Nanopowder Production and Characteristics
Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
Department of PharmaceuticsKLE University College of Pharmacy
BELGAUM-590010Cell No: 0091-9742431000
E-mail: [email protected]
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• Nanotechnology may be defined as the ability to work at the molecular level, atom by atom, to create large structure with fundamentally new molecular organization.
• Many pharmaceutical companies are performing research to decline the particle size.
• If drugs were able to have smaller particle size they would be better absorbed by digestive tract lining therefore the amount necessary would be reduced making medicines more affordable.
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Nanotechnology
Manufacturing Methods
• Several mechanically or chemically based methods are currently in use to manufacture nanomaterials.
• Major mechanical methods include ball milling, laser ablation, etching, sputtering, sonification and electroexplosion.
• Major chemical methods include chemical vapor deposition (CVD), sol-gel processing and molecular pyrolysis.
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What is a Nanopowder
• Nanopowder is a material fabricated on the nanoscale with grain and feature sizes typically under 100 nanometres.
• The basis of nanotechnology is the ability to form nano-sized particles, for example nanopowders, which are solid particles that measure on the nanoscale.
• Nanopowders have been of extreme interest in the pharmaceutical field.
• Drug delivery has been impacted in several ways due to the advances in nanopowder technology.
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Production of Nanopowder
• Conventional Methods - Milling, grinding, jet milling, crushing, and air micronization
• Super Critical Fluids (SCF)1. Rapid Expansion of Supercritical Solutions (RESS)
2. Supercritical Anti-Solvent (SAS)
3. Aerosol Solvent Extraction System (ASES)
4. Solution Enhanced Dispersion by Supercritical fluids (SEDS)
5. Particles from Gas Saturated Solutions (PGSS)
6. Depressurization of Expanded Liquid Organic Solution (DELOS)
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Conventional Methods• Conventional methods of particle size reduction include
milling, grinding, jet milling, crushing, and air micronization.
• CM might not accomplish the desired amount of particle size reduction.
• CM drawback is associated with the physical and chemical properties of the materials undergoing size reduction.
• Certain compounds are chemically sensitive or thermo-liable, such as explosives, chemical intermediates, or pharmaceuticals which can not be processed using conventional methods due to the physical effects of these methods.
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Super Critical Fluid
• A SCF is defined as a substance above its critical temperature (T) and critical pressure (P).
• The critical point represents the highest temperature and pressure at which the substance can exist as a vapor and liquid in equilibrium.
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• Rapid Expansion of Supercritical Solutions (RESS) is a crystallization technique that uses the properties of a supercritical fluid, typically CO2, as a solvent to facilitate nanopowder production.
• The RESS process is described in two steps: solubilization and particle formation.
• The driving force for this process is caused by the rapid depressurization of the supercritical fluid dissolved with the solute of interest through a nozzle to cause fast nucleation and fine particle generation
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Rapid Expansion of Supercritical Solutions (RESS)
Supercritical Anti-Solvent
• The Supercritical Anti-Solvent process (SAS) uses solvent/anti-solvent binary systems to induce the formation of nano and micro-size particles.
• The supercritical fluid (i.e. CO2) acts as an anti-solvent that causes the crystallization of the solute.
• The main driving force for this process is the droplet formation, which is caused by the solvent/anti-solvent interaction.
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• ASES method involves spraying the solution as fine droplets into the supercritical fluid.
• The dissolution of the supercritical fluid is followed by a large volume expansion, which is called the anti-solvent effect.
• This cause a reduction in the liquid solvating power and a sharp increase in the supersaturated within the liquid mixture, which leads to small and uniform particles
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Aerosol Solvent Extraction System (ASES)
• SEDS method was developed to achieve smaller droplet size and intense mixing of supercritical fluid and solution for increased mass transfer rates.
• The supercritical fluid is used for its chemical properties and as a ‘spray enhancer’ by mechanical effects.
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Solution Enhanced Dispersion System(SEDS)
Particle From gas Saturated Solution (PGSS)
• The Particle from Gas Saturated Solution (PGSS) process uses a SCF, usually CO2, as a solute to crystallize a solution.
• The PGSS process can be used to create micro and nano sized particles with the ability to control particle size distribution.
