Pilot Study On Application Of Size Adjustable Nozzle In SCF Preparation Of Ultrafine Drug Particle

A number of studies have suggested that, drug particles prepared bysupercritical fluid (SCF) method was not only with the small size, uniformdistribution and lower solvent residence but also with low preparation temperatureand suitable for preparation of all kinds of heat-sensitive drug particles. But the sizeof existing nozzle used in SCF drug preparation device are fixed and can not beadjusted, which has brought the engineering amplification of this method and devicecleaning much inconvenience. Three-channel size-adjustable coaxial nozzle inventedby professor Wang from Shandong university provide the possibility to the solutionof the problem mentioned above, but the SCF preparation device of the drugparticles using this kind of nozzle is not reported.This paper, on the basis of refrigeration, pressure and control system of theoriginal supercritical extraction device, combined the three-channel size-adjustablecoaxial nozzle invented by professor Wang with the original equipment anddeveloped a set of SCF preparation device of micro-sized drug particles whosenozzle size can be ranged from5to1000micron. Then, using the device,preliminary experiment research on the supercritical anti-solvent method for thepreparation of cefuroxime axetil with acetone as solvent was done, and on the basisof the analysis of the agglomeration mechanism of micro-sized particles, surfactantOP was added to reduce the drug agglomeration. Finally, this paper, by using Fluent,simulates the flow field distribution of size-adjustable nozzle, studies the impact ofthe flow field of pressure and nozzle size changes. Experimental results showed that, with the pressure of11MPa, temperature of40℃and the nozzle size of80microns for all, drug particles of100microns indiameter were received, and after adding surfactants, drug particles of about20~30microns in diameter were got, obviously alleviating the agglomeration. Flow fieldsimulation results showed that, with the increase of the inlet pressure, internalpressure of nozzle gets higher, the solvent volume inflation rate gets bigger, crystalnucleation rate gets faster and particle size gets smaller; with the decrease of thenozzle size, internal pressure drop of nozzle gets bigger, change in velocityquantitative gets bigger and particle size gets smaller.This paper developed the size adjustable device for the preparation of drugparticles based on the original supercritical extraction device, which not only greatlyreduced the manufacturing cost of SCF preparation device of micro-sized drugparticles, but also made it possible for the device cleaning and industrial productionof this preparation method. At the same time, this subject just did some preliminaryresearch on SCF preparation for micro-sized drugs particles using this device andfurther study is still in need.