Partial molar volume of mefenamic acid in alcohol at temperatures between T=293.15 and T=313.15 K

Iqbal, Muhammad J.; Siddiquah, Mahrukh

doi:10.1590/S0103-50532006000500006

Abstracts

Apparent molar volume (Vphi), partial molar volume (V), solute-solute interaction parameter (Sv), partial molar expansivity (E(0)2) and isobaric thermal expansion coefficient (alpha2) of mefenamic acid in six different organic solvents namely, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, and 2-butanol, have been calculated from the measured solution densities over a temperature range of T=293.15 and T=313.15±0.1K. The solution densities were measured by an automated vibrating tube densitymeter (Anton Paar DMA-48). The molality range investigated was between 6×10-3 and 3.25 ×10-2 mol kg -1. The effect of temperature on apparent molar volume and partial molar volume was also determined. Decrease in solute-solvent interactions with an increase in temperature has been noted. Partial molar volume of mefenamic acid changes with the change in solvent polarity.

apparent molar volume; partial molar volume; mefenamic acid; partial molar expansivity; alcohol

Volume molar aparente (Vfi), volume molar parcial (V), parâmetro de interação soluto-soluto (Sv), expansividade molar parcial (E(0)2) e coeficiente de expansão térmica isobárica (alfa2) do ácido mefenâmico em seis diferentes solventes orgânicos : metanol, etanol, 1-propanol, 2-propanol, 1-butanol e 2-butanol, foram calculados a partir das densidades das soluções medidas no intervalo de temperatura entre 293,15 e 313,15±0,1K. As densidades das soluções foram medidas por um densímetro automatizado (Anton Paar DMA-48). O intervalo de concentração investigado foi de 6,00 <FONT FACE=Symbol>´</FONT> 10-3 a 3,25 <FONT FACE=Symbol>´</FONT> 10-2 mol kg -1. O efeito da temperatura sobre o volume molar aparente e o volume molar parcial foi também determinado. Um decréscimo nas interações soluto-solvente foi observado com o aumento da temperatura. O volume molar parcial do ácido mefenâmico também varia com a variação da polaridade do solvente.

ARTICLE

Partial molar volume of mefenamic acid in alcohol at temperatures between T=293.15 and T=313.15 K

Muhammad J. Iqbal^** e-mail: mjiqauchem@yahoo.com; Mahrukh Siddiquah

Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan

ABSTRACT

Apparent molar volume (V_F), partial molar volume (), solute-solute interaction parameter (S_v), partial molar expansivity (E⁰₂) and isobaric thermal expansion coefficient (a₂) of mefenamic acid in six different organic solvents namely, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, and 2-butanol, have been calculated from the measured solution densities over a temperature range of T=293.15 and T=313.15±0.1K. The solution densities were measured by an automated vibrating tube densitymeter (Anton Paar DMA-48). The molality range investigated was between 6×10^-3 and 3.25 ×10^-2 mol kg ^-1. The effect of temperature on apparent molar volume and partial molar volume was also determined. Decrease in solute-solvent interactions with an increase in temperature has been noted. Partial molar volume of mefenamic acid changes with the change in solvent polarity.

Keywords: apparent molar volume, partial molar volume, mefenamic acid, partial molar expansivity, alcohol

RESUMO

Volume molar aparente (V_F), volume molar parcial (), parâmetro de interação soluto-soluto (S_v), expansividade molar parcial (E⁰₂) e coeficiente de expansão térmica isobárica (a₂) do ácido mefenâmico em seis diferentes solventes orgânicos : metanol, etanol, 1-propanol, 2-propanol, 1-butanol e 2-butanol, foram calculados a partir das densidades das soluções medidas no intervalo de temperatura entre 293,15 e 313,15±0,1K. As densidades das soluções foram medidas por um densímetro automatizado (Anton Paar DMA-48). O intervalo de concentração investigado foi de 6,00 ´ 10^-3 a 3,25 ´ 10^-2 mol kg ^-1. O efeito da temperatura sobre o volume molar aparente e o volume molar parcial foi também determinado. Um decréscimo nas interações soluto-solvente foi observado com o aumento da temperatura. O volume molar parcial do ácido mefenâmico também varia com a variação da polaridade do solvente.

