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Supercritical Fluid Technology

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Information about Supercritical Fluid Technology
Education

Published on November 8, 2008

Author: pharmapresentation

Source: authorstream.com

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Slide 1: Supercritical Fluid Technology Applicability in Pharmacy Seminar by G. S. N. Koteswara Rao Regd. No. 97304 Under the guidance of Prof. K. V. Ramana Murthy, M.Pharm., Ph.D., DAS University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam – 530 003. Slide 2: G.S.N. Koteswara Rao Nov 11, 2008 Basic Info Strategies Techniques Applications Conclusion References INTRODUCTION : G.S.N. Koteswara Rao Nov 11, 2008 A supercritical fluid (SCF) is a substance whose temperature and pressure are simultaneously above its critical point. Critical Temperature: The temperature above which the substance can no longer exists as a liquid no matter how much pressure is applied. Critical Pressure: The pressure above which the substance can no longer exists as a gas no matter how much temperature is applied. INTRODUCTION Slide 4: G.S.N. Koteswara Rao Nov 11, 2008 PHASE DIAGRAM Importance of Supercritical Fluid : G.S.N. Koteswara Rao Nov 11, 2008 Importance of Supercritical Fluid Liquids have solubilizing nature Gases have diffusivity and compressibility / expandable nature. Supercitical fluids SCFs offer: Liquid-like density and solubilizing capacity Gas-like viscosity, compressibility and diffusivity allowing for good mixing and mass transfer hence labeled as fluids. Comparison of Gas, Liquid and Supercritical Fluid : G.S.N. Koteswara Rao Nov 11, 2008 Comparison of Gas, Liquid and Supercritical Fluid Key Features : G.S.N. Koteswara Rao Nov 11, 2008 Key Features SCFT offers tremendous potential, as it is safe, inexpensive, eco-friendly, non-toxic and economical. With SCFs at hand, there is no need of any organic solvents. Solvation capacity of SCF α fluid density. Sensitive to small changes in operating conditions. Operating conditions of low temperature and pressure make SCFs attractive for pharmaceutical research, especially thermolabile materials. Choice of SCF : G.S.N. Koteswara Rao Nov 11, 2008 Choice of SCF Depends on Most widely used supercritical fluid is carbon dioxide (SC-CO2). Physico-chemical properties of the compound of interest Role of solvent in the process in terms of solvency or anti-solvency Specific application Safety, flammability, phase behavior at operating conditions Cost of fluid Critical properties of commonly used SCFs : G.S.N. Koteswara Rao Nov 11, 2008 Critical properties of commonly used SCFs Ideal Properties of CO2 : G.S.N. Koteswara Rao Nov 11, 2008 Ideal Properties of CO2 Low critical temperature (31.1° C) Moderate critical pressure of 73 bar Non-flammable Non-toxic Miscible with variety of organic solvents Recoverable after processing Diffuses faster than conventional liquid solvents Generally Recognized As Safe (GRAS) status Approved by FDA for use in food and pharmaceutical operations Eco-friendly Inexpensive Co-solvent : G.S.N. Koteswara Rao Nov 11, 2008 Co-solvent Polar or non-polar miscible solvent (1% to 5%). Purpose: To modify the polarity and solvent strength of the SCF. E.g., Methanol, Ethanol, Acetone & Dimethyl sulfoxide (DMSO). Mechanisms: Hydrogen bonding Complex formation Dipole interactions Solvent / co-solvent / solute interactions Slide 12: G.S.N. Koteswara Rao Nov 11, 2008 Basic Info Strategies Techniques Applications Conclusion References Particle generation : G.S.N. Koteswara Rao Nov 11, 2008 Particle generation Fine particles (µm or nm) with uniform narrow size range are of particular interest in pharmaceutical industry. Slide 14: G.S.N. Koteswara Rao Nov 11, 2008 Particle generating techniques Rapid expansion of supercritical solutions (RESS) or supercritical fluid nucleation (SFN) 2. Anti solvent processes 3. Solution enhanced dispersion by supercritical fluids (SEDS) 4. Impregnation or infusion of polymers with bioactive materials Gas anti solvent recrystallization (GAS) Supercritical anti solvent (SAS) technique Aerosol solvent extraction system (ASES) Rapid expansion of supercritical solutions (RESS)or Supercritical fluid nucleation (SFN) : G.S.N. Koteswara Rao Nov 11, 2008 Rapid expansion of supercritical solutions (RESS)or Supercritical fluid nucleation (SFN) Saturation of supercritical solvent with solute Rapid expansion Supersaturation Precipitation Solute particles (narrow particle size distribution) Slide 16: G.S.N. Koteswara Rao Nov 11, 2008 The morphology and size distribution of the precipitated material is a function of its pre-expansion concentration and expansion conditions. The higher the pre-expansion concentration, the smaller the particles and narrower will be the particle size range. Slide 17: G.S.N. Koteswara Rao Nov 11, 2008 Schematic representation of RESS Anti Solvent Processes: : G.S.N. Koteswara Rao Nov 11, 2008 Anti Solvent Processes: Substances that are not soluble in SCFs Anti solvent process Principle: Salting out technique Dissolution of solid material in a suitable solvent supersaturation precipitation of solute  large amount of a poor solvent Gas anti solvent recrystallization (GAS) : G.S.N. Koteswara Rao Nov 11, 2008 Gas anti solvent recrystallization (GAS) Rapid crystallization can be induced by introducing the antisolvent gas into a solution containing dissolved solute. Size distribution of precipitate depends on the rate of addition of the supercritical fluid. Disadvantage Poor control over the precipitated crystal morphology, size distribution and presence of residual solvents. Slide 20: G.S.N. Koteswara Rao Nov 11, 2008 Schematic representation of GAS Supercritical anti solvent (SAS) technique : G.S.N. Koteswara Rao Nov 11, 2008 Supercritical anti solvent (SAS) technique First solute is to be dissolved in a good solvent then the solution is fed into a pressure vessel under supercritical conditions, through a nozzle (i.e., sprayed into supercritical fluid anti solvent). The anti solvent rapidly diffuses in to that liquid solvent as the carrier liquid solvent counter diffuses in to the anti solvent resulting in precipitation of solute. Slide 22: G.S.N. Koteswara Rao Nov 11, 2008 Schematic representation of SAS Gas Antisolvent (GAS) technique Supercritical anti solvent (SAS) technique : G.S.N. Koteswara Rao Nov 11, 2008 Gas Antisolvent (GAS) technique Supercritical anti solvent (SAS) technique Solution Solution Antisolvent SCF Antisolvent SCF Aerosol solvent extraction system (ASES) : G.S.N. Koteswara Rao Nov 11, 2008 Aerosol solvent extraction system (ASES) To produce microparticles Drug and polymer are to be dissolved / dispersed in an organic solvent and sprayed through a nozzle in to the column with supercritical gas phase. The organics miscible with the supercritical gas phase will be extracted resulting in the formation of solid microparticles. Solution enhanced dispersion with supercritical fluids (SEDS) : G.S.N. Koteswara Rao Nov 11, 2008 Solution enhanced dispersion with supercritical fluids (SEDS) This technique was developed at the University of Bradford to overcome some of the limitations of the RESS and GAS methods. The drug solution and the SCF are introduced simultaneously into the particle formation vessel using a co-axial nozzle arrangement. Causes rapid dispersion, mixing and extraction of the solvent by SCF leading to very high supersaturation resulting in precipitation. Parameters: Temperature, pressure, accurate metering of flow rates. Slide 26: G.S.N. Koteswara Rao Nov 11, 2008 Schematic representation of co-axial nozzles Slide 27: Schematic representation of SEDS SEM microphotographs of nicotinic acid : G.S.N. Koteswara Rao Nov 11, 2008 SEM microphotographs of nicotinic acid Raw sample Sample prepared by SEDS SEM microphotographs of lysozyme : G.S.N. Koteswara Rao Nov 11, 2008 Raw sample Sample prepared by SEDS SEM microphotographs of lysozyme Impregnation or