M.D. Gordillo

Measurement and correlation of solubility of Disperse Blue 14 in supercritical carbon dioxide

Abstract The solubility of solid 1,4-dimethylaminoanthraquinone (Disperse Blue 14) in supercritical carbon dioxide has been determined in the pressure range of 100–350 bar and in the temperature range of 313–353 K. The values obtained have been correlated with two types of model: the first is based on empirical and semiempirical equations and the second is based on thermodynamic aspects and the use of equations of state, namely Redlich–Kwong (RK), Soave–Redlich–Kwong (SRK) and Peng–Robinson (PR) equations. The thermodynamic model, based on fitting the solid sublimation pressure and binary interaction parameter, shows better agreement with the experimental data than the empirical and semiempirical equations.

Effect of the pre-treatment of the samples on the natural substances extraction from Helianthus annuus L. using supercritical carbon dioxide.

The extraction of bioactive compounds from sunflowers (Helianthus annuus L.) with supercritical carbon dioxide has been studied. The samples were treated in four different ways and the effects of two factors (pressure and temperature) were investigated at 100, 500 bar and 35, 50 degrees C. The best yields were obtained using a high temperature and a high pressure (50 degrees C and 500 bar). The dry samples produced better extraction yields than the moist samples. The bioactivities of the extracts were compared for the samples treated in different ways. The best activity profiles were obtained for the moist samples extracted at 35 degrees C and 500 bar.

Supercritical Antisolvent Precipitation of Ethyl Cellulose

Supercritical antisolvent (SAS) technique is an appropriate process to obtain micro- and nanoparticles. The application of this process has, until now, been explored in a variety of different fields including: explosives, polymers, pharmaceutical compounds, colouring matter, superconductors, catalysts, and inorganic compounds. Biocompatible and biodegradable polymers are playing more and more important roles in pharmaceutical areas such as tissue engineering and drug delivery. Formulation of these polymers into suitable solid-state forms plays an important role in safety, stability, and efficiency of the products. Ethyl cellulose is commonly used as drug carrier in controlled delivery systems. In this work, particles of ethyl cellulose have been precipitated by SAS using CO2 as antisolvent and dichloromethane (DCM) as solvent. We studied the effects of concentration on the particle size distribution (PSD) of the precipitates. Ethyl cellulose size-controlled particles have been produced in the micrometer range 3.8–5.0 μm, and an increase of the mean particle diameter (MPD) was observed with the increase of the concentration of the solution.

Thermodynamic modelling of supercritical fluid-solid phase equilibrium data

Abstract The design and development of processes involving supercritical fluids depend on how easy the phase equilibrium can be accurately modelled and predicted. In the work described herein, the supercritical fluid–solid equilibrium has been considered. Modelling the fluid–solid equilibrium is associated with a number of drawbacks, even when it is possible to obtain the experimental solubility data for the solute in the supercritical fluid. In most cases it is necessary to introduce additional adjustment parameters into the model. The developed program, realized in Visual Basic® language, is based on the fitting of two parameters – the binary interaction parameter (k12) and the solid sublimation pressure ( P 2 sat ). This program can be used for any fluid–solid equilibrium even when both parameters are known or supposed. The model has been applied to several systems and, as example, in this work, the Penicillin G-CO2 phase equilibrium data are shown. The results obtained allow affirm that the thermodynamic model applied to fluid–solid equilibrium calculations is useful to predict the behaviour of this system.

Particles Formation Using Supercritical Fluids

The particle precipitation into micro and nanoparticles has been an active research field for decades (Chattopadhyay & Gupta, 2001; Kalogiannis et al., 2005; Rehman et al., 2001; Reverchon, 1999; Velaga et al., 2002; YeoL or using it as antisolvent, the SAS technique (Supercritical AntiSolvent); the choice between one or another depends on the active substance high or low solubility in the supercritical fluid. The RESS process consists of solubilising the active ingredient of interest in the supercritical fluid and then rapidly depressurising this solution through a nozzle, thus causing the precipitation, extremely fast, of this compound. In other words, the process is based on the transition of active compound from soluble to insoluble state when the carbon dioxide passes from the supercritical to the gaseous phase. This technique has been applied on the particle precipitation and co-precipitation of many active ingredients/polymers (Kongsombut et al., 2009; Sane & Limtrakul, 2009; Turk et al., 2006; Vemavarapu et al., 2009; Wen et al., 2010). The SAS technique, in all its variants, generally consists of spraying a solution of the solute to be precipitated into the supercritical fluid. The mass transfer behavior of the droplets is thought to be a key factor affecting particle morphology (Werling & Debenedetti, 1999). The volumetric expansion of the solvent reduces the solvation capacity of the solvent, causing the supersaturation of the liquid phase and the consequent generation of the particles. The SAS process has been carried out for many particles precipitation and polymeric encapsulation of particles of active ingredients (Ai-Zheng et al., 2009; Chong et al., 2009a;