Introduction

In biophysical chemistry drug-macromolecular interaction is an important phenomenon involving complex molecular mechanism. Perceptible thermodynamic changes are found to be associated with the processes of drug transport,¹ drug-protein binding,² anesthesia³ etc. In the case of drug-protein binding, anomalous behaviour has been observed with respect to certain drugs.⁴ Because of the complexities associated with the structure of biomacromolecules or with their data interpretation, it is difficult to carry out these processes in physiological media. Consequently, it is imperative that each component of these systems may be studied individually before going to more complex systems. Thermodynamic methods are well recognized and convenient for studying the molecular interactions in fluids. The partial molar volume, pressure derivative of Gibbs energy, is a useful parameter for interpreting solute-solvent interactions.^5,6 Comparison of the volume of the system with those of its components can assess gross changes in the volume of the system because it is an additive property. In addition, volumetric data can also be interpreted in terms of molecular interactions within the system. Various molecular processes in solutions such as electrostriction,⁷ hydrophobic hydration,⁸ micellization and co-sphere overlap during solute-solute interactions have been interpreted, to a large extent, from the partial molar volume data of many compounds including amino acids, peptides and also some drug compounds.⁵

Mefenamic acid is known as an antipathologistic analgesic and provides relief of mild to moderate pain, especially pain after surgery and fever. Mefenamic acid is known to strongly bind to the plasma protein.⁹ As a part of the longer-term objective to investigate thermodynamic aspects of biochemical processes involving such drug-macromolecule interactions, the results of the determinations of apparent molar volumes (V_F), partial molar volume (), solute-solvent interaction parameter (S_v), partial molar expansivity (E⁰₂) and isobaric thermal expansion coefficient (a₂) of mefenamic acid in six different organic solvents i.e. methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, and 2-butanol between T=293.15 and T=313.15±0.1 K are reported in the present study.

Materials and Methods

Mefenamic acid (N-(2,3-xylyl) anthranilic acid, molar mass = 241.3 g mol^-1) used in this study was supplied by Sigma (99.3%). The structural formula of mefenamic acid is:

The solvents used were methanol (99%, Merck), ethanol (99%, Acros Organics), 1-propanol (99%, Fluka), 2-propanol (99%, Fluka), 1-butanol (99%, Fluka), and 2-butanol (99%, Fluka). Since values for the density of the pure solvents measured at T=293.15 K were comparable with the literature value¹⁰ as shown in Table 1, therefore the solvents were used without further purification. Molal solutions of mefenamic acid were prepared using m/m % method in calibrated flasks at T=293.15 K. The molality range studied was between m=6.00´10^-3 ±10^-5 mol kg^-1 and m=3.25´10^-2 ±10^-5 mol kg^-1. Solutions were prepared immediately prior to measurements by addition of stiochiometric quantity of mefenamic acid to the solvents. The density of various solutions was measured using an automated vibrating tube density meter (Anton Paar DMA 48), with an uncertainty of ±0.0001 g cm^-3, which was calibrated with air and doubly distilled water in the temperature range investigated. The density measurements were made at different temperatures i.e. T=293.15, 298.15, 303.15, 308.15, 310.65 and T=313.15 ± 0.1K. Apparent molar volume of mefenamic acid was calculated using the following equation: ¹¹

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Where r₀ = density of pure component 1 (solvent), r = density of solution of molality m of mefenamic acid having molar mass M₂.

Apparent molar volume (V_F) of mefenamic acid was then plotted against the molality (m) in different organic solvents i.e. methanol, 1-butanol, 2-butanol and DMF in accordance with equation (2)

where S_v, S_vv are the empirical parameters which depend on solvent, solute and the temperature¹² and is the partial molar volume of the solute molecule in the specific solvent. The values of and correlation coefficients have been estimated by the least-square fitting of the apparent molar volume data in the equation (2). Only two parameters of equation (2) i.e. partial molar volume () and solute-solute interaction parameter (S_v), were considered to be sufficient to represent the data adequately.

The values of partial molar expansivity were then calculated¹³ from the partial molar volume by the relation:

Since the changes in the solution structure are very sensitive to temperature changes, the partial molar expansion is a sensitive criterion for the detection of solute-solvent interactions.

