Study of Electrical Conductivity for Salt Diclofenac Potassium in Water and Water-Methanol Mixtures at Different Temperatures

This paper traces the conductivity of diclofenac potassium salts in the low concentrations in water and mixtures of water and methanol (10%, 20% and 30% aqueous methanol) at different temperatures (288.15, 293.15, 298.15, 303.15 and 308.15 K). The conductivity data were analyzed using the Lee-Wheaton conductivity equation to obtain the values of equivalent conductivity at infinite dilution “ ∧ o”, association constants (K A ), the association diameter (R) and Walden product (Λ 0 η 0 ). The results showed that diclofenac potassium salt behaves as weak electrolytes in the solvents used. Moreover, standard thermodynamic parameters of the association (change value in: Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) were calculated and discussed. The results showed that the values of molar conductivity, the distance parameter between the ions (R) and association constants (KA) increase with increasing temperature at the best fit value of the standard deviation (σ). The thermodynamic results also indicated that the ion association process is endothermic (+ΔH) and spontaneous (- ΔG) and increasing degrees of freedom (+ΔS).


INTRODUCTION
Diclofenac potassium is the potassium salt form of diclofenac acid, a benzene acetic acid derivative and nonsteroidal anti-inflammatory drug (NSAID) with analgesic, antipyretic and antiinflammatory activity.
It is available as a medicine in the form of tablets 50 mg (light brown) and as an effervescent powder to be given orally, the chemical name is 2-[(2,6-dichlorophenyl) amino] benzeneacetic acid, mono salt potassium; Molecular weight 334.25 g/mol. Its molecular formula is C 14 H 10 C l2 NKO 2 , and it has the following structural formula: (Helmy et al., 2015)

Fig. 6: The structural formula of Diclofenac potassium salt
Many medicines are weak acids or bases that are in the form of salts to improve their solubility. Diclofenac acid is one of these compounds, and it has a very low solubility in water (17.8 mg / L). The high hydrophobicity of diclofenac is partially preserved even if the drug is in salt form. (Shmukler et al., 2015) The interactions between (ion -ion) and (ion-solvent) or the behavior of electrolytes in solution can be useful in scientific studies depending on the transport properties (conductivity and movement of ions) of such electrolytes in solutions.
One of the most important methods for studying the interactions of ion-ioni, ion-solvent, and solvents -solvent in solution is the study of the electrical conductivity of electrolytes depending on the temperature change at a range of dilute concentrations. (Bešter, 2009) Mixtures of methanol and water at different temperatures exhibit a wide range of relative permittivity and viscosity that affect the conductivity and thermodynamic parameter. (El-Dossoki, 2010). Ion mobility in aqueous solutions, equivalent conductivity, association constants (K A ), all these data are very important to learn about therapeutic efficacy of drugs. (Manca et al., 2005;Chadha et al., 2003) The drug-drug and drug-solvent interactions may be of great importance to understand their physiological action and identify the therapeutic efficacy of drugs. (Shmukler et al., 2015).

EXPERIMENTAL Materials
The chemicals used were: -Diclofenac potassium powder (Pioneer company for pharmaceutical industries-Iraq), Methanol (Fluka Switzerland, 99.8%), Potassium Chloride (Merck, Germany, 99.99%) and water (The freshly prepared bidistilled water was used as the solvent with the specific conductivity of less than 1.5 × 10 −6 S/cm).

Apparatus
The devices and tools that have been used to determine the conductivity of Diclofenac potassium in the range of low concentrations and at different temperatures are: -Professional Benchtop conductivity meter BC3020 (Singapore) (±0.2% μS cm −1 ) connected to the thermostatic water bath of type (HAKKE -NK22) to maintain the temperature constant at the desired temperature (±0.15 °C). A closed Jacket cell connected to the thermostat using isolated rubber tubes was used. 30ml of solvents was placed in conductimetric cell pyrex and then the stock solution was added using plastic syringe. After each addition the solution was mixed using magnetic stirrer. Distillation system (GFL model 2001/4) Germany. Analytical balance (Sartorius) Germany sensitive (±0.0001).

