Dr. Daryl R. Williams Surfaces and Particle Engineering Laboratory
Department of Chemical Engineering Imperial College London
Characterisation of Complex Organic Materials – New Insights using Molecular
Sorption Probes
Complex Organic Materials
• Many of the real world materials developed and manufactured by industry for society are complex in terms of the chemical, morphological, structural, compositional and physically properties. Today we will consider solids or semi-solid materials
• Classes of complex materials include: – Agrichemicals – Pharmaceuticals – Biopharmaceuticals – Foods – Freeze and spray dried products – Personal care products – Biomaterials – Advanced composites – Adsorbents – Building materials
Moisture and Complex Organic Materials
What can be the effects of too little or too much water in a complex organic material?
• Potato crisps loose their crispiness
• Crystalline pharmaceutical hydrates become dehydrated solids
• Proteins can loose their biological activity
• Freeze dried powders transform into liquids
• Free flowing powders turn into rigid/solid cakes
• Dry powders aerosols do not disperse
Water decreases Tg of amorphous glass solidsrubbery
Thermodynamic stability is compromised by low %RH’s
Proteins denature at low %RH’s
Amorphous solids and deliquesce forming solutions
Amorphous solids can crystallise at high moisture contents
Particles adhere to each other or packaging
Characterization of Solids
• EM Radiation as a Probe • Spectroscopy eg Raman, IR • X-Ray Diffraction,NMR
• Analytical and structural information
• Thermal Energy as a Probe • Calorimetry eg DCS, TGA
• Thermodynamic information on solid
• Molecule as a Probe • Sorption techniques eg DVS, IGC
• Thermodynamic and chemical information on vapour-solid interaction
4
Molecules as a Probe of Solids
Molecules In Molecules Out
Molecules Absorbed
Molecules Adsorbed
Molecules as a Probe
•Chemical Interactions IGC, DVS, Wetting, Chemisorption analyzers
•Physical Structure (surface area, pore size, density etc.) DVS, IGC, Volumetric sorption (i.e. BET analyzers), Chemisorption,
Pycnometer
•Thermodynamic Information IGC, DVS, Thermal Analysis Methods
How do we study these moisture dependent behaviour of solid state materials?
TGA Method Name DVS
Gravimetric Principle Gravimetric
~5mg Sample Size ~10mg
Temperature Primary Variable % RH
Usually Ramp Operational Mode Step and Ramp
Thermal Perturbation Core Data Moisture Partitioning
1-4 Hours Run Time 24 Hours
-200C to 400C Measurement Range 0 to 100%RH
T Control T, %RH Control
Dynamic Vapor Sorption Thermogramimetric Analysis
Dynamic Vapour Sorption
Dynamic Vapour Sorption
DVS Experimental Methods • Traditional approach is a series of steps, each conducted at constant T and %RH
with mass monitored as function of time. Output is isotherm.
• Alternate approach is %RH ramp, comparable to a TGA’s T ramp experiment Time
% R
H
Time
Mas
s
Time
% R
H
Time
Mas
s
DVS Typical Kinetics Data
11
DVS Change In Mass (dry) Plot
-5
0
5
10
15
20
25
0 2000 4000 6000 8000 10000 12000 14000
Time/mins
Cha
nge
In M
ass
(%) -
Dry
0
10
20
30
40
50
60
70
80
90
100
Targ
et R
H (%
)
dm - dry Target RH
© Surface Measurement Systems Ltd UK 1996-2001DVS - The Sorption Solution
