Interaction Studies of Chlorpheniramine Maleate in Mono and Dihydric Alcohols by Density, Viscosity, and HPLC Methods

Zainab Khan(1), Summyia Masood(2*), Nighat Shafi(3), Rafia Azmat(4), Salman Khurshid(5), Samreen Begum(6)

(1) Department of Chemistry, University of Karachi, Karachi-75270, Pakistan
(2) Department of Chemistry, University of Karachi, Karachi-75270, Pakistan
(3) Department of Chemistry, University of Karachi, Karachi-75270, Pakistan
(4) Department of Chemistry, University of Karachi, Karachi-75270, Pakistan
(5) Southern-zone Agriculture Research Center, (PARC) Karachi University Campus, Karachi-75270, Pakistan
(6) Department of Chemistry, University of Karachi, Karachi-75270, Pakistan
(*) Corresponding Author


The examination of a drug in water and other aqueous systems gives insight into the chemistry of biological systems. This work aims to study the physico-chemical properties of chlorpheniramine maleate (drug) in water and aq-MeOH/EG (mono/dihydric alcohols) systems at different temperatures by using different techniques. Densities and viscosities of chlorpheniramine maleate in water and also in MeOH/EG aqueous solutions have been measured over a temperature range of 298.15 to 318.15 K. Number of several parameters, i.e., apparent molar volume (ϕv), partial molar volume (ϕvo), Hepler’s constant (∂CΡ/∂Ρ)T, Falkenhagen coefficient (A), and Jones-Dole coefficient (B) have been calculated by using experimentally measured density and viscosity values. The mentioned calculated parameters were found to be valuable in perceiving drug-drug and drug-solvent interactions. Moreover, one of the liquid chromatographic techniques such as RP-HPLC has also been performed, and the outcomes supported the conclusion procured from the volumetric and viscometric studies. Drug interactions help to understand their behavior in different solvent systems during drug development.


apparent molar volume; RP-HPLC; drug-solvent interactions; chlorpheniramine maleate

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[1] Zhang, F., 2016, Physicochemical properties and mechanisms of drug release from melt-extruded granules consisting of chlorpheniramine maleate and Eudragit FS, Drug Dev. Ind. Pharm., 42 (4), 563–571.

[2] Sawhney, N., Kumar, M., Sandarve, S., Sharma, P., Sharma, A.K., and Sharma, M., 2019, Structure-making behaviour of L-arginine in aqueous solution of drug ketorolac tromethamine: volumetric, compressibility and viscometric studies, Phys. Chem. Liq., 57 (2), 184–203.

[3] Munir, A.Q., and Ali, M., 2014, Study of solvent and temperature effects on volumetric, viscometric and conductometric studies of amlodipine besylate, Asian J. Biomed. Pharm. Sci., 4 (35), 22–29.

[4] Rajagopal, K., and Jayabalakrishnan, S.S., 2009, Volumetric and viscometric studies of 4 aminobutyric acid in aqueous solutions of salbutamol sulphate at 308.15, 313.15 and 318.15 K, Chin. J. Chem. Eng., 17 (5), 796–804.

[5] Banipal, T.S., Singh, H., Banipal, P.K., and Singh, V., 2013, Volumetric and viscometric studies on L-ascorbic acid, nicotinic acid, thiamine hydrochloride and pyridoxine hydrochloride in water at temperatures (288.15–318.15) K and at atmospheric pressure, Thermochim. Acta, 553, 31–39.

[6] Chauhan, S., Singh, K., Kumar, K., Neelakantan, S.C., and Kumar, G., 2016, Drug− amino acid interactions in aqueous medium: Volumetric, compressibility, and viscometric studies, J. Chem. Eng. Data, 61 (2), 788–796.

[7] Banipal, T.S., Beri, A., Kaur, N., and Banipal, P.K., 2016, Volumetric, viscometric and spectroscopic approach to study the solvation behavior of xanthine drugs in aqueous solutions of NaCl at T = 288.15–318.15 K and at p = 101.325 kPa, J. Chem. Eng. Data, 62 (1), 20–34.

