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1 In the name of God Particle design using supercritical fluids Supervisor : Dr. Ghaziaskar By: M. Amirabadi By: M. Amirabadi

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2 content Presentation of Supercritical Fluids Reasons of using Supercritical Fluids Processes of Supercritical Fluid producing micro and nano-particles Applications of these processes Conclusion References

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3 Supercritical fluid A substance At temperatures and pressures above its critical temperature and pressure ( its critical point ) is called a supercritical fluid.

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4 Why are we using supercritical fluids ?

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5 Properties of some supercritical fluids CompoundT c ( o C)P c (atm) CO 2 31.772.9 H2OH2O 374.1218.3 NH 3 132.5112.5 Butane(C 4 H 10 ) 15237.5 Freon13(CCLF 3 ) 28.838.2 Acetone(C 3 H 6 O) 235.547 Hexan(C 6 H 14 ) 234.229.9

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6 Why is CO 2 the most commonly used solvent ? It is easy to attain critical conditions of CO2 Inexpensive Nontoxic Non-flamable Providing CO2 in high purity is easy

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7 Particle design in supercritical media

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8 advantages of particle design using supercritical technology to conventional methods Supercritical technology Produces very small particles (micro & nano) Produces narrow particle size distribution (PSD) Separation of fluid from particles is done easily Reduces wastes

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9 Supercritical fluid methods for particle design RESS (Rapid Expansion of Supercritical Solutions) SAS/GAS (Supercritical fluid Anti-Solvent PGSS (Particles from Gas- Saturated Solutions (or Suspensions) DELOS (Depressurization of an Expanded Liquid Solution)

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10 RESS (Rapid expansion of Supercritical Solutions)

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11 Morphology of particles Material structure Crystalline or amorphose Composite or pure RESS parameters Temperature Pressure drop Distance of impact of the jet against the surface Dimensions of the atomization vessel Nozzle geometry

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12 Advantages of RESS Producing solvent free products With no residual trace of solvent, particles are suitable for therapeutic scopes It can be used for heat labile drugs because of low critical temperature It needs simple equipment and it is cheap Produced particles requires no post processing

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13 Key limitations of RESS substrate should be soluble in CO 2 Co-solvent can be used for insoluble substrates but elimination of co-solvent is not easy and cheap

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14 Liquid anti-solvent process There are two liquid solvents (A&B) Solvents are miscible Solute is soluble in A &not soluble in B Addition of B to the solution of solute in A causes precipitation of solute in microparticle

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15 Supercritical fluid anti- solvent Solute is dissolved in a solvent Solute is not soluble in supercritical fluid Supercritical fluid (anti-solvent) is introduced in solvent Supercritical fluid expands the solution and decreases solvent power Solute precipitates in the form of micro or nano particle

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16 Advantages of supercritical fluid antisolvent to liquid antisolvent Separation of antisolvent is easy SAS is faster because of high diffusion rate of supercritical fluid SAS can produce smaller particles In SAS particle size distribution is possible

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17 The solute is recrystallized in 3 ways SAS/GAS (supercritical anti- solvent or gas anti-solvent) ASES (aerosol solvent extraction system) SEDS (solution enhanced dispersion by supercritical fluid)

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18 SAS/GAS (Supercritical Anti-Solvent)

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19 ASES (Aerosol Solvent Extraction System )

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20 SEDS (Solution Enhanced Dispersion by Supercritical Fluids )

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21 Experiments are carried out in three scales Laboratorial scale Pilot scale Plant scale

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22 Supercritical antisolvent fractionation of Propolis in pilot scale Propolis has applications in medicine,hygiene and beauty

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23 Flavonoids Essential oil Separation with extraction High molecular mass components Separation with SAS Components of propolis

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24 Schematic of pilot scale propolis extraction/fractionation plant

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25 Crystal formation of BaCl 2 and NH 4 Cl using a supercritical fluid antisolvent SAS process has been used to produce crystals of BaCl 2 and NH 4 Cl from solutions of dimethyl sulfoxide (DMSO)

