Lamotrigine Solubility in Some Nonaqueous Solvent Mixtures at 298.2

Article pubs.acs.org/jced

Lamotrigine Solubility in Some Nonaqueous Solvent Mixtures at 298.2 K Afsaneh Farjami† and Abolghasem Jouyban*,⊥,§ †

Drug Applied Research Center, ⊥Pharmaceutical Analysis Research Center and Faculty of Pharmacy, and §Kimia Idea Pardaz Azarbayjan (KIPA) Science Based Company, Tabriz University of Medical Sciences, Tabriz, Iran ABSTRACT: Experimental solubility of lamotrigine in binary mixtures of methanol + acetone, ethanol + acetone, 1-propanol + acetone, ethyl acetate + acetone, ethyl acetate + methanol, ethyl acetate + ethanol, ethyl acetate + 1-propanol at 298.2 K are reported. The measured data were fitted to the Jouyban−Acree model and the overall mean percentage deviation (MPD) of back-calculated solubilities was 4.0 %. Also, densities of the saturated solutions were measured and fitted to the Jouyban−Acree model. The overall MPD value for this analysis was 6.0 %.

1. INTRODUCTION Lamotrigine (LMG; 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4triazine) is one of the well-known antiepileptic agents approved for the treatment of partial, primary, and secondary generalized tonic−clonic seizures, and it also is used for the treatment of seizures associated with Lennox−Gastaut syndrome.1 It belongs to Biopharmaceutics Classification System (BCS) class II drugs, because of its low solubility and high permeability. Combinational screening programs can find that 40% or more of active substances are poorly soluble in water.2,3 Conventional formulations of these substances cause drug performance and drug bioavailability to be often poor, erratic, and highly variable in clinical evaluations. The most applicable approach among the formulation approaches available for enhancing solubility for a poorly water-soluble compound is to generate a salt, using cosolvents, surfactants, or complexing agents such as cyclodextrins4−6 and especially emulsion,7,8 microemulsions,9 and solid dispersion technology.10,11 In addition, formulation of poorly water-soluble substances as nanometer-sized drug particles with newer techniques like nanodispersion is an alternative and beneficial approach to increase the solubility of active substances and to improve bioavailability and pharmacokinetics12,13 by increasing the surface areas, dissolution rate, and the saturation solubility that have received considerable attention in recent years.12,14 In addition to the formulation aspect discussed, the preparation of drug nanoparticles is another possibility for better dissolving active compounds and also solves the problems of low bioavailability of drugs.15 The choice of a suitable solvent system in a formulation of water-low soluble drug nanoparticles is an important issue. In the investigations of drug formulations, various methods have been developed to improve drug solubility including solubilization using solvent mixing or cosolvency. Despite the experimental determination © XXXX American Chemical Society

of drug solubility in mixed solvents, cosolvency models are an effective and accurate alternative that could replace timeconsuming and costly experimental determination methods. The Jouyban−Acree model is one of the most practical and versatile models for this purpose. Predictive models provide beneficial information in drug formulation, discovery, and development phases. The aim of this study was to investigate the solubility of LMG in binary mixtures of some widely used solvents in the field of nanoparticles. This investigation was done as a first step in the formulation of LMG nanoparticles by the nanodispersion technique. The solvents used in this study were methanol, ethanol, 1-propanol, acetone, and ethyl acetate. In pharmaceutical formulations, the cosolvent concentration should be kept as low as possible because of the possible induced side effects; these side effects may affect drug stability especially in a liquid formulation, but it should be considered that solvents used in the preparation of nanoparticles would be removed by evaporation or diffusion at the end of the nanodispersion process.13 Therefore, the safety is not a challenging issue for products prepared by this technique from the solvents. Our intent was to measure the solubility of LMG in a series of nonaqueous solvent systems containing methanol + acetone, ethanol + acetone, 1-propanol + acetone, ethyl acetate + acetone, ethyl acetate + methanol, ethyl acetate + ethanol, ethyl acetate +1-propanol at 298.2 K which extends the available solubility data of drugs in mixed solvents.16

