Study On Microstructure Control And Sustained Release Performance Of Venlafaxine Hydrochloride Crystal

Venlafaxine hydrochloride,a phenylethylamine derivative,is the most widely used drug to treat depression and generalized anxiety disorder.Venlafaxine hydrochloride shows obvious polymorphic characteristics.Studies show that it has at least six crystal forms,of which crystal form I and crystal form II are the main crystal forms for medicine.At present,the research on drugs is not only focused on the crystal form,but a large number of studies show that even the same crystal form of the same drug may show different properties in microstructure,which is further reflected in the morphological differences,and will eventually lead to changes in drug properties.Therefore,in order to better understand and ensure the properties of drugs,the crystal growth and microstructure of venlafaxine hydrochloride were deeply studied,and on this basis,venlafaxine hydrochloride sustained-release tablets and new sustained-release preparations with hollow mesoporous silica microspheres as carriers were prepared.The details are as follows:(1)Using the method of molecular dynamics calculation,the crystal microstructure of venlafaxine hydrochloride grown in isopropanol,acetonitrile and dimethyl sulfoxide was simulated by modified adhesion energy model,and the results were compared with the experimental results.The results show that the crystal microstructures of venlafaxine hydrochloride grown in the three solvents simulated by software are basically consistent with the corresponding experimental results,which are cubic hexagonal,long strip and short rod respectively.The main crystal planes are(0 2 0)planes.In addition,the formation of microstructure differences among the three crystals is explained,which shows that it is reasonable to predict the microstructure of venlafaxine hydrochloride by using the modified adhesion energy model.(2)A UV determination and analysis method for the in vitro release curve of venlafaxine hydrochloride was established.The best prescription of venlafaxine hydrochloride sustained-release tablets was determined by screening experiments,including 15% venlafaxine hydrochloride,65% hydroxymethyl propyl cellulose,14%microcrystalline cellulose,5% sodium carboxymethyl cellulose and 1% magnesium stearate.The sustained-release effects of the tablets prepared from the above three forms of venlafaxine hydrochloride crystals were compared.All three tablets showed that the cumulative release rate reached more than 80% within 12 hours,and the cumulative release rate reached more than ninety-seven percent within 24 hours,and the drugs were fully released with high bioavailability.The sustained-release effect of tablets prepared from crystals cultured in isopropanol is slightly better than that of the other two tablets.(3)In view of the shortcomings of the above-mentioned venlafaxine hydrochloride sustained-release tablets,such as short burst release and slow release time,a novel venlafaxine hydrochloride sustained-release preparation was developed with hollow mesoporous silica microspheres as carriers,in which the silica microspheres were prepared with n-heptane as a template.This method avoids high-temperature calcination and is simpler and more economical.In addition,the content of venlafaxine hydrochloride was determined by thermogravimetry,which was 36.67% of the mass of silica microspheres.Finally,the study of its release rate showed that the sudden release phenomenon was greatly reduced,and the release of venlafaxine hydrochloride tended to be stable after 30 hours,reaching more than 70%,and the concentration of venlafaxine hydrochloride in the buffer was close to equilibrium.By comprehensive comparison,the new sustained-release preparation prepared in this study has more excellent sustainedrelease effect.