Pore Structure Analysis of Advanced Pharmaceutical Products

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Pore Structure Analysis of Advanced
Pharmaceutical Products

• Dr. Akshaya Jena and Dr. Krishna
• Porous Materials, Inc.
• 83 Brown Road, Ithaca, NY 14850

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Topics

• Importance of Porosity in Advanced Pharmaceutical
  Products
• Inadequacy of Mercury Intrusion Porosimetry
• Two novel techniques
• Results and Discussion
• Summary and Conclusion

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Importance of Porosity in Advanced Pharmaceutical
Products

• Advanced pharmaceutical products
• Examples
• Artificial skin
• Blood clotting material
• Dialysis membrane
• Blood delivery system
• Hydrogels
• Tissue culture substrates
• And many more

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• Performance and efficiency of such products
• ?
• Pore characteristics

• Important characteristics
• Constricted pore diameter ? Barrier
  properties
• The largest pore diameter ? Barrier
  properties
• Mean pore diameter ? Barrier flow

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• Performance and efficiency of such products
• ?
• Pore characteristics
• Important characteristics
• Constricted pore diameter ? Barrier
  properties
• The largest pore diameter ? Barrier
  properties
• Mean pore diameter ? Barrier flow

• Pore distribution ? Barrier flow

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• Performance and efficiency of such products
• ?
• Pore characteristics
• Important characteristics
• Constricted pore diameter ? Barrier properties
• The largest pore diameter ? Barrier
  properties
• Mean pore diameter ? Barrier flow
• Pore distribution ? Barrier flow

• Pore volume ? Holding capacity

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• Performance and efficiency of such products
• ?
• Pore characteristics
• Important characteristics
• Constricted pore diameter ? Barrier properties
• The largest pore diameter ? Barrier properties
• Mean pore diameter ? Barrier flow
• Pore distribution ? Barrier flow
• Pore volume ? Holding capacity

• Permeability ? Rate of the process

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• Performance and efficiency of such products
• ?
• Pore characteristics
• Important characteristics
• Constricted pore diameter ? Barrier properties
• The largest pore diameter ? Barrier
  properties Mean pore diameter ? Barrier flow
• Pore distribution ? Barrier flow
• Pore volume ? Holding capacity
• Permeability ? Rate of the process

• Need for reliable, accurate and safe techniques

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Inadequacy of Mercury Intrusion Porosimetry

• Mercury intrusion porosimetry often used for pore
  structure analysis

Principle of mercury intrusion porosimetry
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• Mercury is forced in to pores

• Intrusion volume gives pore volume
• Pressure yields pore size, D
• D - 4g cos q /p
• g surface tension of Hgq contact angle of
  HgP differential pressure

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• It cannot measure

• Constricted pore diameter
• The largest pore diameter
• Permeability
• High pressure used in this technique can damage
  pore structure of the delicate products
• Uses toxic mercury, creates health hazards,
  pollutes environment, and makes samples unusable

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Novel Techniques

• Capillary Flow Porometery
• Pores of sample spontaneously filled with wetting
  liquid
• Pressurized gas is used to remove liquid from
  pores to allow gas flow

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• Pressure yields pore diameter, D

• D 4 g cos q/p
• g surface tension of wetting liquidq
  contact angle of wetting liquid P differential
  pressure
• Pressure and flow rates through wet and dry
  samples are used to compute properties
• The PMI Capillary Flow Porometer used in this
  investigation

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• The PMI Capillary Flow Porometer

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Liquid Extrusion Porosimetry

• Sample is placed on a membrane whose largest pore
  size is smaller than the smallest in the sample

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Liquid Extrusion Porosimetry

• Pores of sample and membrane are filled with a
  wetting liquid

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Liquid Extrusion Porosimetry

• Pressurized gas is used to displace liquid from
  pores without the membrane and with membrane
  under the sample

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• Pressure yields pore diameter

• D 4 g cos q/p
• D pore diameterg surface tension of wetting
  liquid q contact angle of wetting liquidP
  differential pressure
• Volume of displaced liquid gives pore volume
  permeability

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• The PMI Liquid Extrusion Porosimeter used in this
  investigation

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Advantages

• All required properties measurable
• Use of low pressure-Samples not damaged
• No toxic materials use
• -no health hazard
• -no environmental pollution
• -no sample contamination

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Results and Discussion

• Dialysis membranes
• Requirements
• Primary function-Filtration
• Important characteristics
• The largest pore diameter
• Mean pore diameter
• Pore distribution
• Flow rate

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Capillary Flow Porometery

• Flow rate vs Differential pressure for dry and
  wet samples

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• Pore diameter ? from measured pressures

• The largest pore diameter ? from pressure
  for flow initiation
  ? 1.023 mm
• Mean flow pore diameter ? from mean flow
  pressure ? 0.458 mm

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• Pore distribution

• Normalized pore distribution function vs. pore
  diameter

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• Pore distribution

• In any pore size range ? area flow through
  pores in the range

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• Pore distribution

• Almost 80 flow ? through 0.2 0.7 mm pores

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• Permeability

• Dry curve yields gas permeability
• Liquid permeability measurable using attachments

• Mercury Intrusion Porosimetry Cannot measure any
  of the these properties

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Conclusion

• All required properties including very small pore
  diameters were measured by capillary flow
  porometry, although mercury intrusion technique
  could not measure any of the properties.
• Pressures required was only about 50 psi
• No toxic material was used
• Capillary flow porometry was the appropriate
  technique

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Artificial skin

• Requirements
• Primary function-allow growth of blood vessels
  and be breathable
• Pores are much larger than the pore providing
  barrier properties
• Pore size distribution are in the range for
  blood vessels to grow
• Adequate gas and vapor permeability to be
  breathable.

