2196 0.2570 0.3032 0.3524 0.0522 0.0640 0.0782 0.0953 0.1151 0.1379 0.1638 0.1922 0.2251 0.1146 0.1336 0.1543 0.1769 0.2027 0.2297 0.2586 0.2895 0.3206

ln γ1 is the logarithm of the activity coefficient of vinpocetine in solution. a

that the solubility of vinpocetine in nine solvents and mixed solvents increases with upward temperature. The order of dissolution of vinpocetine in nine pure solvents follows the “like dissolution” rule, while in the ethanol−water binary solvent, the solubility of vinpocetine shows rising trends with the increasing mole fraction of ethanol. The modified Apelblat model, λh model, NRTL model, and CNIBS/R−K model are suitable to correlate the measured solubility data, respectively, the calculated values are in satisfactory agreement with the experimental data. The thermodynamic parameters including mixed Gibbs energy, mixed enthalpy and entropy are

calculated by the activity coefficients of vinpocetine in different solvents, which were obtained by NRTL model. The results indicate that the mixing process of vinpocetine in the experimental solvents is spontaneous and entropy-driven. It is worth noting that the mixing in pure propanol and butanol is endothermic, while the mixing in other experimental solvents is exothermic. In general, the experimental data of this study and the thermodynamic properties of the mixing process could be useful for optimizing the design and operation of vinpocetine in the industrial crystallization process. I



Article

Table 11. Mixing Thermodynamic Properties of Vinpocetine in Binary Solvent T (K) 283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15 283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

ln γ1a 7.1803 7.1520 7.1155 7.0724 7.0230 6.9680 6.9081 6.8429 6.7727 5.1325 5.1454 5.1514 5.1515 5.1457 5.1347 5.1194 5.0988 5.0740 4.0694 4.0972 4.1183 4.1347 4.1437 4.1482 4.1486 4.1437 4.1332

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

3.4314 3.4665 3.4948 3.5177 3.5341 3.5451 3.5513 3.5509 3.5475

283.15 288.15

3.0125 3.0517

■

ΔmixG (kJ·mol−1) we −14.670 −14.637 −14.603 −14.567 −14.530 −14.492 −14.453 −14.412 −14.370 we −13.335 −13.324 −13.313 −13.301 −13.288 −13.275 −13.261 −13.247 −13.231 we −11.808 −11.809 −11.809 −11.810 −11.810 −11.810 −11.809 −11.808 −11.806 we −10.159 −10.167 −10.174 −10.182 −10.189 −10.196 −10.203 −10.209 −10.215 we −8.407 −8.419

ΔmixH (kJ·mol−1)

ΔmixS (J·K−1·mol−1)

T (K)

= 0.2 −14.512 −14.481 −14.448 −14.412 −14.373 −14.332 −14.289 −14.242 −14.194

0.5590 0.5418 0.5293 0.5214 0.5181 0.5191 0.5243 0.5333 0.5461

−12.936 −12.929 −12.920 −12.911 −12.899 −12.886 −12.872 −12.856 −12.839

1.4083 1.3717 1.3387 1.3093 1.2834 1.2611 1.2420 1.2265 1.2142

−11.172 −11.172 −11.171 −11.170 −11.167 −11.163 −11.158 −11.152 −11.145

2.2431 2.2084 2.1767 2.1474 2.1216 2.0985 2.0781 2.0609 2.0473

−9.348 −9.349 −9.349 −9.349 −9.347 −9.345 −9.341 −9.336 −9.329

2.8627 2.8375 2.8151 2.7949 2.7779 2.7637 2.7523 2.7453 2.7403

−7.500 −7.499

3.2048 3.1919

= 0.3

= 0.4

= 0.5

293.15 298.15 303.15 308.15 313.15 318.15 323.15

3.0835 3.1110 3.1322 3.1452 3.1558 3.1586 3.1570

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.7186 2.7613 2.7955 2.8257 2.8481 2.8643 2.8746 2.8789 2.8787

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.5053 2.5496 2.5868 2.6184 2.6434 2.6595 2.6733 2.6766 2.6781

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.3468 2.3934 2.4325 2.4660 2.4935 2.5117 2.5277 2.5315 2.5324

