Viscosity and Density Studies of Drugs in Aqueous Solution and in Aqueous Threonine Solution at 298 . 15 K

Viscosities (η) and densities (ρ) of atenolol and propranolol hydrochloride in water and in concentrations (0.05 M) and (0.1 M) aqueous solution of threonine have been used to reform different important thermodynamic parameters like apparent molal volumes fv partial molal volumes at infinite dilution fvo, transfer volume fvo(tr), the slop Sv, Gibbs free energy of activation for viscous flow of solution ΔG*1,2 and the B-coefficient have been calculated using Jones-Dole equation. These thermodynamic parameters have been predicted in terms of solute-solute and solute-solvent interaction.


INTRODUCTION
Drug work in human body is known as pharmacodynamics.The efficiency of a drug depends on its bioavailability 1 .The general reason of low oral bioavailability is due to low solubility of drug molecules.Sometimes, low aqueous soluble drugs require high dosages for the coveted action.Low water solubility of drugs is a serious problem for generic developments.Solubility of most drugs is having poor aqueous.Therefore, the raise of drug solubility and its oral bioavailability is a difficult function for drug evaluation process.Sometimes, some carrier molecules are added to the drugs to increase the solubility 2 .Numerous of works related to volumetric and viscometric properties of drugs have been completed by many researchers [3][4][5] .Molecular interaction (solute-solute and solutesolvent) have great importance in physical chemistry and geochemistry.Viscosity beta-coefficient, partial molar volumes and apparent molar volumes are advantageous in understanding solute-solvent interactions 6,7 .L-Threonine (abbreviated as Thr.) distributing polar amino acid, is an essential a-amino acids.It was discovered at last of 20 common proteinogenic amino acids with two chiral centers.4-(2-hydroxy-3-[(1-methylethyl)amino] propoxy)benzeneacetamide is known chemically as atenolol (ATN) 8 , is a β1-selective (cavdio selective) adrenorecepter discount drug used for antiangina therapy to relive symptoms, get better indulgence, and an antiarrhythmic to useful check heartbeat and infections.Atenolol is also used in management of alcohol with drawl, in worry states, headache prophylaxis, increased of metabolism, and tremble 9 .The drug is formal in Indian pharmacopoeia 10 .Isopropyl amino-3-(1-naphthyloxy) propan-2-ol hydrochloride, is known chemically propranolol hydrochloride, is a widely used non-cardio selective beta-adrenergic antagonist and been used for myocardial infarction, arrhythmia, angina pectoris, hypertension, migraine and anxiety 11 .Threonine a polar side chains and exhibits good solubility in water, the nature of solutesolute and solute-solvent interactions have been discussed in terms of the values of f v, fv o , S v and beta-coefficient.Thermodynamic parameters play an important role in detecting the various types of interactions occurring in solution.These are useful in illustrating the nature and effect of solute in solvent, intermolecular interactions and permeation of drug across biological membranes.

RESULT AND DISCUSSION
The apparent molal volume (fv) is calculated using the following equation 12,13,14 .
fv= (1)   Where ρ and ρ o are the densities of solution and solvent respectively, M is molecular weight of solute and (m) is the molality of solution, m is calculated using the following relation: Where (C) is the molar concentration.As the plots of fv against the molal concentration (m) were linear in the studied concentration range, standard partial molar volume fv o was obtained from the Masson equation 15 .
Where fv o is the partial molal volume at infinite dilution which gives information about solute hydrophobicity also a measure of solute-solvent interaction.S v is slop indicating solute-solute interaction.The Gibbs free energy of activation for viscous flow of solution at a given temperature and composition was measure by basing transition theory is given by equation 16 .

(4)
Where h is planks constant, N A is Avogadro's number, R is the gas constant and T is the absolute temperature.Volume of mole solution, 1,2 obtained from the following relation.

ExpERIMENTAL
Amino acid L-threonine obtained from Fluka company is stock solution and used without any further treatment.Atenolol and propranolol hydrochloride were supplied by the state company for drugs industry were medical appliances Samarra Iraq.The viscosity (η) was determined using assuspended-level ubbelohode viscometer described by findly, in a bath controlled to ± 0.01 K for all measurements.Vibrating tube with digital anton parr densimeter (DMA 60/602) according to Shukla et al., in a thermostated bath controlled to ± 0.01 K used to measure densities for all solution.
o o calculated viscosity beta-coefficients.The value of B depends upon the nature of solute-solvent interaction which is specific for solute-solvent system and the size of solute.The standard partial molar volume of transfer was obtained from the following relation 18 .
fv o (tr)= fv o (in aqueous threonine)fv o (in water) (7)   The values of fv o (tr) and Sv are listed in Table 7 and 8.The values of fv o (tr) of drugs in mixed liquids (threonine + water) are higher than those in aqueous solution, fv o (tr) are positive for all solutions studied and S v are positive which indicates ion-ion interaction is greater than post-micellar region.The betacoefficients measure the shape effects, the size as well as the structural effect induced by solute-solvent interaction.It can be seen from Tables (1-6) that all the viscosity B-coefficients for drugs are positive, this may be understanding in expressing of the solute-solvent interaction.

( 5 )
Where M 2 and M 1 are the molecular weight for solute and solvent respectively.The viscosity measurements have been analyzed in terms of Jones-Dole equation 17 .(6) Where η and η o are the viscosities of solution and solvent respectively and C is the molarity of solution, using Jones-Dole equation, was