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Pore Structure Analysis of Advanced Pharmaceutical
Products
Pore Structure Analysis of Advanced Pharmaceutical
ProductsDr. Akshaya Jena and Dr. Krishna
Porous Materials, Inc.
83 Brown Road, Ithaca, NY 14850
Dr. Akshaya Jena and Dr. Krishna
Porous Materials, Inc.
83 Brown Road, Ithaca, NY 14850
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TopicsTopics
Importance of Porosity in Advanced Pharmaceutical Products
Inadequacy of Mercury Intrusion Porosimetry
Two novel techniquesResults and DiscussionSummary and Conclusion
Importance of Porosity in Advanced Pharmaceutical Products
Inadequacy of Mercury Intrusion Porosimetry
Two novel techniquesResults and DiscussionSummary and Conclusion
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Importance of Porosity in Advanced Pharmaceutical Products
Importance of Porosity in Advanced Pharmaceutical Products
Advanced pharmaceutical productsExamples:– Artificial skin– Blood clotting material– Dialysis membrane– Blood delivery system– Hydrogels– Tissue culture substrates – And many more
Advanced pharmaceutical productsExamples:– Artificial skin– Blood clotting material– Dialysis membrane– Blood delivery system– Hydrogels– Tissue culture substrates – And many more
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Important characteristics:
Constricted pore diameter Barrier properties
The largest pore diameter Barrier properties
Mean pore diameter Barrier & flow
Important characteristics:
Constricted pore diameter Barrier properties
The largest pore diameter Barrier properties
Mean pore diameter Barrier & flow
Performance and efficiency of such products
Pore characteristics
Performance and efficiency of such products
Pore characteristics
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Pore distribution Barrier & flowPore distribution Barrier & flow
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
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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Pore volume Holding capacityPore volume Holding capacity
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
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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Permeability Rate of the processPermeability Rate of the process
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
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
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 techniquesNeed for reliable, accurate and safe techniques
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Inadequacy of Mercury Intrusion Porosimetry
Inadequacy of Mercury Intrusion Porosimetry
Mercury intrusion porosimetry often used for pore structure analysis
Mercury intrusion porosimetry often used for pore structure analysis
Principle of mercury intrusion porosimetryPrinciple of mercury intrusion porosimetry
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Intrusion volume gives pore volume Pressure yields pore size, D
D = - 4 cos /p
= surface tension of Hg = contact angle of HgP = differential pressure
Intrusion volume gives pore volume Pressure yields pore size, D
D = - 4 cos /p
= surface tension of Hg = contact angle of HgP = differential pressure
Mercury is forced in to poresMercury is forced in to pores
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– 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
– 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
It cannot measure:It cannot measure:
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Novel TechniquesNovel Techniques
Capillary Flow PorometeryPores of sample spontaneously filled
with wetting liquidPressurized gas is used to remove
liquid from pores to allow gas flow
Capillary Flow PorometeryPores of sample spontaneously filled
with wetting liquidPressurized gas is used to remove
liquid from pores to allow gas flow
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D = 4 cos /p
= surface tension of wetting liquid = 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
D = 4 cos /p
= surface tension of wetting liquid = 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
Pressure yields pore diameter, DPressure yields pore diameter, D
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The PMI Capillary Flow PorometerThe PMI Capillary Flow Porometer
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Sample is placed on a membrane whose largest pore size is smaller than the smallest in the sample
Sample is placed on a membrane whose largest pore size is smaller than the smallest in the sample
