The structural effect on volumetric and acoustic

MOLLIQ-05355; No of Pages 6 Journal of Molecular Liquids xxx (2015) xxx–xxx

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The structural effect on volumetric and acoustic properties of aqueous anti-HIV drugs (Emtricitabine and Lamivudine) at various temperatures☆ Nagaraju Devunuri a, Nagaraj Amminabavi a, Bharath Kumar Chennuri b, Venkatramana Losetty b, Ramesh L. Gardas b,⁎ a b

VFSTR University, Vadlamudi, Guntur, Andhra Pradesh 522 213, India Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India

a r t i c l e

i n f o

Article history: Received 22 June 2015 Received in revised form 19 December 2015 Accepted 23 December 2015 Available online xxxx Keywords: Ionic liquids Apparent molar volume Laplace–Newton equation Anti-HIV drugs

a b s t r a c t In this work, density (ρ) and speed of sound (u) data were measured for aqueous solutions of two drugs namely Emtricitabine and Lamivudine in the various concentrations, m from (293.15 to 318.15) K and at 0.1 MPa pressure. The measured density and speed of sound data were used to calculate the apparent molar volume (Vϕ) and the isentropic compressibility (κs), using Laplace–Newton's equation. The apparent molar volume at infinite dilutions (V∞ ϕ) of drugs has been evaluated from linear equation. The temperature dependence of apparent molar volume at infinite dilution (V∞ ϕ ) can be expressed as the second-order polynomial equation, in turn apparent molar expansibility (E∞ ϕ ) at infinite dilution was calculated. These parameters have been used to understand the effect of temperature on interactions between drugs and water. Moreover, the structure making and breaking ability of drugs are analyzed at experimental conditions. © 2015 Elsevier B.V. All rights reserved.

1. Introduction The knowledge of thermodynamic properties of aqueous solutions is particularly important in biological studies, because of good relations to ions or other kind of solute molecules [1]. In biological system, the solvation behavior of drug molecules in solutions plays a significant role in understanding the activity of drugs. It is difficult to understand these drug–solvent interactions directly in biological system since these interactions can be affected by co-solutes such as salts, polymers, carbohydrates, surfactants, amino acids, proteins, peptides, and alcohols, and also drug–solvent interactions vary with the temperature of solutions [2,3]. Drug–macromolecular interactions are an important phenomenon in physiological media, such as blood, membranes and extracellular fluids. Physicochemical investigations suggest that understanding the nature and the extent of the patterns of molecular aggregation that exist in binary liquid mixtures as well as their sensitivities to variations in composition and the molecular structure of the pure components is important [4,5]. Moreover, thermodynamic properties of mixtures containing components capable of undergoing specific interactions exhibit significant deviations from ideality due to differences in molecular size, shape and structure. In the present work, we have ☆ Dedicated to Dr. Lavu Rathaiah on the occasion of his 64th Birthday. ⁎ Corresponding author. E-mail address: [email protected] (R.L. Gardas). URL: http://www.iitm.ac.in/info/fac/gardas (R.L. Gardas).

chosen two biologically active drugs, namely, Emtricitabine and Lamivudine and their chemical structures (Scheme 1) are presented below. Emtricitabine is the L -enantiomer of a thio analog of cytidine, which differs from other cytidine and it has a fluorine group at 5position. Emtricitabine is a synthetic nucleoside analog with activity against HIV type 1 reverse transcriptase. The chemical name is 4-amino-5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5yl]-1,2-dihydropyrimidin-2-one, molecular formula C8H10N3O3SF and has a molecular weight of 247.25 g·mol−1 [6]. Lamivudine has been used for treatment of chronic hepatitis B at a lower dose for treatment of HIV/AIDS. It is L-enantiomer and similarity of dideoxycytidine can discourage both types of HIV reverse transcriptase and also hepatitis B virus reverse transcriptase [7]. It is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The chemical name of Lamivudine is 4-amino-1[(2R,5S)-2-(hydroxyethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin2-one, molecular formula C8H11N3O3S and has a molecular weight of 229.26 g·mol−1. The density, speed of sound, apparent molar volume and apparent molar isentropic compressibility measurements of drug solution at infinite dilution [8] have been found to be highly useful in understanding the nature of molecular interactions between water and drug molecules. Most of the biochemical processes happen in aqueous media, therefore, understanding molecular interactions existing between

http://dx.doi.org/10.1016/j.molliq.2015.12.084 0167-7322/© 2015 Elsevier B.V. All rights reserved.