[8] Vercher, E., Llopis, J.F., González-Alfaro, V., Miguel, J.P., Orchillés, V., and Martínez-Andreu, A., 2015, Volumetric properties, viscosities and refractive indices of binary liquid mixtures of tetrafluoroborate-based ionic liquids with methanol at several temperatures, J. Chem. Thermodyn., 90, 174–184.

[9] Jamal, M.A., Khosa, M.K., Muneer, M., Ur-Rehman, F., Zia, K.M., and Shahzad, K., 2013, Volumetric and ultrasonic studies of an antidepressant drug in aqueous and alcoholic medium over temperature range 298.15–313.15 K, J. Chem. Soc. Pak., 35 (2), 276–280.

[10] Salman, T.A., and Abd, K.A., 2013, Thermodynamic properties of nicotinic acid in dilute HCl and in aqueous NaCl solutions at (293.15, 298.15, 303.15 and 308.15) K, Baghdad Sci. J., 10 (2), 432–441.

[11] Shafi, N., Siddiqui, F.A., Sultana, N., and Arayne. M.S., 2015, Concurrent determination of diltiazem, lisinopril, captopril, and enalapril in dosage formulations and in human serum by liquid chromatographic technique, J. Liq. Chromatogr. Relat. Technol., 38 (15), 1466–1473.

[12] Siddiqui, F.A., Sher, N., Shafi, N., Sial, A.W., Ahmad, M., Mehjebeen, M., and Naseem, H., 2014, Development of new method for simultaneous analysis of piracetam and levetiracetam in pharmaceuticals and biological fluids: Application in stability studies, BioMed Res. Int., 2014, 758283.

[13] Masood, S., Khan, Z., Ashfaq, M., and Khan, S.R., 2020, Optical studies of acefylline piperazine, chlorpheniramine maleate, thiamine hydrochloride in aqueous, aqueous methanol and aqueous ethylene glycol systems, J. Mol. Liq., 303, 112611.

[14] Zhu, Y., Shah, N.H., Malick, A.W., Infeld, M.H., and McGinity, J.W., 2002, Solid-state plasticization of an acrylic polymer with chlorpheniramine maleate and triethyl citrate, Int. J. Pharm., 241 (2), 301–310.

[15] Sayeed, M.A., and Rana, S., 2013, In vitro and In vivo drug-drug interaction study between ketotifen fumerate and chlorpheniramine maleate at gastric and intestinal pH, e-J. Sci. Technol., 2 (8), 17–25.

[16] Dhondge, S.S., Zodape, S.P., and Parwate, D.P., 2012, Volumetric and viscometric studies of some drugs in aqueous solutions at different temperatures, J. Chem. Thermodyn., 48, 207–212.

[17] Mahmood, K., Shakeel, M., and Siddiq, M., 2016, Volumetric and thermodynamic study of three pharmacologically important drugs in ethanol, Asian J. Chem., 28 (4), 761–764.

[18] Shakeel, M., and Mahmood, K., 2020, Use of Masson’s and Jones-Dole equation to study different type of interactions of three pharmacologically important drugs in ethanol, J. Chin. Chem. Soc., 67 (9), 1552–1562.

[19] Ragab, G.H., Shaleh, H.M., El-Henawee, M.M., and Elsayed, O.F., 2016, Validated ultra-high efficiency RP-HPLC and stability indicating method for determination of tranylcypromines sulphate in bulk and in tablet dosage forms, J. Appl. Pharm. Sci., 6 (2), 64–71.

[20] Masood, S., Rehman, W., Begum, S., Khan, Z., and Gulnar, L., 2020, Drug-drug and drug-solvent interaction studies of Chloroquine phosphate, Acefylline piperazine and Gentamicin sulfate in polymeric systems, Arabian J. Chem., 13 (7), 6221–6235.

[21] Kumar, H., and Behal, I., 2016, Thermodynamics of (solute + solute) and (solute + solvent) interactions of homologous series of amino acids with thiamine hydrochloride in aqueous medium at T = (305.15, 310.15, 315.15) K: A volumetric and acoustic approach, J. Chem. Thermodyn., 102, 48–62.

[22] Singh, S., 2022, Using volumetric method the study of molecular interactions of NSAID (DP) in water and water + 1M urea at different temperatures, Biointerface Res. Appl. Chem., 12 (3), 3956–3965.