Date: 07 Dec 2001 Time: 4:14 pm File: ricestarch071201_reduced.XLS Sample: rice starch
Temp: 24.8 °C Meth: duncan.sao M(0): 40.5303
Moisture sorption behavior of rice starch at 25 °C- 2 cycle experiment
Water Sorption Isotherm
12
DVS Isotherm Plot
0
5
10
15
20
25
0 10 20 30 40 50 60 70 80 90 100Target RH (%)
Cha
nge
In M
ass
(%) -
Dry
Cycle 1 Sorp Cycle 1 Desorp
© Surface Measurement Systems Ltd UK 1996-2001DVS - The Sorption Solution
Date: 07 Dec 2001 Time: 4:14 pm File: ricestarch071201_reduced.XLS Sample: rice starch
Temp: 24.8 °C Meth: duncan.sao M(0): 40.5303
Water Sorption Isotherm for Hydrophobic Powder
13
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.1
0 10 20 30 40 50 60 70 80 90 100
Cha
nge
In M
ass
(%)
-Ref
Sample Relative Humidiy (%)
Metform Hydrochloride Water Sorption Results
Fines (less than 140 Mesh) Sorption Fines (less than 140 Mesh) Desorption
60-140 Mesh Sorption 60-140 Mesh Desorption
60 Mesh Sorption 60 Mesh Desorpiton
© Surface Measurement Systems Ltd UK 1996-2008DVS - The Sorption Solution
• ~150 mg of material
• Higher uptake on smaller particles Higher surface area
Water Sorption Isotherm for Hydrophillic Polymer
Water Sorption Isotherm Plot for Poly vinyl pyrrolidone
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60 70 80 90 100Sample Relative Humidity (%)
Ch
ang
e In
Mas
s (%
) -
Dry
DVS-Microscope Accessory
15
Water Sorption on Coffee @ 25 C
0
5
10
15
20
25
0 100 200 300 400 500
Time/mins
Ch
an
ge
in
Ma
ss
(%
)
0
10
20
30
40
50
60
70
80
90
Ta
rge
t R
H (
%)
DVS-Microscope Accessory
16
Sucrose Crystals – 0% RH
Sucrose Crystals – 95% RH, 60 minutes
DVS-Microscope Accessory
17
Maltodextrin – 0% RH Maltodextrin – 95% RH, 0 minutes
Maltodextrin – 95% RH, 30 minutes Maltodextrin – 95% RH, 50 minutes
Ramp Results for Spray Dried Lactose (25 °C, 6% RH/hour)
Amorphous Lactose
0
2
4
6
8
10
12
14
480 680 880 1080 1280 1480
Time/mins
Net
Cha
nge
In M
ass
(%)
DVS - The Sorption Solution
A
B
C
D
Ramp Results for Spray Dried Lactose (25 °C, 6% RH/hour)
Amorphous Lactose
0
2
4
6
8
10
12
14
480 680 880 1080 1280 1480
Time/mins
Net
Cha
nge
In M
ass
(%)
DVS - The Sorption Solution
A
B
C
D
T, RHg: RH versus Ramping Rate
Glass Transition Humidity (Tg RH) versus Humidity Ramping Rate
y = 1.155x + 29.822R2 = 0.979
28.00
30.00
32.00
34.00
36.00
38.00
40.00
42.00
44.00
0.00 2.00 4.00 6.00 8.00 10.00 12.00
Ramping Rate (%RH/hour)
Hum
idity
at G
lass
Tra
nsiti
on (%
RH
)
Glass Transition (%RH)
Linear (Glass Transition (%RH))
Critical T,RHg = 30% +/- 1% RH at 25 °C
DVS-Raman Accessory
21
1. Raman spectroscopy is the measurement & detection of the wavelength and intensity of inelastically scattered light from molecules. When electromagnetic radiation passes through matter, most of the radiation continues in its original direction but a small fraction is scattered.
2. Rayleigh scattering: Light that is scattered at the same wavelength as the incoming light.
3. Raman scattering: Light that is scattered due to vibrations in molecules or optical phonons in solids.
4. The majority of scattered light is elastic and only one in 106 optical photons are scattered at frequencies different to the incident light – This is the weaker Raman scattered light.
