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Title: The Solution Properties of Amphiphilic Drugs and their Interactions with Surfactants and Human Serum Albumin
Authors: Usman, Muhammad
Keywords: Natural Sciences
Chemistry & allied sciences
Physical chemistry
Techniques, equipment & materials
Issue Date: 2011
Publisher: Quaid-i-Azam University Islamabad, Pakistan
Abstract: This dissertation reports physicochemical behaviour of some amphiphilic drugs as well as their interaction with anionogenic tensides (ionic surfactants) and Human serum albumin (HSA). A detail study of self aggregation of these drugs i.e. Clindamycine Phosphate (CLN), Quinacrine 2HCl (QUN), Chloroquine diphosphate (CLQ), Dexamethasone Sodium Phosphate (DSP) , Pefloxacin Mesylate (PFL), Citalopram HBr (CIT), Fluphenazine 2HCl (FLP), Trifluperazine 2HCl (TRF) and Certizine 2HCl (CRT) has been worked out. Surface tension and specific conductivity were measured to calculate the critical micelle concentration (CMC) of drugs and in this way their surface and thermodynamic parameters have been estimated. Surface activity was studied by measuring surface parameters i.e. surface pressure, Л, surface excess concentration, Г, area per molecule of  drug and standard Gibbs free energy of adsorption, Gads . The electrical conductivity was measured as a function of concentration in the temperature range of 293-323K and CMC was determined. Consequently  thermodynamic parameters like standard free energy of micellization, Gm , standard   enthalpy of micellization, H m and standard entropy of micellization, S m were computed using closed association model. Aggregation properties of some structurally related drugs trifluperazine and fluphenazine and Quinacrine and Chloroquine have also been brought under study. For the most of drugs, association was found to be both enthalpy as well as entropy driven. Dexamethasone sodium phosphate, however, undergoes open association rather than micellization. We have also studied interaction of amphiphilic drugs with anionic surfactants sodium dodecyl sulfate (SDS) and cationic surfactant cetyltrimethyl ammonium bromide (CTAB). Aqueous micellar solutions of these surfactants were used for solublization of these drugs. The change of CMC of surfactant due to drug was determined by UV/Visible spectroscopy and conductivity method. UV/Visible spectroscopy was used to check the qualitative and quantitative features of this interaction and to calculate partition coefficient (Kx), free energy of partition and number of drug molecules per micelle while conductivity method is helpful to calculate different thermodynamic parameters. The complexation of amphiphilic drugs with HSA at physiological conditions (pH 3.0 and 7.4) have also been analyzed by using UV/Visible spectroscopy, fluorescence spectroscopy and dynamic laser light scattering. In this way values of drug-protein binding constant, number of binding sites and hydrodynamic radii were calculated and discussed in detail.
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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