Preparation,Microstructure,and Biological Properties Of Niclosamide Drug Eutectic

The solid form of a drug directly affects its safety and effectiveness.An API(active drug component)molecule may consist of one or more supramolecular synthesizers,and its way assembling depends on the molecular structure of the API.The introduction of different eutectic precursors CCF(Cocrystal Formers)often improve the physicochemical and pharmaceutical properties of API in varying degrees.By introducing CCF and API with different physical and chemical properties to synthesize eutectic drugs,the solubility,melting point,bioavailability and stability of API can be safely improved and regulated.Based on supramolecular chemistry theory and crystal engineering principle,niclosamide was used as active drug ingredient(API,hereinafter referred to as NCL).It was Prepared of drug eutectic from niclosamide and eutectic(malic acid,fumaric acid,tartaric acid,glycine,lysine,tyrosine,sodium carbonate and sodium bicarbonate)by solvothermal method.The eutectic structure was characterized by differential thermal analysis(DSC),powder-X-ray diffraction(XRD),scanning electron microscopy(SEM)and infrared spectroscopy(FT-IR).The dissolution and cytotoxicity of drug eutectic were tested in vitro.The specific research contents are as follows:1.The XRD and DSC results of eutectic of NCL with malic acid,fumaric acid and tartaric acid showed that a new eutectic phase was successfully synthesized.The in vitro solubility of the three novel drug eutectics was 38.9 mg/L,16.4 mg/L,and 18.8 mg/L,respectively.Cytotoxicity studies showed that NCL and malic acid co-crystals had a cell viability of 65%at a molar concentration of 5 ?M;NCL and fumaric acid co-crystals had a cell viability of 79%at a molar concentration of 40?M;NCL and tartaric acid co-crystal had a cell viability of 70%at a molar concentration of 2 ?M,and the cell survival rate of the NCL drug was 10%at a molar concentration of 20 ?M.2.The XRD and DSC results of the co-crystals of NCL with glycine,lysine and tyrosine showed that a new eutectic phase was successfully synthesized.The in vitro solubility of the three novel drug co-crystals was 16.5 mg/L,61.7 mg/L and 18.3 mg/L,respectively.Cytotoxicity studies showed that NCL and glycine co-crystals had a cell viability of 63%at a molar concentration of 20 ?M;NCL and lysine co-crystals had a cell viability of 77%at a molar concentration of 40 ?M;NCL and tyrosine co-crystals had a cell viability of 78%at a molar concentration of 40 ?M.3.The XRD and DSC results of the eutectic of NCL with sodium carbonate and sodium bicarbonate showed that a new eutectic phase was synthesized.The in vitro solubility of the two novel drug co-crystals was 42.1 mg/L and 21.5 mg/L,respectively.Cytotoxicity studies showed that NCL and sodium carbonate co-crystals had a cell viability of 78%at a molar concentration of 40 ?M;The co-crystal of NCL and sodium bicarbonate had a cell viability of 69%at a molar concentration of 40 ?M.