infusion of polymers with bioactive materials using supercritical fluids : G.S.N. Koteswara Rao Nov 11, 2008 Impregnation or infusion of polymers with bioactive materials using supercritical fluids Swelling at high pressure and Impregnation E.g., polypropylene, polyethylene, ethylene-vinyl acetate co polymer and ethylene ethyl acrylate co polymer. When the pressure is reduced, the supercritical fluid is driven out slowly resulting in drug loaded polymer particles. To develop novel controlled release dosage forms To deposit thermo labile materials into polymers. E.g., Microcapsules of protein and peptide drugs Slide 31: G.S.N. Koteswara Rao Nov 11, 2008 Basic Info Strategies Techniques Applications Conclusion References Slide 32: G.S.N. Koteswara Rao Nov 11, 2008 Natural products, foods, pesticides, herbicides, surfactants, polymer additives, fuels, petroleum, explosives and propellants. Several reactions in different areas of biochemistry, polymer chemistry, biotechnology and environmental sciences. Food, Pharma and Material industries. Interdisciplinary SCFT Slide 33: Drug extraction and analysis Chromatography Particle generation Coating Polymer processing Reactions Drug polymorph engineering Preparation of drug delivery systems Purification and sterilization of medical components Concentrating nutraceuticals Recrystallize pharmaceuticals to nanosize Preparation of metal nanoparticles Current Pharmaceutical Applications Supercritical fluid extraction (SFE) : G.S.N. Koteswara Rao Nov 11, 2008 Supercritical fluid extraction (SFE) SCF is used as solvent in extraction process. E.g., SC-CO2. Apparatus: Extraction thimble, pump and collection trap. Supercritical fluid chromatography (SFC) : G.S.N. Koteswara Rao Nov 11, 2008 Supercritical fluid chromatography (SFC) Hybrid of HPLC and GLC with advantages of both. Most applicable to mixtures of organic compounds that are SFC is 10 times faster than HPLC and is used for both analytical and preparative purposes. Mobile phase: supercritical fluid thermally unstable not volatile enough to easily pass through gas chromatograph too high in molecular weight to be well resolved by HPLC Drug Delivery Applications : G.S.N. Koteswara Rao Nov 11, 2008 Drug Delivery Applications Microparticles and Nanoparticles Krukonis first used RESS process to prepare 5- to 100-µm sized particles of lovastatin, polyhydroxy-acids and naproxen using poly (lactic acid) (PLA) and SC- CO2. GAS process was used to produce clonidine-PLA microparticles using methylene chloride as solvent. Slide 37: G.S.N. Koteswara Rao Nov 11, 2008 Liposomes At laboratory scale, small liposomes encapsulating a solution of dextran, water-soluble compound using SC-CO2 as solvent for lipids. Uses 15 times less organic solvent to get the same encapsulation efficiency as conventional techniques. Critical fluid liposomes (CFL), encapsulating hydrophobic drugs, such as doxorubicin, vincristine and cisplatin were prepared. Stable paclitaxel liposomes with a size of 150 to 250 nm were also reported. Aphios Company prepared nanoencapsulation of paclitaxel (TaxosomesTM) and campothecin (CamposomesTM)) in aqueous liposome formulations. Slide 38: G.S.N. Koteswara Rao Nov 11, 2008 Inclusion complexes Piroxicam and ß-cyclodextrin (1:2.5) inclusion complexes. Solid Dispersions Preparation of solvent-free solid dispersions to enhance the solubility of poorly soluble compounds. Model drug: Carbamazepine with polyethylene glycol 4000 (PEG 4000) and acetone. Slide 39: G.S.N. Koteswara Rao Nov 11, 2008 Powders of Macromolecules Peptides, proteins and nucleic acids. SCFT was used to obtain fully active insulin particles of dimensions 1.5-500 µm. Plasmid DNA particles can also be prepared. Product Sterilization High-pressure SC-CO2 exhibits microbicidal activity by penetrating into the microbes, thereby lowering their internal pH to a lethal level. Slide 40: G.S.N. Koteswara Rao Nov 11, 2008 Coating Encapsulation of proteins (from 20 nm to 100 µm). Coating materials, such as