Study On Preparation Of Ultrafine Amorphous Cefuroxime Axetil

Cefuroxime axetil(CFA) is the second generation antibiotic medicine with broad-spectrum,bactericidal ability and so on.Ultrafine CFA possesses some merits such as larger specific surface area,higher dissolution rate.which make it easy to be absorbed, good in biological utilization and curative effect.The preparation of ultrafine amorphous CFA using different methods were adopted in the paper.The svstem of "actone-water" were studied in the paper in Batch Reactor and under ultrasound using anti-solvent precipitation,and the influence factors to the particle size, such as stirring speed,volume ratio of solvent/anti-solvent(S/AS),concentration, temperature and time,were experimentally investigated.The results show that amorphous CFA with average particle size 500nm was obtained in the svstem of "acetone-water" in Batch Reactor,and the optimal conditions are as follows:temperature was 4℃. concentration was 10%.the solvent/anti-solvent(S/AS) volume ratio was 1:20.and stirring rate was 2000r/min.And amorphous CFA with average particle size 500nm was obtained in the svstem of "acetone-water" under ultrasonic irradiation,and the optimal conditions were as follows:temperature was 4℃,concentration was 10%,the volume ratio of solvent/anti-solvent(S/AS) was 1:20,and time was 10min.Base on the above experimental result,the microreaction technology was introduced to combine with anti-solvent precipitation method to establish a novel method.The CFA nanoparticles were successfully prepared,which were amorphous with the particle size of 500nm,the narrow particles size distribution.The identical FT-IR spectra curves suggest that there was no chemical structure change in the CFA molecular structure,which proved that the characteristics of CFA were not affected by the process.The XRD proved that the raw CFA was in crystalline form.However.instead of those intense crystalline peaks. only one broad and diffuse maxima peakwas detected in the patterns of the ultrafine particles of CFA,which indicates the amorphous form of nanoparticles of CFA.Compared with the raw CFA,the ultrafine CFA had higher solubility,and the content of A、B components was accord with Chinese Pharmacopoeia.In this study,a novel method by microreator combined with anti-solvent precipitation was established.The technique offered a direct and continuous process to massively prepare drug ultrafine particles with simple physical precipitation process.Furthermore, the process was easy to be scaled up for industrial application.In addition,the elaborately investigation of the effect of various parameters on the particle shape and size can be used for reference to prepare other pharmaceutical ultrafine particles.