Radiation damage and protection of polymers, FTIR Microscopy, Micro-Chemical Analysis, Shelf Life Study, Sterilization, Failure Analysis

1. Effects of Radiation
and Accelerated Aging
Part 6: Radiation Sterilization Issues

2. ATR Spectrum
Reflection from smear
on aluminum sheet
The bloom visible on this catheter
was analyzed both by contacting
its surface with the ATR Objective
and by smearing the bloom onto
aluminum sheet and analyzing
the smear by Reflectance.
The smear shows only the DEHP
while the ATR sees both the
DEHP and the PVC catheter.
Radiation Increases PVC Blooming
Of Cytotoxic DEHP Plasticizer

3. Radiation Generates Free Radicals in Polypropylene

4. Free Radicals Generate Carbonyl Groups in Polymers

5. Test Method Development
Decreased Ductility Can Cause Devices To Break During Use.
Radiation may increase the force to strain the device, but the strain
at break decreases. Devices seldom fail because they’re too stiff.
They fail because they break.
A Syringe barrel wall may be unbreakable
during use despite receiving the highest
radiation dose allowed. Syringe tips may
be much more fragile. Customer complaint
history and product history may indicate
what areas of a product are areas of concern;
what are the products’ weakest links. It is
these modes of failure that must be tested.
Testing must mimic the mode of failure
expected during customer use. Breakage
tests must be performed at a speed of
deformation similar to that experienced
by the product during customer use.
Testing samples subjected to Accelerated
Aging will provide data quickly that predicts
the future behavior of products. The Test
Protocols will define the Accelerated Aging
to be used.

6. Measuring Radiation Damage using Micro-FTIR
Mounting Aluminum Sheet On 3X2 Glass Slide

7. Shavings off Polypropylene Barrel’s Surface Analyzed Herein:
Shavings Obtained with Razor Blade

8. Close-ups of Polypropylene Shavings Analyzed Herein

9. 0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
Same Polypropylene Film Before and After 40 kGYs of Cobalt Radiation
Blue is after

10. 0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0.55
0.60
0.65
0.70
Absorbance
20002500300035004000
Wavenumbers (cm-1)
Same Polypropylene Film Before and After 40 kGYs of Cobalt Radiation
Blue is after
Hydroperoxides Carbonyls

11. 0.08
0.10
0.12
0.14
0.16
0.18
0.20
0.22
0.24
0.26
Absorbance
16001700180019002000
Wavenumbers (cm-1)
Same Polypropylene Film Before and After 40 kGYs of Cobalt Radiation
Blue is after
Scissioned Polymer Chains Oxidize

12. IR Spectrum Shows Radiation Induced Oxidation of Polypropylene
as per J. Donohue MDDI

13. Polypropylene Oxidation from 20 and 40 kGYs of Cobalt Radiation

14. The “Dark Reaction” of Irradiated Polypropylene
Oxidative Degradation Continues Long After Irradiation Has Ceased
This is the Reaction that is Accelerated by Accelerated Aging

15. Dr. Apostolou and I “wrote the book” on Accelerated Aging Methods that work

16. Oxygen Can More Easily Penetrate and React
with the Polymer in a Thin Film

17. This Post Rad Oxidation is Not Just Peroxide Scissions.
Ambient Oxygen Continues to React with the Polymer.
This is Proven by this Vacuum Oven Aging.

18. Polyethylene Undergoes Similar Oxidation
when Irradiated with 20 and 40 kGYs

19. A Carbonyl Index Can be Defined to Measure this Oxidation

20. Statistical Results for Micro-FTIR Dosimetry of Gamma vs Control
The Micro-FTIR Method is Accurate, Precise, and Robust

21. 0.10
0.20
0.30
0.10 0.20 0.30
0.00
0.00 0.40
X = Thickness of slice (area of 1304 cm-1 Absorbance)
Area of C=O
Absorbance
divided by X
(Carbonyl Index)
Radiation Damage (= Dose) Measured for Thin Surface
Shavings of Sterilized Polypropylene Medical Devices
Shavings of samples with 0 Mrads
Shavings of samples with 3.5 Mrads
Shavings of sterile product
Shavings of underdosed product
FTIR Microscopy can determine a competitor’s dose or detect underdosed non-sterile devices.

22. Stability of Fina Syndiotactic and Isotactic
Polypropylenes to Cobalt Radiation
and Accelerated Aging

23. Ziegler-Natta and Metallocene Catalysts
Controlled Orientation of Monomer Approach To Active Site
Yields Controlled Stereoregularity of Polymer Chain Formed.
For Z-Ns, Solid Catalysts Control Approach to Active Site.
For Metallocenes, Molecular Structure Controls Approach.

