Micronization of creatine monohydrate via Rapid Expansion of Supercritical Solution (RESS)

In the pharmaceutical industry, an even greater number of products are in the form of particulate solids. In the case of pharmaceutical substances the particle size is quite important since it can limit the bioavailability of poorly water soluble drugs. Since the mid-1980s, a new method of powder generation has appeared involving crystallization with supercritical fluids. In this study, RESS was used to micronize the creatine monohydrate particles. The RESS process consists in solvating the product in the fluid and rapidly depressurizing this solution through an adequate nozzle, causing an extremely rapid nucleation of the product into a highly dispersed material. In addition, the effect of six different RESS parameters including, extraction temperature (313-333 K), extraction pressure (140-220 bar), nozzle length (2-15 mm), effective nozzle diameter (450-1700 μm), spraying distance (1-7 cm) and pre-expansion temperature (353-393 K) were investigated on the size and morphology of the precipitated particles of creatine monohydrate. The characterization (size and morphology) of the precipitated particles of creatine monohydrate was determined by scanning electron microscopy (SEM). The results show great reduction in the size of the precipitated particles of creatine monohydrate (0.36-9.06 μm) compared with the original particles of creatine monohydrate. Moreover, a slight change into spherical form was observed for the precipitated particles of creatine monohydrate while the original particles were irregular in shape.     

超临界流体快速膨胀法制备超细微粒

超临界流体快速膨胀法（RESS）是一项近10年发展起来的制备超细微粒的新技术，它将溶解有饱和溶质的超临界流体在非常短的时间内（10^-8-10^-5s)通过一个喷嘴（25－60um)进行减压膨胀，利用强烈的机械扰动以达到极高的过饱和度（约10^6)和均相成核条件，从而产生纳米至微米级粒径且粒径及形态分布均匀的超细微粒，该方法已经在制备药物微粒，聚合物微粒和纤维，有机材料和无机材料与陶瓷先驱物等方面得到广泛的应用研究，不仅可以制备单组分的形态不同的微粒或纤维，还可以制备双组分的包覆型微粒，但理论研究目前还处于探索阶段，不能准确解释装置结构参数和操作条件对最终产物形态的影响，在此主要就超临界流体的性质，RESS方法的基本原理，理论和应用研究成果进行简单介绍。     

Solid Solubilities of Sulfonamides and Use of Rapid Expansion of Supercritical Solutions for Microparticle Production

The solubility of solid active pharmaceutical ingredients in supercritical fluids is a major thermodynamic criterion for selection and screening of microparticle generation processes. To develop an efficient method for solubility prediction, a solution model was adopted to establish the correlations of the solid solubilities of six sulfonamides in supercritical CO₂. The model was capable of determining solubility correlations. Accordingly, it was attempted to simplify and generalize the model, yielding a predictive solution model, which provided order-consistent solubility predictions. A case study for model extrapolation was conducted. After understanding the mechanisms underlying the solubility of sulfonamides, the rapid expansion of supercritical solutions (RESS) process was applied to produce microparticles of p-toluenesulfonamide, an anticancer drug. The effects of RESS process parameters were investigated.     

超临界流体快速膨胀用于细颗粒包覆技术

研究超临界流体在快速膨胀过程中的热力学状态变化,超临界流体在喷嘴端部快速膨胀过程中温度急剧降低,在一定条件下,降低的温度与流体体积流率平方成线性关系。超临界流体在快速膨胀射流中产生数十纳米量级的微核颗粒,流体膨胀前温度对微核粒径有显著影响。通过超临界流体在流化床中的快速膨胀,使包覆剂微核在颗粒表面形成均匀的薄膜包覆,实现颗粒或颗粒中关键组分在溶剂中的控制释放。     

Fabrication of fine microcapsulated red phosphorus particles by SCF-RESS with a new structure nozzle

A novel process of preparing microencapsulated red phosphorus particles by rapid expansion of supercritical fluids (RESS) was tested, in which a new kind of nozzle and supercritical CO₂ as a solvent were used. The structure of the microencapsulated red phosphorus particles were characterized by scanning electron microscope (SEM) and transmission electron microscope (TEM). These results show that red phosphorus particles can be effectively encapsulated with paraffin by using the method. At the same time, how the moisture absorption ratio of microencapsulated red phosphorus particles was dependent on the experimental conditions was further investigated. The results suggest that paraffin-microencapsulated red phosphorus particles show a lower moisture absorption ratio within the experimental conditions of the extraction column and nozzle temperature of 120°C, extraction column pressure of more than 16 MPa, and a mass flow of core particles (0.5 g/min).     

超临界萃取在天然植物成分提取中的应用进展

本文针对超临界萃取(SFE)技术在医药、食品、化妆品及香料工业等领域的研究现状和应用前景,结合传统萃取技术的不足,从SFE技术的原理、特点出发,重点综述了SFE技术在生物碱、黄酮类、挥发油和油脂类等天然植物有效成分提取中的研究及应用近况,并简述其发展前景。     

RESS法制备微细颗粒的喷嘴内流动特性的数值模拟

为了对RESS法制备微细颗粒过程中喷嘴内流体规律进行研究,通过对超临界流体快速膨胀法（rapid expansion of supercritical solution,RESS）流动过程的研究与分析,建立了喷嘴内超临界流体流动数学模型。对喷嘴内流场和温度场进行研究,考察了预膨胀压力、预膨胀温度、长径比等操作参数对RESS过程的影响,模拟结果表明,喷嘴内部的密度曲线在喷嘴入口段,几乎没有发生变化,而在直管段和出口膨胀段超临界流体密度发生急剧下降;随着长径比的增大,喷嘴内密度曲线变陡;随着长径比的增大,喷嘴出口处流体的温度都变小,过饱和度变大,结晶颗粒使得更为细小。该模型和模拟过程能够为实现制备均一微细颗粒的实际操作条件和优化过程参数奠定基础。     

超声传质增强式超临界溶液快速膨胀技术制备类胡萝卜素超细微粒

类胡萝卜素的低溶解性和在肌体中较低的生物利用度限制了其商业应用,微粒化是解决这些问题的有效途径。普通超临界微粒化技术受到类胡萝卜素低溶解性的限制,难以产业化。综述了超临界溶液快速膨胀微粒化技术的研究进展,建议将超声波应用于超临界微粒化技术领域,提出了超声传质增强式超临界溶液快速膨胀技术概念,设计研制出超声传质增强式超临界微粒化装置和喷嘴,对于低溶解性和对氧化高敏感性的药物制剂化有重要的工业应用价值。