STUDIES ON STRUCTURAL PROPERTIES OF THE BINARY MIXTURES OF PHARMACEUTICAL INTERMEDIATES THROUGH DIELECTRIC INVESTIGATIONS

STUDIES ON STRUCTURAL PROPERTIES OF THE BINARY MIXTURES OF PHARMACEUTICAL INTERMEDIATES THROUGH DIELECTRIC INVESTIGATIONS

A. Prathima*^{1, 2}, S. Karthikeyan ³, M. Prabhakaran ² and T. Thenappan ¹

School of Physics, Alagappa University ¹, Karaikudi - 630 003, Tamil Nadu, India

Department of Physics ², Department of Mechanical Engineering ³, Syed Ammal Engineering College, Ramanathapuram-623 502, Tamil Nadu, India

ABSTRACT: The homo and hetero interaction in the binary mixtures of Ethyl acetate + n-Butylamine, Ethyl acetate + Cyclohexylamine and Ethyl acetate + Diethylamine has been investigated through the orientation of dipoles using dielectric polarization method. The dielectric and thermodynamic parameters such as Kirkwood correlation factor, Excess permittivity, Bruggemann factor and Dipolar excess free energy for the above systems have been calculated from the experimentally measured values of capacitance and refractive index of solutions, at temperatures 303K, 313K and 323K.In all the studied systems, the dielectric parameters obtained show systematic change in the molecular structure with the concentration of amine in the solution. It indicates that the β-multimer formation due to the presence of hetero interaction between the components of above mixtures.

Liquid mixtures, Hetero interaction, Kirkwood correlation factor, Dipolar excess free energy, and Bruggeman factor, Multimer

INTRODUCTION: The pharmaceutical sciences are a group of interdisciplinary areas of study concerned with the design, action, delivery, disposition, inorganic, physical, biochemical and analytical biology, epidemiology, statistics, chemometrics, mathematics, physics and chemical engineering, and apply their principles to the study of drugs. Compounds used as medicines are most often mixture of organic compounds. Therefore it is seemed important to examine the molecular interaction studies on the mixture of organic liquids ¹. Dielectric studies are of great help in the assignment of the molecular structure or configurations, particularly those of organic compounds ².

In this study, Ethyl acetate has been used as a solvent and n-Butyl amine, Cyclohexylamine and Diethyl amine as solute. Ethyl acetate is a moderately polar solvent that has the advantage of being volatile, relatively non-toxic, and non-hygroscopic. It is a weak hydrogen bond acceptor, and is not a donor due to the lack of an acidic proton. In the pharmaceutical industry it is an important component in extractants for the concentration and purification of antibiotics. It is also used as an intermediate in the manufacture of various drugs. And amines are used in the production of pesticides, pharmaceuticals, rubber chemicals, emulsifiers ³ and also used as an intermediate in synthesis of other organic compounds ¹. A survey of literature shows that a few workers ^4-5 have tried to investigate some binary systems taking amines as one of the constituent components in the binary mixtures. The objective of this paper is to investigate the molecular interaction between amine and ester molecules through dielectric study of the above systems at temperatures 303K, 313K and 323K.It makes one to understand the solute-solvent interaction and liquid structure ⁶.

THEORY: The determination of the structure and properties of associated liquids could provide deeper insight into the phenomena of the molecular interactions and is of great importance in Biology and Chemical Physics. The IR and NMR spectroscopic methods were extensively used for determining the nature of association. However, these methods could give only circumlocutory information regarding the alignment of neighboring molecules. This vital information could be obtained from dielectric measurements by virtue of its influence on the correlation between the permanent dipole moments in such a molecule. There are various mixture formulae with which one can correlate dielectric parameters with molecular activities in liquid.

The Kirkwood model: The Kirkwood correlation factor is a measure of the short- range interaction between the components in the liquid mixtures. For pure liquids and liquid mixtures, it can be described by the following expression^7-10

……………….(1) …(2)

….(3)

Where m is the dipole moment in the gas phase, r is the density at temperature T, M is the molecular weight, k is the Boltzmann constant, N is the Avogadro’s number, e_o is the static permittivity ande_¥  is thestatic permittivity at high frequency, often represented by the square of refractive index corresponding to sodium D-line. X is the volume fraction and suffices m, A and B represents mixture, liquid A and liquid B respectively.

The departure of Kirkwood correlation factor from unity is an indication for the molecular association. It means that if g >1 indicates the parallel orientation among the dipoles, g < 1 indicates the anti - parallel orientation among the dipoles and g = 1 represents an equilibrium between the multimers or non – association among the dipoles.