ΔmixG (kJ·mol−1) we −8.431 −8.442 −8.454 −8.464 −8.475 −8.485 −8.494 we −6.554 −6.568 −6.581 −6.594 −6.606 −6.618 −6.629 −6.640 −6.650 we −4.587 −4.600 −4.611 −4.623 −4.634 −4.645 −4.655 −4.663 −4.671 we −2.468 −2.476 −2.484 −2.492 −2.499 −2.505 −2.510 −2.513 −2.515

ΔmixH (kJ·mol−1)

ΔmixS (J·K−1·mol−1)

−7.498 −7.496 −7.493 −7.488 −7.483 −7.475 −7.465

3.1821 3.1732 3.1676 3.1677 3.1681 3.1748 3.1848

−5.639 −5.636 −5.632 −5.628 −5.621 −5.613 −5.603 −5.590 −5.575

3.2344 3.2327 3.2358 3.2388 3.2473 3.2599 3.2770 3.2994 3.3256

−3.767 −3.762 −3.756 −3.749 −3.740 −3.727 −3.714 −3.694 −3.674

2.8958 2.9049 2.9174 2.9315 2.9501 2.9776 3.0042 3.0443 3.0839

−1.884 −1.878 −1.870 −1.861 −1.851 −1.835 −1.819 −1.794 −1.768

2.0607 2.0756 2.0945 2.1151 2.1390 2.1739 2.2065 2.2582 2.3106

= 0.6

= 0.7

= 0.8

= 0.9

= 0.6

ln γ1 is the logarithm of the activity coefficient of vinpocetine in solution. we denotes the mole fraction of ethanol in a binary solvent. a

Funding

ASSOCIATED CONTENT

We are grateful for the financial support of the National Natural Science Foundation of China (Grant NNSFC21706183).

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.8b00663.

■

ln γ1a

Notes

Detailed PXRD analysis patterns of vinpocetine in different solvents and verification of measurement method in this work (PDF)

The authors declare no competing financial interest.

■

REFERENCES

(1) Swarbrick, J.; Boylan, J. C. Encyclopedia of Pharmaceutical Technology; Marcel Dekker: New York, 2002. (2) Sheikholeslamzadeh, E.; Chen, C. C.; Rohani, S. Optimal Solvent Screening for the Crystallization of Pharmaceutical Compounds from Multisolvent Systems. Ind. Eng. Chem. Res. 2012, 51, 13792−13802. (3) Zhou, L. N.; Yin, Q. X.; Guo, Z. Q.; Lu, H. J.; Liu, M. Y.; Chen, W.; Hou, B. H. Measurement and correlation of solubility of

