Solution-Based Particle Formation of Pharmaceutical Powders by Supercritical or Compressed Fluid Co2 and Cryogenic Spray-Freezing Technologies

Micronization is an important procedure used in the pharmaceutical industry to reduce the particle size of active pharmaceutical ingredients (APIs). The spray-drying and milling techniques presently used to micronize drug substances cannot be used to process thermolabile or physically unstable drug substances. Therefore, new micronization techniques, including particle precipitation with supercritical or compressed fluid CO₂ and spray-freezing of drug solutions and suspensions into cryogenic gas to produce solid frozen microparticles, are currently being perfected for future use in the pharmaceutical industry. This review highlights the compressed gas and cryogenic liquid technologies being developed as potential solution-based particle formation technologies for drugs that cannot be processed by conventional micronization techniques.     

Micronization of arbutine using supercritical anti-solvent

Arbutine has been used as skin whitening agent in cosmetics and pharmaceuticals. The objective of this study was to precipitate arbutine micro-particles using a supercritical anti-solvent. Ethanol and supercritical CO₂ were used as solvent and anti-solvent, respectively, under various conditions. The effects of pressure, temperature and solution flow rate on the particles were studied. The particle size and morphology were analyzed by field emission scanning electron microscopy.     

气溶胶溶剂萃取系统技术制备聚乳酸纳米颗粒

采用气溶胶溶剂萃取系统制备聚乳酸（PLA）微细颗粒.用扫描电镜考察了工艺参数温度(35～55℃)、压力(8～20 MPa)、PLA溶液浓度(0.1～0.5 g•ml^-1)及其流速(140～400 ml•h^-1)、PLA相对分子质量(M_w：10000～100000)对产品颗粒形貌及粒径的影响;采用X射线衍射谱仪分析了产品的结晶性能.结果表明,当M_w＝100000或PLA溶液浓度达到1 g•ml^-1时,产品为黏性薄膜,无法得到微球状颗粒产品,当M_w小于100000或PLA溶液浓度小于1 g•ml-¹时,产品为微球状颗粒,在本研究范围内,温度和压力是影响粒径的主要因素,升高压力、降低温度可显著降低PLA颗粒粒径.在20 MPa,35 ℃,PLA溶液流速为240 ml•h^-1、浓度0.1 g•ml^-1、相对分子质量M_w=10000条件下成功制备了粒径介于200～600nm 的PLA微球.XRD分析显示产品晶型几乎没有变化,但结晶度大大减小.     

Solution-Based Particle Formation of Pharmaceutical Powders by Supercritical or Compressed Fluid Co2 and Cryogenic Spray-Freezing Technologies

Micronization is an important procedure used in the pharmaceutical industry to reduce the particle size of active pharmaceutical ingredients (APIs). The spray-drying and milling techniques presently used to micronize drug substances cannot be used to process thermolabile or physically unstable drug substances. Therefore, new micronization techniques, including particle precipitation with supercritical or compressed fluid CO₂ and spray-freezing of drug solutions and suspensions into cryogenic gas to produce solid frozen microparticles, are currently being perfected for future use in the pharmaceutical industry. This review highlights the compressed gas and cryogenic liquid technologies being developed as potential solution-based particle formation technologies for drugs that cannot be processed by conventional micronization techniques.     

自治供电系统的一种混合控制

研究自治供电系统(ASES)控制问题,基于"状态空间区域划分"和"切换控制"原理,提出一种混合型控制器.仿真表明,相比于近年来文献[1]中提出的动态滑模变结构控制方案,在保持系统基本性能前提下,可有效克服该方案中不可避免的抖振与高频切换等严重问题.     

自治供电系统的一种混合控制

研究自治供电系统 (ASES)控制问题, 基于“状态空间区域划分”和“切换控制”原理, 提出一种混合型控制器. 仿真表明, 相比于近年来文献 [1]中提出的动态滑模变结构控制方案, 在保持系统基本性能前提下, 可有效克服该方案中不可避免的抖振与高频切换等严重问题.     

Recrystallization of tetracycline hydrochloride using supercritical anti-solvent process

Tetracycline hydrochloride (TTC) was micronized by an Aerosol Solvent Extraction System (ASES) using supercritical CO₂. The effects of solvent, pressure and temperature of CO₂, solution concentration, and solution feed rate on particle size were investigated. Mean particle sizes of processed TTC were 0.16–0.31 μm, but the morphologies of processed particles were affected by agglomeration between the primary particles. Mean particle sizes of unprocessed TTC were ca. 200 μm and the shapes were irregular with rough surfaces. Especially, particle sizes increased from 0.18 to 0.31 μm as CO₂ temperature increased. In addition, particle sizes increased from 0.18 to 0.23 μm as TTC concentration increased. Powder X-Ray diffractometry revealed that processed particles were amorphous whereas unprocessed particles showed strong crystallinity.     

Preparation of poly(L-lactic acid) submicron particles in aerosol solvent extraction system using supercritical carbon dioxide

The aerosol solvent extraction system process (ASES), which is one of the supercritical anti solvent processes (SAS), was used to produce poly(L-lactic acid) (PLLA) into the submicron particles. Dichloromethane (DCM, CH₂Cl₂) and carbon dioxide were selected as a solvent and as an antisolvent for PLLA, respectively. The objective of this study was to investigate the effect of the various process parameters such as temperature, pressure, and solution concentration on PLLA particles. With increasing temperature and pressure, particle size was increased. Also, higher PLLA concentration led to larger particle size and broader particle size distribution. A scanning electron microscope (SEM) was used to observe the morphology and size of PLLA particles recrystallized by ASES process. The mean particle size and its distribution of processed particles were measured by using a laser diffraction particle size analyzer (PSA).     

超临界抗溶剂制粒装置的现状及其展望

超临界抗溶剂法是一种新型超细微粒制备技术,现已在许多领域得到广泛应用。本文简要陈述了超临界抗溶剂技术的基本原理、装置组成和操作方式,详细阐述了超临界抗溶剂装置喷嘴部件的演进,从该角度介绍了GAS制粒装置、ASES制粒装置、SEDS制粒装置和SAA制粒装置的发展和优化历程,并对超临界抗溶剂制粒装置的多功能化、喷嘴的进一步优化、结晶釜的可视化等提出展望。