Research On The Crystallization Process Of Praziquantel

Schistosomiasis is widely prevalent in poverty countries such as Southeast Asia,Africa,and South America.According to statistics,approximately 240 million people are infected with schistosomiasis,and praziquantel is the only specific drug designated by the World Health Organization for the treatment of schistosomiasis.In view of the problems of aggregation and wide particle size distribution in the production of praziquantel in our country’s pharmaceutical industry,the crystallization process of praziquantel was systematically studied.The original crystallization process of praziquantel was optimized to produce the narrow particle size distribution product.The solubility of praziquantel in 12 pure solvents was determined by the static method.Based on the modified Apelblat simplified equation,Van’t Hoff equation,λh equation,and NRTL equation,the solubility model in the pure solvent system were established.The solubility difference of praziquantel in different solvents was explained by analyzing the polarity of the solvent,the cohesive energy density,and the ability of hydrogen bond donor and acceptor.Based on the thermodynamic data,the kinetic data during the crystallization of praziquantel was determined.The crystallization kinetics equation is established according to the particle sizeindependent growth model.Scanning electron microscope(SEM),Malvern Mastersizer particle size analyzer,X-ray powder diffraction(PXRD),and other detection instruments were used to detect the praziquantel crystals.According to the calculation of surface entropy factor,it is speculated that the nucleation of praziquantel crystals is dominated by surface nucleation,which makes the crystal growth process difficult,and it is prone to burst nucleation during the cooling crystallization,which eventually leads to aggregation.Guided by the crystallization thermodynamics,crystallization kinetics during the crystallization of praziquantel,the cooling crystallization was further optimized by changing different operating parameters(amount of seed,size,cooling rate,and stirring rate).Adopt optimizing process,the coefficient of variation of praziquantel crystals was reduced from 83.08% to 57.33%,the product morphology changed from a long needle shape to a short rod shape,and the bulk density was increased from 0.205g/mL to 0.312g/mL.The optimizing process effectively improves the subsequent processing processes such as filtration,transportation,and storage.The above relevant research content has not been reported in the literature.