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Capillary Flow Porometry

• Flow rate vs Differential pressure for dry and
  wet samples

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• Pore diameter ? from measured pressures

• The largest pore diameter ? from pressure
  for flow initiation ? 74.932
  mm
• Mean flow pore diameter ? from mean flow
  pressure ? 31.489 mm

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• Pore distribution

Normalized pore distribution function vs pore
diameter

• A broad pore range
• Uniform distribution

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• Permeability

• Appreciable gas permeation shown by dry curve

• Flow through dry curve as a function of
  differential pressure

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• Mercury Intrusion Porosimetery Cannot measure any
  of the these properties

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Conclusion

• Large constricted pore diameters, broad
  distribution and permeability were measured by
  capillary flow poromerty, although mercury
  intrusion technique could not measure any of
  these properties.
• Pressures required was only about 3 psi
• No toxic material was used
• Capillary flow porometry was the appropriate
  technique

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Hydrogels

• Requirements
• Primary applications
• Dressings
• Wound gels
• Burn dressings
• Electrodes
• Skin disorders treatments
• Carriers for hormones and drugs
• Drug delivery implants

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Hydrogels

• Requirements
• Properties
• Pore volumes ? liquid holding capacity
• Pore size distribution ? flow rates
  barrier
  property
• Liquid permeability ? rate of the process

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Hydrogels

• Requirements
• Properties
• Pore volumes ? liquid holding capacity
• Pore size distribution ? flow rates
  barrier
  property
• Liquid permeability ? rate of the process

• Mercury Intrusion Porosimetry In Appropriate
• Hydrogels retain their integrity only in water
• Therefore, mercury intrusion extrusion
  porosimetry can be used

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Hydrogels

• Requirements
• Properties
• Pore volumes ? liquid holding capacity
• Pore size distribution ? flow rates
  barrier
  property
• Liquid permeability ? rate of the process
• Mercury Intrusion Porosimetry in Appropriate
• Hydrogels retain their integrity only in water
• Therefore, mercury intrusion extrusion
  porosimetry can be used

• Liquid extrusion Porosimetry
• Water extrusion porosimetry appropriate

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Pore volume of hydrogel

• Pore volume
• Total pore volume ? 0.421 cm 3/g
• Porosity ? 67.12
• Pressure only about 5 psi

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• Pore volume distribution

• Pore distribution of hydrogel
• For a given range Area pore volume
• Pores have a narrow range ? 5-20 mm

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• Liquid permeability

• The flow rate yields liquid permeability

• Typical plot of flow rate of water vs pressure

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Summary and Conclusion

• 1. Two novel techniques discussed. Capillary
  flow porometry Liquid extrusion porosimetry
• 2. These techniques measured constricted pore
  diameter, the largest pore diameter, mean flow
  pore diameter, flow distribution, pore volume,
  pore volume distribution, liquid permeability and
  gas permeability.

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Summary and Conclusion

• 1. Two novel techniques discussed. Capillary
  flow porometry Liquid extrusion porosimetry
• 2. These techniques measured constricted pore
  diameter, the largest pore diameter, mean flow
  pore diameter, flow distribution, pore volume,
  pore volume distribution, liquid permeability and
  gas permeability.

3. These techniques used low pressures so that
sample damage was minimized.
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Summary and Conclusion

• 1. Two novel techniques discussed. Capillary
  flow porometry Liquid extrusion porosimetry
• 2. These techniques measured constricted pore
  diameter, the largest pore diameter, mean flow
  pore diameter, flow distribution, pore volume,
  pore volume distribution, liquid permeability and
  gas permeability.
• 3. These techniques used low pressures so that
  sample damage was minimized.

4. No toxic and harmful material was used.
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Summary and Conclusion

• 1. Two novel techniques discussed. Capillary
  flow porometry Liquid extrusion porosimetry
• 2. These techniques measured constricted pore
  diameter, the largest pore diameter, mean flow
  pore diameter, flow distribution, pore volume,
  pore volume distribution, liquid permeability and
  gas permeability.
• 3. These techniques used low pressures so that
  sample damage was minimized.
• 4. No toxic and harmful material was used.

5. Products like hydrogels, which retain their
integrity in only certain liquid environments,
could be tested.
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Summary and Conclusion

• 2. These techniques measured constricted pore
  diameter, the largest pore diameter, mean flow
  pore diameter, flow distribution, pore volume,
  pore volume distribution, liquid permeability and
  gas permeability.
• 3. These techniques used low pressures so that
  sample damage was minimized.
• 4. No toxic and harmful material was used.
• 5. Products like hydrogels, which retain their
  integrity in only certain liquid environments,
  could be tested.

6. Mercury intrusion could not used for such
measurements.
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Thank You