Excess permittivity (ε^E): The excess static permittivity is used to explain the formation of mutimers in the mixture^11-12. It is defined as,

…(4)

The excess permittivity provides qualitative information about multimer formationin the mixture as given below. If

ε^E = 0 indicates that there is no interaction between the unlike molecules.

ε^E < 0 indicates the interaction between the molecules in such a way that the effective dipoles get reduced. The two liquids mix in such way that the mixture may form multimers leading to the less effective dipoles.

ε^E > 0 indicates that the two liquids interact in such a way that the effective dipoles increase. This may be due to the formation of monomers and dimers.

Bruggeman factor (f_B): The Bruggeman factor is another parameter which may be used as an indicator of   hetero interaction. The Bruggeman factor f_B   is given by¹³,

……………...(5)

From equation (5), a linear relationship is expected when plotted f_B against X_B.Any deviation from this linear relation indicates molecular interactions. It is practically observed that in our experimental data for binary mixtures do not fit well with equation (5).To fit the experimental data, the equation (5) has been modified

………………………..(6)

Where a is a numerical fitting parameter known as Bruggeman parameter. The value of a contain information regarding the nature of interaction between solute and solvent, as follows.

a > 1 indicates that the effective microscopic volume of solvent gets more than actual  volume. The solute exerts a repulsive force in the system.

a < 1 indicates that the effective microscopic volume of solvent gets less than actual  volume.

The solvent exerts an attractive macroscopic force in the system.

a = 1 indicates no change in effective microscopic volume of the system and corresponds to the ideal Bruggeman mixture factor.

Dipolar excess free energy (DF^E): The excess Helmholtz free energy of mixing DF^E is given by ¹⁴,

=DF₀^E+DF_rr^E+DF_AB^E………..(7)

This first term DF₀^E in equation (7) represents the excess dipolar energy due to long-range electrostatic interaction.

The second term DF_rr^E gives the excess dipolar energy due to short-range interaction between identical molecules and

The third term DF_AB^E gives the excess dipolar energy due to short-range interaction between dissimilar molecules.

The term R_fro and R_fr which give the reaction field parameters in the pure liquid and in the mixture, are given by,

It gives excess thermodynamic functions in binary mixtures that take into account the contribution due to both short-range and long-range dipolar interactions between both like and unlike molecules is adopted for polar-nonpolar mixtures.

 MATERIALS AND METHODS: Compounds used in the present study were of AR grade and were all procured from SRL, India. The static permittivity e_om at 1 KHz was measured using a digital VLCR-7 meter supplied by M/S Vasavi electronics, India, after calibrating it for standard liquids like carbon tetrachloride, benzene, toluene and chlorobenzene.

The permittivity at optical frequency e_¥m was obtained by squaring the refractive Index for sodium D-line, which was measured with the help of an Abbe’s refractometer. The uncertainties in static permittivity, refractive index and density were ±0.0005, ±0.0002 and ±0.0001 g/cc respectively.

All measurements were made at 303±1K, 313±1K, and 323±1K using a water circulating thermostat arrangement.

RESULTS AND DISCUSSION: The dielectric and thermodynamic parameters such as static permittivity (e_om), thestatic permittivity at high frequency (e_¥m), often represented by the square of refractive index corresponding to sodium D-line, Kirkwood correlation factor (g), Excess permittivity (ε^E), Bruggemann factor (f_B) and Dipolar excess free energy (DF^E) for the above systems are listed in tables 1-3 at temperatures 303K, 313K and 323K.

The value of e^E is negative for the Ethyl acetate + n-Butyl amine system for all temperatures except Ethyl acetate + Cyclohexylamine and Ethyl acetate + Diethyl amine systems. In the case of Ethyl acetate + Cyclohexylamine and Ethyl acetate + Diethyl amine systems, e^E was found to be positive in the amine-rich region. The negative excess permittivity value indicates the formation of multimer structure, which leads to a decrease in the total number of dipoles in the system whereas the positive value indicates formation of monomeric or polymeric structure, which increases the total number of dipoles in the system ⁶. This change in structure occurs due to the interaction between the components of the mixture.

In all the systems, the g^eff value increases with the increase in concentration of amine in the solution. For pure Ethyl acetate, g^eff<1, indicates the anti-parallel orientation of dipoles. The g^eff values increase above unity in amine rich region indicating the parallel alignment of dipoles in this region. This indicates that intermolecular interaction between Ethyl acetate and amine increases with increase in the number of amine molecules in the solution. Similar behavior is observed at all temperatures for other amines used in this study. Thenappan et al., ¹⁵ have concluded on similar lines for the mixture of ester and acid.

The interaction between the unlike molecules produces an electric field which makes the dipoles to have parallel orientations ¹⁶. In all mixtures studied, the value of g_f is less than unity for all concentrations and temperatures. This may indicate the presence of a weak interaction between acetate and amine molecules ⁶.

