Rapid Expansion Of Supercritical Solutions Research Articles

新規な超臨界凍結造粒法による粉末吸入製剤の設計

In the particulate design for dry powder inhalation (DPI), the drug particles are required to have a good flowability in handling and dispersibility in delivering the drug to the lung in order to effectively treat pulmonary and systemic diseases. In this study, the preparation process of drug particles for DPI using a novel supercritical carbon dioxide freeze granulation based on the rapid expansion of supercritical solutions (RESS process) has been developed. When a drug dissolved into supercritical carbon dioxide is sprayed through a nozzle, frozen carbon dioxide lumps are generated due to the rapid temperature drop (i. e., Joule-Thomson effect), resulting in the granulation of fine drug particles. The granules prepared under the conditions of lower temperatures and higher pressures of supercritical carbon dioxide, in which more frozen carbon dioxide lumps are generated, have a good flowability and dispersibility because of the increased granule size and the decreased bulk density.

Formation of phenytoin nanoparticles using rapid expansion of supercritical solution with solid cosolvent (RESS-SC) process

Nanoparticles are of significant importance in drug delivery. Rapid expansion of supercritical solution (RESS) process can produce pure and high-quality drug particles. However, due to extremely low solubility of polar drugs in supercritical CO 2 (sc CO 2), RESS has limited commercial applicability. To overcome this major limitation, a modified process rapid expansion of supercritical solution with solid cosolvent (RESS-SC) is proposed which uses a solid cosolvent. Here, the new process is tested for phenytoin drug using menthol solid cosolvent. Phenytoin solubility in pure sc CO 2 is only 3 μmol/mol but when menthol solid cosolvent is used the solubility is enhanced to 1302 μmol/mol, at 196 bar and 45 °C. This 400-fold increase in the solubility can be attributed to the interaction between phenytoin and menthol. Particle agglomeration in expansion zone is another major issue with conventional RESS process. In proposed RESS-SC process solid cosolvent hinders the particle growth resulting in the formation of small nanoparticles. For example, the average particle size of phenytoin in conventional RESS process is 200 nm whereas, with RESS-SC process, the average particle size is 120 nm, at 96 bar and 45 °C. Similarly at 196 bar and 45 °C, 105 nm average particles were obatined by RESS and 75 nm average particles were obtained in RESS-SC process. The particles obtained were characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS) and differential scanning calorimetery (DSC) analyses. Phenytoin nanoparticle production rate in RESS-SC is about 400-fold more in comparision to that in RESS process.

Novel Semiconducting Polymer Particles by Supercritical Fluid Process

AbstractSummary: A simple method to prepare surfactant‐free and solvent‐free semiconducting polymer particles by using an environmentally benign supercritical carbon dioxide (scCO2) process is reported. The process of the rapid expansion of supercritical solutions (RESS) is used to produce spherical particles of poly[2‐(3‐thienyl)acetyl 3,3,4,4,5,5,6,6,7,7,8,8,8‐tridecafluorooctanoate] (PSFTE), 50–500 nm in size, from 0.1–0.5 wt.‐% PSFTE solutions in CO2 at pre‐expansion temperatures of 40 °C and pre‐expansion pressures of 276 bar.An FESEM image of PSFTE particles produced by the RESS process with CO2.magnified imageAn FESEM image of PSFTE particles produced by the RESS process with CO2.

Formation of ultrafine aspirin particles through rapid expansion of supercritical solutions (RESS)

The performance of pharmaceuticals in biological systems can be enhanced by reducing the particle size of pharmaceuticals. Rapid expansion from supercritical solution (RESS) has provided a promising alternative to comminute contaminant-free particles of heat-sensitive materials such as drugs. In this work, aspirin has been successfully precipitated by the RESS technology. The performances of the RESS process under different operating conditions are evaluated through the analysis of the particle characteristics. Our results show that extraction pressure and extraction temperature can significantly affect the morphology and size of the precipitated particles whereas the nozzle diameter and pre-expansion temperature are not observed to apparently influence the RESS particles. The RESS process could produce ultrafine spherical particles (0.1–0.3 μm) of aspirin as reflected by SEM observations.

Rapid Expansion of Supercritical Solution with Solid Cosolvent (RESS−SC) Process: Formation of Griseofulvin Nanoparticles

In the conventional RESS process, a supercritical solution is rapidly expanded through a nozzle to precipitate the solute as microparticles. The modeling of RESS has shown that the precipitated par...

Deposition of polymer coatings onto SAW resonators using AC electrospray

Polymers were deposited onto the surface of surface acoustic wave (SAW) resonators using AC electrospray. The film quality and resulting device performance was investigated and compared to similar devices coated using DC electrospray, airbrush and the method known as rapid expansion of supercritical solutions (RESS). It was demonstrated that the AC electrospray method is capable of producing coatings with much higher quality than both DC electrospray and airbrush methods and of comparable quality to the coatings produced using RESS. The simplicity of the AC electrospray polymer deposition method makes it particularly attractive for the deposition of nanoscale polymer films onto microelectrodes.

Development of Layered Polymer Nanocomposites Using Supercritical Fluid Technology

Layered organic polymer nanocomposites were developed utilizing supercritical fluid technology and solid-state polymerization. Intimately mixed composite particles consisting of one amorphous and one crystalline component were precipitated by the method known as rapid expansion of supercritical solutions (RESS). The crystalline component was 2,5-distyrylpyrazine (DSP), a diolefinic monomer with solid-state reactivity. The amorphous component was a fluoroalkyl acrylate (FAA) polymer. The DSP monomer, though normally highly crystalline, was rapidly precipitated in a nonequilibrium state and recrystallized and polymerized in the solid state. The process of DSP monomer reorganization within the organic polymer matrix resulted in the formation of well-organized alternating nanoscale layers of DSP and FAA phases throughout the particle volume.

Production of Nanocrystalline RDX by Rapid Expansion of Supercritical Solutions

AbstractNanoscale crystals of cyclotrimethylenetrinitramine (RDX) were produced by Rapid Expansion of Supercritical Solutions (RESS). The experiments were performed by expansion of supercritical solutions of RDX in carbon dioxide through sapphire nozzles (ID: 100 and 150 μm) at pressures of 15.0–29.5 MPa and temperatures of 343–348 K. Recrystallized particles were characterized by Field Emission Scanning Electron Microscopy (FESEM), X‐ray diffraction, HPLC and melting point analysis. The process produced particles with a mean size in the range 110–220 nm and a narrow size distribution. The product was crystalline as determined by X‐ray diffraction. The effect of process conditions (T, P, nozzle diameter) on the crystal size distribution was determined.

Particle formation of ibuprofen–supercritical CO 2 system from rapid expansion of supercritical solutions (RESS): A mathematical model

A one-dimensional flow model has been proposed to describe the particle formation through the rapid expansion of supercritical solutions (RESS). This model includes the wall friction in the nozzle and heat exchange with the surrounding in the supersonic free jet region. The calculations were performed on the ibuprofen–supercritical CO 2 system in terms of the supersaturation, nucleation rate, critical nucleus size and number concentration of the critical nuclei. The results show that very high supersaturation (approximately 10 9), thus high nucleation rate, can be attained when the fluid leaves the nozzle exit to the supersonic free jet region. Simultaneously, the critical nucleus size, in the nanometer size, decreases, whereas the number concentration of critical nuclei increases. Besides, sensitivity analyses of pre-expansion pressures, pre-expansion temperatures and nozzle length have been carried out but found that they seem to not significantly influence the flow field properties.

Modeling of the PGSS process by crystallization and atomization

AbstractA particles from gas‐saturated solution (PGSS) process for the model system hydrogenated palm oil (HPO) with CO2 was implemented and particle information, including size, size distribution, and morphology, is reported. The PGSS process in a capillary nozzle is modeled to be in steady, one‐dimensional, inviscid, and two‐phase (CO2‐rich phase and liquid HPO/CO2 phase) annular‐mist flow. The Peng–Robinson equation of state is applied for the nonideality of the binary CO2/HPO and the fluid hydrodynamic equations of two phases are established to describe the system's pressure, temperature, velocity, and density along the nozzle. The aerosol dynamic equation for the crystallization of HPO in the CO2‐rich phase is used to explain the HPO crystal formation and growth under supercooling and supersaturation. For the liquid HPO/CO2 phase, the atomization mechanism in terms of the interaction of the two phases gives HPO droplet information. The coupled model equations are numerically solved to obtain the HPO particle size and particle size distribution at the nozzle exit under several operating conditions. Different distribution modes are found, in agreement with the experimentally obtained particle spectra, an indication of the soundness of the model's particle formation mechanisms. Particles produced by atomization usually prevail over those formed from crystallization; yet, there exist special operating conditions under which the rapid expansion of supercritical solution (RESS) mechanism cannot be neglected and melt crystallization may be significant. The comparison between theoretical and experimental particle morphologies indicates that atomization may produce mainly spherical but relatively large particles; melt crystallization provides amorphous crystal particles, and the RESS process gives small and irregular crystals. © 2005 American Institute of Chemical Engineers AIChE J, 2005

Polymeric Nanofibers from Rapid Expansion of Supercritical Solution

The use of the supercritical fluid technique, rapid expansion of a supercritical solution into a liquid solvent (RESOLV), to process polymers into nanofibers (less than 100 nm in diameter) is reported. It is found that the polymer concentration in the preexpansion supercritical solution plays a critical role in determining the dominating product morphology between nanoparticles and nanofibers. For the CO2-soluble poly(heptadecafluorodecyl acrylate) (PHDFDA), as an example, the rapid expansion of the polymer solutions in supercritical CO2 with low and high PHDFDA concentrations into an ambient aqueous NaCl solution produces exclusively nanoparticles and nanofibers, respectively. The RESOLV processing of poly(methyl methacrylate) (PMMA) and biodegradable polymer poly(l-lactic acid) (PLA) in supercritical CO2−cosolvent system into nanofibers is also described and discussed.

