Partition coefficient n-octanol/water of propranolol and atenolol at different temperatures: Experimental and theoretical studies M. Mohsen-Nia a,b,⇑ , A.H. Ebrahimabadi c , B. Niknahad a a Thermodynamics Research Laboratory, University of Kashan, Kashan, Iran b Division of Chemistry and Chemical Engineering, California Institute of Technology, CA, USA c Essentail Oils Research Center, University of Kashan, Kashan, Iran article info Article history: Received 23 March 2012 Received in revised form 18 May 2012 Accepted 18 May 2012 Available online 27 May 2012 Keywords: Propranolol Atenolol Partition coefficient Phase equilibrium Activity coefficient model abstract The n-octanol/water partition coefficients of propranolol and atenolol were experimentally determined by ultraviolet (UV) spectroscopy at T = (298.15, 310.15 and 314.15) K. All measurements were made at the maximum wavelength corresponding to maximum absorption. The results showed that the n-octanol/water partition coefficients of propranolol and atenolol increase with the increase of temper- ature. The experimental data of this work were also used to examine the phase equilibrium correlating capability of some liquid-phase models. The equilibrium experimental data were correlated using the NRTL and UNIQUAC activity coefficient models and the binary interaction parameters were reported. The average root-mea n-square deviations (RMSD) between the experimental and calculated mass fractions of the (n-octanol + propranolol + water) and (n-octanol + atenolol + water) systems were deter- mined. From the partition coefficients obtained, it is concluded that propranolol (log P ow = 3.12 ± 0.14) is more hydrophobic than the atenolol (log P ow = 0.16 ± 0.01) at T = 298.15 K. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Propranolol is a non-selective beta blocker mainly used in the treatment of hypertension. It was the first successful beta blocker developed. Propranolol is currently being investigated as a poten- tial treatment for post-traumatic stress disorder [1]. Propranolol is available in generic form as propranolol hydrochloride. Atenolol is a selective b 1 receptor antagonist, a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. Atenolol was developed as a replacement for propranolol in the treatment of hypertension [2]. The biological properties of drugs can be described in terms of partition between two phases, polar (most frequently water) and non-polar (lipid phase). The ratio of the equilibrium concentration of the substance in the non-polar phase to that in the polar phase has been used for quan- titative measurement of the partition process between two phases. Knowledge of the preferred partitioning of substances is essen- tial in pharmacology and rational drug-design strategies. Besides such biological and medical applications, partition coefficients are also extensively used in environmental engineering to deter- mine the behaviour and fate of drug molecules chemicals [3]. It is an important factor for determining the drug molecular transfer, permeation, absorption, distribution, elimination, and biological activity. The measurement of liquid–liquid partition coefficients has been also studied for the various applications such as purifica- tion and extraction of chemicals in the separation processes [4]. Considering the complexity of biological membranes, the informa- tion obtained from the partitioning behaviour of drugs in simple hydrophobic/hydrophilic systems such as n-octanol/water system can be used for prediction of the drug partitioning behaviour in realistic biological membranes [5]. The n-octanol/water system is considered as a reference for of the partition behaviour of drugs be- tween water and a lipid biophase. The amphipathic character of n- octanol makes it similar to lipids. The n-octanol has a polar head and a long non-polar tail which form the basis for a number of areas of research in chemistry and biochemistry [6]. The n-octanol/water partition coefficient is the accepted physicochem- ical method for measuring of the hydrophobicity of chemicals especially pharmaceutical drugs [7]. The partition coefficient is the most widely employed descriptor for the quantitative struc- ture–activity relationship (QSAR) studies [8–11]. Although lipophilicity of pharmaceutical drugs is often described as partition coefficient in the n -octanol/water system, the study of temperature dependency and modelling of the drug partition coefficient is a research field of interest for scientists [12]. The partition coefficient between n-octanol and water, P ow , is defined as the ratio of the equilibrium concentrations of the test chemical in n-octanol saturated with water and water saturated 0021-9614/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jct.2012.05.021 ⇑ Corresponding author at: Thermodynamics Research Laboratory, University of Kashan, Kashan, Iran. Tel.: +1 (626) 359 4194; fax: +1 (626) 568 8743. E-mail address: moh.moh@cheme.caltech.edu (M. Mohsen-Nia). J. Chem. Thermodynamics 54 (2012) 393–397 Contents lists available at SciVerse ScienceDirect J. Chem. Thermodynamics journal homepage: www.elsevier.com/locate/jct