【作者】 曲延鹏；

【导师】 王威强；

【作者基本信息】 山东大学 ， 过程装备工程， 2014， 博士

【摘要】 超临界流体沉淀(Supercritical Fluid Precipitation, SFP)技术是一种新的超微粉体制备方法。该技术在药物微粉化、固体分散体制备以及多孔物质的吸附等方面显示出良好的应用前景。喷嘴作为SFP技术的关键设备,不仅影响粉体的质量,而且影响粉体的产量。作者所在课题组首先提出了在SFP领域中使用环隙可调结构喷嘴,该种喷嘴与传统毛细管喷嘴相比,具有缝隙大小可调、通流面积大、不易堵塞、可分散强化等优点。但是,在实际应用中,环隙喷嘴的膨胀特性、分散特性、调节特性、结构形式和尺寸等方面问题亟待研究。研究环隙可调喷嘴,有利于SFP技术的发展和相关理论的完善,可为环隙喷嘴在SFP的工业化应用提供指导。作者首先分析了新型环隙喷嘴的基本结构特点和调节特性。确定环隙喷嘴的基本功能包括节流、可调、密封,其基本结构包括芯体、配合孔、调节结构、导向结构、密封结构,此外,环隙喷嘴还应具有调节锁紧、调节刻度显示、调节限程、接管、喷嘴固定等功能结构。推导了环隙喷嘴的调节函数,得出为保持线性调节,芯体型线或者配合孔型线之一应选用直线。结合结构特点,通过对单环隙喷嘴进行径向扩展和轴向扩展,可以得到内混、外混、内外混等多种形式的多环隙喷嘴,从而满足各种SFP过程的需要。根据使用要求和加工经验确定了环隙喷嘴的加工精度。获得了用于超临界流体纳微米材料制备的球孔配合环隙喷嘴创新结构,该型喷嘴可以调整修正加工和安装工艺难以消除的误差,提高环隙的调节精度。根据具体实现过程的差异,SFP方法主要分为超临界流体快速膨胀(Rapid Expansion of Supercritical Solution,RESS)、超临界流体反溶剂(Supercritical Anti-Solvent,SAS)和饱和气体溶液沉淀(Precipitation from Gas Saturated Solution, PGSS)过程。对这些过程进行分析,深入研究SFP制备超微粉体的机理,同时考察其中影响超微颗粒制备的主要因素,从而为环隙喷嘴的结构设计和工艺参数优化提供支持,为发展SFP理论做出贡献。对于RESS过程,分析了流场属性,提出了相关假设条件、所适用的方程以及影响流场的参数;在RESS过程的成核主要为一次均匀成核和不能充分长大的假设前提下,提出了RESS过程颗粒析出的流管模型,并在此基础上导出颗粒的粒度分布；通过单流管内颗粒析出预测颗粒的粒度分布,给出超微颗粒产量计算方法,其中,进口压力、出口压力、进口温度、喷嘴的流通面积等因素决定SCF质量流量,同时也决定超微颗粒的产量。针对SAS过程,提出了SAS过程分析的假设条件,研究了SAS过程的流场属性及主要影响因素；在液滴与微粒对应、反溶剂充分溶解液滴中溶剂的假设前提下,得出雾化获得的液滴数量和初始大小是影响SAS过程制备粉体粒度的关键因素；并在此基础上导出了SAS过程制备颗粒的粒度分布公式,当已知液滴的初始直径、液滴中溶质的浓度、溶液密度和颗粒的密度就可求出颗粒的粒度和粉体产量；给出了溶液与SCF进料比的确定原则：为确保制备的颗粒中没有溶剂残留,溶液与SCF的进料比必须小于结晶釜出口溶剂在SCF中的溶解度；进一步分析了颗粒团聚原因,认为：为了减少液滴转化为颗粒过程中的团聚,提高SCF的反溶效率,获得较大的进料比,应合理设计喷嘴和结晶釜的结构尺寸,消除溶剂体积分数过小及过大的区域,应使液滴充分分散在SCF中。简要分析了PGSS过程特点,认为喷嘴雾化获得的液滴数量和初始大小同样是影响PGSS过程制备超微粉体粒度的关键因素。针对单环隙喷嘴的流场分析是进一步进行喷嘴设计和应用的基础,因此对单环隙喷嘴的RESS过程流场进行了研究。首先进行了模拟方案设计,内容包括：确定环隙喷嘴的几何模型和相关尺寸,进行网格划分,选择适当的物性模型与控制方程,分析过程的主要影响因素等。利用FLUENT软件,选用NIST实际气体模型、二维轴对称几何模型,模拟了纯SCF的快速膨胀流场,获得了膨胀过程流场具有的特征：在喷嘴喉部速度明显上升,在喷嘴出口为超音速流动；流体温度沿着喷嘴流动方向大幅度下降,最低温度出现在喷嘴出口,最高温度出现在马赫盘处,当喷嘴环隙中的温度下降到流体凝点以下时喷嘴就会堵塞。流体压力沿着喷嘴流动方向急剧下降,最低压力出现在喷嘴出口区。根据模拟出的快速膨胀流场可以得到参数沿流线的变化规律,在喷嘴的同一横截面上,温度变化很小,但是压力、密度和速度的变化较大。分析了喷嘴的结构参数(环隙大小、环隙位置、入射角度、喉部长径比等)对膨胀过程的影响规律,认为应该提高喷嘴的径隙比,限制入射角度,减小喉部长径比。考察了操作参数(进口压力、进口温度、出口压力)对膨胀过程的影响,随着进口压力的提高,喷嘴出口流体的密度、压力变大,但喷嘴出口的流体最大速度反而降低,温降变小,同时提高进口压力可以提高流体的流量,进而提高超微粉体的产量；随着进口温度的提高,喷嘴出口流体的密度、压力变小,速度和温降变大。对膨胀过程冰堵产生条件进行了分析,并提出了解决措施,即：根据溶质在超临界流体中的溶解度关系适当选取进口压力和进口温度；对喷嘴处进行局部加热；采用在线可调的轴向扩展环隙喷嘴或者具有自净化作用的超声波喷嘴。SEDS过程制备超微颗粒的关键是充分雾化和快速分散。溶液经过环隙喷嘴雾化后的情况可以用流通截面环隙尺寸、环隙位置、雾化角、入射角,以及截面流速表征。利用FLUENT软件,选用VOF混合模型、二维轴对称几何模型,溶剂选择乙酸乙酯,反溶剂选择CO2,并对溶液进口区域进行离散处理,获得了分散过程流场。根据溶剂的体积分数云图,分析得到操作参数对单环隙喷嘴分散过程的影响规律：雾化角、入射角、流速对分散区域和分散效果具有较大的影响,而溶剂的体积分数、结晶釜压力、结晶釜温度等因素对分散过程的影响较小。在溶液出口与对称轴线之间开环槽或中心孔通入SCF,以外混方式辅助分散,可以增大有效分散面积,强化分散效果。上述结果可以为雾化分散用环隙喷嘴的设计以及SEDS过程优化提供依据。在此基础上,介绍了用于SFP环隙喷嘴的一般设计方法：在给定物性参数和操作参数条件下,通过工艺计算确定喷嘴的关键工艺参数,并进行密封、调节、连接等结构设计及相关强度计算,确定出适当的加工精度。对径向扩展和轴向扩展的环隙喷嘴进行了实例设计,获得了环隙喷嘴的具体结构尺寸,并按照实例设计结果加工了实验用二通道和三通道径向可调环隙喷嘴；结合已有实验装置,提出了使用环隙喷嘴的SFP工艺流程,设计并加工了超微制备模块；利用径向扩展三通道喷嘴进行了布地奈德和头孢呋辛脂药物粉体的制备,获得了比较满意的结果。总之,作者对用于超临界流体沉淀的环隙喷嘴结构和调节特性、快速膨胀特性、反溶剂过程中的分散特性,以及环隙喷嘴的设计和应用等方面开展研究,创新提出了超临界流体纳微米材料制备用球孔配合精调环隙组合喷嘴结构,提出了RESS过程的流管分析模型,解释了RESS过程的冰堵机理、产生原因并提出了解决措施,获得了RESS过程和SAS过程的颗粒析出机理、粒度分布公式和主要因素的影响规律。作者的研究结果可以为环隙喷嘴在超临界流体沉淀的工业化应用提供指导,有利于超临界流体沉淀技术发展和相关理论完善。然而,由于实际气体模型适用范围限制等原因,尚未完成用于定量确定快速膨胀过程操作参数的曲线绘制,多环隙喷嘴的强化分散特性也有待继续研究。更多还原

【Abstract】 Supercritical Fluid Precipitation (SFP) is a new developing technology for preparing superfine particles. It has been shown in many fields such as medicine powdering, solid dispersing and porous material absorbing. The nozzle, which is the key device of the technology, plays an important role on the quality and quantity of powders.Our project group proposed a new type of adjustable nozzle with the annulus gap. Compared with the traditional aperture structure, the annulus nozzle has some outstanding advantages such as adjustable ejection gap, low fabrication costs, flexible product yield, easy