Characterization of the rapid expansion of supercritical solutions by Fourier transform infrared spectroscopy in situ

A new apparatus for the in situ characterization of the rapid expansion of supercritical solutions (RESS) by Fourier transform infrared spectroscopy is presented. The infrared characterization is complemented by particle sizing with a scanning mobility particle sizer, by three-wavelengths-extinction measurements, and by scanning electron microscopy. Several examples show that a wide range of information about particle properties can be obtained with this setup. One new aspect is the possibility to expand into the vacuum which also allows us to investigate the conditions in the collision-free region before the Mach disk. These investigations elucidate that in the free jet region the solvent CO2 condenses to particles with mean radii >50nm for pre-expansion pressures between 100–400bar and temperatures between 298–398K.

Polymeric nanoparticles from rapid expansion of supercritical fluid solution.

In this concept paper we highlight applications of supercritical fluid technology in particle formation and production, especially some recent advances in the rapid expansion of supercritical solutions (RESS) processing technique. We also highlight the simple but significant modification to the traditional RESS by using a liquid solvent or solution at the receiving end of the supercritical solution expansion, or the rapid expansion of a supercritical solution into a liquid solvent (RESOLV), and applications of the technique to the preparation of nanoparticles. In particular, successes and challenges in the use of RESOLV for nanoscale (<100 nm) polymeric particles and the subsequent protection of the suspended nanoparticles from agglomeration are discussed.

Micronization of Phenylbutazone by Rapid Expansion of Supercritical CO&lt;sub&gt;2&lt;/sub&gt; Solution

Rapid expansion of supercritical solutions (RESS) technique was applied for the preparation of phenylbutazone fine particles. The operating temperature and pressure affected the yield of the drug fine particles, which was evaluated by dissolving the sprayed product of drug into ethanol. Effect of pre- and post-expansion conditions on the particle size distribution of phenylbutazone was investigated and the smallest sample (mean particle size: 1.59 microm) was obtained when the RESS method was operated at a pressure of 26 MPa combined with a temperature of 32 degrees C. Physicochemical properties of the fine particles were investigated by powder X-ray diffraction and differential scanning calorimetry. It was found that the phenylbutazone fine particles obtained were meta-stable beta form under the experimental conditions tested, suggesting polymorphic transformation during the RESS process.

Materials processing using supercritical fluids

One of the most interesting areas of supercritical fluids applications is the processing of novel materials. These new materials are designed to meet specific requirements and to make possible new applications in Pharmaceuticals design, heterogeneous catalysis, micro- and nano-particles with unique structures, special insulating materials, super capacitors and other special technical materials. Two distinct possibilities to apply supercritical fluids in processing of materials: synthesis of materials in supercritical fluid environment and/or further processing of already obtained materials with the help of supercritical fluids. By adjusting synthesis parameters the properties of supercritical fluids can be significantly altered which further results in the materials with different structures. Unique materials can be also obtained by conducting synthesis in quite specific environments like reversed micelles. This paper is mainly devoted to processing of previously synthesized materials which are further processed using supercritical fluids. Several new methods have been developed to produce micro- and nano-particles with the use of supercritical fluids. The following methods: rapid expansion of supercritical solutions (RESS) supercritical anti-solvent (SAS), materials synthesis under supercritical conditions and encapsulation and coating using supercritical fluids were recently developed.

Application of a modified RESS process for polypropylene microparticle production

The aim of this work is to investigate the production of polypropylene microparticles from polypropylene/n-butane solutions using a modified rapid expansion of supercritical solutions (RESS) technique. A commercial polypropylene sample (Polibrasil Resinas S.A.) produced from a Ziegler-Natta catalyst was employed in the experiments. The experiments were performed in a laboratory scale unit where the effects of pre-expansion temperature (373–423K), polymer concentration in the solution (0.1–1.0wt.%) and the ratio of length to capillary diameter (20–100) were evaluated. Scanning electronic microscopy was employed to analyze the morphology and size of the produced particles. Results show that polymer concentration was the variable that exerted a more pronounced effect on the morphology of the precipitated particles. Besides, it is shown that the proposed technique can be used to transform polypropylene particles with very broad size distributions into a variety of products, ranging from interconnected fibers to monodisperse micro-spheres, through manipulation of the operation variables of the expansion process.

Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes: Part I: Micronization of neat particles

In this first of two articles, we discuss some issues surrounding the dissolution rate enhancement of poorly-soluble active ingredients micronized into nano-particles using several supercritical fluid particle design processes including rapid expansion of supercritical solutions (RESS), supercritical anti-solvent (SAS) and particles from gas-saturated solutions/suspensions (PGSS). Experimental results confirm that dissolution rates do not only depend on the surface area and particle size of the processed powder, but are greatly affected by other physico-chemical characteristics such as crystal morphology and wettability that may reduce the benefit of micronization.

Stabilized nanoparticles of phytosterol by rapid expansion from supercritical solution into aqueous solution

The basic objective of this work was to form stable suspensions of submicron particles of phytosterol, a water-insoluble drug, by rapid expansion of supercritical solution into aqueous solution (RESSAS). A supercritical phytosterol/CO2 mixture was expanded into an aqueous surfactant solution. In these experiments 4 different surfactants were used to impede growth and agglomeration of the submicron particles resulting from collisions in the free jet. The concentration of the drug in the aqueous surfactant solution was determined by high-performance liquid chromatography, while the size of the stabilized particles was measured by dynamic light scattering. Submicron phytosterol particles (<500 nm) were stabilized and in most cases a bimodal particle size distribution was obtained. Depending on surfactant and concentration of the surfactant solution, suspensions with drug concentrations up to 17 g/dm3 could be achieved, which is 2 orders of magnitude higher than the equilibrium solubility of phytosterol. Long-term stability studies indicate modest particle growth over 12 months. Thus, the results demonstrate that RESSAS can be a promising process for stabilizing submicron particles in aqueous solutions.

Synthesis and Formation of Silica Aerogel Particles By a Novel Sol−Gel Route in Supercritical Carbon Dioxide

A new method to obtain silica aerogel particles using acetic acid as the condensation agent for silicon alkoxides in supercritical carbon dioxide (scCO2) is proposed. The objective of this study was to determine the mechanism of silica aerogel formation in scCO2 using in situ analysis techniques. The synthesis and formation of silica aerogel particles was carried out by a modified sol−gel route, based on the hydroxylation and condensation of silicon alkoxides in scCO2; both submicron and micron-size aerogel spheres were obtained. By means of in situ Fourier Transform infrared spectroscopy (FTIR), the activity of acetic, formic, benzoic, and chloroacetic acids were studied for the condensation of tetraethyl orthosilicate (TEOS). Formic and acetic acid gave slower rates than benzoic and chloroacetic acids. Increasing the concentration of acid and addition of extra water led to an acceleration of the reaction. The reactions were also studied as a function of temperature and pressure. Higher rates of reaction were obtained at higher temperatures and lower pressures. Results from particle formation studies indicated that by slowing the rate of reaction, precipitation and agglomeration of particles could be minimized. A submicron particle size range was obtained by depressurization of the sol−gel solution inside the reaction vessel, while the rapid expansion of supercritical solutions (RESS) process was found to yield particles in the size range of approximately 100 nm.

Micronization of titanocene dichloride by rapid expansion of supercritical solution and its ethylene polymerization

One of the existent problems of metallocene catalyst is the difficulty in controlling its polymer morphology in despite of its numerous advantages. According to the morphology replication nature of ethylene polymerization, the polymer morphology could be improved by controlling the morphology of catalyst particle. The catalyst microparticles with narrow particle size distribution were obtained by rapid expansion from a supercritical solution (RESS). Propane was chosen as a supercritical solvent to micronize Cp 2TiCl 2 as metallocene catalyst sample. The ethylene polymerization was conducted in hexane medium. Cp 2TiCl 2 solubility in supercritical propane was studied at temperature of 393.15 and 403.15 K and in the pressure range from 10 to 35 MPa. The solubility data were fitted by using the Peng–Robinson (PR) equation of state with the AARD of 2.32%. RESS experiments were performed at different operation conditions, including solute concentration, pre-expansion temperature and pressure, nozzle length and diameter, sample collection distance and fluid flow rate, etc. Quasi-spherical and spherical particles of catalyst with several microns size were obtained and tested through ethylene slurry polymerization. Compared with the original catalyst particles, the size distribution and morphology of reformed catalyst particles and the related polymer were rapidly improved. Based on the analysis of SEM photos, three levels structure of particles prepared by RESS were revealed by scale-up of catalyst during polymerization. These multi-level particles were primary particle, globule and particle, respectively. Simultaneously, the primary particle size was determined to tens of nanometers because there was a one-to-one correspondence between catalyst and polymer at the microparticle, mesoparticle and macroparticle level scales. The size of the primary particle was consonant with the size calculated by model in literature.