• The driving force of the PGSS is a sudden temperature drop of the solution below the melting point of the solvent.
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Particle From gas Saturated Solution (PGSS)
• This occurs as the solution is expanded from a working pressure to atmospheric conditions due to the Joule-Thompson effect.
• The rapid cooling produces amorphous powder which is mainly used in pharmaceutical industries.
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Depressurization of an Expanded Liquid Organic Solution (DELOS)
• Depressurization of an expanded liquid organic solution (DELOS) is a process that uses a supercritical fluid, as a co-solvent for the formation of micro and nano- sized particles.
• DELOS process is best for organic solutes in organic solvents and it is particularly useful for pharmaceuticals, dyes, and polymers, where conventional methods of particle size reduction tend to be ineffective due to physical and chemical limitations
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Applications of Nanopowders
• Nanopowder has many applications in different fields • Ceramics used in nano sized powders are more ductile at
elevated temperatures compared to coarse grained ceramics and can be sintered at low temperatures
• Nano sized powders of iron and copper have hardness about 4-6 times higher than the bulk materials because bulk materials have dislocations.
• Nano sized copper and silver are used in conducting ink and polymers
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• Nano powder has various applications in the pharmaceutical and medical field.
• Drug delivery has impacted by the advancement in nano powders smaller particles are able to be delivered in new ways to patients, through solutions, oral or injected, and aerosol, inhaler or respirator.
• New production processes allow for encapsulation of pharmaceuticals which allow for drug delivery where needed with in the body.
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Applications of Nanopowders
Nanopowder Characteristics
1. Morphology
2. Surface
3. Chemical
4. Other
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1. MORPHOLOGY
i. Size (Primary particle)
ii. Size (Primary/aggregate/agglomerate)
iii. Size distribution
iv. Molecular weight
v. Structure/Shape
vi. Structure/Shape(3D structure)
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i. Size (Primary particle)
a. TEM – Transmission electron microscopy
b. SEM – Scanning electron microscopy
c. AFM – Atomic absorption spectroscopy
d. XRD – X-ray diffraction
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ii. Size (primary/aggregate/agglomerate)a. TEM – Transmission electron microscopy
b. SEM – Scanning electron microscopy
c. AFM – Atomic force microscopy
d. DLS – Dynamic light scattering
e. FFF – Field flow fractionation
f. AUC – Analytical ultracentrifugation
g. CHDF – Capillary hydrodynamic fractionation
h. XDC – X-ray disk centrifuge
i. HPLC – High performance liquid chromatography
j. DMA(1) – Differential mobility analyzer
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iii. Size distribution
a. TEM – Transmission electron microscopy
b. SEM – Scanning electron microscopy
c. AFM – Atomic force microscopy
d. DLS – Dynamic light scattering
e. AUC – Analytical ultracentrifugation
f. FFF – Field flow fractionation
g. HPLC – High performance liquid chromatography
h. SMA – Scanning mobility particle sizer
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iv. Molecular weight
a. SLS – Static light scattering
b. AUC – Analytical ultracentrifugation
c. GPC – Gel permeation chromatography
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v. Structure Shape
a. TEM – Transmission electron microscopy
b. SEM – Scanning electron microscopy
c. AFM – Atomic force microscopy
d. NMR – Nuclear magnetic resonance
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vi. Stability (3D structure)
a. DLS – Dynamic light scattering
b. AUC – Analytical ultracentrifugation
c. FFF – Field flow fractionation
d. SEM – Scanning electron microscopy
e. TEM – Transmission electron microscopy
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2. SURFACE
i. Surface area
ii. Surface charge
iii. Zeta potential
iv. Surface coating composition
v. Surface coating coverage
vi. Surface reactivity
vii.Surface-core interaction
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i. Surface area
a. BET – Brunauer, Emmett, and Teller method
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ii. Surface charge
a. SPM – Surface probe microscopy (AFM, STM, NSOM/SNOM, etc)
b. GE – Gel electrophoresis
c. Titration methods -
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iii. Zeta potential
a. LDE – Laser doppler electrophoresis
b. ESA – Electroacoustic spectroscopy
c. PALS – Phase analysis light scattering
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iv. Surface coating composition
a. SPM – Surface probe microscopy (AFM, STM, NSOM/SNOM, etc.)