2. EXPERIMENTAL SECTION 2.1. Materials. LMG (256.091 g·mol−1) with mass fraction purity of 0.999 was purchased from Arasto Pharmaceutical Received: April 21, 2015 Accepted: July 20, 2015

A

DOI: 10.1021/acs.jced.5b00355 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

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Table 1. List of the Materials Used

a

materiala

purity/in mass fraction

company

country

lamotrigine ethanol methanol acetone 1-propanol ethyl acetate water

0.999 0.999 0.999 0.999 0.999 0.999 conductivity < 1.5 μS·cm−1

Arasto Pharmaceuticals Scharlau Scharlau Scharlau Merck Merck lab-made

Iran Spain Spain Spain Germany Germany Iran

The chemicals were used as received from the supplier without any further purification.

could be calculated using a no intercept least-squares regression Sat Sat of (ln CSat m,T − w1 ln C1,T − w2 ln C2,T) against w1w2/T, (w1w2(w1 − w2))/T, and (w1w2(w1 − w2)2)/T. Equation 1 requires a minimum number of experimental data for calculating the numerical values of the constants. A globally trained version of the model could be used to provide a predictive model. In a previous work a general form of the model was proposed as

Company (Tehran, Iran). Ethanol (purity of 0.999 in mass fraction), methanol (purity of 0.999 in mass fraction), acetone (purity of 0.999 in mass fraction) was purchased from Scharlau (Spain), 1-propanol (purity of 0.999 in mass fraction) and ethyl acetate (purity of 0.999 in mass fraction) were purchased from Merck (Germany). Daily prepared double distilled water with the conductivity of 72 h), the supernatants of precipitate solutions were collected and diluted with double distilled water and assayed at 306 nm by UV−vis (Beckman DU-650, Fullerton) spectrophotometer. Concentration of diluted solution was calculated according calibration curve with six data points within the dynamic range of 3.9·10−5 to 1.9·10−4 mol·L−1. Each experimental data point represents the average of at least three repetitive experiments with the measured molar solubilities being reproducible to within ± 4.3 %. The RSDs vary between 0.6 % and 8.9 %. Calculated standard deviations varied from σn‑1 = 1.3·10−4 mol·L−1 to 4.8· 10−3 mol·L−1. Densities of the saturated solutions were measured by a 5 mL pycnometer. 2.3. Solubility Calculations. The Jouyban−Acree model provides accurate description for effects of both temperature and solvent composition on the solubility of a solute in binary solvent mixtures is shown as16 ln CmSat, T = w1 ln C1,SatT + w2 ln C2,SatT +

w1w2 T

2

∑ Ji (w1 − w2)

ln CmSat, T = w1ln C1,SatT + w2 ln C2,SatT +

⎛ w1w2 ⎞ 2 2 ⎜ ⎟ W + W [(c − c ) ] + W [E(e − e ) ] 2 1 2 3 1 2 ⎝ T ⎠{ 1

+ W4[S(s1 − s2)2 ] + W5[A(a1 − a 2)2 ] + W6[B(b1 − b2)2 ] + W7[V (v1 − v2)2 ]} ⎛ w w (w − w2) ⎞ +⎜ 1 2 1 ⎟{W1′ + W 2′[(c1 − c 2)2 ] ⎝ ⎠ T + W3′[E(e1 − e 2)2 ] + W 4′[S(s1 − s2)2 ] + W5′[A(a1 − a 2)2 ] + W6′[B(b1 − b2)2 ] + W 7′[V (v1 − v2)2 ]} ⎛ w w (w − w )2 ⎞ 2 ⎟{W1″ + W 2″[(c1 − c 2)2 ] +⎜ 1 2 1 T ⎠ ⎝ + W3″[E(e1 − e 2)2 ] + W 4″[S(s1 − s2)2 ] + W5″[A(a1 − a 2)2 ] + W6″[B(b1 − b2)2 ] + W 7″[V (v1 − v2)2 ]}