Liquid Extrusion PorosimetryLiquid Extrusion Porosimetry
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Pores of sample and membrane are filled with a wetting liquid
Pores of sample and membrane are filled with a wetting liquid
Liquid Extrusion PorosimetryLiquid Extrusion Porosimetry
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Pressurized gas is used to displace liquid from pores without the membrane and with membrane under the sample
Pressurized gas is used to displace liquid from pores without the membrane and with membrane under the sample
Liquid Extrusion PorosimetryLiquid Extrusion Porosimetry
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D = 4 cos /p
D = pore diameter = surface tension of wetting liquid = contact angle of wetting liquidP = differential pressure
Volume of displaced liquid gives pore volume & permeability
D = 4 cos /p
D = pore diameter = surface tension of wetting liquid = contact angle of wetting liquidP = differential pressure
Volume of displaced liquid gives pore volume & permeability
Pressure yields pore diameterPressure yields pore diameter
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The PMI Liquid Extrusion Porosimeter used in this investigation
The PMI Liquid Extrusion Porosimeter used in this investigation
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All required properties measurableUse of low pressure-Samples not damagedNo toxic materials use
-no health hazard
-no environmental pollution
-no sample contamination
All required properties measurableUse of low pressure-Samples not damagedNo toxic materials use
-no health hazard
-no environmental pollution
-no sample contamination
AdvantagesAdvantages
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Results and DiscussionResults and Discussion
Dialysis membranes
RequirementsPrimary function-FiltrationImportant characteristics:
The largest pore diameterMean pore diameter Pore distributionFlow rate
Dialysis membranes
RequirementsPrimary function-FiltrationImportant characteristics:
The largest pore diameterMean pore diameter Pore distributionFlow rate
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Capillary Flow PorometeryCapillary Flow Porometery
Flow rate vs Differential pressure for dry and wet samples
Flow rate vs Differential pressure for dry and wet samples
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– The largest pore diameter from pressure for flow initiation
1.023 mm– Mean flow pore diameter from mean flow
pressure 0.458 mm
– The largest pore diameter from pressure for flow initiation
1.023 mm– Mean flow pore diameter from mean flow
pressure 0.458 mm
Pore diameter from measured pressures
Pore diameter from measured pressures
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Normalized pore distribution function vs. pore diameterNormalized pore distribution function vs. pore diameter
Pore distributionPore distribution
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– In any pore size range area = % flow through pores in the range– In any pore size range area = % flow through pores in the range
Pore distributionPore distribution
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– Almost 80% flow through 0.2 – 0.7 m pores– Almost 80% flow through 0.2 – 0.7 m pores
Pore distributionPore distribution
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Permeability Permeability – Dry curve yields gas permeability – Liquid permeability measurable using
attachments
– Dry curve yields gas permeability – Liquid permeability measurable using
attachments
Mercury Intrusion Porosimetry Cannot measure any of the these properties
Mercury Intrusion Porosimetry Cannot measure any of the these properties
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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 usedCapillary flow porometry was the
appropriate technique
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 usedCapillary flow porometry was the
appropriate technique
ConclusionConclusion
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Requirements Primary function-allow growth of
blood vessels and be breathablePores are much larger than the pore
providing barrier propertiesPore size & distribution are in the
range for blood vessels to growAdequate gas and vapor permeability
to be breathable.
Requirements Primary function-allow growth of
blood vessels and be breathablePores are much larger than the pore
providing barrier propertiesPore size & distribution are in the
range for blood vessels to growAdequate gas and vapor permeability
to be breathable.