Please cite this article as: N. Devunuri, et al., The structural effect on volumetric and acoustic properties of aqueous anti-HIV drugs (Emtricitabine and Lamivudine) at various te..., J. Mol. Liq. (2015), http://dx.doi.org/10.1016/j.molliq.2015.12.084

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N. Devunuri et al. / Journal of Molecular Liquids xxx (2015) xxx–xxx Table 2 The molality (m), densities (ρ) and apparent molar volumes (Vϕ) of Emtricitabine and Lamivudine drugs with water at T = (293.15 to 318.15) K and 0.1 MPa pressure. m mol·kg−1

Scheme 1. The chemical structures of Emtricitabine (A) and Lamivudine (B) drugs.

Vϕ·106 m3·mol−1

ρ·10−3 kg·m−3


ρ·10−3 kg·m−3


Emtricitabine + water T/K = 293.15 0.0146 0.99965 148.22 0.0328 1.00144 148.26 0.0520 1.00331 148.43 0.0906 1.00702 148.75 0.0994 1.00786 148.78 0.1515 1.01265 149.84 0.1984 1.01697 149.96 0.2481 1.02137 150.50

T/K = 298.15 0.99849 148.69 1.00026 149.12 1.00212 149.18 1.00579 149.65 1.00661 149.82 1.01136 150.82 1.01564 150.92 1.02000 151.45

T/K = 303.15 0.99709 149.31 0.99885 149.74 1.00068 150.19 1.00433 150.49 1.00514 150.69 1.00984 151.75 1.01408 151.86 1.01841 152.35

T/K = 308.15 0.99546 150.30 0.99721 150.54 0.99902 151.11 1.00265 151.28 1.00344 151.62 1.00811 152.60 1.01232 152.69 1.01661 153.20

T/K = 313.15 0.99363 151.37 0.99537 151.38 0.99716 152.07 1.00077 152.10 1.00155 152.49 1.00619 153.41 1.01036 153.55 1.01462 154.03

T/K = 318.15 0.99162 152.10 0.99335 152.08 0.99512 152.95 0.99870 152.99 0.99948 153.31 1.00408 154.27 1.00822 154.39 1.01245 154.86

0.0146 0.0328 0.0520 0.0906 0.0994 0.1515 0.1984 0.2481

drugs–water and also their temperature dependence play an important role in evaluating the drug action across the biological membrane [9]. Many researchers have studied density and speed of sound of biologically active drugs with water systems [10–12] and interpreted results in terms of hydrophilic–hydrophilic and hydrophilic–hydrophobic interactions [13,14]. To the best of our knowledge there are no apparent molar volume (Vϕ) and isentropic compressibility (κs) data available in the literature for the studied binary systems. So, in order to understand the structural and chemical bonding pattern (solute–solvent interactions) of Emtricitabine and Lamivudine with water, the apparent molar volumes, and isentropic compressibilities of drug solutions have been studied at T = (293.15, 298.15, 303.15, 308.15, 313.15 and 318.15) K and 0.1 MPa pressure. Apparent molar volume at infinity dilution (Vϕ∞) is calculated by linear fitting between apparent molar volumes and drug concentration in molality at different temperatures, and in turn used to calculate the apparent molar expansibility (Eϕ∞).

ρ·10−3 kg·m−3

Lamivudine + water

2. Experimental 2.1. Materials and methods

0.0259 0.0337 0.0617 0.0914 0.1096 0.1578 0.2002 0.2536

T/K = 293.15 1.00040 144.30 1.00106 144.42 1.00339 144.63 1.00580 145.18 1.00727 145.37 1.01115 145.49 1.01448 145.74 1.01862 145.90

T/K = 298.15 0.99923 145.03 0.99988 145.11 1.00218 145.59 1.00461 145.65 1.00606 145.94 1.00992 146.02 1.01324 146.23 1.01736 146.40

T/K = 303.15 0.99782 145.82 0.99846 146.04 1.00075 146.29 1.00315 146.49 1.00458 146.85 1.00841 146.87 1.01170 147.07 1.01577 147.29

0.0259 0.0337 0.0617 0.0914 0.1096 0.1578 0.2002 0.2536

T/K = 308.15 0.99619 146.43 0.99683 146.53 0.99909 147.10 1.00147 147.30 1.00289 147.63 1.00668 147.71 1.00994 147.91 1.01398 148.10