Sample
Incident Laser Light
Rayleigh Scattering
Raman Scattering
Step Data for Spray Dried Lactose DVS Mass Plot
20.5
21
21.5
22
22.5
23
23.5
0 500 1000 1500 2000 2500 3000Time/mins
Mas
s/m
g
0
10
20
30
40
50
60
70
80
90
100
Targ
et %
P/P
o
Mass Target % P/Po
© Surface Measurement Systems Ltd UK 1996-2007DVS - The Sorption Solution
Date: 21 Nov 2007 Time: 5:57 pm File: amorphous lactose 21st Nov 2007.xls Sample:
Temp: 24.9 °C Meth: anhydrate.SAO MRef: 20.6428
Raman scans - absorbtion cycle 1
-200
0
200
400
600
800
1000
1200
1400
1600
-500 0 500 1000 1500 2000 2500 3000 3500 4000 4500
Raman shifts (check this - might not be)
Coun
ts
0%RH
10%RH
20%RH
30%RH
40%RH
50%RH
60%RH
70%RH
80%RH
90%RH
95%RH
Raman Frequency (cm-1)
Sig
nal C
ount
s
Crystalline
Amorphous
Amorphous versus Crystalline Salbutamol Sulphate
Ethanol vapor induced polymorph conversion d b mannitol
Carbamazepine Acetone Solvate: Desolvation Kinetics at 30C
78
80
82
84
86
88
90
92
94
96
98
100
0 50 100 150 200 250 300 350 400
Time (minute)
Mas
s lo
ss (%
)
0%RH
5%RH
10%RH
15%RH
30%RH
Crystal form at 30ºC, 250sccm
Avrami-Erofe’ev sigmoidal rate reaction
sigmoid rate
α
deceleratory rate
t
α
α
α
t
t t
Accelerated-deceleratory rate
Small evolution of gas
Carbamazepine Dehydration Rates
86
88
90
92
94
96
98
100
0 100 200 300 400 500 600 700Time (minutes)
Cha
nge
in m
ass
(%)
20ºC
30ºC
40ºC
50ºC
60ºC
1st order deceleratory rate reaction
sigmoid rate
α
deceleratory rate
t
α
α
α
t
t t
Accelerated-deceleratory rate
Small evolution of gas
The Future for DVS
• Multi-component gas-vapour mixtures – BET of a hydrate – Competitive adsorption
• More Fibre optic spectroscopy- IR, NIR
• Smaller samples, faster analysis eg a few hours
• Advanced modelling of isotherms for understanding sorption parameters from polymer solution theory eg c • True high throughput sampling
Conclusion
•Water Sorption in organic materials can be a complex phenomena
•DVS data describes physical, morphological and chemical state of the materials, including recrystallisation and amorphous collapse events
•Raman spectroscopy and video images support the comprehensive understanding of DVS sorption data
•DVS information not often attainable using any other approach
Thank You
Verentas Model of Solute-Polymer Dissolution
glassy rubbery
Fp
p
2
2210
1
1 exp c
RTT
Tdw
dTccwMF
g
gmppg /1
1
2
21
2
2210
1
1 exp c
p
p
Vrentas’ model
0F
Does the BET model work for Water Sorption in Amorphous Solids?
• Define “Work” • Can we fit data to model- YES • But so to do many other models eg Young and Nelson • Does the model provide a physical insight into the
sorption process? NO • Does that mean the BET model has no use, certainly
not. • Do better models exist……
Water Sorption Keratin Fibres 25C
90 100
Cha
nge
In M
ass
(%) -
Dry
DVS Isotherm Plot for Yak fibre at 25oC
25
0
5
10
15
20
0 10 20 30 40 50 60 70 80
Target RH (%)
Cycle 1 Sorption Cycle 1 Desorption
sorption
desorption
90 100
Cha
nge
In M
ass
(%) -
Dry
DVS Isotherm Plot for Yak fibre at 25oC
25
0
5
10
15
20
0 10 20 30 40 50 60 70 80
Target RH (%)
Cycle 1 Sorption Cycle 1 Desorption
sorption
desorption
The Water Sorption Isotherm
Glass Transition Temperatures and Adsorption/Sorption
Amorphous- Glassy Solid
T <Tg
Surface and local bulk adsorption
Fast kinetics, low uptake levels
Amorphous- Rubbery Solid
T >Tg
Deep bulk sorption
Slower kinetics, medium to high uptake levels
Crystalline No Tg
Surface adsorption
Very fast kinetics, very low uptake
levels
Collapse RH versus Ramping Rate
Collapse Humidity versus Humidity Ramping Rate
y = 1.252x + 58.106R2 = 0.995
58
60
62
64
66
68
70
72
0.00 2.00 4.00 6.00 8.00 10.00 12.00
Ramping Rate (%RH/hour)
Hum
idity
at R
ecry
stal
lizat
ion
(%R
H)
Recyrystallization (%RH)
Linear (Recyrystallization (%RH))
Critical Collapse RH = 58% RH at 25 °C
Sorption behaviour is Complex
• Solute uptake levels of 0.02% to 60% • Isotherm shapes can vary widely • Sorption kinetics : a few minutes to a few days • Solutes- water to hydrocarbons • Substrates
– Inorganic or organic – Glassy – Crystalline – Porous – Reactive – Combinations of all of the above
• No one theory can account for all of these !! • What about the BET model!
