【作者】 刘松明；

【导师】 李爱菊；

【作者基本信息】 山东大学 ， 材料学， 2008， 硕士

【摘要】 超细微粒,特别是纳米级粒子的研制,在当前的高新技术中已成为一个热门领域,在材料、化工、轻工、冶金、电子、生物医学等领域得到广泛应用。超临界流体（SCF）技术制备超微粉体是一项新技术。采用超临界流体技术可以制备出颗粒小且粒径分布比较均匀的超微粉体。本课题细化的物料为布地奈德（Budsonide,BUD）,是一具有高效局部抗炎作用的糖皮质激素,主要用于治疗哮喘,主要的给药方式为气雾剂和粉雾剂。由于气雾剂和粉雾剂要求药物的颗粒尺寸比较小,需对BUD进行微粉化处理。本课题的主要研究目的是制备出平均粒径为1-5μm、粒径分布较窄的BUD粉体,以提高其药物吸收率和治疗效果。论文中,对BUD的制备过程、产物的物相、形貌和粒度、过程影响因素及制粉机理进行了分析。由于BUD不溶于超临界CO₂,且其临界温度低（T_c =31.1℃）、无毒、不可燃、价格低廉,所以本实验采用超临界CO₂流体,并选择二氯甲烷（DCM）为溶剂,抗溶剂法（SAS）制备BUD微细粉体。具体的研究内容如下:借助XRD对产物的物相进行了分析,结果表明:用此实验方法得到的BUD粉体的晶形未发生改变。借助SEM对产物的形貌进行了分析,分析认为:随着颗粒生长时间的增加,颗粒的形貌和尺寸从由成核过程转变为由生长过程所控制,颗粒的形貌由球形颗粒向多面体晶体和大的块体转变。探索了粉体粒度的分析方法（显微镜法）,并用此方法对产物的粒度进行了表征,并可计算颗粒的形状因子圆度。分析认为:本实验的结果达到了预期的要求。文中对SAS法制备BUD粉体的过程影响因素（排气位置、收集粉体的位置、溶液出口大小、超临界流体出口大小、溶液流量、溶液浓度、操作温度、操作压力）进行了分析。分析认为:排气位置设置在结晶釜底部能够使DCM和CO₂更好的混合,充分带走溶剂;溶液流量过大时,会导致粉体的分级沉积;随着溶液喷嘴口径的减小,得到的粉体颗粒粒径减小,粒径分布范围也变窄;CO₂出口比较大,粉体能够有效的沉积在釜壁上;当CO₂出口比较小,粉体不能沉积在结晶釜壁上,而被CO₂流体冲到了结晶釜的底部;CO₂出口大幸不岫苑厶宓淖钪招翁跋?减小CO₂出口大小,能使CO₂产生喷雾效果,对溶液起强制分散作用,能够得到尺寸较小的粉体颗粒,但同时强制分散溶液,所得液滴分布不均匀,最终获得的粉体颗粒的粒径分变宽。而溶液流量和溶液浓度对粉体的最终形态的影响比较复杂,具有两面性,一方面,随溶液流量和溶液浓度的增加,颗粒的粒径也随着增加,另一方面,有时适当的增加溶液流量和溶液浓度能得到更小的粉体颗粒;当温度较低时,颗粒尺寸随着压力的升高而增大,而当温度较高时,颗粒的尺寸随着压力的升高而减小;高压下升高温度能得到尺寸较小的颗粒,低压下则不然。对布迪奈德SAS法制粉的机理进行了探讨。分析认为,最终颗粒形态及尺寸取决于晶核初期尺寸、晶体的生长速率和晶体生长时间。更多还原

【Abstract】 Micropaticles, especially the nanometer micropaticles, becomes a popular field in current high new technique, getting the extensive application in the realms, such as material, chemical engineering, light work, metallurgy, electronics and biomedical science, etc.Using the supercritical fluid（ the SCF ） to get the ultrafine powder is a new technique by which wo could get ultrafine powder with small particle size （PS） and narrow particle size distribution （PSD）. This work was to prepare the ultrafine powder of Budsonide （BUD）. BUD, a potent anti-inflammatory corticosteroid is currently marketed as a dry powder inhaler and an aqueous nasal spray for the treatment of asthma. Dry powder inhaler and an aqueous nasal spray need small particle size, so it is need to micronize the BUD. The main purpose of this work was to prepare BUD powder 1-5μm PS and narrow PSD, in order to increase the absorptivity and curative effect of drug. This paper analysed the process of preparing of BUD, phase of production, morphorlogy and PS, influencing factor and mechanism of micronization.Because of the insoluble of BUD in supercritical CO₂ and low critical temperature （T_c=31.1℃）, innocuity, apyrous and low price of CO₂, this work used CO₂ as supercritical fluid and Dichloromethane （DCM） as the solvent and the SAS method was used to prepare the BUD ultrafine powder. It contained as follows:Phase transformation was analyzed using XRD, and the result indicated that there was no phase transformation take place to BUD in the SAS experiment.The particle size （PS） and morphology was analyzed by SEM, and the results indicated that with the increase of the particle growth time, the particle size （PS） and morphology was controled by growth process instead of nucleation and the PS increased with the morphology change from sphere to polyhedral crystal and bulk.The distribution of the particle size was counted by microscope method which can also calculate the shap factor: circularity. It indicated that this work can prepared the prospective product.This paper also discussed the influence of exhaust position, collect position, size of the solution and CO₂ channels, the solution flow rate, solution concentration, temperature and pressure. The results indicated that: it was better to sit the exhaust position on the bottom of the precipitation column （PC）; mass solution flow rate might induced classification precipitation; the particle size （PS） and particle size distribution （PSD） were smaller and narrower with the decrease of the solution channels; The powder will precipitate on the wall of the PC when the CO₂ channels is large, and the powder will be rushed to the bottom of the PC when decrease size of the CO₂ channels; The CO₂ channels also effected the final particle size and morphology, because the decreasing the size of CO₂ channels would make the CO₂ flow to spray which would force to disperse the solution, which would lead to gain smaller solution droplet and smaller particles, but the forced dispersal would lead to wider distribution of solution droplet which would lead to wider PSD; the effect of solution flow rate and concentration was more complex, it had two sides; one side, the PS increased with the increasing of the solution flow rate and solution concentration, on the other side, proper increasing the solution flow rate and solution concentration would gain smaller particles; when the temperature was low, the PS increased with increasing of the pressure, but when the temperature was high, the PS decreased with the increasing of the pressure; increasing the temperature would decrease the PS at high pressure but not at the low pressure.This paper also studied the mechanism of the preparation of micropaticles by SAS, and the study considered that the final particle size and morphology was determined by the critical nucleus size, paticle growth rate and the time of its growth.更多还原