24. Stereostructure of
Isotactic Polypropylene
Hydroperoxide Formation
by “Backbiting” Oxidation
Strings of Close, Unstable,
Pendant Hydroperoxides
Free Radical Degradation of Isotactic Polypropylene

25. 0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
Isotactic Polypropylene Before and After 38 kGy & 17 Days @ 70 C
Hydroperoxides Carbonyls
The Isotactic Polymer is extensively Oxidized by Irradiation.
It sizzles like bacon when it is melted.

26. 0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
Syndiotactic Polypropylene Before and After 38 kGy & 17 Days @ 70 C
The Syndiotactic Polymer exhibits very little Rad-induced Oxidation

27. 0.08
0.10
0.12
0.14
0.16
0.18
0.20
0.22
0.24
Absorbance
16001700180019002000
Wavenumbers (cm-1)
IPP & SPP: 38 kGy & 70 C Aging Study
Accelerated Aging Increases IPP Oxidation
but has Very Little Effect on SPP
IPP @ 70 C: 17 Days
88 Hrs
16 Hrs
0 Hrs
IPP 0 Dose
SPP 0 Dose
SPP @ 70 C:
0 to 17 Days

28. 0.08
0.10
0.12
0.14
0.16
0.18
0.20
0.22
0.24
Absorbance
16001700180019002000
Wavenumbers (cm-1)
IPP & SPP: 38 kGy & 40 C Aging Study
IPP @ 40 C: 17 Days
88 Hrs
16 Hrs
0 Hrs
IPP 0 Dose
SPP 0 Dose
SPP @ 40 C:
0 to 17 Days
Accelerated Aging Increases IPP Oxidation
but has Very Little Effect on SPP

29. Carrier Gas Flowpath to Mass Spec Detector
Pure He flowing through
glass lined steel tube
that contains sample.
Tube is injected into
GC Inlet and heated.
Volatiles separate on
column and are analyzed
by the MS.

30. Radiation Sterilized
Syndiotactic Polypropylene
Generates an Order of
Magnitude Less Volatiles
than an Equal Mass of
Irradiated Isotactic Polypropylene
THDSB/GC/MS Analyses
of Post-Rad Volatiles

31. The Close, Unstable, Pendant Hydroperoxides Explode Like a String of Firecrackers
CO2
acetaldehyde
acetone
acetic acid
4-hydroxy4-methylpentanone
2,4-dimethylfuran
cyclopropylacetone
allylacetone
acetic anhydride
3,5,5-trimethylfuranone
acetoacetone
THDSB/GC/MS IDENTIFICATION
OF IPP POST-RAD VOLATILES
Heated Irradiated Isotactic Polypropylene Degrades
into Volatiles Based on C-C-O Units that Reveal the
Chemical Mechanisms of its Oxidation

32. Thermally Degraded Post Rad Isotactic Polypropylene
Emits Low Mass Scission Products Based on C-C-O Units …
Air & Water
Desorbed Out
Of Tube
Acetone
Acetic Acid
… Because Similar Oxidized Structures Degrade into Similar Volatiles
THDSB/GC/IR Analyses of Post-Rad Volatiles

33. Thermally Degraded Post Rad Syndiotactic Polypropylene
Emits a Far More Random Mix of Scission Products …
Air & Water
Desorbed Out
Of Tube
2-Hydroxy-Propionic Acid
3-Methyl-2,4-Pentanediol
4-Butyl-Gamma-Octanolactone
… Because a More Random Dispersion of Oxidized Structures Yields
a More Random Mix of Volatile Degradation Products
THDSB/GC/FTIR Analyses of Post-Rad Volatiles

34. Phenolic Antioxidants Protect Against Radiation Damage by
Scavenging the Free Radicals Formed in the Polymer by Radiation
Part 7: Additives; their Analysis and Issues

35. But Phenolic Antioxidants Turn Plastic Yellow When Irradiated

36. Hindered Amine Light Stabilizers Form Cytotoxic Hydroxylamines
as they Protect the Polymer from Radiation Damage
Without Discoloration

37. Millad 3988 Clarifies Polypropylene
Molding Heat Causes Hydrolysis, Releasing Benzaldehyde Derivatives
This Causes the Polymer to Emit a “Cherry Candy” Smell
Millad makes Polypropylene more brittle

38. Clarified Polypropylene Crystallized at 130 C from the Melt
Nucleation Determines Morphology
ClarifiedNot Clarified
Sublimation depletes Boundary of MilladPolypropylene Spherulites grow
Millad prevents
Spherulite growth

39. Millad Forms Thermally Unstable Precipitate if it is Overheated During
Injection Molding. Precipitate’s Sizzling Decomposition into Gaseous,
Superheated Aldehyde Strips Char out of Molding Press and Into Molded Parts.
Heated excised precipitate chunks undergoing thermal decomposition on Hotplate

40. Sizzling Decomposition into Aldehyde and Arylate
>Tiny orange spots were
scattered across the
Polypropylene matrix
>Any attempt to get the spectrum
of more than one orange spot at
a time yielded only a spectrum
of the Polypropylene matrix
>But the IR-Plan can can zoom in
on a single tiny orange spot to
yield the Arylate spectrum
shown …
… and Thermal Desorption of the
degrading material into the
GC/MS can show the formation
of the Aldehydes and Alcohol
Intermediates.