(2)

where E is the excess molar refraction, S is dipolarity/ polarizability of solute, A denotes the solute’s hydrogen-bond acidity, B stands for the solute’s hydrogen-bond basicity and V is the McGowan volume of the solute. In eq 2 the coefficients c, e, s, a, b, and v are the model constants (i.e., solvent’s coefficients), which depend upon the solvent system under consideration. The W terms are the model constants computed using least-square analysis. The Abraham solvent coefficients (c, e, s, a, b, and v) and Abraham solute parameters (E, S, A, B, and V) represent the extent of all known interactions between solute and solvents in the solution.17 For mathematical representation of the solubility data of a given solute in different mixed solvent systems, the Abraham solute parameters are constant values for a drug and could be considered in the model constants. Therefore, eq 2 could be simplified as

i

i=0

(1)

where CSat m,T is the mole per liter solubility of a solute in mixed Sat solvents, CSat 1,T and C2,T are molar solubility of a solute in monosolvents 1 and 2 at temperature T, respectively, w1 and w2 denote the mass fractions of the solvents 1 and 2, and Ji coefficients are the model constants. These constants are related to solvent−solvent and solvent−solute interactions and B

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The minimum solubility of LMG (1.06·10−2 mol·L−1) among the investigated solvent systems was observed in neat ethyl acetate. LMG solubility in neat ethanol is in good agreement with other reported data (1.39·10−2 mol·L−117 and 1.40·10−2 mol·L−118). The maximum solubility (7.40·10−2 mol·L−1) was obtained from a 1-propanol + acetone (0.7 + 0.3 mass fractions) mixture. This demonstrates that 1-propanol is a more efficient solvent for increasing the solubility of LMG. The solubility data of LMG in seven binary nonaqueous solvent mixtures were fitted to the Jouyban−Acree model, using eq 1, and then the model constants (J terms) were computed. The calculated J terms and the MPD values for the back-calculated solubility data are listed in Table 4. Using the reported model constant, it is possible to predict LMG solubility in all composition ranges of the solvent mixtures at various temperatures using the monosolvents solubility values at the interested temperatures.19−21 The calculated correlation errors vary between 2.6 % and 6.9 % for solubility of LMG in binary solvent mixtures. The J terms reported in Table 4 present the extent of solute−solvents’ interactions and are specific for the drug−solvent 1−solvent 2 system. As noticed above, to provide a more general model for correlating the solubility of a given drug in various solvent mixtures, one may use eq 3. The trained version of eq 3 (by including significant constants (p < 0.05)) for the solubility of LMG dissolved in the investigated nonaqueous solvent mixtures is

ln CmSat, T = w1 ln C1,SatT + w2 ln C2,SatT +

⎛ w1w2 ⎞ 2 2 ⎜ ⎟ B + B ( c − c ) + B (e − e ) 2 1 2 3 1 2 ⎝ T ⎠{ 1

+ B4 (s1 − s2)2 + B5(a1 − a 2)2 + B6 (b1 − b2)2 + B7 (v1 − v2)2 } ⎛ w w (w − w2) ⎞ +⎜ 1 2 1 ⎟{B1′ + B2′ (c1 − c 2)2 + B3′(e1 − e 2)2 ⎝ ⎠ T + B4′ (s1 − s2)2 + B5′(a1 − a 2)2 + B6′(b1 − b2)2 + B7′ (v1 − v2)2 } ⎛ w w (w − w )2 ⎞ 2 ⎟{B1″ + B2″(c1 − c 2)2 +⎜ 1 2 1 T ⎠ ⎝ + B3″(e1 − e 2)2 + B4″(s1 − s2)2 + B5″(a1 − a 2)2 + B6″(b1 − b2)2 + B7″(v1 − v2)2 }

