Transcript Nanopowder Production and Characteristics Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph.

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: [email protected]
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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)
1.
2.
3.
4.
5.
6.
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 antisolvent 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 cosolvent 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
i. Surface area
ii. Surface charge
iii. Zeta potential
iv. Surface coating composition
v. Surface coating coverage
vi. Surface reactivity
vii.Surface-core interaction
viii.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
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.
ii.
iii.
iv.
Drug loading
Drug potency/functionality
In vitro release (detection)
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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Instruments for Nanocharacterstics
AAS
AFM
BET
CHDF
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AUC
DLS
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Instruments for Nanocharacterstics
DMA(1)
DMA(2)
ESA
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DSC
FFF
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Instruments for Nanocharacterstics
FTIR
HPLC
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GE
ICP-MS
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GPC
ITC
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Instruments for Nanocharacterstics
LDE
PALS
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MS
RS
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NMR
SEM
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Instruments for Nanocharacterstics
SLS
SMA
TGA
UV-Vis
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SPM
XDC
TEM
XPS
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XRD
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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 YOU
Cell No: 0091-9742431000
E-mail: [email protected]
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