lipids, biodegradable polyesters or polyanhydride polymers. Supercritical bio-catalyst Medium for crystallization Solubilization of pharmaceuticals Slide 41: G.S.N. Koteswara Rao Nov 11, 2008 Polymer processing Conventional methods are very difficult to produce polymers with narrow molecular weight distributions. Difficulties: Low vapor pressure and similar solubility values. Solubility of polymers varies with molecular weight or chain length. Separation of polymers from multi component mixtures. Principle: By varying the solubility parameter of super critical fluids based on density. Slide 42: G.S.N. Koteswara Rao Nov 11, 2008 Reactions The SCF will act either as solvent or as one of the reactants. The solvent properties of supercritical fluids can be economically exploited in chemical reactions by: Enhancing the solubility of components and catalysts Influencing the kinetic rates Shifting the equilibrium constants to favour desired products Removal of contaminants Separation and recovery of different reaction products Slide 43: G.S.N. Koteswara Rao Nov 11, 2008 Extraction And Purification Caffeine production, oil from nut-meg seeds, capsaicin from chilies, extraction of steroids and alkaloids from plant sources and extraction of chemicals from the soil & Isolation of Taxol from the bark of the Taxus brevifolia. Extraction of statins, natural products and production of fat free products. Separation of impurities mainly organic complexes from the pharmaceuticals. Chiral separations. Recovery of organic solvents from a mixture. Slide 44: G.S.N. Koteswara Rao Nov 11, 2008 Micronization Pharmaceuticals, biologicals and polymers. RESS technique for dugs soluble in SCF E.g., Estradiol Phenacetin Antisolvent technique for drugs insoluble in SCF E.g., Insulin Lysozyme Trypsin Methylprednisolone Hydrocortisone acetate Exploitation : G.S.N. Koteswara Rao Nov 11, 2008 Exploitation Nektar Therapeutics Solution Enhanced Dispersion by Supercritical fluids offer commercial benefits such as high yield and consistency.    Nektar Particle Engineering - designs precise drug particles and optimizes delivery using expertise in supercritical fluid technology. Slide 46: G.S.N. Koteswara Rao Nov 11, 2008 Slide 47: G.S.N. Koteswara Rao Nov 11, 2008 Basic Info Strategies Techniques Applications Conclusion References Slide 48: G.S.N. Koteswara Rao Nov 11, 2008 Supercritical fluids offer exciting opportunities to produce and modify pharmaceutical substances. In this respect, this innovative technology will help in meeting more stringent requirements of regulatory authorities in terms of solid-state characterization, purity and environmental acceptability. Supercritical fluids can be considered in a prominent way in the development processes of drug products for the 21st century. CONCLUSION Slide 49: G.S.N. Koteswara Rao Nov 11, 2008 Basic Info Strategies Techniques Applications Conclusion References REFERENCES : G.S.N. Koteswara Rao Nov 11, 2008 REFERENCES Andrian Tandya a, Raffaella Mammucaria, Dense gas processing of polymeric controlled release formulations. Int. Jour. of Pharm. 2007; 328, 1-11. Kompella UB, Koushik K. Preparation of drug delivery systems using supercritical fluid technology. Crit Rev Therapeut Drug Car Sys. 2007; 18(2): 173-199. Van Hees T, Piel G, Evrard B, Otte X, Thunus T, Delattre L. Application of supercritical carbon dioxide for the preparation of a piroxicam-beta-cyclodextrin inclusion compound. Pharm Res. 2003; 16(12): 1864-1870. Peter York. Strategies for particle design using supercritical fluid technologies. Research Focus PSTT. 2001; 2(11): 430-440. True L. Rogers, Keith P. Johnston. Solution base particle formation of pharmaceutical powders by SC-CO2. DDIP. 2001; 27(10):1003-1015. Frederiksen L, Anton K, Hoogevest PV, Keller HR, Leuenberger H. Preparation of liposomes encapsulating water-soluble compounds using supercritical carbon dioxide. J Pharm Sci. 2000; 86(8): 921-928. www.pharmainfo.net

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