Viscometric Study of Metformin Complexes with some Transition Metal Ions at different Temperatures

 

Kalyan R. Langore

Department of Chemistry, E. S. Divekar College, Varvand - 412215, (M.S.) India.

 

ABSTRACT:

The measurement of densities, specific viscosities of metformin drugs complexes with some transition metal ions at different concentration in the range (1 x10^-2 M to 6 x10^-4 M) in 70% (DMSO + water) solvent at 303K are reported. The experimental data shows, the effect of concentration of solute on viscosity in DMSO-water mixtures which gives idea about the molecular interactions present in different solutions. Appreciable molecular interactions were observed between the metal complexes of metformin and binary mixture. The thermodynamic properties such as free energy change (∆G), enthalpy change (∆H) and entropy change (∆S) of metal complexes of metformin drugs were analyzed in 70% (DMSO + water) mixture at different temperature such as 308 K, 313 K and 318 K. The experimental data gives the idea about effect of temperature on the molecular interaction and structural changes in solute.

 

 

 

1. INTRODUCTION:

Physiochemical and thermodynamic investigations gives valuable information about nature of molecular interactions and patterns of molecular aggregation that exist in binary mixtures¹. In biophysical chemistry are physical sciences that used the physics and physical concepts for study of biological systems. The interactions between drug and macromolecule are important phenomenon to understand a complex mechanism of action of drugs². All the biochemical processes occurred in aqueous medium, the studies on the thermodynamic and transport properties of drug in aqueous solution gives valuable information for pharmaceutical and medicinal chemistry³. The effect of temperature on drug-solvent molecular interaction play important role to understand action of drug. Viscometric and thermodynamic parameters explain solute-solvent interaction in solution phase. These analyzed data helpful in prediction of absorption of drug and transport of drug across the biological membranes.

 

 

Therefore, it may be interesting to study thermodynamic properties with temperature for understanding the mechanism of drug action. Metformin hydrochloride has great importance in clinical applications⁴. Metformin can produce a hypoglycaemic effect after total pancreatectomy and in complete absence of insulin⁵. Metformin used to lowers the blood sugar level to the minimum physiological limit and also destroys malarial parasites by attraction. It is used as an antimaiariai, antidiabetic and anaigesic⁶.

 

The present work gives a systematic investigation of the viscometric properties of drugs in binary solutions at various temperatures. Viscosity is important physical property that explains solute-solvent interaction. Intermolecular force of attraction in the liquid is responsible for the viscous nature of the liquid. The molecular interaction of electrolyte in binary mixtures studied viscometrically^7-11. Many researchers can study effect of temperature on action of drug^12,13. The Jones-Doles equation¹⁴ helps to evaluate the observed viscosity concentration dependence of dilute electrolyte solutions.

 

2. MATERIAL AND METHODS:

2.1 Material and Measurements:

All the compounds used in the present investigation were of analytical grade and were purchased from E. Merck, Germany (99.5%), were used as such without further purification. The densities of pure solvent and solutions of various concentrations were measured at different temperature using a bicapillary pycknometer. All the weighing was made on one pan digital balance with an accuracy of (± 0.001)gm. The relative viscosities of the solutions were determined by using an Ubbelohde suspended-level viscometer, calibrated with water and organic solvents.

 

2.2 Preparation of solid Complexes:

Preparation of the solid complexes 0.004mol of the ligand was dissolved completed in 50ml distilled water. Then 0.002 M ethanolic solution of metal ion added drop by drop. Then added 0.0038M solution of KOH in above mixtures caused precipitation. The colour of precipitate depends on the nature of metal ion used. A reddish-orange in the case of Co (II); yellow for Ni (II); violet for Cu (II); and colorless for Zn (II). After stirring the reaction mixture for about 3 h, then filtered by vacuum pump and washed with ethanol then ether and dried in oven. The apparatus and working procedures were as described previously¹⁵.

 

3. RESULTS AND DISCUSSION:

To determine the relative and specific viscosity, the different concentration of metal complexes of metformin solution were prepared and there viscosities were measured with help of the following mathematical relation.

              d_s X t_s

ŋ_r     =--------------------- ŋ_w                                                               (1)

                  t_w X t_w

Where,

ŋ_r     = Relative viscosity

ŋ_w   = Viscosity of water

d_s   = Density of solution

d_w  = Density of water

t_s     = Flow time for solution

t_w   = Flow time for water

 

From the calculated values of relative viscosities (ŋ_r) and the temperature (T), the graph between log (ŋ_r) vs 1/T can be plotted. The relative viscosities of metal complexes of metformin at different concentration are presented in table 1.

 

The viscosity data have been analyzed by Jones–Dole equation.

 

                                                                                                (2)

 

Where,

A = Falkenhagen coefficient

B = Jones-Dole coefficient

C = concentration of solutions

The Falkenhagen coefficient (A) measures the solute-solute interactions while Jones-Dole coefficient (B) measures the solute-solvent interaction. The present study deals with the viscosity investigation of the complexes of Co (II); Ni (II), Cu (II) and Zn (II) ions with metformin in 70% DMSO-Water mixture at different concentration. The results obtained are tabulated in Table 1. Calculated values of A and B-coefficient are tabulated in Table 2. From the results, it is observed that, the density and relative viscosity of metal complexes of metformin is directly proportional to its concentration for in 70% DMSO –Water mixture. This may be due to the solvation effect which interprets solute-solvent interaction^16,17.

