Volumetric and ultrasonic approach in the investigation of critical micellar phenomenon of amphiphilic drugs in aqueous solutions at different temperatures Doyel M. Bhattacharya, Umesh R. Pratap, Atul V. Wankhade, Sangesh P. Zodape ⁎ Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur 440-010, Maharashtra, India abstract article info Article history: Received 18 August 2015 Received in revised form 10 November 2015 Accepted 22 November 2015 Available online xxxx The apparent molar volumes (V ϕ ) along with apparent molar isentropic compressibilities (κ ϕ ) of aqueous solu- tions of the amphiphilic drugs namely amantadine hydrochloride and semicarbazide hydrochloride have been determined from density and ultrasound data at T = (288.15, 293.15, 298.15, 303.15 and 308.15) K. The critical micelle concentration along with the free energy change ( ΔG m 0 ), enthalpy change (ΔH m 0 ) and (T · ΔS m 0 ) of micell- ization was obtained for the aqueous binary mixtures of drugs. The volume changes due to micellization (ΔV ϕ m ) were also estimated for both the studied drugs at different temperatures. Negative deviation from the Debye– Hückel limiting law of the apparent molal volume was obtained for water + amantadine hydrochloride system while positive deviation was observed in the case of water + semicarbazide hydrochloride system. The aggregation number (n) for the studied drugs in the aqueous environment has been also determined at 298.15 K. The results obtained at different temperatures have been interpreted in terms of drug–water interac- tions and solute–solute interactions which seem to depend upon the structural features of the solute molecule and also on the surrounding environment of drug molecules. © 2015 Published by Elsevier B.V. Keywords: Density Speed of sound Micellization Critical micelle concentration Free energy change Solute–solvent interactions Aggregation number Partial molar volume 1. Introduction Amphiphilic compounds have hydrophobic and hydrophilic do- mains that are separated by intermediate alkyl chains. The amphiphilic behavior of drugs is important in the biological and membranous activ- ity of these drugs. This membranous activity results into different type of interactions of drug molecules with the environment outside the membrane. The changes in the structural features and the interactions of the drug can also serve as deciding criteria for the selective perme- ability of the drugs through the membrane and into the interior of the cells and lymph of the organism [1]. Also the accumulation of the drug molecules at certain sites in the body may cause a localized high concen- tration resulting into aggregation and subsequent changes in biological activity due to decreased transport rates or decreased ability to pass through biological barriers [2]. The amphiphilic drugs also feature the micelle formation which is an important characteristic property of bio- logical importance. The critical concentration for micelle formation can be estimated by the inflections or discontinuity in the physical property such as conductivity, surface tension, light scattering and many more. Essential information can be obtained on the critical micellar concentration and the thermodynamics involved in it to have detailed and thorough approach to understand the dynamics underlying the phenomenon [3]. The thermodynamics of aggregation can be deeply studied by the systematic volumetric and acoustic investigations of the aqueous binary systems of the drugs at different temperatures. Free energy of micellization also holds importance as it gives an esti- mate of the spontaneity of the process and the energetic of micellization [4]. In the present investigation, two amphiphilic drugs namely Aman- tadine hydrochloride and Semicarbazide hydrochloride have been stud- ied for their micellization characteristics in the aqueous environment at five different temperatures T = (288.15, 293.15, 298.15, 303.15 and 308.15) K. Amantadine hydrochloride drug is found to possess antiviral properties against influenza with type A virus and also exhibits mild action against Parkinson disease. It also affects the brain in many ways including release of neurotransmitters such as dopamine and nor- epinephrine from nerve endings [5]. On the other hand, semicarbazide hydrochloride is found to have carcinogenic effects in animals and is highly toxic. It is also used as building block for the carbonyl compounds [6]. Thus, it would be interesting to know the chemical interactions of these molecules with water at temperatures close to our body temper- ature. This study comprises of the investigations into the solute–solvent interaction (hydrophobic hydration) in pre-micellar concentration and solute–solute association (hydrophobic interaction) in post-micellar concentration region. Journal of Molecular Liquids 214 (2016) 117–127 ⁎ Corresponding author. E-mail addresses: sangesh02@gmail.com, sangesh_02@yahoo.co.in (S.P. Zodape). http://dx.doi.org/10.1016/j.molliq.2015.11.039 0167-7322/© 2015 Published by Elsevier B.V. Contents lists available at ScienceDirect Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq