超临界二氧化碳制备超细粉体的工艺研究进展

Progress in preparation of ultrafine powder by supercritical carbon dioxide

【目的】为了解决使用传统工艺制备超细粉体时存在的粒径分布宽、颗粒均匀性差、溶剂残留多、操作条件苛刻等问题,寻求更为优异的超细粉体制备工艺。【研究现状】综述超临界CO_(2)制备超细粉体在医疗、材料和化学等领域的应用;总结超临界CO_(2)作为溶剂、抗溶剂和辅助介质时的代表超临界溶液快速膨胀法(rapid expansion of supercritical solutions,RESS)、气体抗溶剂法(gas anti-solvent,GAS)、超临界抗溶剂法(supercritical anti-solvent,SAS)、气体饱和溶液法(particles from gas-saturated solutions,PGSS)、带鼓泡干燥器的CO_(2)辅助雾化法(carbon dioxide assisted nebulization with bubble dryer,CAN-BD)、超临界流体辅助雾化法(supercritical assisted atomization,SAA)、强化混合超临界流体辅助雾化法(supercritical fluid assisted atomization introduced by hydro-dynamic cavitation mixer,SAA-HCM)、膨胀流体减压至有机溶剂法(depressurization of an expanded liquid organic solution,DELOS)等工艺、原理和优缺点。【展望】提出超临界CO_(2)制备超细粉体工艺是传统制备工艺的有效代替,具有工艺流程简单、工艺条件温和、产物粒径分布窄、产物平均粒径小、有毒溶剂使用少等优点。认为缺少具体的模型来描述和预测该工艺运行过程中的相平衡、物化性质、流体动力学、结晶与生长过程;今后研究重点应是建立具有代表性和可靠性的模型来对该工艺进行模拟与预测等。

Significance The production of ultrafine powders from supercritical CO_(2) has generated considerable scientific and technological attention due to its eco-friendliness, safety, elevated product purity, and regulated particle morphology, thus, it presenting enormous potential for medicinal, chemical, and material science applications. Classic methods for producing ultrafine powders comprise spray drying, freeze drying, solvent evaporation, and granulation flow. However, traditional processes for obtaining ultrafine powders often produce powders with significant drawbacks, such as toxic solvent residues, irregular particle morphology, and a wide particle size distribution. Numerous studies have shown that supercritical fluid preparation of ultrafine powders can overcome the above shortcomings, and thus has become a research hotspot in the past decade.Progress To date, the preparation of ultrafine powders using supercritical CO_(2) has evolved into various processes. The initial method, invented by Matson Dean in 1987, was the rapid expansion of supercritical solution(RESS). However, as the need for ultrafine powder preparation increased, various processes based on the RESS method, such as supercritical fluid antisolvent and gas-saturated solution, were gradually developed in 2015, Mohsen Hosseinpour et al. used RESS to successfully reduce the particle size of beclomethasone dipropionate, obtaining particles with an average particle size ranging from 64.1^(2)94 nm and the shape of the processed particles was more regular. However, RESS was limited by the solubility of the prepared substance in supercritical CO_(2). Therefore, some other processes have been proposed and applied to preparing ultrafine powders.In order to prevent agglomeration of the wetted particles due to gravitational forces of various physicochemical properties including VDW(Van der Waals' force) and surface tension of the liquid. In 2021, Razmimanesh et al used the US-RESOLV(ultrasonic-assisted rapid expansion of a supercritical CO_(2) solution) method by incorporating ultrasonic waves for the treatment of the suspension. High amplitude sound waves were generated by high power frequency ultrasound and propagated into the liquid medium to produce alternating high and low pressure cycles. In this process, the liquid medium because of the acoustic vibration generates small vacuum bubbles and continuously absorbs the energy in the acoustic wave until it can not be absorbed, then a small violent implosion will occur, the liquid jet generated by the implosion can effectively prevent the particles from agglomerating. In 2019 Renata Adam et al. used poly vinyl pyrrolidone(PVP) and lu teolin(LUT) to reduce the crystallisation tendency of palmitoyl ethanol amide(PEA) by supercritical assisted atomisation(SAA) co-precipitation under different process parameters and obtained particles with an average particle size of 400 nm and spherical particle morphology. So far, most of the powders prepared by researchers using the SAA process are submicron in size, and only a few documents have documented the production of drug nanoparticles using SAA. The method improves the mixing efficiency between supercritical CO_(2) and aqueous solutions. The main improvement is the use of specialized solution mixing kettles instead of solution mixing in a tiny volume, such as the CAN-BD, to achieve complete mixing between the solution and supercritical CO_(2). This allows for fuller atomization of the solution, as the decompression of CO_(2) from supercritical CO_(2)-saturated droplets results in secondary atomization. Nina et al used solution-enhanced dispersion by supercritical CO_(2)(SEDS) for the preparation of well-defined and nitrate-loaded various C-doped metal oxide spherical nanoparticles with particle sizes ranging from 60 to 160 nm. Since the solvent is present in the autoclave from the beginning of the drying process until the start of collection, the process is very prone to produce over-crystallized particles. This can result in the production of drug particles that are too large in size and do not have high crystallization kinetics, and therefore are not conducive to controlling the morphology of the final product.Conclusions and Prospects Supercritical CO_(2) can play a variety of specific roles in the production process of ultrafine powders(solvent, anti-solvent, auxiliary media), so the processes for the preparation of ultrafine powders with supercritical CO_(2) are essentially similar. Often the decision on which supercritical process to use depends more on the solubility of the target substance in supercritical CO_(2) and solvent and how the substance behaves under different process conditions. Disadvantages that are typical for one series of supercritical CO_(2)-based processes can sometimes be used as advantages for another type of supercritical CO_(2) process(insolubility of a substance can often be translated into excellent solvent resistance in other processes). All supercritical processes are valid alternatives to conventional milling processes. The preparation of ultrafine powders using supercritical CO_(2) remains exploratory. Successful laboratory results are achieved for all processes above utilizing supercritical CO_(2). However, fundamental obstacles to the widespread adoption of this technology persist due to unresolved issues during actual production. These limitations stem from the qualitative analysis of factors affecting the final product through laboratory results, as well as the lack of a reliable and representative model to describe and predict the operation of technology. This includes phase equilibria, physical and chemical properties, fluid dynamics, crystallization, and growth processes. These challenges are pervasive in all nanotechnology processes and call for solutions through extensive research in related fields and cross-disciplinary cooperation.