(3)

where B terms are the model constants. Table 2 lists the numerical values of the Abraham solvent coefficients of the investigated solvents in this work. Table 2. Abraham Solvent Coefficients Taken from Literature17 solvent

c

e

s

a

b

v

1-propanol acetone ethanol ethyl acetate methanol

0.139 0.313 0.222 0.328 0.276

0.405 0.312 0.471 0.369 0.334

−1.029 −0.121 −1.170 −0.446 −0.714

0.247 −0.608 0.326 −0.700 0.243

−3.767 −4.753 −4.250 −4.904 −3.320

3.986 3.942 3.857 4.150 3.549

ln CmSat, T = w1 ln C1,SatT + w2 ln C2,SatT +

− 10525.96(e1 − e 2)2 + 141.65(s1 − s2)2 + 368.67(a1 − a 2)2 − 86.57(b1 − b2)2 + 251.30(v1 − v2)2 } ⎛ w w (w − w2) ⎞ +⎜ 1 2 1 ⎟{ − 191.11 + 30503.53[(c1 − c 2)2 ] ⎝ ⎠ T

The accuracy of fitted and predicted values (solubility/ density) was checked by the mean percentage deviation (MPD) computed by 100 MPD = N

⎛ |calculated − experimental| ⎞ ⎟ ∑⎜ experimental ⎠ ⎝

⎛ w1w2 ⎞ 2 ⎜ ⎟ 238.81 + 5221.44[(c − c ) ] 1 2 ⎝ T ⎠{

+ 94447.51(e1 − e 2)2 − 1446.39(s1 − s2)2 − 954.07(a1 − a 2)2 + 465.31(b1 − b2)2 } ⎛ w w (w − w )2 ⎞ 2 ⎟{303.74 − 197.26(s1 − s2)2 +⎜ 1 2 1 T ⎠ ⎝

(4)

3. RESULTS AND DISCUSSION The LMG solubility and density values of saturated solutions in the investigated binary solvent mixtures are listed in Table 3. The solubility of LMG is increased with the addition of methanol, ethanol, 1-propanol, and ethyl acetate to acetone (solvent 2), and reached a maximum value corresponding to 0.4, 0.3, 0.7, and 0.3 mass fractions of the solvents, respectively. The solubility then decreases with the further addition of solvents. The maximum solubility values in methanol + acetone, ethanol + acetone, 1-propanol + acetone, ethyl acetate + acetone mixtures are (4.68·10−2, 6.21·10−2, 7.41·10−2 and 2.50·10−2) mol·L−1, respectively. With the addition of methanol, ethanol, and 1-propanol to ethyl acetate, the solubility of LMG is increased and reaches a maximum value corresponding to 0.4, 0.4, 0.5 mass fractions of methanol, ethanol, 1-propanol, respectively, and then decreases with further addition of these solvents. The maximum solubility values of LMG in ethyl acetate + methanol, ethyl acetate + ethanol, ethyl acetate + 1-propanol mixtures are (3.55·10−2, 3.36·10−2, and 6.06·10−2) mol·L−1, respectively.

+ 111.22(b1 − b2)2 − 1831.16(v1 − v2)2 }

(5)

Equation 5 back-calculates the solubility data with the overall MPD of 3.8 ± 4.3%. The Jouyban−Acree model could also be used to correlate density of saturated solutions of a drug in binary solvent mixtures at various temperatures. The experimental densities of LMG in the mentioned solvent mixtures were fitted to eq 6 ln ρmSat, T = w1 ln ρ1,Sat + w2 ln ρ2,SatT + T

w1w2 T

2

∑ Ai(w1 − w2)

i

i=0

(6)

ρSat m,T,

ρSat 1,T,

ρSat 2,T

where and are the densities of the saturated solution in a mixture and solvents 1 and 2 at temperature 298.2 K, respectively, and Ai coefficient is the model constants.21,22 The Ai values could be calculated using the solute free density of solvent mixtures, and the density of saturated solutions could be predicted by using experimental densities of the drug C

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Table 3. Solvent Composition, Density (ρ) of Saturated Solutions, Experimental Solubility of Lamotrigine (CExp m ) in Binary a Mixtures at 298.2 K, and the Calculated (CCalc m ) Values Using the Jouyban−Acree Model CExp m w1 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70

