Nanopowder Production and Characteristics

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Nanopowder Production and Characteristics

• Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
• Department of Pharmaceutics
• KLE University College of Pharmacy
• BELGAUM-590010
• Cell No 0091-9742431000
• E-mail nanjwadebk_at_gmail.com

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Nanotechnology
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Nanotechnology

• 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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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)
• Rapid Expansion of Supercritical Solutions (RESS)
• Supercritical Anti-Solvent (SAS)
• Aerosol Solvent Extraction System (ASES)
• Solution Enhanced Dispersion by Supercritical
  fluids (SEDS)
• Particles from Gas Saturated Solutions (PGSS)
• 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)

• 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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Schematic of RESS Process
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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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Schematic of SAS Process
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Aerosol Solvent Extraction System (ASES)

• 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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Schematic of ASES Process
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Solution Enhanced Dispersion System(SEDS)

• 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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Schematic of SEDS Process
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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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Schematic of PGSS Process
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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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Schematic of DELOS Process
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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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Applications of Nanopowders

• 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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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

1. Surface area
2. Surface charge
3. Zeta potential
4. Surface coating composition
5. Surface coating coverage
6. Surface reactivity
7. Surface-core interaction
8. Topology

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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
• f. NMR Nuclear magnetic resonance

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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

1. Chemical composition (core, surface)
2. Purity
3. Stability (chemical)
4. Solubility (chemical)
5. Structure (chemical)
6. Crystallinity
7. 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

1. ICP-MS - Inductively coupled plasma mass
   spectrometry
2. AAS Atomic absorption spectroscopy
3. AUC Analytical ultracentrifugation
4. HPLC High performance liquid chromatography
5. DSC Differential scanning calorimetry

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iii. Stability (chemical)

1. MS Mass spectrometry (GCMS, TOFMS, SIMS, etc.)
2. HPLC High performance liquid chromatography
3. RS Raman spectroscopy
4. FTIR Fourier transform infrared spectoscopy

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iv. Solubility (chemical)

• a. Varies with nanomaterial

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v. Structure (chemical)

1. NMR Nuclear magnetic resonance
2. XRD X-ray diffraction

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vi. Crystallinity

1. XRD - X-ray diffraction
2. DSC Differential scanning calorimetry

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viii. Catalytic activity

• Varies with nanomaterial

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4. OTHER

1. Drug loading
2. Drug potency/functionality
3. In vitro release (detection)
4. Deformability

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i. Drug loading

1. MS mass spectrometry (GCMS, TOFMS, SIMS, etc.)
2. HPLC High performance liquid chromatography
3. UV-Vis Ultraviolet-visible spectrometry
4. Varies with nanomaterial

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ii. Drug potency/functionality

• a. Varies with nanomaterial

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iii. In vitro release (detection)

1. UV-Vis - Ultraviolet-visible spectrometry
2. MS Mass spectrometry (GCMS, TOFMS, SIMS, etc.)
3. HPLC High performance liquid chromatography
4. Varies with nonmaterial

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iv. Deformability

1. AFM Atomic force microscopy
2. DMA(2) Dynamic mechanical analyzer

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Instruments for Nanocharacterstics
AAS
AFM
AUC
CHDF
DLS
BET
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Instruments for Nanocharacterstics
DMA(1)
DMA(2)
DSC
ESA
FFF
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Instruments for Nanocharacterstics
FTIR
GE
GPC
ITC
HPLC
ICP-MS
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Instruments for Nanocharacterstics
LDE
MS
NMR
SEM
PALS
RS
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Instruments for Nanocharacterstics
SLS
SMA
SPM
TEM
UV-Vis
XDC
XPS
XRD
TGA
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Conclusion
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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THANK YOUCell No 0091-9742431000E-mail
nanjwadebk_at_gmail.com