T/K = 313.15 0.99436 147.09 0.99499 147.37 0.99723 147.95 0.99959 148.13 1.00100 148.44 1.00476 148.51 1.00799 148.72 1.01200 148.89

T/K = 318.15 0.99234 147.97 0.99297 148.07 0.99519 148.73 0.99753 148.93 0.99893 149.22 1.00266 149.29 1.00587 149.47 1.00984 149.68

The standard uncertainties are u(T) = 0.01 K, u(m) = 9.50 × 10−6 mol·kg−1, u(ρ) = 1

The details of chemicals are given in Table 1. The drugs were used after drying over P2O5 in vacuum desiccators at room temperature for 48 h. For the preparation of aqueous solution, freshly double distilled, degassed water was used. The aqueous solutions were prepared on the basis of mass at room temperature over a concentration range from 0.01 to 0.25 mol·kg− 1 and kept in airtight bottles to minimize the adsorption of atmospheric moisture. An electronic analytical balance (Sartorius, Model CPA225D) with a precision of ± 0.01 mg was used for mass measurements. The density (ρ) and speed of sound (u) data of aqueous solutions were measured simultaneously by using vibrating-tube digital density and speed of sound analyzer (Anton Paar DSA 5000 M) on the same day of sample preparation. The density and speed of sound cells are temperature controlled by a built-in Peltier thermostat (PT-100) having an accuracy of ±0.01 K. The speed of sound can be regarded as thermodynamic property, as the ultrasonic absorption is negligible due to the use of low frequency (3 MHz) and low amplitude of the acoustic waves [15,16]. According to the supplier's manual instructions, deionized, double distilled, degassed water were used for the calibration of instrument. The uncertainty of measurements

kg·m−3, u(P) = 1 kPa, u(Vϕ) = (0.06–0.020) × 106 m3·mol−1 for low and high concentration ranges of drugs, respectively.

for the density and speed of sound is 1 kg·m−3 and 0.5 m·s−1, respectively [17]. 3. Results and discussions 3.1. Partial molar properties The experimentally measured density (ρ) and speed of sound (u) data of binary mixture of drugs with water, as a function of molality (m) at T = (293.15, 298.15, 303.15, 308.15, 313.15 and 318.15) K and 0.1 MPa pressure are given in Tables 2 and 3. The measured density and speed of sound data versus concentration at various temperatures for both the drugs are graphically represented in Figs. 1–4, respectively. It was experimentally observed that the density of solutions (drugs + water) increases with increases the drug concentration, i.e. for Emtricitabine (0.99965–1.02137) × 103 kg·m− 3 in the

Table 1 Name of the drug, source, molar mass, solubility and purity in mass fraction. Name of the drug

Source

Molar mass (g·mol−1)

Appearance

Solubility

Purity in mass fraction

Emtricitabine Lamivudine

Mylan Mylan

247.25 229.26

White powder White powder

Water, methanol Water, sparingly soluble in methanol

0.99 0.99


N. Devunuri et al. / Journal of Molecular Liquids xxx (2015) xxx–xxx

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Table 3 The molality (m), speed of sound (u) and isentropic compressibility (κs) of Emtricitabine and Lamivudine drugs with water at T = (293.15 to 318.15) K and 0.1 MPa pressure. m mol·kg−1

u m·s−1

κs .1012 (Pa−1)

u m·s−1

κs .1012 (Pa−1)

u m·s−1

κs .1012 (Pa−1)

Emtricitabine + water T/K = 293.15 0.0146 1483.4 452.7 0.0328 1484.3 450.5 0.0520 1486.4 448.9 0.0906 1488.8 445.1 0.0994 1490.0 442.8 0.1515 1493.7 438.9 0.1984 1496.8 435.2 0.2481 1500.0 431.3

T/K = 298.15 1497.5 445.0 1498.2 443.0 1500.2 441.5 1502.3 437.9 1503.5 435.9 1506.8 432.2 1509.7 428.7 1512.6 425.2

T/K = 303.15 1509.8 438.6 1510.5 436.7 1512.2 435.3 1514.1 432.0 1515.2 430.2 1518.2 426.7 1520.8 423.4 1523.5 419.9

T/K = 308.15 1520.4 433.3 1521.0 431.6 1522.6 430.3 1524.3 427.2 1525.2 425.6 1528.0 422.3 1530.3 419.2 1532.7 415.7

T/K = 313.15 1529.3 429.2 1529.9 427.6 1531.3 426.3 1532.9 423.4 1533.7 421.9 1536.2 418.8 1538.3 415.9 1540.5 413.0

T/K = 318.15 1536.8 426.0 1537.4 424.5 1538.6 423.3 1540.0 420.6 1540.8 419.2 1543.0 416.3 1544.9 413.5 1546.8 410.7

0.0146 0.0328 0.0520 0.0906 0.0994 0.1515 0.1984 0.2481

Fig. 2. Plot of density versus Lamivudine drug concentration in molality at 293.15 K (■), 298.15 K (●), 303.15 K (▲), 308.15 K (▼), 313.15 K (♦) and 318.15 K (◄).

