VISCOMETRIC STUDY OF SYNTHESIZED DILTIAZEM-VANADIUM (V) COMPLEX IN NON-AQUEOUS SOLVENTS
HTML Full TextVISCOMETRIC STUDY OF SYNTHESIZED DILTIAZEM-VANADIUM (V) COMPLEX IN NON-AQUEOUS SOLVENTS
Shrivastava, M. Kapoor * and M. Tekriwal
Department of Chemistry, Faculty of Basic and Applied Sciences, Vivekananda Global University, Jaipur, Rajasthan, India.
ABSTRACT: In the present research work, measurement of viscometric parameters - Density, Molar Volume, Apparent Molar Volume, Viscosity, Specific Viscosity, and Fluidity of synthesized Vanadium (V) complex of commercial antihypertensive drug, Diltiazem has been reported in non-aqueous solvents of varying compositions. Composition of non-aqueous solvents selected for study is 20% and 40% methanol-water mixture. Experimental results showed the effect of Concentration of solute (Diltiazem drug) on density and viscosity in a methanol-water mixture. The density of Diltiazem-V (V) complex showed an irregular pattern in 20% methanol-water mixture, whereas an increase was observed in 40% methanol-water mixture. The molar volume value for the complex solution in both 20% & 40% methanol-water mixture showed rapid increase with the increase in complex Concentration. The apparent molar volumes (φv) decreased with an increase in Concentration of complex and same trend was followed in both 20% and 40 % methanol-water solvent system. Study of the viscous behavior of complex molecules in solution gives an understanding of the transport process mechanism and information about the shape and size of molecules. Specific viscosity ‘ηsp’ values of diltiazem-V(V) in 20% and 40% methanol-water mixture show that it raises with a rise in complex Concentration. This in turn gives a picture of molecular interactions taking place in different solutions. Information about molecular interactions between a metal complex of drug and various solvent compositions helps in the formulation of the stable, effective, and safe dosage form. It also helps in the understanding of their oral absorption by increasing the solubility or dissolution rate.
Keywords: Antihypertensive drug, Diltiazem, Metal complex, Density, Viscosity
INTRODUCTION: Biophysical chemistry, study of physicochemical parameters, is an important tool to study the interactive behavior of drugs and also to study about the complex mechanism of their action 1-4.
Once injected, drug actions take place in a fluid medium inside the body, and hence study of viscometric parameters give valuable information about transport properties and molecular interaction pattern 5-9.
Detail analysis of solute-solvent interaction during the solution phase of the drug helps in understanding the transport mechanism and absorption of the drug within cells 10-16. Diltiazem, which is chemically 1, 5-benzothiazepin - 4(5H)-one, 3- (acetyloxy)-5 [2-(dimethyl amino) ethyl]- 2, - 3 – dihydro – 2 (4-methoxyphenyl) -, mono hydrochloride, (+)-cis] is a significant calcium channel blocker coronary vasodilator antihypertensive drug 17-19. Diltiazem forms 1:1 complex with transition metal Vanadium (V). In this research work, various compositions have been reported viscometric investigation of the drug diltiazem– vanadium (V) metal complex in binary solution (water-methanol). Parameters investigated for the complex include density, molar volume, apparent molar volume, viscosity, specific viscosity and fluidity. This is helpful in understanding the formulation of stable, effective, and safe dosage form. It helps in the understanding of their oral absorption by increasing the solubility or dissolution rate.
EXPERIMENTAL:
Purification of Solvents: Water and Methanol mixture were used as solvents in various compositions. A Distillatory column is used for the double distillation of water. The distillate so obtained was refluxed over sodium metal, and it was again distilled. For the methanol purification, it was kept over potassium hydroxide for twenty-four hours and then distilled. The distillate obtained was refluxed with one percent of calcium metal for about eight hours and then distilled again. The fraction was collected at 65oC for experimental purposes.
