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?