41. Thermal Decomposition of Precipitate Forms Aldehyde.
Cannizzaro Reaction of Aldehydes Forms Acid and Alcohol.
Condensation of Acid and Alcohol Forms Arylate.
Arylate Forms The Orange Spots

42. Thin Layer Chromatography (TLC) can Separate Chemical Mixtures that the
GC/MS can’t: Chemicals that are non-Volatile or Thermally Unstable
Liquid carries chemicals in spot of extract up the plate, separating them

43. >TLC is done on a Plate Covered with
Fluorescent Silica
>UV Light makes the Separated
Chemicals from the Mixture
Visible
>The Regions of Silica Containing
these Chemicals are scraped off
the plate, separated from the Silica,
and Identified using the Analytical
Instrumentation
Under Visible Light
Under UV Light
After Scraping

44. 0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
Measuring Durometer of FINISHED (competitive) Devices:
FTIR of DEHP Plasticized PVC Device vs Pure PVC
Pure PVC
Part 8: Tricks of the Trade

45. -0.4
-0.2
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
2.2
Absorbance
1450150015501600
Wavenumbers (cm-1)
FINISHED Device: Measuring Plasticized PVC Durometer
Hard Endotracheal Tube
Soft Nasogastric Tube
DEHP
PVC
Spectra “normalized” for equal plasticizer (DEHP) content show
that the harder PVC has a higher PVC to Plasticizer Ratio
Such a test can tell the Durometer used by a Competitor
Higher
PVC
conc.

46. 0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
Reverse engineering competitive catheters
Micro-FTIR Spectrum of Pellethane
zoom in here next slide

47. 0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0.55
0.60
Absorbance
1360138014001420
Wavenumbers (cm-1)
Micro-FTIR ID: FINISHED Device Pellethane Durometer
80A
90A
75D
>Many catheters have tips made from a softer grade
material than the shaft.
>FTIR can measure the Durometer of finished
Polyurethane devices quickly and easily
>Multiple runs below show that the method is robust

48. 0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
Micro-FTIR Spectrum of Tecothane
zoom in here next slide

49. 0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
Absorbance
1360138014001420
Wavenumbers (cm-1)
Micro-FTIR ID: FINISHED Device Tecothane Durometer
74A
85A
55D
75D

50. 0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0.55
0.60
0.65
0.70
0.75
0.80
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
Micro-FTIR Spectrum of Tecoflex with 20% BaSO4
zoom in here next slide

51. 0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
Absorbance
130013201340136013801400
Wavenumbers (cm-1)
Micro-FTIR ID: FINISHED Device Tecoflex Durometer
80 A
85 A
100 A
65 D
60 D
NOTE:
This method is more accurate than the
manufacturer’s ability to control or measure
their Durometer. The Hardness Pucks that
were supplied by the manufacturer (after
measuring Durometer with a Hardness Tester)
and were supposed to be 60 D were instead
HARDER than the supposed 65 D pucks.

52. HIGH-GLOSS
ABS CRACKS
LOW-GLOSS ABS
RESISTS CRACKING
FTIR Shows Why High-Gloss ABS Has Less ESCR Than Low-Gloss ABS
More Styrene/Butadiene Rubber dispersed in the Acrylonitrile matrix
yields High Gloss ABS with less resistance to Environmental Stress Cracking

53. Packaging Materials
>There are a lot of “Tricks of the Trade” in Materials Analysis.
>For example, Most packaging films are laminates with outer
heat-sealable plies and an inner strength ply.
>The FTIR Microscope requires Liquid Nitrogen (LN2) to operate
and this LN2 can be used to cryo-fracture materials.
>Cryo-fractured laminated films can be separated easily into their
individual plies for material identification and also for accurate
thickness measurements free from thickness artifacts caused by
cutting techniques that can decrease the measured thicknesses.

54. The film contains K-Resin…
…and the stretched Heat Seal Ply is EVA
Device package bottom web was
cryo-fractured with liquid N2 and
the heat seal ply was stretched over
aluminum sheet.

55. Device package bottom web was
cryo-fractured with liquid N2 and
the protruding and overhanging
plys show a Surlyn center ply
sandwiched in EVA heat seal plys.
Surlyn center ply
protruding from
fractured laminated
film
Surlyn ply and EVA heat
seal ply together

56. Device package bottom web was
cryofractured with liquid N2 and
this two ply film separated into
a K Resin ply and a more flexible
EVA heat seal ply.
K Resin ply is stiffer
EVA heat seal ply