Formation of polymer particles with supercritical fluids: A review

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Abstract

Recent developments on particle formation from polymers using supercritical fluids have been reviewed with an emphasis on articles published during 2000–2003. First, a brief description of the basic operating principles of the various particle formation processes is presented. These include the rapid expansion of supercritical solutions (RESS), the gas antisolvent process (GAS), supercritical antisolvent process (SAS) and its various modifications, and the particles from gas-saturated solution (PGSS) processes. An account of the general review articles that have been published in previous years is then provided. The publications that have appeared over the past 4 years have been reviewed under two groupings, one involving the production of particles from pure polymers, and the other involving the production of polymer particles that contain active ingredients, especially those that pertain to pharmaceuticals. The majority of the efforts in the current supercritical particle formation technology is indeed on the production of polymer particles that are of pharmaceutical significance. In each grouping, the publications were further categorized according to the primary role played by the supercritical fluid in the process, namely whether it was used as a solvent, or as an antisolvent, or as a solute. This review is the first comprehensive review specifically focused on the formation of particles from polymers.

Introduction

Interest in supercritical fluids and their potential use for process improvements has significantly increased in the past decade. These fluids, the properties of which can be tuned by changing the fluid density between those of liquid and gases, have been adopted or are being explored as: (a) alternative solvents for classical separation processes such as extraction, fractionation, adsorption, chromatography, and crystallization, (b) as reaction media as in polymerization or depolymerization, or (c) simply as reprocessing fluid as in production of particles, fibers, or foams. Some of the extraction processes such as decaffeination, and some polymerization and foaming processes have become commercial. Particle formation will most likely be the next major commercial application area that uses supercritical fluids.

The particle formation technology that uses supercritical fluids has evolved in many different forms during the last 20 years. Several review articles have already appeared in the literature [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. A wide variety of organic and inorganic materials have been processed in the form of particles, fibers, films, and foams, employing the supercritical fluids as solvents or as antisolvents. Supercritical fluids were used as solvents, for example, to crystallize a supercritical fluid-soluble compound [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], or as non-solvents to precipitate supercritical fluid-insoluble materials [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54]. In some cases, these fluids were employed as cosolvents or coantisolvents along with an organic liquid solvent to produce particles with a targeted morphology [31]. The versatile operating conditions that are possible with supercritical fluids and their mixtures, provide the flexibilities in controlling the size of the particles that span from microns to nanometers. Indeed, the recent advances in these techniques are opening new horizons for the supercritical fluid technology in the area of particle design by extending the utilization domain to nanotechnology-based applications.

Among the various organic and inorganic compounds that have been processed with supercritical fluids, polymers have been of special interest and significance. A variety of polymers including polyolefins [14], fluoropolymers [25], polyamides [37], and biopolymers [45] have been explored. A range of protocols and flow arrangements and their influence on the particle size and shapes have been reported. General observations from these studies have been that the external shape of the resulting particles is relatively insensitive to process variables, and that the particle morphology depends more strongly on the properties of the polymer itself. For example, if the polymer is semicrystalline such as polyesters, particles are found to be spherical [46], and if molecules have stiff chains such as polyamides, fibrous forms are likely to be formed [37]. It remains a challenge to design for a specific particle shape and size in “any” targeted range for “every” type of polymer. Even though many forms of particles may be generated, finding their niche use areas presents another challenge. Therefore, the knowledge that is being generated is shifting more towards those applications where polymer particles that are produced have more clearly identifiable use areas, such as the case with pharmaceutical applications. In this respect, the more attractive polymers are the biopolymers. Particles of various biodegradable polymers have been produced for applications of drug delivery, or for use in agricultural and biological applications [8]. An important objective of the particle formation with biopolymers is to encapsulate a biologically active ingredient in the polymer matrix to be used for a controlled release of the compound to a targeted location. Two approaches are common, one is the formation of pure biopolymer particle which is then impregnated with the active ingredients, and the other is the coproduction of the polymer and other active ingredients. Many technical methods were developed to control the concentration of the active compounds inside the polymer particles. The variation of experimental conditions and contacting mechanism between supercritical fluids and liquid solutions that contain polymers and biologically active compounds result in different loading efficiencies in the polymer particles. The key challenge in these techniques is to successfully impregnate the active ingredient into polymeric matrix at a target concentration, or when coproduced, to overcome the segregated particle formation of the two components upon their coprecipitation.