RESULTS AND DISCUSSION Physical properties
For procedure accurate measurements to the conductivity of electrolyte should know some of the properties of the solvent used as density (ρ), viscosity (η) and relative permittivity (ε). Pevious values of the100% water and 10, 20 and 30% (MeOH-H2O) mixtures at different temperature (288.15,293.15,298.15,303.15 and 308.15K) were tabulated in (Table 1). (Stokes and Mills, 1965;Wensink et al., 2003;Hus et al., 2015;González et al., 2007)  R is the distance between the cation and anion. When the short-range forces are strong enough that they induce closer proximity of the ions to allow the formation of either contact ion pair (CIP) or separated solvent ion pair (SSIP). The value of R depends on the exchange reactions between the ion and the solvent (Ion-solvent) in the solution. The simplest form of Lee-Wheaton equation for electrolyte solutions of type (1:1) is: (Lee and Wheaton, 1979); (Al-Healy and Hameed, 2020) where C1 to C5 are complex functions. Є = (|Z|2 e 2 /DKT) K 2 = (8πN2 e|Z|2C/1000DKT) P= (Fς|Z|/3πη) ζ = conversion factor; C=concentration (mole/liter); D=Dielectric constant of solvent. F=Faraday's constant = 9.64867 x10 4 ; : Viscosity of the Solvent.
The electrical conductivity of solution of Diclofenac potassium was studied using conductivity water and mixture from water and methanol (10%, 20% and 30%) whose conductivity of solvent was subtracted from the conductivity values of Diclofenac potassium at different temperature. Kohlorousch equation was used, after the conductance was measured, and then the equivalent conductance was calculated at different concentration as shown in (Table 2). It was found that diclofenac potassium salt behaves in all the above measurements as weak electrolytes. This was proved by drawing the relationship between the square root of several concentrations in the dilute range of diclofenac potassium solution versus the equivalent conductivity calculated at different temperatures. Figs. (3, 4, 5, 6) illustrate this behavior and it turned out to be in a curved shape, and none of the solution showed a straight line, indicating that these solutions behave like a weak electrolyte.  After analyzing the information, it was confirmed that the solutions of the drug compound used are weak electrolytes. As a result of the analysis, the values of: the equivalent conductance at infinite dilution(ₒ), association constants (K A ), the distance parameter between the ions (R), As well as obtaining the values of the Standard Deviation : (Al-Obaidi, 2010). Table 3 shows the results of the analysis using the equation Lee-Wheaton.     Table (3) show that the equivalent conductance at infinite dilution (ₒ) values increase with increasing temperature and this is due to the increase in the solvent fluidity with increasing temperature (decreasing viscosity of the medium), which affects the mobility of ions. Equivalent Conductivity at Infinite dilution of Diclofenac Potassium Inversely proportional to the ratios of organic-aqueous property for solvents at the same temperature as follows 30% < 20% < 10%. This behavior is attributed to the formation of a hydrogen bond between water and alcohol molecules leading to the binding of alcohol and H 2 O molecules and an increase in the viscosity of the medium this will cause reduce the movement of ions and decrease the values of (ₒ) with increasing percentages of organic solvent. It may also result from a decrease in the relative permittivity with the increase of the organic percentage in the solvent. It also shows that the values of the association constants (K A ) increase with increasing temperature. This is due to the decrease in the dielectric constant and density of the solvent as the temperature increases. An increase in the value of the association constant with increasing temperature indicates that the association process is endothermic. This behavior is supported by other studies by several authors. (Dash et al., 2006;El-Dossoki et al., 2011;Bhat and Shivakumar, 2004).

equivalent conductance at infinite dilution(ₒ), the distance parameter between the ions (R), the standard deviations (σ) and association constants (K A ) of the Diclofenac potassium salt in the used solvents at different temperatures
It was also found that as the temperature increased, the distance parameter between the ions (R) increased (and the state of the ions changed from contact ion pair (CIP) to separated solvent ion pair (SSIP). The higher the percentage of organic solvent (% Methanol), the closer the distance between the ions, while maintaining the separated solvent ion pair (SSIP).
As for the standard deviation values (σ), their values were few, and this confirms that the use of the Lee-Wheaton equation is appropriate in this study.

