Dissolving biomolecules and modifying biomedical implants with supercritical carbon dioxide (original) (raw)
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Advanced Drug Delivery Reviews, 2008
Supercritical CO 2 has the potential to be an excellent environment within which controlled release polymers and dry composites may be formed. The low temperature and dry conditions within the fluid offer obvious advantages in the processing of water, solvent or heat labile molecules. The low viscosity and high diffusivity of scCO 2 offer the possibility of novel processing routes for polymer drug composites, but there are still technical challenges to overcome. Moreover, the low solubility of most drug molecules in scCO 2 presents both challenges and advantages. This review explores the current methods that use high pressure and scCO 2 for the production of drug delivery systems and the more specialized application of the fluid in the formation of highly porous tissue engineering scaffolds.
Supercritical carbon dioxide design strategies: from drug carriers to soft killers
Philosophical transactions. Series A, Mathematical, physical, and engineering sciences, 2015
The integrated use of supercritical carbon dioxide (scCO(2)) and micro- and nanotechnologies has enabled new sustainable strategies for the manufacturing of new medications. 'Green' scCO(2)-based methodologies are well suited to improve either the synthesis or materials processing leading to the assembly of three-dimensional multifunctional constructs. By using scCO(2) either as C1 feedstock or as solvent, simple, economic, efficient and clean routes can be designed to synthesize materials with unique properties such as polyurea dendrimers and oxazoline-based polymers/oligomers. These new biocompatible, biodegradable and water-soluble polymeric materials can be engineered into multifunctional constructs with antimicrobial activity, targeting moieties, labelling units and/or efficiently loaded with therapeutics. This mini-review highlights the particular features exhibited by these materials resulting directly from the followed supercritical routes.
An overview on the application of supercritical carbon dioxide for the processing of pharmaceuticals
Arhiv za farmaciju
Supercritical carbon dioxide (scCO2) application in the pharmaceutical industry is still undeveloped regardless of significant research interests in this processing medium shown in the last decades. ScCO2 technologies can improve drug solubility, bioavailability, and therapeutic effect. These technologies can lead to the development of new formulations that will contribute to a decrease in drug dose, medication frequency, and increase patients' well-being. Considering the significant decrease in the price of high-pressure equipment and society's growing need for cleaner production and safer products, it is expected that symbiosis between supercritical fluid and pharmaceutical technologies will happen soon. Therefore, this review was focused on the latest contributions of scCO2 technologies to the pharmaceutical field. The main aim was to bring these technologies closer to pharmaceutical specialists. For this purpose, the most commonly used technologies were explained and dis...
Synthesis and Functionalization of Nanoparticles in Supercritical CO2
Advanced Supercritical Fluids Technologies [Working Title]
A review of recent results on fabrication of inorganic and organic nanoparticles in supercritical carbon dioxide will be presented, with particular emphasis on the metallic and polymeric nanoparticles used in biomedicine. The use of the water-in-scCO 2 microemulsion in the synthesis of metal nanoparticles will be also discussed. The recent progress in preparation of polymeric nanoparticles with desired size and porosity obtained through processing methods in scCO 2 as drug delivery systems will be described. The efficiency of the drug encapsulation in organic and inorganic nanoparticles using supercritical CO 2 as dissolving media is another topic of interest. Various methods to achieve surface functionalization of nanoparticles in supercritical and subcritical CO 2 will be evaluated, considering the challenges and limitations in efficiency, scalability, and development of new applications.
