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Solution Properties of Certain Drugs in Water and Organic Solvent, Their Interaction With Amino Acids and Surfactants

Thesis Info

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Author

Shakeel, Muhammad

Program

PhD

Institute

Hazara University

City

Mansehra

Province

KPK

Country

Pakistan

Thesis Completing Year

2016

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/2799/1/Muhammad_Shakeel_Chemistry_2016_HSR_HU_Mansehra_21.02.2017.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727189404

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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 (Vf) were calculated which were used to find partial molar volume (V°f), semi empirical parameter (Sv), Hepler’s constant, partial molar expansivity (E°2) and isobaric thermal expansion coefficient (a2). 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 (b), degree of counterion binding (a), 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.
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Biological Control of Damping off Pythium Debaryanum Diseases of Chilies

Cardiovascular complications, such as myocardial infarction, atherosclerosis, cardiomyopathy and heart failure are amongst the major causes of morbidity and mortality among diabetic patients. Diabetic cardiomyopathy (DCM) is a progressive disease of the heart muscle mediated by hyperglycemia and oxidative stress. Endothelial progenitor cells (EPCs) have shown promising potential to repair the diabetes induced cardiac damage. EPCs differentiate into functional and mature endothelial cells. However, challenges such as deteriorated functional abilities and survival of EPCs derived from diabetic subjects limit the possible outcome of autologous EPCs based therapies. Diazoxide (DZ), a highly selective mito-KATP channel opener, has been shown to improve the ability of mesenchymal stem cells and skeletal myoblasts for the repair of damage to heart muscles. In the present study, effect of DZ preconditioning was evaluated in determining the ability of diabetes affected bone marrow-derived EPCs to repair streptozotocin (STZ) induced DCM in rats. Diabetic EPCs (DM-EPCs) were characterized by immunocytochemistry, flow cytometry and reverse transcriptase PCR for endothelial markers: vWF, VE Cadherin, VEGFR2, PECAM, CD34 and eNOS. Preconditioning was performed in vitro, by incubation of DM-EPCs in 200 μM DZ for 30 minutes, followed by H2O2 induced oxidative stress and hyperglycemic stress. Oxidative stress to preconditioned and non preconditioned DM-EPCs was induced by exposure to 200 μM H2O2 for 2 hours whereas for hyperglycemic stress induction, the cells were exposed to 30 mM glucose media. Non-preconditioned EPCs with and without exposure to H2O2 were served as controls. IX The treated cells were evaluated for survival (XTT cell viability assay), senescence, paracrine potential (by ELISA for VEGF) and alteration in gene expression (VEGF, SDF-1α, HGF, bFGF, Bcl2 and caspase-3). DZ preconditioning of DM-EPCs significantly increased survival accompanied by enhanced release of VEGF and reduced senescence in DZ DM-EPCs+H2O2 group as compared to DM EPCs+H2O2 group under oxidative and hyperglycemic stress conditions. Furthermore, DZ preconditioned DM-EPCs exhibited upregulated expression of prosurvival genes under oxidative stress (VEGF, SDF-1α, HGF, bFGF and Bcl2) and under hyperglycemic stress (VEGF and Bcl2) while down regulated the expression of Caspase-3 in DZ DM-EPCs+H2O2 group as compared to DM-EPCs+H2O2 group under oxidative and hyperglycemic stress conditions as determined by reverse transcriptase PCR and real time PCR. For in vivo studies, diabetes was induced in Wistar rats by injecting 40 mg/kg streptozotocin. After eight weeks, 2x106/70 μl of serum free medium, each of DZ preconditioned DM-EPCs and non-preconditioned DM-EPCs were transplanted into the left ventricle (LV) of diabetic rats (n꞊6 rats per group). After four weeks, DZ preconditioned DM-EPCs transplanted group showed improved contractility of diabetic heart as compared to untreated DM-EPCs group. There was decrease in collagen content estimated by Masson''s trichrome and Picrosirius red staining in DZ DM-EPCs transplanted group as compared to untreated DM-EPCs transplanted group. Furthermore, reduced cells injury were observed in DZ DM-EPCs group as evidenced by decreased expression of caspase-3 and increased expression of prosurvival genes Bcl2, VEGF and bFGF by semi-quantitative real time PCR. X In conclusion, the present study demonstrated that DZ preconditioning enhanced DM-EPCs survival under oxidative and hyperglycemic stresses and their ability to treat DCM.