Study On Thermodynamic Properties And Polymorphic Transformation Of Sulfamethazine-Saccharin Cocrystals

In recent years,due to the ability to improve the physicochemical properties of the parent compound,cocrystals have received attention in the fields of material science and medicine industry as a potential material or a new form of medicine.At the same time,polymorphism generally occurs in cocrystal systems.In this paper,the sulfamethazine-saccharin cocrystal is selected as the model system,and a combination method of experiment and simulation is used to systematically study the thermodynamic properties of the cocrystal polymorphs and the conversion process of the polymorph.The main research contents are as follows:1.New methods for preparing high purity products of two forms of sulfamethazine-saccharin cocrystal in batches were proposed.Several characterization methods such as optical microscope,powder X-ray diffraction,Fourier infrared spectrometer,Raman spectrometer,differential scanning Calorimetry and thermogravimetric analysis were used to qualitatively and quantitatively analyze the morphology,structure and thermal properties of the prepared products.And the stability relationship between the two forms was analyzed.2.The thermodynamic behavior of sulfamethazine-saccharin cocrystal in solution was studied.The solubility of form Ⅱ in different solvents was determined by gravimetry method.The modified Apelblat model,λh equation,NRTL model,JouybanAcree model and CNIBS/RK model were used to fit the solubility data.All models gave good fitting results.Based on the solubility data and the NRTL model,thermodynamic properties of the dissolution process were calculated.3.The polymorphic transformation of sulfamethazine-saccharin cocrystal was studied.The solubility of form Ⅰ in acetonitrile was determined by gravimetry method,and the stable relationship between the two crystal forms was further determined.An online Raman spectrometer,an off-line microscope and PXRD were used to monitor the conversion of the metastable crystal form of the cocrystal to a stable crystal form.The rate control step of the crystal form conversion was determined.The effects of temperature,supersaturation and initial solid-liquid ratio on the conversion process were investigated through control experiments.