Full Length Research Paper
ABSTRACT
The supercritical fluid technology has been target of many pharmaceuticals investigations in particles production for almost 35 years. This is due to the great advantages it offers over others technologies currently used for the same purpose. A brief history is presented, as well the classification of supercritical technology based on the role that the supercritical fluid (carbon dioxide) performs in the process.
Key words: Supercritical fluid technology, supercritical carbon dioxide, pharmaceuticals.
INTRODUCTION
Caignard de la Tour (1822) discovered the critical phenomena by observation of natural mineralization. The supercritical fluid technology (SCF) is based on the discovery of this phenomenon. Although the SCF is known since late nineteenth century, the basic concept of rapid expansion of supercritical solutions (RESS) was first described by Hannay and Hogarth (1879), in a study of the solubility of metal chlorides in supercritical ethanol to understand natural mineralization, observed by Caignard de la Tour (1822), in this study the authors reported the great power of SCF solvation. However, was Worthy (1981) whom steered the study of SCF to optimize micromeritic of organic materials difficult to form powders.
For more than one hundred years the broad assortment of techniques, limitation of the equipment and specific conditions to achieve the supercritical state made an accelerated advancement scientific research difficult (Berche et al., 2009). The concept of SCF technology as said by Jung and Perrut (2001) was better understood and developed after the pioneering work of Krukonis (1984) and, especially, by the disclosure of the Battelle Institute's research (Smith, 1985; Petersen et al., 1986; Matson et al., 1987a, b), they described and modeled flow pattern and nucleation process at supercritical conditions. Since then, many methods using this technology have been published and patented.
A supercritical solvent is one that at a certain temperature and pressure, does not condense or evaporate, it exists as a fluid (Yasuji et al., 2008). This happens when a substance is high above its critical temperature and pressure, and passes it to a condition called “supercritical fluid state”. Under these conditions, the densities of the liquid and vapor are identical, and for this reason the meniscus, on the interface between the two phases, disappears (Moribe et al., 2008).
In SCF conditions, substances exhibit physical properties that are intermediate between gases and liquids of the start material. Thus, the density of a SCF can be altered by the variation of the pressure applied on the fluid. When the fluid is compressed at high temperatures it can have a density varying between those displayed by gases up to typical values of liquids. Likewise, a SCF maintained at a relatively high density has the ability to dissolve a variety of materials, exactly as conventional liquids do, but with the power of gases penetration (Chan and Kwok, 2011).
The use of environmentally more acceptable intermediaries, such as carbon dioxide (CO2) and water, is an advantage of SCF technology. The SCF most used in pharmaceutical applications is the CO2, due to its low cost and also because of its supercritical milder condition, which enables the processing of pharmaceuticals and other thermolabile raw materials (DeSimone, 2002).
Increased bioavailability of poorly-soluble molecules, development of modified release systems of drugs, and drug delivery via oral, pulmonary or transdermal - which are less invasive than the parenteral route – are the main objectives of the pharmaceutical industry. These objectives can be achieved by SCF technology which demonstrates dramatic change in the solid morphology after processing, that is, medium-size and particle size distribution, particle shape and porosity, and, consequently, surface area and dissolution rate are often quite different from those of the starting material (Perrut, 2003).
The supercritical CO2 (SC-CO2) is easily obtained in critical temperature (Tc) of 304K and critical pressure (pc) of 7.38 MPa (Yasuji et al., 2008) but there are other substances such as nitrogen, ethanol and water, which also have interesting solvent properties in its supercritical state. However, for reasons of cost, danger of explosion, flammability, toxicity and adverse physical properties (conditions for Tc and pc too high), these substances are less used commercially (Maul, 1999).
Currently, the SCF technology is an alternative for application in drug release technology, in addition to meeting the principles of green chemistry, who’s most accepted definition (Anastas and Warner, 1998)is "the design, development and implementation of chemical processes and products to reduce or eliminate hazardous substances to human health and the environment". This definition has been expanded by Poliakoff et al. (2002) in 12 principles.
The traditional methods for developing drug delivery systems, either in micro or nanoscale, using technologies such as co-precipitation, coacervation and solvent evaporation polymerization, use large amounts of organic solvents and/or surfactants which, in general, are harmful to the environment (Kawashima et al., 1989; Yoshida et al., 2015). The aforementioned methods used to produce particles which commonly exhibited low rates of drug entrapment and difficulties in scaling, and most often require further treatment to remove solvent(s) and/or impurities from the particles. Although the pharmaceutical industry shows interest in innovative technologies involving production of micro and nanoparticles, the solvent disposal strongly limits the industrial production and generates increased costs (Jung and Perrut, 2001). Hence, the subject of several studies has been about the development of other technologies that minimize the problems related to pollution, toxicity and ease of production scale-up (De Zordi et al., 2012).
PROCESSES IN SCF TECHNOLOGY
PROCESSES THAT DO NOT DEPEND ON THE CARBON DIOXIDE SOLVENT POWER
CONCLUSION
CONFLICT OF INTERESTS
ACKNOWLEDGEMENT
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