Screening,Solid-State Transformation And Properties Study Of Salts Of 5-Sulfosalicylic Acid And Amine

In the pharmaceutical industry,developing new drugs or improving the physical and chemical properties of existing drugs through effective methods has always been an important research content of drug researchers.Instead,the drug co-crystal is to select a co-crystal forming agent?CCF?that matches the active drug ingredient?API?to form cocrystal or salt,which can improve the stability,solubility,bioavailability and so on.Drug co-crystals provide a more efficient method for modifying drug molecules,and are increasingly concerned by drug workers.In this dissertation,amine compounds isonicotinate?INZ?,amantadine?AMD?and lamivudine?LAM?are used as APIs,and 5-sulfosalicylic acid dihydrate?5-SSA?is selected as CCF.Crystal engineering strategies have synthesized a series of drug crystal salts.The main research contents are as follows:1.The salt SSA₁·INZ₁ was obtained by the solution crystallization method,and the structure was characterized and determined by infrared spectroscopy?FTIR?,X-ray powder diffraction?PXRD?and single crystal X-ray diffraction.Through Hirshfeld surface analysis to further understand the interaction between SSA₁·INZ₁·H₂O and SSA₁·INZ₁ molecules.The 2D fingerprint shows that the main intermolecular interactions are H···H and O···H,which account for a large proportion of more than 60%of the intermolecular interactions.2.The two salts SSA₁·AMD₁ and SSA₁·LAM₁ were obtained by liquid assisted grinding and solution crystallization.They were carried out by infrared spectroscopy?FTIR?,X-ray powder diffraction?PXRD?and single crystal X-ray diffraction.Put the same amount of SSA₁·LAM₁ in the ball mill and grind at the same frequency?30 HZ?for different times respectively.SEM electron microscope showed that the microscopic morphology of the particles changed through the increase of the ball milling time,but the X-ray powder diffraction results showed that The salt SSA₁·LAM₁ can maintain its own stability very well,and there is no phase change or amorphous state.The SSA₁·LAM₁ was measured with a Warikari eclipse fluorescence spectrophotometer at room temperature.When the grinding time was increased to 12h,the photoluminescence intensity was the strongest and was higher than lamivudine itself.