Solute Diltiazem-Vanadium (V) Complex Preparation: For synthesis of diltiazem–Vanadium (V) Complex, a standard solution of Diltiazem was prepared by dissolving a tablet (brand name Tizac- 90mg diltiazem per tablet) in 100 ml distilled water. 0.01 M solution of vanadium pentoxide was prepared by dissolving 0.181 gm of vanadium pentoxide in 100 ml double distilled water. Solutions of lower concentrations were prepared by diluting aliquots of standard stock solution.
On mixing both the solutions at 35 oC and pH 2.6, the diltaizem –Vanadium (V) complex was synthesized with λmax 290 nm. The synthesized complex was then solidified and used as a solute for viscometric analysis. For accurate density measurements, the calculated amount of solid diltiazem-Vanadium (V) complex was weighed on a watch glass and dissolved in the required amount of water and methanol to prepare the solution.
In this way, solutions containing different concentrations of complex Diltiazem-V (V) in water-methanol solvent system at varying compositions were prepared.
Procedure: For the study of Diltiazem-Vanadium (V) metal complex density, a simple instrument Pycnometer, was used Fig. 1.
FIG. 1: PYCNOMETER WITH THERMOMETER V11204
For calculation of density‘d’ of complex solution, the relationship used was:
d= W/Wo---------------- (1)
Where W and W0 are the weights of the same sample solution and water volume, respectively, the calculated density of the complex solution was then used further to determine the molar volume and apparent molar volume. Molar volume calculation involves the relationship
V = X1M1 + X2M2 + X3M3 / d ---------------- (2)
Where X1= Mole fraction of the complex of molecular weight M1, ‘X2’ and ‘X3’ are the mole fraction of the water and methanol of molecular weight M2 and M3, respectively, d = density of the solution.
Apparent molar Volume was calculated by using the formula:
Φν = M/d0 + 1000(d0-d)/ C.d0 ---------------- (3)
Where do= density of the solvent, d=Density of complex solution, M= Molecular weight of the complex, and C= Concentration of the solution in gmolL-1.
For measurement of viscosity, Ostwald’s viscometer was used Fig. 2.
FIG. 2: OSTWALD VISCOMETER
The viscosities, specific viscosity, and fluidity of the complex solutions were calculated using relationships (4), (5), and (6), respectively.
ղ0/ղ = d0t0/dt ------------- (4)
ղsp = ղ-ղ0 /ղ0 ------------------ (5)
Fluidity (φ) = 1/Viscosity (ղ)---------------- (6)
RESULTS AND DISCUSSION:
Density Measurement: As per the experimental results, the density of Diltiazem-V (V) in 20% methanol-water mixture initially showed a slight increase with the increase in the Concentration of complex, then decreased and then again increased.
Whereas in the 40% methanol-water mixture, density variations of the complex were different. It showed a decrease followed by a very slight increase in the volume percent of methanol solvent Fig. 3.
FIG. 3: DENSITY OF DILTIAZEM-V (V)COMPLEX IN DIFFERENT % VOLUMES OF METHANOL-WATER MIXTURE
Molar Volume Measurement: The value of molar volume for the complex solution in 20% methanol-water mixture showed a rapid increase with the increase in complex Concentration. The same pattern of variation was visible in 40% methanol-water mixture but with lower values Fig. 4.
FIG. 4: MOLAR VOLUME OF DILTIAZEM-V (V) COMPLEX IN DIFFERENT % VOLUMES OF METHANOL-WATER MIXTURE
Apparent Molar Volume: Apparent molar volume provides valuable information about different types of interaction occurring in solutions. Thus the interaction of the V (V) complex of diltiazem with solvents having different polarity is worth to be analyzed. On plotting the value of apparent molar volume with Concentration of complex, the trend showed a decrease in the value of apparent molar volume with the increase in Concentration of complex molecule, with a sharp peak in between. The apparent molar volumes (φv) followed the same trend in the 20% and 40 % methanol-water solvent systems Fig. 5.
