Shouguang Fukang Pharmaceutical Co. Ltd.

Natural polymer additives including ethyecellulose (EC), hydroxy Pr cellulose (HPC), hydroxypropyl Me cellulose (HPMC), and sodium lignin sulfonate (SLS) were selected to modify the crystal form and morphol. of clozapine crystals.The effects of cooling crystallization, anti-solvent crystallization and additives on clozapine crystal morphol. were studied.The type of additive has an obvious effect on the morphol. of crystal, while the dosage of additive has a great effect on the average particle size of crystal.Medicinal crystal form of clozapine anhydrate can be obtained after enhanced drying of clozapine monohydrate.Clozapine crystal particles with controllable crystal form, morphol. and particle size can be prepared by anti-solvent crystallization method with additive.To further explore the mechanism of natural polymer additives on morphol. regulation, mol. simulation was used to analyze the interaction between the main crystal surface, solvent and additives.

The solubility of 2-mercapto-1,3,4-thiadiazol (MTD) in four kinds of aqueous mixed solvents including water + (methanol, ethanol, n-propanol, and acetone) was measured by the static gravimetric method in a temperature range of 278.15-323.15 K.The solubility of MTD in all selected aqueous mixed solvents was pos. correlated with temperatureThe solubility of MTD in the water + acetone solvent is higher than that in the other three solvents.There is a cosolvency phenomenon in the solvent systems of water + n-propanol and water + acetone.The polarity of good solvents plays an important role in the solubility of MTD in mixed solvents.Three thermodn. models including the modified Jouyban-Acree model, NRTL model, and Wilson model were chosen to correlate the exptl. data of MTD.The NRTL model fits the solubility data of MTD best among all of the selected thermodn. models (with RAD = 0.0104, RMSD = 0.000432).The results demonstrate that all of the models can fit the exptl. data well.