dredging, and high dispersing intensity. However, we found that some researches on the nozzle should be further investigated, such as expansion features, regulating properties, structural types and sizes. The further investigation on the nozzle can benefit developing the SFP technology and relevant theories, and can give a guide to the industrial application.The author analyzed the basic structure features and the regulating properties about the annulus nozzle; We determined that its basic functions include throttling, regulating and sealing, and its basic structures contain mating hole, core body, regulating part, guiding part, and sealing part; In addition, the nozzle should have some functional structures, such as locking tight, indicating scale, regulating limit, and fixing installation. The author derived the regulating function of the annulus nozzle, and drew that the straight line of the core body or mating hole profile should be chosen to keep the linear regulating feature. According to the structural properties, we extended the single-annulus nozzle in radial or axial direction, and obtained the multi-annulus gap nozzle, which can achieve different mixing modes such as internal, external or internal and external to meet the requirements of SFP. Basing on the operation demand and fabrication experiences, we determined the manufacture precision of the nozzle. We also designed a novel structure of annulus nozzle with a matching between a ball and a hole surface, and the novel structure can automatically correct the position, and modify the error during the fabrication and installation, so it can improve the regulating accuracy.There are three different ways to form the superfine particles by SFP technology, and they are usually named as the rapid expansion of supercritical solutions (RESS). supercritical anti-solvent crystallization process (SAS), and precipitation from gas saturated solution (PGSS). Further analysis on the different process, more research on the SFP mechanism, and investigation of the influence on the preparation results can help design the annulus nozzle and optimize the operation parameters.According to the fluid field properties of RESS process, some assumptions, suitable equations and related parameters were put forward. Assuming primary homogeneous nucleation and limited grow-up during RESS process, the stream tube model for particles precipitation was proposed, and the particle size distribution was derived. The particle size distribution was predicted by particles precipitation in the single stream-tube. The calculation method of ultrafine particles yield was given. It was found that the mass flow rate of SCF and the ultra fine particles yield are both affected by some factors, including inlet pressure, outlet pressure, inlet temperature and the circulating area of the nozzle. The assumptions were put forward to analyze SAS process. At the same time, the fluid field features and main influence factors were studied. The main assumptions are as follows:a droplet is corresponding to the particle; the anti-solvent is fully dissolved into the solvent in droplets. The author got that the key factors influencing the particle size are the quantity and initial size of the droplet. The particle size distribution formula was also deduced. When the initial diameter of the droplet, solute concentration, solution density and particle density are known, the particle size and powder production can be obtained. The determining principle of the feed ratio of solution and SCF was given. In order to ensure that none of solvent residue exists in the particles, the feed ratio of solution and SCF must be less than the solubility of solvent in SCF. The