NMR Studie's Of The Mechanism Of Drug Solubilization Within Amphiphilic Systems And Its Properties

As a non-invasive analytical technique,nuclear magnetic resonance(NMR)can provide both structure and kinetic information.Amphiphilic systems based on surfactants,such as micelle and emulsion,are able to effectively improve the solubility of poorly soluble organic matter in water,which plays an important role in pharmaceutics,food,cosmetic and others fields.However,the process and mechanism of micelle solubilization and the formation process and properties of emulsion at the molecular level are still unknown.In this thesis,the solubilization of thymol within Tween 80 micelles and the formation process and componants of oil-in-water emulsion are investigated by NMR spectroscopy.The main works are as follows:First,the characteristics of amphiphilic systems and the formations and properties of both surfactant micelle and emulsion were reviewed.The characteristics of amphiphilic systems studied by NMR spectroscopy were also introduced.Then,we summarized some important applications of NMR chemical shift,diffusion ordered spectroscopy(DOSY)and NOESY in amphiphilic systems and the research progresses of drug solubilization within micelles.Second,the solubilization process and mechanism of thymol within Tween 80 micelles and the intermolecular interactions were studied by NMR spectroscopy.A series of Tween 80 and thymol mixed solutions with the concentration of thymol from low to high were prepared.The chemical shift variations of Tween 80 and thymol before and after solubilization were obtained by 1H NMR spectroscopy,and found that the thymol is solubilized in the palisade layer of Tween 80 micelles.Then,we explored the effect of thymol concentration on the mixed solutions by 1H NMR spectroscopy,DOSY and NOESY.It was found that thymol was originally located in the hydrophobic core of Tween 80 micelles,as the concentration of thymol increased,reaching its solubilization amount in Tween 80 micelles core,and the excess thymol was solubilized in the palisade layer of Tween 80.Eventually,thymol exceeding the max solubilization amount of Tween 80 micelles,to solubilize as much thymol as possible,a part of micellar Tween 80 formed a new aggregate and its particle size was much bigger.Third,NMR spectroscopy were used to study the formation process and the properties of emulsion.A series of oil-in-water emulsions emulsified by Tween 80 and glycerol were prepared with different concentration of tricaprylin.With the oil concentration increasing,the compositions of emulsion became more and more complex and emulsion droplets with different size and type appeared.According to the diffusion coefficient of tricaprylin,the droplet size distribution of oil-in-water emulsions with different oil concentration were calculated,which are consistant with those from the microscope observation.