Supercritical Antisolvent Process Applied to the Pharmaceutical Industry

Pharmaceutical preparations are the final product of a technological process that gives the drugs the characteristics appropriate for easy administration, proper dosage, and enhancement of the therapeutic efficacy. The design of pharmaceutical preparations in nanoparticulate form has emerged as a new strategy for drug delivery (Pasquali, Bettini, and Giordano, 2006). Particle size (PS) and particle size distribution (PSD) are critical parameters that determine the rate of dissolution of the drug in the biological fluids and, hence, have a significant effect on the bioavailability of those drugs that have poor solubility in water, for which the dissolution is the rate-limiting step in the absorption process (Perrut, Jung, and Leboeuf, 2005; Van Nijlen et al., 2003). Supercritical antisolvent (SAS) processes have been widely used to precipitate active pharmaceutical ingredients (APIs) (Chattopadhyay and Gupta, 2001; Rehman et al., 2001) with a high level of purity, suitable dimensional characteristics, narrow PSD, and spherical morphologies. The SAS process is based on the particular properties of the supercritical fluids (SCFs). These fluids have diffusivities two orders of magnitude larger than those of liquids, resulting in a faster mass transfer rate SCF properties (solvent power and selectivity) can be also adjusted continuously by altering the experimental conditions (temperature and pressure). As a consequence, SCFs can be removed from the process by a simple change from the supercritical to room conditions, which avoids difficult post-treatments of waste liquid streams. Carbon dioxide (CO2) at supercritical conditions, among all possible SCFs, is largely used because of its relatively low critical temperature (31.1°C) and pressure (73.8 bar), low toxicity, and low cost. In this article, we show some results about processed antibiotics (ampicillin and amoxicillin), two of the worlds most widely prescribed antibiotics, when they are dissolved in 1-methyl-2-pyrrolidone (NMP) and carbon dioxide is used as antisolvent.

Polymer encapsulation of amoxicillin microparticles by SAS process

Abstract Encapsulation of amoxicillin (AMC) with ethyl cellulose (EC) by a supercritical antisolvent process (SAS) was investigated. AMC microparticles obtained previously by an SAS process were used as host particles and EC, a biodegradable polymer used for the controlled release of drugs, was chosen as the coating material. In this work, a suspension of AMC microparticles in a solution of ethyl cellulose in dichloromethane (DCM) was sprayed through a nozzle into supercritical CO2. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and HPLC analyses were carried out. The effects of AMC:EC ratio, the initial polymer concentration of the solution, temperature and pressure on the encapsulation process were investigated. Although all the experiments led to powder precipitation, the AMC encapsulation was achieved in only half of the cases, particularly when the lower drug:polymer ratios were assayed. In general, it was observed that the percentages of AMC present in the precipitates were higher on increasing the AMC:EC ratio. In these cases composites rather than encapsulates were obtained. The in vitro release profiles of the resulting materials were evaluated in order to ascertain whether composites can be used as encapsulated systems for drug delivery systems.

Hydrodynamics Influence on Particles Formation Using SAS Process

Particle size and particle size distribution play an important role in many fields such cosmetic, food, textile, explosives, sensor, catalysis and pharmaceutics among others. Many properties of industrial powdered products can be adjusted by changing the particle size and particle size distribution of the powder. The conventional methods to produce microparticles have several drawbacks: wide size distribution, high thermal and mechanical stress, environmental pollution, large quantities of residual organic solvent and multistage processes are some of them. The application of supercritical fluids (SCF) as an alternative to the conventional precipitation processes has been an active field of research and innovation during the past two decades (Jung & Perrut, 2001; Martin& Cocero, 2008; Shariati P this also meets the pharmaceutical requirements for the absence of residual solvent, correct technological and biopharmaceutical properties and high quality (Benedetti et al., 1997; Elvassore et al., 2001; Falk& Randolph, 1998; Moneghini et al., 2001; Reverchon& Della Porta, 1999; Reverchon, 2002; Subramaniam et al., 1997; Yeo et al., 1993; Winters et al.,1996), as well as giving enhanced therapeutic action compared with traditional formulations (Giunchedi et al., 1998; Okada& Toguchi, 1995). The revised literature demonstrates that there are two principal ways of micronizing and encapsulating drugs with polymers: using supercritical fluid as solvent, the RESS technique (Rapid Expansion of Supercritical Solutions); or using it as antisolvent, the SAS technique (Supercritical AntiSolvent); the choice of one or other depends on the high or low solubility, respectively, of the polymer and drug in the supercritical fluid. Although the experimental parameters influences on the powder characteristic as particle size and morphologies is now qualitatively well known, the prediction of the powder characteristics is not feasible yet. This fact it is due to different physical phenomena involved in the SAS process. In most cases, the knowledge of the fluid phase equilibrium is