SOLUTION PROPERTIES OF CERTAIN DRUGS IN WATER AND ORGANIC SOLVENT, THEIR INTERACTION WITH AMINO ACIDS AND SURFACTANTS

Abstract

Densities of seven drugs Benzalkonium Chloride (BAC), Losartan Potassiun (LP), Chlorpheniramine Maleate (CPAM), Metformin Hydrochloride (MHCl), Sodium Valporate (SV), Levofloxacin (LF) and Chloramphenicol (CP) were measured at four different temperatures (288 K to 318 K) in water and organic solvent (ethanol for all drugs except MHCl for which methanol was used). From these values of density, apparent molar volumes (V) were calculated which were used to find partial molar volume (V°), semi empirical parameter (Sv), Hepler’s constant, partial molar expansivity (E°2) and isobaric thermal expansion coefficient (2). Viscosities of drugs solutions in water and ethanol solvents were determined at four different temperatures i.e. 288K to 318K. These values were used to calculate the constants of Jones-Dole equation. Different thermodynamic parameters like Gibbs free energy of activation of solution (ΔG#2), molar activation enthalpy (ΔH#2) and molar activation entropy (ΔS#2) of viscous flow were calculated. The critical micelle concentration (CMC) of six drugs was calculated in aqueous and ethanolic media (except MHCl for which methanol solvent was used) at four different temperatures (288 K to 318 K) by using electrical conductivity, surface tension and refractive index measurements. From conductometric measurements degree of ionization (), degree of counterion binding (), enthalpy of micellization (ΔH°m), free energy of micellization (ΔG°m) and entropy of micellization (ΔS°m) were calculated. From surface tension values surface excess concentration (Г2), minimum area per molecule (A) and free energy of adsorption (ΔG°ads) were calculated. The interaction of two surfactants SDS and CTAB with six drugs was studied at one temperature (298 K) in aqueous solution using UV/Visible spectroscopy and electrical conductivity. Measurements of UV/Visible spectroscopy were used to calculate partition coefficient (Kx), standard free energy of partition (ΔGp), binding constant (Kb) and standard free energy of binding (ΔGb). The effect of three amino acids i.e. glycine, L-tryptophan and L-tyrosine on CMC of five drugs were studied in aqueous solution at one temperature using electrical conductivity measurements which are useful to understand the solubilization of amino acids into the micelles of drugs. The determination of apparent molar volumes, partial molar volumes and other related parameters and constants of Jones-Dole equation is carried out to find the types of interaction of drugs with solvent. Another purpose of this study is to find same trend for effect of drugs on solvent from volumetric and viscometric study. Decrease in apparent molar volume with concentration in both solvents shows solvophobic interaction of all drugs with solvents. Values of partial molar volumes of these drugs are lower in aqueous medium than in alcoholic due to greater polarity of water. Sv is found to be negative for drugs showing weak solute-solute interaction except CPAM. Positive value of Hepler’s constant shows structure promoting effect of drugs on solvent except CPAM in ethanol. B-coefficient of Jones-Dole equation is positive representing strong solute- solvent interaction. ΔG#2 is positive and higher than ΔG#1 representing structure promoting effect and stronger solute-solvent interaction in ground than in transition state. Positive value of ΔH#2 means that the process of transition state formation is endothermic. From the values of Hepler’s constant and B-coefficient the order of hydrophobic interaction in aqueous medium was found to be in same order which is BAC > LP > CPAM > SV > MHCl In case of alcoholic solution the order of solvophobic interaction is also same as determined by viscometric and volumetric study which is MHCl > LF > CP > BAC > SV > CPAM The determination of CMC at different temperatures is carried out to get thermodynamic and other related parameters which are very useful to understand micellization process and the effect of presence of drug on solution. Values of surface excess concentration for all drugs show higher drug concentration at solution-air interface than in bulk of solution phase. ΔG°ads has more negative value than ΔG°m representing that the adsorption of drug molecules at surface is more spontaneous than micellization. ΔH°m is negative, showing micellization is exothermic while for SV in ethanolic solution and for CPAM and LP in both solvents it is positive. Positive ΔS°m represents that the micellization process results in increase in entropy of solution. The same type of behaviour is reported in literature for different amphiphilic drugs e.g. Chloroquine Diphosphate, Citalopram HBr.