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27 Parameters that affect on crystallization of BaCl 2 & NH 4 Cl Injection rate of CO 2 Initial chloride concentration in DMSO Temperature

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28 Instruments used for determining particle properties Morphology Scanning electron microscope (SEM) Composition Energy dispersive X-Ray spectrometer (EDS) Internal structure X-Ray diffractometer (XRD) Particle size Image size of SEM photomicrographs

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29 Crystal habit of BaCl 2 Slow injection rate of CO 2 Cubic shaped crystals (Equant habit)Equant habit Rapid injection rate of CO 2 Needle-like crystals (Acicular habit)Acicular habit The variation in crystal habit result from the alteration of the relative growth rate of crystal faces

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32 Crystal habit of NH 4 CL Slow injection rate of CO 2 Equant Rapid injection rate of CO 2 tabular tabular

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35 Internal structure of BaCl 2 Unprocessed particles (Orthorhombic space lattice) Processed particles (Hexagonal space lattice)

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36 Internal structure of NH 4 Cl Unprocessed particles (Cubic) Processed particles (Cubic) Cubic space lattic is the only possible crystal system for NH 4 Cl

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37 Crystal size & composition Crystal size The slower injection rate of CO 2,the larger crystal size Crystal composition Composition of crystals did not changed after processing by CO 2

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38 Separation of BaCl 2 & NH 4 Cl mixtures in DMSO The SAS process enables the separation of multicomponent mixtures if the nucleation of each component occurs at different pressures

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39 SAS has used in following applications Explosives and propellants Polymers and biopolymers Pharmaceutical principles Coloring matter, catalysts, superconductors and inorganic compounds

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40 Explosives and propellants Small particles of these compound improves the combustion process Attainment of the highest energy from the detonation depends on particle size

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41 Polymers and biopolymers Polymer microspheres can be used as: Stationary phases in chromatography Adsorbents Catalyst supports Drug delivery system

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42 Pharmaceutical principles Increasing bio-availability of poorly-soluble molecules Designing formulations for sustained-release Substitution of injection delivery by less invasive methods, like pulmonary delivery

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43 Coloring matter, catalysts, superconductors and inorganic compounds Color strength is enhanced if dying matter is in the form of micro particles Catalysts in the form of nanoparticles have excellent activity because of large surface areas

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44 RESS & SAS Regarding the materials RESS & SAS are complementary RESS Compound is soluble in CO 2 SAS Compound is insoluble in CO 2

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45 Conclusion

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46 Rapid expansion of supercritical fluid (RESS) CO 2 is reached to the desired pressure and temperature In extraction unit solute(s) is dissolved in CO2 In precipitation unit solution is depressurized Solubility of CO 2 is decreased and solute(s) precipitates in the form of very small particle or fibers and films

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47 SAS/GAS(supercritical anti-solvent) In this method a batch of solution is expanded by mixing with supercritical fluid

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48 ASES (aerosol solvent extraction system) This method involves spraying the solution through an atomization nozzle as fine droplets into compressed carbon dioxide

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49 SEDS (solution enhanced dispersion by supercritical fluids) In this method a nozzle with tow coaxial passages allows to introduce the supercritical fluid and a solution of active substance(s) into the vessel

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50 Steps of fractionation of Propolis CO2 is supplied from cylinders. Solution of Propolis in Ethanol is in storage tank1. Propolis solution and CO2 are mixed before precipitation chamber EX1. In EX1 the Propolis solution becomes supersaturate and high molecular mass components precipitate. CO2 and Propolis solution will furture face two pressure drop. In SV1 flavonoids precipitate. In SV3 essential oil and ethanol precipitate.

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51 Morphology of particles Material structure Crystalline or amorphose Composite or pure RESS parameters Temperature Pressure drop Distance of impact of the jet against the surface Dimensions of the atomization vessel Nozzle geometry