The objective of the present review is to provide a critical account of the current state of formation of particles from polymers with a special focus on pharmaceutical applications. This is the first comprehensive review that is specifically devoted to particle formation from polymers. We first briefly describe the various supercritical particle formation technologies that have been developed, and then survey the previously published review articles on the supercritical particle formation processes that cover processing of not only polymers but also other organic and inorganic materials. Next, we present a review of the recent technical papers on polymer particle production with an emphasis on developments in the last 4 years. The review is presented in subsections according to the type of polymer particles generated, and the role of supercritical fluids in the experimental technology used. The review describes the recent advances made in the formation of particles from pure polymers, followed by coprocessing of polymers with non-polymeric materials. The focus is more on the practical applications, especially the pharmaceutical applications of this technology. Articles on chemical reaction-based particle formation such as particle formation in polymerization under supercritical conditions were excluded from the review. Even though the focus is on pharmaceutical applications of polymer particles, we hope that this review demonstrates the significant strides that are being made in the supercritical fluid-based particle formation technology for the downstream processing of polymer products in general.

Section snippets

Summary of supercritical particle formation methodologies

Twenty years of usage of supercritical fluids in the particle formation technology has given birth to a number of modified processes that use different nucleation and growth mechanisms of precipitating particles. These are summarized in Table 1 and are briefly described in the following sections.

Previous review articles

Several review articles on supercritical fluid-based particle formation technology have been published during the past decade. These are listed in Table 2. These reviews have concentrated either on a particular experimental technique or on a specific type of material being processed. A survey of these earlier review articles is of value since their appearance, in some measure, correlates with the expansion of interest in the relevant technology within academic institutions and industry. They

Formation of particles from pure polymers

The small size particles of a pure polymer find use in chromatographic applications, as solid adsorbents, as standards for particle sizers and counters, as catalytic support materials, and in other applications where uniformly distributed polymer microparticles are needed. Production of micro- or nanoparticles of polymers using supercritical technology is especially attractive for providing alternative solutions to various problems encountered in traditional techniques. For example, the

Formation of polymer particles containing active ingredients

The successful production of microspheres of pure biopolymers has fueled the interest in generation of polymer particles containing active ingredients that can be used for controlled release applications. Additives such as pharmaceuticals, cosmetics, and agricultural chemicals can be incorporated into the biopolymer particles in order to achieve the delivery of these active ingredients to a targeted location in a controlled manner either by a diffusional process or by degradation of the host

Concluding observations and future trends

This review which covered the recent articles published during 2000–2003 clearly is not and was not meant to be exhaustive. Since the initial submission of this manuscript several new reviews on the broader aspects of particle formation has appeared in the literature [84], [85], [86]. The studies included in the present and in these other reviews have addressed a variety of issues such as particle size reduction, narrowing the particle size distribution, creation of homogeneous particle

References (89)

  • J.J. Shim et al.

    Aqueous latexes formed from polymer/CO2 suspensions2. Hydrophilic surfactants in water

    Ind. Eng. Chem. Res.

    (2002)
  • T.W. Randolph et al.

    Sub-micrometer-sized biodegradable particles of poly(l-lactic acid) via the gas antisolvent spray precipitation process

    Biotechnol. Prog.

    (1993)
  • R. Ghaderi et al.

    Preparation of biodegradable microparticles using solution-enhanced dispersion by supercritical fluids (SEDS)

    Pharm. Res.

    (1999)
  • M. Sarkari et al.

    Generation of microparticles using CO2 and CO2-philic antisolvents

    AIChE J.

    (2000)
  • Y. Pérez et al.

    An improved PCA process for the production of nano- and microparticles of biodegradable polymers

  • R.Y. Hsu et al.

    Formation of micron-sized cycloolefin copolymer from toluene solution using compressed HFC-134a as antisolvent

    J. Appl. Polym. Sci.

    (2002)
  • S. Taki et al.

    Controlled release system formed by supercritical anti-solvent coprecipitation of a herbicide and a biodegradable polymer

    J. Supercrit. Fluids

    (2001)
  • N. Elvassore et al.

    Production of protein-loaded polymeric microcapsules by compressed CO2 in a mixed solvent

    Ind. Eng. Chem. Res.

    (2001)
  • L. Sze Tu et al.

    Micronisation and microencapsulation of pharmaceuticals using a carbon dioxide antisolvent

    Powder Technol.

    (2002)
  • P. Chattopadhyay et al.