Lamivudine + water 0.0259 0.0337 0.0617 0.0914 0.1096 0.1578 0.2002 0.2536

T/K = 293.15 1483.6 454.1 1484.3 453.4 1486.7 450.9 1489.1 448.4 1490.5 446.8 1494.3 442.9 1497.5 439.6 1501.2 436.7

T/K = 298.15 1497.6 446.2 1498.3 445.5 1500.5 443.2 1502.7 440.8 1504.3 439.2 1507.5 435.7 1510.5 432.6 1513.8 429.3

T/K = 303.15 1509.9 439.6 1510.6 438.9 1512.5 436.8 1514.5 434.6 1516.3 433.0 1519.1 429.7 1521.8 426.8 1524.7 423.9

0.0259 0.0337 0.0617 0.0914 0.1096 0.1578 0.2002 0.2536

T/K = 308.15 1520.5 434.2 1521.2 433.5 1522.8 431.6 1524.7 429.5 1526.3 428.0 1528.9 425.0 1531.5 422.2 1534.0 419.2

T/K = 313.15 1529.5 429.9 1530.1 429.3 1531.6 427.5 1533.3 425.5 1534.7 424.2 1537.1 421.2 1539.5 418.6 1541.9 415.7

T/K = 318.15 1537.0 426.6 1537.5 426.0 1538.9 424.3 1540.5 422.4 1541.7 421.2 1544.0 418.4 1546.2 415.9 1548.3 412.4

The standard uncertainties are u(T) = 0.01 K, u(P) = 1 kPa, u(m) = 9.50 × 10−6 mol·kg−1, u(u) = 0.5 m·s−1, u(κs) = 0.02 × 10−12 Pa−1 for low and high concentration ranges of drugs, respectively.

Fig. 1. Plot of density versus Emtricitabine drug concentration in molality at 293.15 K (■), 298.15 K (●), 303.15 K (▲), 308.15 K (▼), 313.15 K (♦) and 318.15 K (◄).

concentration range (0.0146–0.2481) mol·kg− 1 and Lamivudine (1.00040–1.01862) × 10 3 kg·m− 3 in the concentration range (0.0259–0.2536) mol·kg−1 at 293.15 K. In addition the density values, for the particular concentration of the solution, decreases with increase in the temperature T = (293.15–318.15) K, e.g. density of Emtricitabine decreases (0.99965–0.99162) × 103 kg·m−3 at 0.0146 mol·kg−1 and density of Lamivudine decreases (1.00040–0.99234) × 103 kg·m−3 at 0.0259 mol·kg−1. The speed of sound data of solutions increases with increase in the concentration of the drug from 1483.4–1500.0 m·s−1 and 1483.6–1501.2 m·s−1 for Emtricitabine and Lamivudine respectively, at 293.15 K and also speed of sound increases with increase in the temperature. In general, the difference between the volume of the solution and pure solvent per mole of solute is called apparent molar volume [18] as shown in Eq. (1), V ϕ ¼ V n1 V 10 =n2

ð1Þ

Fig. 3. Plot of speed of sound versus Emtricitabine drug concentration in molality at 293.15 K (■), 298.15 K (●), 303.15 K (▲), 308.15 K (▼), 313.15 K (♦) and 318.15 K (◄).


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Fig. 4. Plot of speed of sound versus Lamivudine drug concentration in molality at 293.15 K (■), 298.15 K (●), 303.15 K (▲), 308.15 K (▼), 313.15 K (♦) and 318.15 K (◄).

where V, V10, and n1 and n2 are the volume of the solution, molar volume of the solvent, and number of moles of solvent and solute, respectively. The apparent molar volumes (Vϕ) of binary mixtures of Emtricitabine and Lamivudine drugs with water were calculated from measured density and speed of sound data as a function of molality (m) of drug, at various temperatures and 0.1 MPa pressure by following mathematical Eq. (2),

Vϕ ¼

M ρ ρ0 1000 ρ mρρ0

ð2Þ

where M and m are the molar mass (kg·mol−1) and molality (mol·kg−1) of the drugs, ρ and ρ0 are the density (kg·m−3) of the binary solution and pure solvent, respectively.