FIG. 5: APPARENT MOLAR VOLUME OF DILTIAZEM V(V) COMPLEX IN DIFFERENT % VOLUME OF METHANOL-WATER SYSTEM
Viscosity: The viscous behavior of complex molecules in solution is important to understanding the transport process mechanism. The viscosity variable provides valuable information about the shape and size of these molecules. The effect of complex Concentration on viscosity of Diltiazem-V (V) solution in 40% methanol-water mixture of varying composition is almost the same as that of 20% methanol-water mixture. The viscosity of the complex increased with the increase in complex Concentration and then decreased after a definite concentration as was visible in the viscosity-concentration plot. The viscosity pattern observed with the increase in Concentration of complex solution may be due to the increasing tendency of complex molecules to associate Fig. 6.
FIG. 6: VISCOSITY OF DILTIAZEM V (V) COMPLEX INDIFFERENT % VOLUME OF METHANOL-WATER SYSTEM
Specific Viscosity: Specific viscosity ‘ηsp’ values of diltiazem-V (V) in 20% and 40% methanol-water mixture were recorded. The outcomes showed that the specific viscosity (ηsp) of Diltiazem-V (V) rose in complex Concentration. This rise might be due to the rising trend of the complex solution molecules to form aggregates with increasing complex Concentration Fig. 7.
FIG. 7: SPECIFIC VISCOSITY OF DILTIAZEMV (V) COMPLEX IN DIFFERENT % VOLUMES OF METHANOL-WATER SYSTEM
Fluidity: The fluidity ‘φ’ of Diltiazem-V (V)in 40% methanol-water mixture is similar to that of 20% methanol-water mixture. The value of fluidity initially decreased with an increase in complex Concentration and ended up at a peak Fig. 8.
FIG. 8: FLUIDITY OF DILTIAZEMV (V) COMPLEXIN DIFFERENT % VOLUMES OF METHANOL-WATER SYSTEM
CONCLUSION: The present research work reports the viscometric measurements of the Diltiazem-V (V) complex at different solvent compositions of the methanol-water solvent mixture. Density, molar volume, viscosity, and fluidity values of the complex's 20% methanol water solvent system are higher than the 40% methanol-water system. Density and molar volume values are directly proportional to the Concentration of complex; this shows strong solute-solute interaction. The increase in viscosity and specific viscosity with the increase in complex Concentration might be due to the increased solute-solvent interactions.
ACKNOWLEDGEMENT: The authors are thankful to Vivekananda Global University Jaipur Rajasthan for providing instrumental facilities and basic resources to carry out the research work.
CONFLICTS OF INTEREST: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.
REFERENCES:
- Attiya HG, Al-Dulaimy ZAH, Sadiq KA and Saleem MH: Viscosity and density studies of drugs in aqueous solution and in aqueous threonine solution at 298.15 K. Orient J Chem 2019; 35: 337-342.
- Chatpalliwar Vivekanand A, Porwal Pawan K and Upmanyu Neeraj: Validated gradient stability indicating HPLC method for determining Diltiazem hydrochloride and related substances in bulk drug and novel tablet formulation. J Pharmaceut Anal 2012; 2(3): 226-237.
- Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T and Liao FF: Antidiabetic drug metformin (Glucophage R) increases biogenesis of Alzheimer’s amyloid peptides via up-regulating BACE1 transcription. Proc Nat Academy Sci 2009; 106(10): 3907–3912.
- Dhondge SS, Zodape SP and Parwate DV: Volumetric and viscometric studies of some drugs in aqueous solutions at different temperatures. J Chem Thermo 2012; 48: 207–212.
- Iqbal MJ and Chaudhry MA: Thermodynamic study of three pharmacologically significant drugs: Density, viscosity, and refractive index measurements at different temperatures. J Chem Thermo 2009; 41(2): 221–226.
- Iqbal MJ and Siddiquah M: Partial molar volume of mefenamic acid in alcohol at temperatures between T = 293.15 and T = 313.15 K. J Brazilian Chem Soc 2006; 17(5): 851–858.