    Supercritical CO2 based production of magnetically responsive micro- and nanoparticles for drug targeting

    Ind. Eng. Chem. Res.

    (2002)
    Y. Wang et al.

    Polymer coating/encapsulation of nanoparticles using a supercritical anti-solvent process

    J. Supercrit. Fluids

    (2004)
  • E. Weidner et al.

    PGSS (particles from gas saturated solutions): a new process for powder generation

    E. Weidner et al.

    Manufacture of particles from high viscous melts using supercritical fluids

    Z. Knez et al.

    Particle formation and particle design using supercritical fluids

    Curr. Opin. Solid State Mater. Sci.

    (2003)
    (d)S. Beuermann, M. Buback, M. Juergens, E. Weidner, M. Petermann, C. Schwede, P. Klostermann, Supercritical fluid...
  • J. Kerc et al.

    Micronization of drugs using supercritical carbon dioxide

    Int. J. Pharm.

    (1999)
  • G. Upper et al.

    High pressure crystallization in supercritical or dense fluids

  • S. Palakodaty et al.

    Phase behavioral effects on particle formation processes using supercritical fluids

    Pharm. Res.

    (1999)
  • A.I. Cooper

    Polymer synthesis and processing using supercritical carbon dioxide

    J. Mater. Chem.

    (2000)
  • U.B. Kompella et al.

    Preparation of drug delivery systems using supercritical fluid technology

    Crit. Rev. Ther. Drug Carrier Syst.

    (2001)
  • T.L. Rogers et al.

    Solution-based particle formation of pharmaceutical powders by supercritical or compressed fluid CO2 and cryogenic spray-freezing technologies

    Drug Dev. Ind. Pharm.

    (2001)
  • H.S. Tan et al.

    Particle formation using supercritical fluids: pharmaceutical applications

    Expert Opin. Ther. Pat.

    (2001)
  • L.A. Stanton et al.

    Improving drug delivery using polymers and supercritical fluid technology

    Aust. J. Chem.

    (2002)
  • X. Ye et al.

    Making nanomaterials in supercritical fluids: a review

    J. Chem. Educ.

    (2003)
  • V. Krukonis

    Supercritical fluid nucleation of difficult-to-comminute solids

  • D.W. Matson et al.

    Rapid expansion of supercritical fluid solutions: solute formation of powders, thin films, and fibers

    Ind. Eng. Chem. Res.

    (1987)
  • R.C. Petersen et al.

    The formation of polymer fibers from the rapid expansion of supercritical fluid solutions

    Polym. Eng. Sci.

    (1987)
  • D.W. Matson et al.

    Production of powders and films from supercritical solutions

    J. Mater. Sci.

    (1987)
  • J.W. Tom et al.

    Formation of bioerodible polymeric microspheres and microparticles by rapid expansion of supercritical solutions

    Biotechnol. Prog.

    (1991)
  • L. Benedetti et al.

    Production of micronic particles of biocompatible polymer using supercritical carbon dioxide

    Biotechnol. Bioeng.

    (1997)
  • A.K. Lele et al.

    Morphology of polymers precipitated from a supercritical solvent

    AIChE J.

    (1992)
  • S. Mawson et al.

    Formation of poly(1,1,2,2-tetrahydroperfluorodecyl acrylate) submicron fibers and particles from supercritical carbon dioxide solutions

    Macromolecules

    (1995)
  • J.N. Hay et al.

    Review: environmentally friendly coatings using carbon dioxide as the carrier medium

    J. Mater. Sci.

    (2002)
  • G. Tepper et al.

    Polymer deposition from supercritical solutions for sensing applications

    Ind. Eng. Chem. Res.

    (2000)
    J.L. Fulton et al.

    Thin fluoropolymer films and nanoparticles coating from rapid expansion of supercritical carbon dioxide solutions with electrostatic collection

    Polymer

    (2003)
  • E.M. Glebov et al.

    Coating of metal powders with polymers in supercritical carbon dioxide

    Ind. Eng. Chem. Res.

    (2001)
  • F.E. Henon et al.

    Effect of polymer coatings from CO2 on water vapor transport in porous media

    AIChE J.

    (2002)
  • T.J. Wang et al.

    Mechanism of particle coating granulation with RESS process in a fluidized bed

    Powder Technol.

    (2001)
  • K. Matsuyama et al.

    Environmentally benign formation of polymeric microspheres by rapid expansion of supercritical carbon dioxide solution with nonsolvent

    Environ. Sci. Technol.

    (2001)
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