Fig. 5. Plot of apparent molar volume (Vϕ) versus Emtricitabine drug concentration in molality at different temperatures.

Fig. 6. Plot of apparent molar volume (Vϕ) versus Lamivudine drug concentration in molality at different temperatures.

Isentropic compressibility (κs) is evaluated from the measured density (ρ) and speed of sound (u) data by using the following relation (Eq. (3)), κs ¼

1 : ρu2

ð3Þ

In the present study, κs data decreases with temperature at each composition due to an increase in thermal agitation, facilitating the release of solvent molecules from the solute and resulting in an increase in the solution volume, making the solution more compressible. The resultant Vϕ and κs values of Emtricitabine and Lamivudine mixtures data are listed in Tables 2 and 3 and are plotted in Figs. 5–8. In general Vϕ values increase with an increase in temperature and concentration of solute for each binary system. The variation in Vϕ values observed in this work is similar to the trend observed by Moattar et al. [19] and Bahadur et al. [20]. At low concentration of drug, the solute molecules are surrounded by the solvent molecules resulting in strong solute– solvent interactions. When the concentration of drug is increased, solute–solute interactions increased and the resulting apparent molar volumes also increased for presently studied binary solutions. At infinite

Fig. 7. Plot of isentropic compressibility (κs) versus Emtricitabine drug concentration in molality at different temperatures.



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Table 5 The infinite dilution apparent molar expansibility (Eϕ∞) of Emtricitabine and Lamivudine drugs with water at T = (293.15 to 318.15) K and 0.1 MPa pressure. Eϕ∞·10−6/m3·mol−1·K−1 T/K

Emtricitabine

Lamivudine

293.15 298.15 303.15 308.15 313.15 318.15

0.130 0.145 0.161 0.177 0.192 0.208

0.519 0.522 0.525 0.528 0.531 0.534

The standard deviations in Eϕ∞ ranges from 0.02 to 0.04 × 10−6 m3 mol−1 K−1, standard uncertainties are u(p) = 1 kPa, and u(T) = 0.01 K.

Fig. 8. Plot of isentropic compressibility (κs) versus Lamivudine drug concentration in molality at different temperatures.

dilution, solute molecules are surrounded by solvent molecules and being infinitely distant with other solute molecule, it's suggested that Vϕ is unaffected by solute–solute molecular interactions [21,22]. The variation of the apparent molar volumes at different concentrations and temperature of (Emtricitabine, Lamivudine + water) binary solutions were listed in Table 2. A representative plots for apparent molar volumes of (Emtricitabine + water) binary solutions as a function of drug concentration and temperature is shown in Figs. 5 and 6. The plots depicts that regions of various colors such that the Vϕ values for (drugs + water) binary solutions increased with increase in concentration of drugs as well as temperature. As the Vϕ values increases the color of the plot changes from the blue to green and then dark orange, where blue color of the plot represents low Vϕ values and dark orange color represents the high Vϕ values. For non-electrolytes Vϕ versus molality, m has been evaluated by least square fitting of the following relation (Eq. (4)): V ϕ ¼ V ϕ∞ þ Sv m

ð4Þ

where Vϕ∞ the limiting apparent molar volume at infinite dilution, Sv is the experimental slope and m is the molality of the solution. The Table 4 The apparent molar volume at infinite dilution (V∞ ϕ), Sv parameter and standard deviation σ(V∞ ϕ) for the binary mixtures of Emtricitabine and Lamivudine drugs with water at T = (293.15 to 318.15) K and 0.1 MPa pressure. Vϕ∞·106 m3·mol−1

Sv·106 mol·kg−1

σ(Vϕ∞)

Emtricitabine + water 293.15 298.15 303.15 308.15 313.15 318.15

147.9 148.6 149.3 150.2 151.2 152.1

10.4 11.9 12.9 12.6 11.9 12.2

0.17 0.18 0.23 0.24 0.23 0.27

Lamivudine + water 293.15 298.15 303.15 308.15 313.15 318.15

143.2 144.8 145.7 146.5 147.2 148.0

7.1 5.8 6.1 7.1 7.2 7.3

0.13 0.11 0.14 0.15 0.17 0.19

T/K

Standard uncertainties of u(p) = 1 kPa, and u(T) = 0.01 K.