Artificial skinArtificial skin
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Flow rate vs Differential pressure for dry and wet samples
Flow rate vs Differential pressure for dry and wet samples
Capillary Flow PorometryCapillary Flow Porometry
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– The largest pore diameter from pressure for flow initiation
74.932 m– Mean flow pore diameter from mean flow
pressure 31.489 m
– The largest pore diameter from pressure for flow initiation
74.932 m– Mean flow pore diameter from mean flow
pressure 31.489 m
Pore diameter from measured pressures
Pore diameter from measured pressures
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A broad pore range Uniform distribution
A broad pore range Uniform distribution
Pore distributionPore distribution
Normalized pore distribution function vs pore diameter
Normalized pore distribution function vs pore diameter
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Flow through dry curve as a function of differential pressure
Flow through dry curve as a function of differential pressure
Permeability Permeability – Appreciable gas permeation shown by
dry curve– Appreciable gas permeation shown by
dry curve
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Mercury Intrusion Porosimetery Cannot measure any of the these properties
Mercury Intrusion Porosimetery Cannot measure any of the these properties
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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 psiNo toxic material was used Capillary flow porometry was the
appropriate technique
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 psiNo toxic material was used Capillary flow porometry was the
appropriate technique
ConclusionConclusion
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Requirements Primary applications:– Dressings–Wound gels– Burn dressings– Electrodes– Skin disorders treatments– Carriers for hormones and drugs– Drug delivery implants
Requirements Primary applications:– Dressings–Wound gels– Burn dressings– Electrodes– Skin disorders treatments– Carriers for hormones and drugs– Drug delivery implants
HydrogelsHydrogels
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RequirementsProperties – Pore volumes liquid holding capacity– Pore size & distribution flow rates &
barrier property– Liquid permeability rate of the process
RequirementsProperties – Pore volumes liquid holding capacity– Pore size & distribution flow rates &
barrier property– Liquid permeability rate of the process
HydrogelsHydrogels
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Requirements Properties
– Pore volumes liquid holding capacity– Pore size & distribution flow rates &
barrier property– Liquid permeability rate of the process
Requirements Properties
– Pore volumes liquid holding capacity– Pore size & distribution flow rates &
barrier property– Liquid permeability rate of the process
HydrogelsHydrogels
Mercury Intrusion Porosimetry In Appropriate– Hydrogels retain their integrity only in water– Therefore, mercury intrusion extrusion
porosimetry can be used
Mercury Intrusion Porosimetry In Appropriate– Hydrogels retain their integrity only in water– Therefore, mercury intrusion extrusion
porosimetry can be used
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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
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
HydrogelsHydrogels
Liquid extrusion Porosimetry–Water extrusion porosimetry
appropriate
Liquid extrusion Porosimetry–Water extrusion porosimetry
appropriate
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Pore volume– Total pore volume 0.421 cm 3/g– Porosity 67.12%– Pressure only about 5 psi
Pore volume– Total pore volume 0.421 cm 3/g– Porosity 67.12%– Pressure only about 5 psi
Pore volume of hydrogelPore volume of hydrogel
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Pore distribution of hydrogel– For a given range
Area = pore volume– Pores have a narrow range 5-20 m
Pore distribution of hydrogel– For a given range
Area = pore volume– Pores have a narrow range 5-20 m
Pore volume distributionPore volume distribution
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Typical plot of flow rate of water vs pressureTypical plot of flow rate of water vs pressure
Liquid permeability Liquid permeability
– The flow rate yields liquid permeability – The flow rate yields liquid permeability
0.7
0.8
0.9
1
1.1
1.2
1.3
0.35 0.45 0.55 0.65Pressure, PSI
Flo
wra
te (
cc/s
ec)
0.7
0.8
0.9
1
1.1
1.2
1.3
0.35 0.45 0.55 0.65Pressure, PSI
Flo
wra
te (
cc/s
ec)
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Summary and ConclusionSummary and Conclusion
1. Two novel techniques discussed.Capillary flow porometryLiquid 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.
1. Two novel techniques discussed.Capillary flow porometryLiquid 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 ConclusionSummary and Conclusion1. Two novel techniques discussed.
Capillary flow porometryLiquid 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.
1. Two novel techniques discussed.Capillary flow porometryLiquid 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.
3. These techniques used low pressures so that sample damage was minimized.
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Summary and ConclusionSummary and Conclusion1. Two novel techniques discussed.
Capillary flow porometryLiquid 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.
1. Two novel techniques discussed.Capillary flow porometryLiquid 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.4. No toxic and harmful material was used.
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Summary and ConclusionSummary and Conclusion1. Two novel techniques discussed.
Capillary flow porometryLiquid 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.
1. Two novel techniques discussed.Capillary flow porometryLiquid 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.
5. Products like hydrogels, which retain their integrity in only certain liquid environments, could be tested.
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Summary and ConclusionSummary and Conclusion2. 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.
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.
6. Mercury intrusion could not used for such measurements.
Thank YouThank You