 

The viscosity coefficients, A and B, were obtained from the intercepts and slopes of the plots (η_sp/√C) against concentration of solutions (√C). The values of A and B are listed in Table 2. The negative values of B-coefficient characterized as ‘structure-breaker’ indicating a solute-solvent interaction^18,19. The relation between viscosity (η_sp/√C) and concentration of solution (√C) for ([Co (L₂)] in 70% DMSO + Water) represented by plotting the graph shown by fig. 1. Similar nature of graph obtained for Ni (II), Cu (I1) and Zn (II)-Metformin Complexes in 70% DMSO + Water. These plotted graphs prove the validity of Jones-Dole equation by giving linear straight line for the evaluation of the thermodynamic parameters. The viscosity measurement was carried out at four different temperatures (303, 308, 313 and 318 K).

 

The relationship between coefficient of viscosity of liquid and temperature is expressed as

 

                                                                                                (3)

 

The graphs are plotted between log ŋ_r and 1/T and The graphs obtained for each system gives linear straight line. The thermodynamic parameters i.e. free energy change (∆G), enthalpy change (∆H) and entropy change (∆S) can be determine by using following relation,

 

                                                                                                (4)

                (5)

                                                                                                (6)

 

These thermodynamic parameters for solution of metal complexes of metformin at different concentrations are represented in table 4. The value ∆G and ∆H indicate reaction is spontaneous and exothermic and negative value of ∆S indicates there is an association of solvent molecule around the ligand mentioned in table 4.

 

 

 

Table 1: Densities (d) and viscosities (η_r) of Co (II), Ni (II), Cu (I1) and Zn (II)-Metformin Complexes of different concentration in 70% (DMSO + water) solvent at 303 K.

Conc (C) (mol/lit)	√ C (mol1/2lit-1/2)	Density (gm/cc)	Relative Viscosity ŋr= ŋ/ŋ0	Specific Viscosity ŋsp= ŋr-1	ŋsp/√C
[Co (L2)]
0.01	0.1	1.0325	1.6367	0.6367	6.367
0.005	0.0707	1.0287	1.5068	0.5068	7.168
0.0025	0.05	1.0253	1.3906	0.3906	7.812
0.00125	0.0354	1.0239	1.2896	0.2896	8.181
0.000625	0.025	1.0217	1.2426	0.2426	9.704
[Ni (L2)]
0.01	0.1	1.0208	1.8367	0.8367	8.367
0.005	0.0707	1.0197	1.6068	0.6068	8.583
0.0025	0.05	1.0179	1.4806	0.4806	9.612
0.00125	0.0354	1.0162	1.3896	0.3896	11.006
0.000625	0.025	1.0595	1.3126	0.3126	12.504
[Cu (L2)]
0.01	0.1	1.0154	1.4367	0.4367	4.367
0.005	0.0707	1.0148	1.3268	0.3268	4.622
0.0025	0.05	1.0137	1.2906	0.2906	5.812
0.00125	0.0354	1.0126	1.2496	0.2496	7.051
0.000625	0.025	1.0114	1.2126	0.2126	8.504
[Zn (L2)]
0.01	0.1	1.0205	1.9367	0.9367	9.367
0.005	0.0707	1.0194	1.8068	0.8068	11.412
0.0025	0.05	1.0182	1.7906	0.7906	15.812
0.00125	0.0354	1.0177	1.6896	0.6896	19.480
0.000625	0.025	1.0173	1.5426	0.5426	21.704

 

 

Fig 1: √ C Vrs ŋ_sp/√C for ([Co (L₂)] in 70% DMSO + Water)

 

Table 2: The Falkenhagen coefficient (A) and Jones-Dole coefficient (B) values for Metformin complexes in 70 % (DMSO + Water)

Metformin Complexes	A (lit3/2 mol-1/2)	B (lit/mol)
[Co (L2)]	10.039	-38.993
[Ni (L2)]	12.983	-52.814
[Cu (L2)]	9.0658	-53.265
[Zn (L2)]	25.093	-169.65

 

Table 3: Densities (d) and relative viscosities (η_r) of substituted-Metformin of 0.01M concentration in 70% (DMSO + Water) solvent at different temperature (T = 303, 308, 313 and 318 K).

 

Table 4: The thermodynamic parameters for temperature difference 303K and 308 K.

System	∆G (J mol-1 K-1)	∆H (J mol-1 K-1)	∆S (J mol-1 K-1)
[Co (L2)]	-3862.74	-4073.75	-0.6851
[Ni (L2)]	-1695.15	-2092.82	-1.2912
[Cu (L2)]	-2939.27	-3330.39	-1.2698
[Zn (L2)]	-1980.58	-2349.76	-1.1947

 

4. CONCLUSIONS:

The present study deals with the in viscometric measurements of metal complexes of metformin at different temperatures by using their solutions of different concentrations. The relative viscosity of metal complexes of metformin increases with increase in the concentration of solutions. The increase in viscosity with increase in concentration may be attributed to the increase in the solute-solvent interactions. The values of Falkenhagen coefficient (A-coefficient) are positive in all the systems, shows that there is strong solute-solute interaction in all the systems. The B-coefficient is found to be negative for all the systems and it is a measure of disorder introduced by the solute into the solvent in all the systems. The negative values of ∆G and ∆H indicate reactions are spontaneous and exothermic. The negative value of ∆S indicates that there is an association of solvent molecules around the complex.

 

5. ACKNOWLEDGMENTS:

The authors would like to thank the Management and the Principal, E. S. Divekar College, Varvand for providing laboratory facilities to carry out this research work and for their encouragement.

 

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Accepted on 12.05.2020           © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(3):1511-1514.