The value of Bruggeman parameter is also nearly unity and do not vary much from unity. This also shows that the strength of the interaction between the components for all the systems is feeble and the Bruggeman parameters are listed in table 4. It also indicates the strength of the interaction is very small between the component molecules. Value of a is in the order of Cyclohexylamine > n-Butyl amine > Diethyl amine for the system with Ethyl acetate. The excess free energy DF^E for mixtures due to long range interaction DF₀^E, short range interaction between identical molecules DF_rr^E and short range interaction between dissimilar molecules DF_AB^E are reported in tables 1 to 3 and the plots of DF_rr^E for the studied systems are shown in figures 1 to 3.

In all the systems, for all the three studied temperatures, values of DF₀^E, is positive indicating the existence of the long-range dipole-dipole interaction. The variation in the magnitude of DF₀^E value with concentration of one of the components and temperatures implies that the variation in the strength of the hetero interaction ¹⁷. For all the systems at all the three studied temperatures, DF_rr^E value is negative. This indicates that the existence of short-range interaction between the amine molecules. Conclusion on similar lines has been reported by Thenappan et al ¹⁸.

The magnitude of DF_rr^E suggests that the strength of the interaction is weak. Negative value of DF_rr^E shows the structure making property of the amine molecules. Similar views have been expressed by Thenappan et al ^19-20. The magnitude of DF_AB^E indicates the existence of a weak hetero interaction between the components in the mixtures. Values of DF^E for all the systems at all the three studied temperatures are positive, which implies the formation of β-multimers with anti-parallel orientation. The electric field created inside the mixture is such that it favors anti-parallel alignment between the dipoles. Similar views have been expressed by Gupta et al ⁴.

TABLE 1: VALUES OF ε_{0m ,} ε_{∞m ,}  g^eff,g_{f ,}ε^E, f_B, ΔF₀^E,ΔF_rr^E, ΔF_AB^E AND ΔF^E OF BINARY MIXTURES OF ETHYL ACETATE WITH n-BUTYL AMINE AS A FUNCTION OF MOLE FRACTION AT  303K, 313K AND 323K

TABLE 2: VALUES OF ε_0m, ε_∞m,  g^eff, g_{f ,}ε^E, f_B, ΔF₀^E,ΔF_rr^E, ΔF_AB,^E AND ΔF^E OF BINARY MIXTURES OF ETHYL ACETATE WITH CYCLOHEXYLAMINE AS A FUNCTION OF MOLE FRACTION AT 303K, 313K AND 323K

 TABLE 3: VALUES OF ε_0m, ε_∞m, g^eff, g_{f ,}ε^E, f_B, ΔF₀^E,ΔF_rr^E, ΔF_AB,^E AND ΔF^E OF BINARY MIXTURES OF ETHYL ACETATE WITH DIETHYL AMINE  AS A FUNCTION OF MOLE FRACTION AT 303K, 313K AND 323K          

TABLE 4: VALUES OF BRUGGEMAN FACTOR A FOR THE SYSTEMS AT 303K, 313K AND 323K

FIGURE 1: VARIATION OF EXCESS FREE ENERGY ΔF_rr^E WITH %MOLE FRACTION OF ETHYL ACETATE + n-BUTYL AMINE BINARY MIXTURES AT DIFFERENT TEMPERATURES

FIGURE 2: VARIATION OF EXCESS FREE ENERGY ΔF_rr^E WITH %MOLE FRACTION OF ETHYL ACETATE + CYCLOHEXYLAMINE BINARY MIXTURES AT DIFFERENT TEMPERATURES 

FIGURE 3 VARIATION OF EXCESS FREE ENERGY ΔF_rr^E WITH %MOLE FRACTION OF ETHYL ACETATE + DIETHYL AMINE BINARY MIXTURES AT DIFFERENT TEMPERATURES

CONCLUSIONS: Values static permittivity, e_0m and the permittivity at optical frequency, e_¥m, which was by square of the refractive Index for sodium D-line, for ester – amine mixtures, are used to evaluate Kirkwood linear correlation factor, excess permittivity, Bruggeman factor and dipolar excess free energy of mixing.

The values of these parameters have been reported for various temperatures and concentrations. These results are used to interpret liquid structure in above mixtures.

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    How to cite this article:

    Prathima A, Karthikeyan S, Prabhakaran M and Thenappan T: Studies on structural properties of the Binary mixtures of Pharmaceutical intermediates through Dielectric investigations. Int J Pharm Sci Res 2013: 4(7); 2753-2760. doi: 10.13040/IJPSR. 0975-8232.4(7).2753-60

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