reason of the particles agglomeration was further analyzed. In order to reduce the reunion in the process, improve the dissolving efficiency of SCF and get larger feed ratio, we should design the reasonable nozzle structure and choose the suitable precipitator size. At the same time, the area of volume fraction unsuitable should be eliminated, and the droplets should be dispersed fully in SCF. The features of PGSS process was analyzed briefly. We think that the powder particle size is significantly affected by the number and initial size of atomized droplets.The flow field analysis of the single annular nozzle is the foundation of further design and application of nozzle. Therefore, the author studied the flow field of RESS process in the single annular nozzle. The author firstly designed the simulation scheme, which included the determination of geometric model and related dimension of annular nozzle, the meshing for the model, the selection of appropriate physical model and control equation, and the analysis of main influence factors on process. Using the NIST actual gas model and the two-dimensional axisymmetric geometry model in FLUENT software, the author obtained the rapid expansion flow field of pure SCF. The characteristics of expansion process flow field are as follows:the velocity increases obviously in the nozzle throat and the supersonic flow appears obviously in the nozzle outlet; the fluid temperature decreases sharply along with the direction of fluid flow, the minimum temperature appears in the nozzle outlet, and the highest temperature appears in the location of Mach Disk. When the temperature in the annular nozzle decreases below the freezing point of fluid, the nozzle clogging occurs; the fluid pressure declines sharply along with the direction of fluid flow, and the minimum pressure appears in nozzle outlet area. The author got the change rules of parameters along the streamline through further investigation. In the same cross section of nozzle, the temperature changes little, but the pressure, density and velocity change large. The author further analyzed the influence of nozzle structural parameters (annular gap size, annular location, incidence angle, the ratio of length and radius in throat, etc.) on the expansion process. And we should adapt some measures to improving RESS such as increasing the annular gap ratio of nozzle, limiting the incident angle and reducing the ratio of length and radius in throat. The author further investigated the effects of operating parameters (inlet pressure, inlet temperature, and outlet pressure) on expansion process. With the increase of inlet pressure, the fluid density and pressure in nozzle outlet increase, and the maximum velocity of fluid in nozzle outlet and the temperature drop reduce. Meanwhile, the fluid flux and the production of superfine powders increase with the increase of inlet pressure. With the increase of inlet temperature, the fluid density and the pressure in nozzle outlet decrease, and the velocity and the temperature drop increase. The condition of ice clogging in expansion process was analyzed, and the author proposed the solving measures such as selecting appropriate inlet pressure and inlet temperature according to the solubility relationship of solid solute in supercritical fluid, local heating of the nozzle, using the annular nozzle with axial extension which can be adjusted online or the ultrasonic nozzle with self-purification.Full atomization and rapid dispersion are the key points to superfine particles preparation by SEDS process, and the homogeneity of dispersion is important to obtain uniform particles. Through preliminary analysis, the state of solution after annular nozzle