AUTHOR INFORMATION

Corresponding Author

*Tel.: +86-022-27405754. Fax: +86-022-27374971. E-mail: [email protected]. ORCID

Lina Zhou: 0000-0001-6348-4020 J



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ciclesonide in seven pure organic solvents. J. Chem. Thermodyn. 2017, 105, 133−141. (4) Li, X. N.; Han, D. D.; Wang, Y.; Du, S. C.; Liu, Y. M.; Zhang, J. Q.; Yu, B.; Hou, B. H.; Gong, J. B. Measurement of Solubility of Thiamine Hydrochloride Hemihydrate in Three Binary Solvents and Mixing Properties of Solutions. J. Chem. Eng. Data 2016, 61, 3665− 3678. (5) Kawabata, Y.; Wada, K.; Nakatani, M.; Yamada, S.; Onoue, S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int. J. Pharm. 2011, 420, 1−10. (6) Bereczki, D.; Fekete, I. A systematic review of vinpocetine therapy in acute ischaemic stroke. Eur. J. Clin. Pharmacol. 1999, 55, 349−352. (7) Luo, Y. F.; Chen, D. W.; Ren, L. X.; Zhao, X. L.; Qin, J. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J. Controlled Release 2006, 114, 53−59. (8) Wu, M. P.; Zhang, Y. S.; Xu, X. B.; Zhou, Q.; Li, J. D.; Yan, C. Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis. Cardiovasc. Drugs Ther. 2017, 31, 157−166. (9) Sun, P. P.; Wang, Y. P.; Rohani, S.; Liu, E. G.; Du, S. C.; Xu, S. J.; Chen, M. Y.; Wei, Z. P.; Gong, J. B. Controlled Recrystallization of Tubular Vinpocetine Crystals with Increased Aqueous Dissolution Rate and In Vivo Bioavailability. Cryst. Growth Des. 2017, 17, 5790− 5800. (10) Cui, S. X.; Nie, S. F.; Li, L.; Wang, C. G.; Pan, W. S.; Sun, J. P. Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine. Drug Dev. Ind. Pharm. 2009, 35, 603− 611. (11) Ferreira, O.; Pinho, S. P. Solubility of flavonoids in pure solvents. Ind. Eng. Chem. Res. 2012, 51, 6586−6590. (12) Jouybangharamaleki, V.; Jouybangharamaleki, K.; Soleymani, J.; Acree, W. E.; Jouyban, A. Solubility Determination of Tris(hydroxymethyl)aminomethane in Water + Methanol Mixtures at Various Temperatures Using a Laser Monitoring Technique. J. Chem. Eng. Data 2014, 59, 2305−2309. (13) Apelblat, A.; Manzurola, E. Solubilities of L-aspartic, DLaspartic, DL-glutamic, p-hydroxybenzoic, o-anistic, p-anisic, and itaconic acids in water from T = 278 K to T = 345 K. J. Chem. Thermodyn. 1999, 31, 85−91. (14) Apelblat, A.; Manzurola, E. Solubility of oxalic, malonic, succinic, adipic, malic, citric, and tartaric-acids in water from 278.15-K to 338.15-K. J. Chem. Thermodyn. 1987, 19 (3), 317−320. (15) Buchowski, H.; Ksiazczak, A.; Pietrzyk, S. Solvent activity along a saturation line and solubility of hydrogen-bonding solids. J. Phys. Chem. 1980, 84, 975−979. (16) Long, B.; Li, J.; Song, Y.; Du, L. Temperature dependent solubility of α-form l-glutamic acid in selected organic solvents: measurements and thermodynamic modeling. Ind. Eng. Chem. Res. 2011, 50 (13), 8354−8360. (17) Renon, H.; Prausnitz, J. M. Local compositions in thermodynamic excess functions for liquid mixtures. AIChE J. 1968, 14, 135−144. (18) Acree, W. E.; Zvaigzne, A. I. Thermodynamic properties of non-electrolyte solutions: Part 4. Estimation and mathematical representation of solute activity coefficients and solubilities in binary solvents using the NIBS and Modified Wilson equations. Thermochim. Acta 1991, 178, 151−167. (19) Jouyban, A. Handbook of solubility data for pharmaceuticals; CRC Press: Boca Raton, FL, USA, 2009. (20) Smith, J. M.; Van Ness, N. C. Introduction to Chemical Engineering Thermodynamics, 3rd ed.; McGraw-Hill: New York, 1975. (21) Li, J.; Wang, Z.; Bao, Y.; Wang, J. Solid-Liquid Phase Equilibrium and Mixing Properties of Cloxacillin Benzathine in Pure and Mixed Solvents. Ind. Eng. Chem. Res. 2013, 52, 3019−3026. (22) Hojjati, H.; Rohani, S. Measurement and prediction of solubility of paracetamol in water isopropanol solution. Part 1.

Measurement and data analysis. Org. Process Res. Dev. 2006, 10, 1101−1109. (23) Zou, F.; Zhuang, W.; Wu, J.; Zhou, J.; Liu, Q.; Chen, Y.; Xie, J.; Zhu, C.; Guo, T.; Ying, H. Experimental measurement and modelling of solubility of inosine-5 -monophosphate disodium in pure and mixed solvents. J. Chem. Thermodyn. 2014, 77, 14−22. (24) Delgado, D. R.; Martínez, F. Solubility and solution thermodynamics of sulfamerazine and sulfamethazine in some ethanol + water mixtures. Fluid Phase Equilib. 2013, 360, 88−96.

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Measurement and Correlation of Solubility and Thermodynamic

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