Thermodynamics of association:
Thermodynamic functions of Diclofenac potassium can be estimated through value of association constants (K A ) at different temperatures by Van 't Hoff equation: Plotting of (ln K A ) versus the reciprocal (1/T) for all systems results a linear relationship as shown in Fig. (7). sulphadiazine diazotized sulfadiazine

Fig. 7: Relation between (lnkA) and (1/T) in water and mixtures of water and methanol (10%, 20% and 30% aqueous methanol) at different temperatures.
From Fig. (7) it is found that the inverse relationships between (lnkA) and (1/T). This means that the system is endothermic (+ΔH). Also, the thermodynamic parameters (ΔG) were obtained from (K A ) values with temperatures according to the Gibbs free energy equation   As expected, it is noted from ( Table 4) that the value of (ΔH) for ionic association is positive (endothermic).
The obtained values of (ΔG) were negative, which indicates the spontaneous of the association process. Decreased Gibbs free energy by increasing temperatures indicates more spontaneous processes.
While the values of (ΔS) were positive, the reason for this is due to the lack of arrangement or coordination (disorientation) of the solvent molecules when forming the ionic pair. It was noted that the positive values of ΔS° do not vary significantly with increasing temperature this indicates that the number of degrees of freedom during the ionic association process does not change significantly possibly due to the poor solubility of the positive ion. These thermodynamic results are in a good agreement with what many authors have mentioned in other theories and studies. (Bhat and Shivakumar, 2004;Gomaa et al., 2017;Helmye et al., 2015) Walden product Walden product (Λ 0 η 0 ) which is an indicator from the point of view of the interaction of ionsolvent (Walden, 1920).
The change in the temperature of the electrolyte solution will lead to a change in the viscosity values. As the temperature increases, the viscosity decreases. Therefore, the transitional movement that causes the equivalent conduction of ions will increase. Therefore, the Walden product (Λ 0 η 0 ) for Diclofenac potassium was calculated at different temperatures. Walden product has formulated its rule (for 1:1electrolyte) in the form as in Eq. (6) Λ 0 η 0 = 0.82 [1/r⁺ s + rˉs ] ……6 the factor [1/r⁺ s + rˉs ] is a measure of the hydrodynamic radii of the ions.
Table (5) shows the values Walden product and inverted dielectric constant at different temperatures. From the (Table 5) it was found that the values of Walden's product decrease as the dielectric constant of the solvent decreases as shown in Fig. (8). We also notice from the ( Table 5) that Walden's product values decrease with increasing temperature. The reason for this may be related to increase in the diameter of the ions solvated in mixtures with increasing temperature. (Robinson and Stokes, 1965) Walden's product is mainly affected by two factors. The equivalent conductance at infinite dilution (Λ 0 ) and viscosity (η 0 ) whereas η 0 is inversely proportional to temperature, while Λ 0 is directly proportional to temperature, from here we conclude the contribution of the viscosity value is the most influential in the inverse behavior of Walden product with temperature. CONCLUSION The present study reports to the conductivity data of solutions of diclofenac potassium salts in water and mixtures of water and methanol at different temperatures in the range of low concentrations, which were measured with the help of the Lee-Wheaton equation that diclofenac potassium salt behaves as a weak electrolyte in the above solvents. We observed that the values of conductivity parameters such as K A , R, ₒ differ from one solvent to another depending on viscosity and the dielectric constant of the used solvents and interactions in the solution. Ion-association process in the solution is spontaneous process (ΔG= -ve), endothermic (ΔH=+ve) and lead to increased randomness. (ΔS= +ve).