atomization is affected by annular gap size, annulus location, atomization angle, incidence angle, flow velocity in cross section and so on. According to the geometric characteristics, the author established a two-dimensional axisymmetric geometry model. By choosing the ethyl acetate as solvent and CO2as anti-solvent and discretizing the solution inlet area, the author proceeded the simulation calculation through VOF mixture model in FLUENT software, then the author got the parameters contours in the flow field, such as pressure, temperature, velocity, and the volume fraction of ethyl acetate. According to the volume fraction contour of solvent, the author got the influence rules of operation parameters on the dispersion process of single annulus nozzle as follows:atomization angle, incidence angle and flow velocity have great influences on the dispersed area and the dispersion effect; however, the volume fraction of solvent in inlet, vessel pressure and temperature have little influence on the dispersion process. When the SCF is imported through a loop slot or center hole, the auxiliary dispersion by outside mixing can be achieved, and the effective dispersion area and the dispersion effect can be increased.On the basis of above discussions, the author introduced the general design method of annular nozzle for SFP. Under the condition of given physical properties and operating parameters, the key process parameters of nozzle were determined through process calculation. Then the author proposed the sealing structure, the adjustment structure, and the connection structure; we also calculated the strength and determined an available machining precision. We designed the annular nozzle which is extended in radial and axial direction for specific application occasion, and the detail sizes were obtained. According to the design results, the annulus nozzles extended in radial direction with two channels and three channels for experiment were manufactured. On the premise of present experimental equipment in lab, the author proposed the SFP technological process involving annular nozzle; in the meanwhile, we designed and manufactured ultrafine particle preparation modules. Relative researchers prepared the powders of Budesonide and Cefuroxime axetil using our nozzle with three channels, and the experiment results show satisfactory.In short, the author had studied the structural and regulating characteristics of the annulus nozzles used in supercritical fluid precipitation; meanwhile, the rapid expansion properties, the dispersion figures in anti-solvent process, and the design and application of annulus nozzles were also investigated. In this paper, the author innovatively had proposed the structure of fine adjustment annulus nozzle assembled by hole and ball which is used to prepare nano and micron materials by supercritical fluid and the flow tube analysis model for RESS process. In addition, the author had explained the mechanism and the reason of ice clogging in RESS process and proposed solving measures further. The particle precipitation mechanism, particle size distribution formula and the effect laws of main factors in RESS process and SAS process were obtained too. The relevant research results can provide guidance to the industrial application of annulus nozzles in SFP, and which were benefit to the developments of SFP technique and relevant theories. However, the author has not completed the drawing of the curves for determining operating parameters in rapid expansion process due to the application scope restrictions of the actual gas model and other reasons. And the enhanced dispersion characteristics of multi-annulus nozzle are also needed to be further studied.更多还原