0 to 90% RH for Different Ramping Rates
Amorphous Lactose
0
2
4
6
8
10
12
14
0 500 1000 1500 2000 2500 3000
Time/mins
Net
Cha
nge
In M
ass
2% RH/hour
4% RH/hour
6% RH/hour
8% RH/hour
10 % RH/hour
DVS - The Sorption Solution
Temp: 25.0 °C
Vrentas' model: Water Sorption in Keratin
0
0.05
0.1
0.15
0.2
0.25
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 p/po
Wat
er m
ass
frac
tion
w1
Rubbery Flory-Huggins Model Experimental sorption data
Vrentas Model for glassy state
RHg
Raman scans of ALF A - adsorb cycle1
-2000
0
2000
4000
6000
8000
10000
12000
14000
16000
-500 0 500 1000 1500 2000 2500 3000 3500 4000 4500
Raman shifts (check)
Inte
nsity
(cou
nts)
0%RH10%RH20%RH30%RH40%RH50%RH60%RH70%RH80%RH90%RH95%RH
Example: ALF A (Example Anhydrate Drug)
Adsorption Cycle 1
DVS Mass Plot
22
22.5
23
23.5
24
24.5
25
25.5
0 500 1000 1500 2000 2500 3000Time/mins
Mas
s/m
g
0
10
20
30
40
50
60
70
80
90
100
Targ
et R
H (%
)
Mass Target RH
© Surface Measurement Systems Ltd UK 1996-2007DVS - The Sorption Solution
Date: 26 Nov 2007 Time: 5:21 pm File: ALF A 26th Nov 2007.xls Sample:
Temp: 25.0 °C Meth: anhydrate.SAO MRef: 22.3815
Raman scans ALF A - desorb cycle 1
-2000
0
2000
4000
6000
8000
10000
12000
14000
-500 0 500 1000 1500 2000 2500 3000 3500 4000 4500
Raman shifts (check)
Inte
nsity
(cou
nts)
90%RH80%RH70%RH60%RH50%RH40%RH30%RH20%RH10%RH0%RH
Desorption Cycle 1
Ramp Results for Spray Dried Lactose (25 °C, 6% RH/hour)
Amorphous Lactose
0
2
4
6
8
10
12
14
480 680 880 1080 1280 1480
Time/mins
% N
et C
hang
e in
Mas
s
0
10
20
30
40
50
60
70
80
90
100
Rel
ativ
e H
umid
ity (%
)
DVS - The Sorption Solution
Ramp Results for Spray Dried Lactose (25 °C, 6% RH/hour)
0
2
4
6
8
10
12
14
480 680 880 1080 1280 1480
Time/mins
% C
hang
e in
Mas
s
0
10
20
30
40
50
60
70
80
90
100
Rel
ativ
e H
umid
ity (%
)
Bulk Absorption -
Rubbery
DVS - The Sorption Solution
Glass Transition
Linear Sorption -
GlassyT,RHg
Ramp Results for Spray Dried Lactose (25 °C, 6% RH/hour)
0
2
4
6
8
10
12
14
480 680 880 1080 1280 1480
Time/mins
% C
hang
e in
Mas
s
0
10
20
30
40
50
60
70
80
90
100
Rel
ativ
e H
umid
ity (%
)
DVS - The Sorption Solution
Recrystallization and Collapse
Onset of Recrystallisaton?