b. XPS – X-ray disk centrifuge
c. MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.)
d. RS – Raman spectroscopy
e. FTIR – Fourier transform infrared spectroscopy
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v. Surface coating coverage
a. AFM – Atomic force microscopy
b. AUC – Analytical ultracentrifugation
c. TGA – Thermal gravimetric analysis
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vi. Surface reactivity
a. Varies with nanomaterial
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vii. Surface-core interaction
a. SPM – Surface probe microscopy (AFM, STM, NSOM, etc. )
b. RS – Raman spectroscopy
c. ITC – Isothermal titration calorimetry
d. AUC – Analytical ultracentrifugation
e. GE – Gel electrophoresis
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viii. Topology
a. SEM – Scanning electron microscopy
b. SPM – Surface probe microscopy (AFM, STM, NSOM/SNOM, etc.)
c. MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.)
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3. CHEMICAL
i. Chemical composition (core, surface)
ii. Purity
iii. Stability (chemical)
iv. Solubility (chemical)
v. Structure (chemical)
vi. Crystallinity
vii.Catalytical activity
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i. Chemical composition (core, surface)
a. XPS – X-ray photoelectron spectroscopy
b. MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.)
c. AAS – Atomic absorption spectroscopy
d. ICP-MS – Inductively coupled plasma mass spectrometry
e. RS – Raman spectroscopy
f. FTIR – Fourier transform infrared spectroscopy
g. NMR – Nuclear magnetic resonance
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ii. Purity
a. ICP-MS - Inductively coupled plasma mass spectrometry
b. AAS – Atomic absorption spectroscopy
c. AUC – Analytical ultracentrifugation
d. HPLC – High performance liquid chromatography
e. DSC – Differential scanning calorimetry
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iii. Stability (chemical)
a. MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.)
b. HPLC – High performance liquid chromatography
c. RS – Raman spectroscopy
d. FTIR – Fourier transform infrared spectoscopy
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iv. Solubility (chemical)
a. Varies with nanomaterial
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v. Structure (chemical)
a. NMR – Nuclear magnetic resonance
b. XRD – X-ray diffraction
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vi. Crystallinity
a. XRD - X-ray diffraction
b. DSC – Differential scanning calorimetry
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viii. Catalytic activity
• Varies with nanomaterial
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4. OTHER
i. Drug loading
ii. Drug potency/functionality
iii. In vitro release (detection)
iv. Deformability
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i. Drug loading
a. MS – mass spectrometry (GCMS, TOFMS, SIMS, etc.)
b. HPLC – High performance liquid chromatography
c. UV-Vis – Ultraviolet-visible spectrometry
d. Varies with nanomaterial
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ii. Drug potency/functionality
a. Varies with nanomaterial
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iii. In vitro release (detection)
a. UV-Vis - Ultraviolet-visible spectrometry
b. MS – Mass spectrometry (GCMS, TOFMS, SIMS, etc.)
c. HPLC – High performance liquid chromatography
d. Varies with nonmaterial
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iv. Deformability
a. AFM – Atomic force microscopy
b. DMA(2) – Dynamic mechanical analyzer
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AAS AFM AUC
BET CHDF DLS
Instruments for Nanocharacterstics
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DMA(1) DMA(2) DSC
ESA FFF
Instruments for Nanocharacterstics
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FTIR GE GPC
HPLC ICP-MS ITC
Instruments for Nanocharacterstics
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LDE MS NMR
PALS SEMRS
Instruments for Nanocharacterstics
Instruments for Nanocharacterstics
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SLS SMA SPM TEM
TGA UV-Vis XDC XPS XRD
RESS PGSS DELOS
Application Small Mol High purity Large Mol
Role of SCF Solvent Solute Co Solvent
Driving force Pressure Temperature Temperature
Working pressure Dependence SCF Morphology SCF
Working temperature dependence SCF Highest SCF
Length of procedure 2 Steps 2 Steps 3 Steps
Particle size Micro & Nano
Micro & Nano
Micro & Nano
Encapsulation Yes Yes Yes
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Conclusion
THANK YOUCell No: 0091-9742431000
E-mail: [email protected]
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