- Kale KB, Shinde MA, Patil RH and Ottoor DP: Exploring the interaction of Valsartan and Valsartan-Zn (ll) complex with DNA by spectroscopic and in silico methods. Spectrochimica Acta Part A: Mol Biomol Spectro 2022; 264: 120329.
- Karges J: Combining Inorganic Chemistry and Biology: The underestimated potential of metal complexes in medicine. Chem Bio Chem 2020; 21: 3044– 3046.
- Kumar H and Behal I: Densities and speeds of sound of antibiotic drug chloramphenicol with L-leucine and glycyl-L-leucine in aqueous medium at T= (288.15–318.15) K: a volumetric, ultrasonic, and UV absorption study. J Chem Eng Data 2016; 61(11): 3740-51.
- Langore KR: Viscometric study of metformin complexes with some transition metal ions at different temperatures. Res J Pharm Tech 2021; 14(3):1511-4.
- Liu L, Scott L, Tariq N, Kume T, Dubins DN, Macgregor RB and Chalikian TV: Volumetric interplay between the conformational states adopted by guanine-rich DNA from the c-MYC promoter. J Phy Chem B 2021; 125(27): 7406-16.
- Ray S, Maiti S and Sa B: Polyethyleneimine-treated xanthan beads for prolonged release of diltiazem: in-vitro and in-vivo Arch Pharm Res 2010; 33(4): 575-83.
- Sumathi S, Tharmaraj P, Sheela CD and Ebenezer R: Synthesis, spectral, bioactivity and NLO properties of chalcone metal complexes. Journal of Coordination Chemistry 2011; 64(10): 1707–1717.
- Schöbel JH, Elbers P, Truong KN, Rissanen K and Bolm C: 1, 2-Benzothiazine derivatives from sulfonimidamides by metal-catalyzed annulation reactions in solution and under solvent-free mechanochemical conditions. Adv Synth Catal 2021; 363: 1322–1329.
- Shrivastava R, Mour M and Kapoor M: Synthesis and application of cobalt and vanadium complexes for quantitative estimation of anticancer drug, Mesna. Materials Today: Proceedings 2021; 42: 1718-1722.
- Sadaf Noreen and Sajjad H. Sumrra: Aminothiazole-Linked Metal Chelates: Synthesis. Density Functional Theory and Antimicrobial Studies with Antioxidant Correlations: ACS Omega 2021; 6 (48): 33085-33099.
- Shrivastava R: Spectrophotometric determination of Diltiazem in pharmaceutical and in-vivo samples with Pd(II): Inter J Pharma Sci Res 2013; 4(12): 4676-4681.
- Sumrra S. H. Arshad, Z. Zafar, W. Mahmood, K. Ashfaq, M. Hassan, A. U. Mughal, E. U. Irfan and A. Imran M: Metal incorporated aminothiazole-derived compounds: Synthesis, density function theory analysis. In-vitro Antibacterial and Antioxidant Evaluation R Soc Open Sci 2021; 8: 210910.
- Sumrra S. H, Zafar W, Asghar ML, Mushtaq F, Raza MA, Nazar MF, Nadeem MA, Imran M and Mumtaz S: Computational investigation of molecular structures, spectroscopic properties, cholinesterase inhibition and antibacterial activities of triazole Schiff bases endowed metal chelates. J Mol Struct 2021; 1238: 130382.
How to cite this article:
Shrivastava R, Kapoor M and Tekriwal M: Viscometric study of synthesized diltiazem-vanadium (v) complex in non-aqueous solvents. Int J Pharm Sci & Res 2022; 13(10): 4154-58. doi: 10.13040/IJPSR.0975-8232.13(10). 4154-58.
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IJPSR
R. Shrivastava, M. Kapoor * and M. Tekriwal
Department of Chemistry, Faculty of Basic and Applied Sciences, Vivekananda Global University, Jaipur, Rajasthan, India.
mahima01khanna@yahoo.com
26 February 2022
09 April 2022
25 April 2022
10.13040/IJPSR.0975-8232.13(10).4154-58
01 October 2022