−1

mol·L

CCalc m −1

mol·L

methanol (1) + acetone (2) 1.67·10−02 1.67·10−02 −02 2.97·10 2.81·10−02 3.83·10−02 3.87·10−02 4.53·10−02 4.53·10−02 −02 4.68·10 4.64·10−02 −02 4.25·10 4.30·10−02 3.55·10−02 3.72·10−02 3.22·10−02 3.10·10−02 −02 2.46·10 2.57·10−02 −02 2.40·10 2.19·10−02 1.99·10−02 1.99·10−02 ethanol (1) + acetone (2) 1.67·10−02 1.67·10−02 −02 2.62·10 2.86·10−02 4.14·10−02 4.02·10−02 5.21·10−02 4.76·10−02 −02 4.38·10 4.87·10−02 3.78·10−02 4.41·10−02 3.32·10−02 3.61·10−02 −02 2.92·10 2.74·10−02 −02 2.05·10 1.97·10−02 1.54·10−02 1.37·10−02 1.34·10−02 1.34·10−02 1-propanol(1) + acetone (2) 1.67·10−02 1.67·10−02 2.93·10−02 2.78·10−02 3.85·10−02 3.94·10−02 −02 4.98·10 4.99·10−02 −02 5.85·10 5.88·10−02 6.32·10−02 6.55·10−02 6.82·10−02 6.90·10−02 −02 7.41·10 6.73·10−02 −02 5.77·10 5.85·10−02 4.00·10−02 4.28·10−02 −02 2.45·10 2.45·10−02 ethyl acetate (1) + acetone (2) 1.67·10−02 1.67·10−02 2.01·10−02 1.92·10−02 −02 2.18·10 2.11·10−02 −02 2.50·10 2.23·10−02 2.19·10−02 2.27·10−02 2.09·10−02 2.21·10−02 −02 1.87·10 2.07·10−02 −02 1.82·10 1.86·10−02

ρ g·cm

CExp m −3

w1

8.528·10−01 8.522·10−01 8.513·10−01 8.504·10−01 8.494·10−01 8.481·10−01 8.467·10−01 8.448·10−01 8.424·10−01 8.391·10−01 8.347·10−01

0.80 0.90 1.00 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00

8.528·10−01 8.530·10−01 8.531·10−01 8.531·10−01 8.532·10−01 8.532·10−01 8.532·10−01 8.531·10−01 8.529·10−01 8.524·10−01 8.517·10−01

0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00

8.528·10−01 8.568·10−01 8.608·10−01 8.649·10−01 8.690·10−01 8.731·10−01 8.773·10−01 8.814·10−01 8.856·10−01 8.897·10−01 8.938·10−01

0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00

8.528·10−01 8.704·10−01 8.870·10−01 9.027·10−01 9.177·10−01 9.320·10−01 9.457·10−01 9.588·10−01

mol·L

−1

CCalc m

ρ

mol·L−1

g·cm−3

ethyl acetate (1) + acetone (2) 1.75·10−02 1.61·10−02 −02 1.38·10 1.33·10−02 1.06·10−02 1.06·10−02 ethyl acetate (1) + methanol (2) 1.99·10−02 1.99·10−02 −02 2.21·10 2.24·10−02 2.58·10−02 2.56·10−02 2.88·10−02 2.91·10−02 −02 3.14·10 3.21·10−02 −02 3.34·10 3.38·10−02 3.55·10−02 3.33·10−02 3.01·10−02 3.01·10−02 −02 2.52·10 2.43·10−02 −02 1.54·10 1.73·10−02 1.06·10−02 1.06·10−02 ethyl acetate (1) + ethanol (2) 1.34·10−02 1.34·10−02 1.56·10−02 1.57·10−02 2.00·10−02 2.05·10−02 −02 2.34·10 2.38·10−02 −02 2.77·10 2.67·10−02 3.16·10−02 3.00·10−02 3.36·10−02 3.35·10−02 −02 3.32·10 3.57·10−02 −02 3.03·10 3.30·10−02 2.75·10−02 2.33·10−02 1.06·10−02 1.06·10−02 ethyl acetate (1) +1-propanol (2) 2.45·10−02 2.45·10−02 3.32·10−02 3.59·10−02 4.84·10−02 4.55·10−02 −02 5.34·10 5.28·10−02 −02 5.72·10 5.80·10−02 6.06·10−02 6.09·10−02 −02 5.92·10 6.01·10−02 −02 5.61·10 5.39·10−02 3.87·10−02 4.14·10−02 2.64·10−02 2.49·10−02 −02 1.06·10 1.06·10−02