From the partial molar volume () data, the isobaric thermal expansion coefficient of solute at infinite dilution, a₂ was also calculated, by the following equation:¹⁴

Results and Discussion

The apparent molar volume data for mefenamic acid dissolved in methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and 2-butanol (Figures 1-6) increases with concentration at a particular temperature. The apparent molar volume of mefenamic acid at a constant concentration decreases with an increase in temperature of the system in all the solvents (Tables 2-7). The slope of the lines, drawn in accordance with equation (2), resulted in positive values of S_v for all the solutions. In case of positive S_v values (Table 8), the solvent molecules are believed to be more structured in the bulk phase than in the solvation sphere and an increase in the concentration of the drug compound results in the release of solvent molecules from the solvation shell into the bulk solvent that is more structured.¹³ The characteristic of the co-sphere depends upon the drug structure, size, shape and solvophobicity.¹⁴Table 8 shows that the partial molar volume (), partial molar expansivity (E⁰₂) and isobaric thermal expansion coefficient (a₂) are independent of concentration and that the values of for mefenamic acid increase with rise in temperature in all the solvents employed here.

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According to the scaled particle theory (SP),¹⁵ the expression for the partial molar volume of a solute at infinite dilution is given as follows:

Where V_cav and V_int are the contributions for the formation of a cavity and from intermolecular interactions respectively, b⁰ is the isothermal compressibility of the solvent, R is the gas constant and T is the absolute temperature. The creation of a cavity is by definition a positive contribution to the partial molar volume of a solute, whereas the attractive intermolecular solute-solvent interactions cause a negative contribution by shrinking the cavity. The results are also viewed in terms of the geometrical fit of the drug molecules in an ordered solvent. It is difficult to accommodate a complex structured solute such as mefenamic acid in an ordered solvent environment like alcohols. As the temperature of the solution is increased, cavities are produced in the ordered solvent environment, resulting in the better fit of the complex structured solutes in the solvent. With increasing temperature the contribution from the drug-solvent binding is weakened and the partial molar volume of the drug compounds increases significantly with temperature. It is apparent from Table 8 that S_v values showed somewhat irregular change with increasing temperature.

The isobaric thermal expansion coefficient (a₂) for mefenamic acid obtained from equation (4) showed a decreasing behaviour with increasing temperature in all the solvents studied in the present work because when the temperature is increased the density of the solution decreased (Tables 2-7), resulting in a decrease in partial molar expansivity coefficient (a₂). A similar trend was observed by Iqbal and Verrall⁵ for aqueous solutions of compounds having more than one OH- group, whereas the opposite effect for mono-functional alcohols was observed by Neal and Goring.¹⁶ The largest value of the partial molar volume was obtained in 2-butanol while its value was smallest in methanol as shown in Table 8. The value of is larger in 2-butanol as compared to that in 1-butanol (Table 8) with a transfer volume of 25.13 ± 3.98 cm³ mol^-1 in the studied temperature range. The difference in partial molar volume of mefenamic acid in 1- and 2-butanol is considered to be due to differences in the structure of the two solvents in their solvation pattern. For instance, 1-butanol displaying straight chain showed self-association¹⁷ to a much greater extent in comparison to 2-butanol. The number of molecules in 1-butanol aggregates is greater as compared to the aggregates of 2-butanol. The extent to which 1-butanol molecules are bonded to one another in 1-butanol is higher than that in 2-butanol. This resulted in larger partial molar volume of mefenamic acid in 1-butanol than in 2-butanol. Same is the reason for the higher value of partial molar expansivity of the drug compound in two solvents.

Partial molar volume of mefenamic acid was plotted as a function of solvent dielectric constant, which is a measure of solvent polarity as shown in Figure 8. It is evident that the partial molar volume of mefenamic acid decrease with increase in the solvent polarity. This indicates that by increasing solvent polarity, the solute-solvent interactions are decreased.

The partial molar volume of mefenamic acid was then plotted against the temperature in accordance with equation (3) (Figure 7) and the values of partial molar expansivity of mefenamic acid in different solvents were obtained (Table 9). Highest value of partial molar expansivity () of mefenamic acid (0.2262±0.0001 cm³ mol^-1 K^-1) was obtained for 1-propanol as compared to those obtained for methanol, ethanol, 2-propanol, 1-butanol (Table ). The increasing order of partial molar expansivity () of mefenamic acid in different solvents represented as:

1-propanol > 2-butanol >methanol > 2-propanol > ethanol > 1-butanol.

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Conclusions

Partial molar volume of mefenamic acid is a function of temperature and increases linearly with temperature. When the solvent polarity was increased, partial molar volume showed a decreasing trend.

Received: January 17, 2006

Published on the web: June 12, 2006

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