estimated Vϕ∞ values are positive and increases with increasing the temperature [23,24]. This indicates the presence of solute–solvent interactions and these interactions are strengthened with the rise in temperature. From the Vϕ∞ values binary solutions of Emtricitabine + water has the strong solute–solvent interactions than Lamivudine + water binary solutions. The observed results of limiting apparent molar volume at infinite dilution data are listed in Table 4. In the present work, the parameter Sv can be useful to understand the nature of interactions (solute–solute and solute–solvent) for the binary solutions. The positive Sv magnitude observed for both the systems (Emtricitabine and Lamivudine) at all temperatures. The trend in In Sv values strong in Emtricitabine + water binary solution than Lamivudine + water binary solutions. In literature, positive values of Sv were also observed for some other drugs like penicillin V [25], amphiphilic [26] and ampicillin [27] drugs with polar solvents. The temperature dependence of apparent molar volume at infinite dilution, Vϕ∞ can be expressed as the second-order polynomial of the absolute temperature, Eq. (5), V ϕ∞ ¼ A þ BT þ CT2

ð5Þ

where, A, B and C are the empirical parameters and T is temperature of the solution. The infinite dilution apparent molar expansibility (Eϕ∞) can be calculated by differentiating Eq. (5) and can calculated as follows (Eq. (6)), Eϕ∞ ¼ ∂V ϕ∞ =∂T ¼ B þ 2CT: P

ð6Þ

The E∞ ϕ data, calculated using Eq. (6), are presented in Table 5. It is observed that E∞ ϕ values for all binary systems are positive, and also increases with the temperature, which is characteristic of solvation and electrostriction property of binary solutions [28,29]. The positive magnitude of apparent molar expansibility values indicate that with increase in the temperature, water expands more rapidly upon heating than the solution containing solutes [30,31]. 4. Conclusions In this work, we have chosen highly biological active drugs such as Emtricitabine and Lamivudine and estimated their solvation behavior with water. As a part of this estimation, density (ρ) and speed of sound (u) data were measured at various temperature ranges as a function of molality (m). For both systems the density data increases with increase in the concentration of drugs and decreases with increase in the temperature. The measured density and speed of sound data were useful to calculate the apparent molar volume (Vϕ) and apparent molar isentropic compressibility (κs,ϕ). The Vϕ∞ values for the (Emtricitabine + water) binary solutions are higher than (Lamivudine + water) binary solutions, which indicate that solute–solute interactions are stronger for studied (Emtricitabine + water) solutions than those for (Lamivudine + water) binary systems. The infinite dilution apparent


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molar expansibility (Eϕ∞) was calculated from the data of apparent molar volume at infinite dilution (Vϕ∞). Finally, the structure making and breaking ability of drugs were analyzed at experimental conditions. Acknowledgment Authors would like to acknowledge Mylan Laboratories Limited, Hyderabad for providing drug samples. Venkatramana Losetty and Bharath Kumar Chennuri are thankful to Department of Science and Technology (DST) (CHY/13-14/310/DSTX/EDAM), India and University Grants Commission (UGC) (F.Acad./R3/J.Rpt/2013), India for the financial support in the form of Research Associate (RA) and Senior Research Fellowship (SRF), respectively. The authors are also thankful to Dr. Vickramjeet Singh for his assistance in drawing few figures. References [1] A. King, I. Phillip, J. Antimicrob. Chemother. 18 (1986) 1–20. [2] T.S. Banipal, H. Singh, P.K. Banipal, J. Chem. Eng. Data 55 (2010) 3827–3881. [3] S. Ryshetti, B.K. Chennuri, R. Noothi, S.J. Tangeda, R.L. Gardas, Thermochim. Acta 597 (2014) 71–77. [4] A. Ali, A.K. Nain, Acoust. Lett. 19 (1996) 181–187. [5] K. Din, A.B. Khan, A.Z. Naqvi, J. Mol. Liq. 187 (2013) 374–380. [6] P. Honkoop, H.G.M. Niesters, R.A.M. de Man, A.D.M.E. Osterhaus, S.W. Schalm, J. Hepatol. 26 (1991) 1393–1395. [7] P.L. Anderson, J.J. Kiser, E.M. Gardner, J.E. Rower, A. Meditz, R.M. Grant, J. Antimicrob. Chemother. 66 (2011) 240–250.

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