9.714·10−01 9.836·10−01 9.954·10−01 8.347·10−01 8.633·10−01 8.871·10−01 9.069·10−01 9.238·10−01 9.386·10−01 9.518·10−01 9.640·10−01 9.753·10−01 9.859·10−01 9.954·10−01 8.517·10−01 8.718·10−01 8.900·10−01 9.067·10−01 9.220·10−01 9.361·10−01 9.493·10−01 9.617·10−01 9.734·10−01 9.846·10−01 9.954·10−01 8.938·10−01 9.058·10−01 9.174·10−01 9.286·10−01 9.394·10−01 9.499·10−01 9.599·10−01 9.695·10−01 9.786·10−01 9.872·10−01 9.954·10−01

a

The standard uncertainties u are ur(w) = 0.01, ur(C) = 0.043, ur(ρ) = 0.004, u(T) = 0.2 K, and the measurements were made at atmospheric pressure.

saturated solutions in the monosolvents.22 The numerical values of the Ai terms computed using the density of solute free solvent mixtures and the MPD values for the investigated binary solvent systems were listed in Table 5. With the use of the density of LMG saturated solutions in the monosolvents at T and model constants, the density of saturated solutions in binary mixtures could be predicted. The overall MPD value for this analysis was 6.0 %.

acetate were reported which extends the solubility database of pharmaceuticals for developing cosolvency models.16,17,23 Experimental solubility and density data were fitted to the Jouyban−Acree model, and the constants were computed. The results showed that the overall MPD value of back-calculated solubility of binary mixtures was 4.1 %. Also, the same analyses were done for the densities of same saturated solutions mixtures with the overall MPDs of 6.0 %. The maximum solubility (7.41·10−2 mol·L−1) was obtained from the 1propanol + acetone (0.7 + 0.3 mass fractions) mixture.

4. CONCLUSIONS The solubility and density data of LMG in nonaqueous binary mixtures of methanol, ethanol, 1- propanol, acetone, and ethyl D

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Table 4. Numerical Values of the Model Constants (J0, J1, and J2) of eq 1, Number of Data Points in Each Set (N), and the Mean Percentage Deviation (MPD) for the Calculated Solubilities of Lamotrigine in Solvent Mixtures at 298.2 K Using eqs 1 and 5 MPD

a

solvent 1

solvent 2

J0

J1

J2

N

eq 1

eq 5

methanol ethanol 1-propanol ethyl acetate ethyl acetate ethyl acetate ethyl acetate