[23] Frank, H.S., and Wen, W.Y., 1957, Ion-solvent interaction. Structural aspects of ion-solvent interaction in aqueous solutions: a suggested picture of water structure, Discuss. Faraday Soc., 24 (24), 133–140.

[24] Singh, J., Singh, M., Sharma, S., Sharma, S., and Sharma, M., 2021, Molecular interactions of diphenhydramine-hydrochloride with some imidazolium-based ionic liquids in aqueous media at T = 293.15–313.15 K: Volumetric, acoustic, and UV absorption studies, ACS Omega, 6 (35), 22655–22671.

[25] Shekaari, H., and Kazempour, A., 2011, Solution properties of ternary D-glucose +1-ethyl-3-methylimidazolium ethyl sulfate + water solutions at 298.15 K, J. Solution Chem.,40 (9), 1582.

[26] Rafiee, H.R., and Frouzesh, F., 2017, The study of solute–solvent interactions in the ternary {amino acid (glycine or L-serine)+ ionic liquid (1-butyl-3-methylimidazolium tetra fluoroborate [Bmim][BF4])+ H2O} system at different temperatures and ambient pressure: Volumetric study, J. Mol. Liq., 230, 6–14.

[27] Friedman, H.L., and Krishnan, C.V., 1973, Studies of hydrophobic bonding in aqueous alcohols: enthalpy measurements and model calculations, J. Solution Chem., 2 (2), 119–140.

[28] Xie, H., Zhao, L., Liu, C., Cao, Y., Lu, X., Lei, Q., and Fang, W., 2016, Volumetric property of glycine, L-serine, L-alanine and L-proline in aqueous solutions of 1-phenylpiperazinium tetrafluoroborate, J. Chem. Thermodyn., 99, 75–81.

[29] Sarkar, A., and Sinha, B., 2016, Solution properties and taste behaviour of lactose monohydrate in aqueous ascorbic acid solutions at different temperatures: Volumetric and rheological approach, Food Chem., 211, 590–597.

[30] Hepler, L.G., 1969, Thermal expansion and structure in water and aqueous solutions, Can. J. Chem., 47 (24), 4613–4617.

[31] Rani, R., Kumar, A., and Bamezai, R.K., 2017, Effect of glucose/lactose on the solution thermodynamics of thiamine hydrochloride in aqueous solutions at different temperatures, J. Mol. Liq., 240, 642–655.

[32] Zhang, J.B., Zhang, P.Y., Ma, K., Han, F., Chen, G.H., and Wei, X.H., 2008, Hydrogen bonding interactions between ethylene glycol and water: Density, excess molar volume, and spectral study, Sci. China, Ser. B: Chem., 51 (5), 420–426.

[33] Chauhan, S., Chaudhary, P., Sharma, K., Kumar, K., and Kiran, K., 2013, Temperature-dependent volumetric and viscometric properties of amino acids in aqueous solutions of an antibiotic drug, Chem. Pap., 67 (11), 1442–1452.

[34] Rehman, W., Masood, S., Begum, S., Chandio, A.D., Khan, S.R., Gulnar, L., Khattak, R., and Khan, M.S., 2021, Viscometric and FTIR studies of chloroquine phosphate, acefylline piperazine and gentamicin sulfate in aqueous-polyethylene glycol and aqueous-polyvinyl pyrrolidone at different temperatures, Arabian J. Chem., 14 (8), 103265.

[35] Tomaš, R., Jovanović, T., and Bešter-Rogač, M., 2015, Viscosity B-coefficient for sodium chloride in aqueous mixtures of 1,4-dioxane at different temperatures, Acta Chim. Slov., 62 (3), 531–537.

[36] Banipal, T.S., Kaur, J., Banipal, P.K., Sood, A.K., and Singh, K., 2011, Volumetric and viscometric studies of some amino acids in aqueous solutions of cadmium chloride at T = (288.15 to 318.15) K and at atmospheric pressure, J. Chem. Eng. Data, 56 (6), 2751–2760.

[37] Jafari, P., Rahimpour, E., Acee, W.E., and Jouyban, A., 2021. Prediction of drug solubility in ethylene glycol+water mixtures using generally trained cosolvency models, J. Mol. Liq., 328, 115325.


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