GENG Kuifa¹, WU Gongpeng¹, MIAO Huaming², CONG Rigang², WEI Zhenwen³, HE Yan¹

(1. College of Electromechanical Engineering, Qingdao University of Science and Technology, Qingdao 266061, China;2. Dijia Pharmaceutical Group Company Limited , Weihai 264200, China;3. Qingdao Doright Energy Saving Equipment Company Limited, Qingdao 266060, China)

Abstract

Significance The production of ultrafine powders from supercritical CO₂ 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 CO₂ 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~ 294 nm and the shape of the processed particles was more regular. However, RESS was limited by the solubility of the prepared substance in supercritical CO₂. 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 CO₂ 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 palmitoy leth anolamide (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 CO₂ 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 CO₂. This allows for fuller atomization of the solution, as the decompression of CO₂ from supercritical CO₂-saturated droplets results in secondary atomization. Nina Jiang et al used solution enhanced dispersion by supercritical CO₂( 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 CO₂ 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 CO₂ are essentially similar. Often the decision on which supercritical process to use depends more on the solubility of the target substance in supercritical CO₂ and solvent and how the substance behaves under different process conditions. Disadvantages that are typical for one series of supercritical CO₂ -based processes can sometimes be used as advantages for another type of supercritical CO₂ 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 CO₂ remains exploratory. Successful laboratory results are achieved for all processes above utilizing supercritical CO₂. 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.

Keywords: supercritical carbon dioxide; nanoparticle; ultrafine powder

Get Citation:GENG K F, WU G P, MIAO H M, et al. Progress in preparation of ultrafine powder by supercritical carbon dioxide[J]. China Powder Science and Technology, 2024, 30(2): 123-137.

Received: 2023-10-09,Revised:2023-12-25,Online:2024-01-17。

Funding Project:国家自然科学基金项目,编号:52336003;山东省重点研发计划项目,编号:2022CXGC020504;山东省泰山学者特聘专家工程项目,编号:ts20190937。

First Author:耿奎发(1999—),男,硕士生,研究方向为粉体材料。 E-mail: geng13046495227@163.com。

Corresponding Author:何燕(1973—),女,教授,博士,泰山学者,博士生导师,研究方向为纳米材料。 E-mail: heyanqustjd@163.com。

DOI:10.13732 / j.issn.1008-5548.2024.02.011

CLC No: TB44; O351. 2              Type Code:A

Serial No:1008-5548(2024)02-0123-15