acetone acetone acetone acetone methanol ethanol 1-propanol

432.00 538.32 607.88 262.17 438.38 485.32 687.78

−345.82 −401.20 112.40 NSa 219.25 426.73 274.26

86.74 NSa 249.81 NSa NSa 361.97 313.87

11 11 11 11 11 11 11

2.7 7.0 2.7 4.8 2.6 5.2 3.2 4.0

3.0 6.9 2.7 2.8 3.0 4.8 3.1 3.8

Not significant (p > 0.05). (11) Serajuddin, A. Solid Dispersion of Poorly Water-Soluble Drugs: Early Promises, Subsequent Problems, and Recent Breakthroughs. J. Pharm. Sci. 1999, 88, 1058−1066. (12) Krause, K.; Müller, R. Production and Characterisation of Highly Concentrated Nanosuspensions by High Pressure Homogenisation. Int. J. Pharm. 2001, 214, 21−24. (13) Horn, D.; Rieger, J. Organic Nanoparticles in the Aqueous PhaseTheory, Experiment, and Use. Angew. Chem., Int. Ed. 2001, 40, 4330−4361. (14) Jacobs, C.; Kayser, O.; Müller, R. Production and Characterisation of Mucoadhesive Nanosuspensions for the Formulation of Bupravaquone. Int. J. Pharm. 2001, 214, 3−7. (15) Dressman, J.; Reppas, C. Drug Solubility: How to Measure It, How to Improve It. Adv. Drug Delivery Rev. 2007, 59, 531−532. (16) Jouyban, A. Handbook of Solubility Data for Pharmaceuticals; CRC Press: Boca Raton, 2010. (17) Jouyban, A.; Soltanpour, S.; Soltani, S.; Tamizi, E.; Fakhree, M. A. A.; Acree, W. E., Jr. Prediction of Drug Solubility in Mixed Solvents Using Computed Abraham Parameters. J. Mol. Liq. 2009, 146, 82−88. (18) Shayanfar, A.; Fakhree, M. A. A.; Acree, W. E., Jr.; Jouyban, A. Solubility of Lamotrigine, Diazepam, and Clonazepam in Ethanol + Water Mixtures at 298.15 K. J. Chem. Eng. Data 2009, 54, 1107−1109. (19) Jouyban, A.; Shokri, J.; Barzegar-Jalali, M.; Hassanzadeh, D.; Acree, W. E., Jr.; Ghafourian, T. Solubility of Chlordiazepoxide, Diazepam, and Lorazepam in Ethanol + Water Mixtures at 303.2 K. J. Chem. Eng. Data 2009, 54, 2142−2145. (20) Jouyban, A.; Acree, W. E., Jr. Comments on “Solubility of Ethyl Maltol in Aqueous Ethanol Mixtures. J. Chem. Eng. Data 2009, 54, 1168−1170. (21) Ahmadian, S.; Panahi-Azar, V.; Fakhree, M. A. A.; Acree, W. E., Jr.; Jouyban, A. Solubility of Phenothiazine in Water, Ethanol, and Propylene Glycol at (298.2 to 338.2) K and Their Binary and Ternary Mixtures at 298.2 K. J. Chem. Eng. Data 2011, 56, 4352−4355. (22) Soltanpour, S.; Jouyban, A. Solubility of Acetaminophen and Ibuprofen in Polyethylene Glycol 600, Propylene Glycol and Water Mixtures at 25 C. J. Mol. Liq. 2010, 155, 80−84. (23) Jouyban, A.; Shayanfar, A.; Panahi-Azar, V.; Soleymani, J.; Yousefi, B. H.; Acree, W. E., Jr. Solubility Prediction of Drugs in Mixed Solvents Using Partial Solubility Parameters. J. Pharm. Sci. 2011, 100, 4368−4382.

Table 5. Numerical Values of the Model Constants, Number of Data Points in Each Set (N), and the Mean Percentage Deviation (MPD) for the Calculated Densities of Lamotrigine in Binary Solvent Mixtures solvent 1 methanol ethanol 1-propanol ethyl acetate ethyl acetate ethyl acetate ethyl acetate a

A0

solvent 2 acetone acetone acetone acetone methanol ethanol 1-propanol

20.365 −9.164 12.217 8.231 −57.033 5.13 0.85

A1 32.787 NSa −9.346 −10.586 −44.374 −7.006 NSa

A2

N

MPD

a

11 11 11 11 11 11 11

7.8 4.3 7.1 6.7 4.5 6.3 5.5 6.0

NS NSa 15.451 16.701 −148.252 15.243 NSa

Not significant (p > 0.05).

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*Tel.: +98 41 33379323. Fax: +98 41 33363231. E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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REFERENCES

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DOI: 10.1021/acs.jced.5b00355 J. Chem. Eng. Data XXXX, XXX, XXX−XXX