Supercritical CO2: A twenty-first century solvent for the chemical industry
Half a glass of water may be described as half full or half empty, but if the water is in a supercritical state we have to agree that the glass is filled with something that is neither a gas nor a liquid. Steam and boiling water when in equilibrium are two different phases that are clearly separated by a phase boundary, but if the temperature and pressure are raised, after a point the phase boundary disappears and water becomes a supercritical fluid (SCF). While by appropriate changes in temperature and pressure the supercritical phase for many other substances could also be reached, from the point of view of applications, supercritical carbon dioxide (scCO 2) is of special interest. The main impetus for the wide-scale application of scCO 2 and other SCFs comes from the desire to develop environmentfriendly chemical processes 1-3. The environmental impact of a chemical process can be measured by its Efactor (amount of waste per unit mass of desired product). The E-factor has an inverse relationship with its environment-friendliness and includes solvent loss in the process 4. Many industrial solvents are not only hazardous (toxic, flammable, etc.), but their full recovery and recycling often are not easy, or economically viable. An appropriate example is the pharmaceutical industry where approximately only about 1% (w/v) product comes out of the solvent used, with about 50% solvent recovery in the whole process 5. Furthermore even a non-hazardous hydrocarbon solvent in the long run is converted to CO 2 and adds to the carbon cycle. Therefore, from the point of view of the overall environment-friendliness, replacement of common organic solvent is an important objective. Although the main motivation for the wide-scale application of scCO 2 in recent times originated from environmental considerations, studies on scCO 2 have also led to many important scientific findings 6-8. In this review we present some of the recent scientific and technological advances associated with the use of SCF in the industry. The focus is mainly on the chemical aspects and the underlying principles of SCF-based technologies, but technologies other than chemical are also mentioned.
Medical Device Sterilization Using Supercritical CO2 Based Mixtures
Recent Patents on Chemical Engineering, 2010
A critical analysis is presented of the supercritical fluids based technologies that have been proposed in polymer processing for pharmaceutical and medical applications. The formation of polymer-drug microparticles and microspheres, the production of simple or loaded membranes and the formation of temporary scaffolds are reviewed and the future trends in these areas are analyzed.
Journal of Applied Polymer Science, 2003
Microspheres based on synthetic polymers such as poly(methyl methacrylate) (PMMA) and PMMA blends are known for their medical and optical applications. The development of methods for processing polymeric microspheres using a nontoxic solvent, like supercritical carbon dioxide (SCCO 2), is desirable. This work investigates the solubility and behavior of polymers (PMMA and PMMA/ polycaprolactone blend) and solutes (cholesterol and albumin) in SCCO 2 and SCCO 2 ϩ cosolvent (acetone, ethanol, and methylene chloride). The knowledge of solubility behavior of materials in SCCO 2 aids in the selection and/or design of the most appropriate technique for materials processing. Processing PMMA-based polymers with pure SCCO 2 leads to polymer swelling. The lack of polymer sol-ubility in pure CO 2 precludes their micronization by the RESS (rapid expansion of supercritical solutions) process, but on the other hand allows their impregnation. Polymer plasticization caused by CO 2 can be exploited in the PGSS (particles from gas-saturated solutions) process. Addition of a liquid cosolvent to CO 2 enhances the dissolution of solutes and polymers. Precipitation of the studied polymers by antisolvent techniques seems feasible only by use of CO 2 ϩ methylene chloride.
Pharmaceutical processing with supercritical carbon dioxide
Journal of Pharmaceutical Sciences, 1997
Replacement of traditional solvents with “environmentally benign” carbon dioxide is receiving increased attention in pharmaceutical processing. Among the reported applications, particle formation with dense carbon dioxide and the “clean” synthesis of drug compounds using carbon dioxide as a reaction medium hold immense potential for large-scale application in the pharmaceutical industry. This paper provides an overview of these rapidly emerging technologies along with examples of the wide variety of relatively contaminant-free pharmaceutical compounds that have been processed via these technologies on a laboratory scale. Challenges facing successful implementation in practice include demonstration of continuous production and harvesting of particles with desired and reproducible product characteristics. Mathematical models aimed at a better fundamental understanding of the underlying thermophysical phenomena are essential for rational design and scale-up of these technologies.
Advanced drug delivery reviews, 2018
Low drug bioavailability, which is mostly a result of poor aqueous drug solubilities and of inadequate drug dissolution rates, is one of the most significant challenges that pharmaceutical companies are currently facing, since this may limit the therapeutic efficacy of marketed drugs, or even result in the discard of potential highly effective drug candidates during developmental stages. Two of the main approaches that have been implemented in recent years to overcome poor drug solubility/dissolution issues have frequently involved drug particle size reduction (i.e., micronization/nanonization) and/or the modification of some of the physicochemical and structural properties of poorly water soluble drugs. A large number of particle engineering methodologies have been developed, tested, and applied in the synthesis and control of particle size/particle-size distributions, crystallinities, and polymorphic purities of drug micro- and nano-particles/crystals. In recent years pharmaceutic...