Micro ftir5-measuring radiation effects,durometer

Effects of Radiationand Accelerated Aging

Part 6: Radiation Sterilization Issues

ATR Spectrum

Reflection from smearon aluminum sheet

The bloom visible on this catheterwas analyzed both by contactingits surface with the ATR Objectiveand by smearing the bloom ontoaluminum sheet and analyzingthe smear by Reflectance.The smear shows only the DEHPwhile the ATR sees both theDEHP and the PVC catheter.

Radiation Increases PVC BloomingOf Cytotoxic DEHP Plasticizer

Radiation Generates Free Radicals in Polypropylene

Free Radicals Generate Carbonyl Groups in Polymers

Test Method DevelopmentDecreased Ductility Can Cause Devices To Break During Use.

Radiation may increase the force to strain the device, but the strainat 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.

Measuring Radiation Damage using Micro-FTIRMounting Aluminum Sheet On 3X2 Glass Slide

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

Close-ups of Polypropylene Shavings Analyzed Herein

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Same Polypropylene Film Before and After 40 kGYs of Cobalt RadiationBlue is after

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Same Polypropylene Film Before and After 40 kGYs of Cobalt RadiationBlue is after

Hydroperoxides Carbonyls

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Same Polypropylene Film Before and After 40 kGYs of Cobalt RadiationBlue is after

Scissioned Polymer Chains Oxidize

IR Spectrum Shows Radiation Induced Oxidation of Polypropylene

as per J. Donohue MDDI

Polypropylene Oxidation from 20 and 40 kGYs of Cobalt Radiation

The “Dark Reaction” of Irradiated PolypropyleneOxidative Degradation Continues Long After Irradiation Has Ceased

This is the Reaction that is Accelerated by Accelerated Aging

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

Oxygen Can More Easily Penetrate and Reactwith the Polymer in a Thin Film

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.

Polyethylene Undergoes Similar Oxidationwhen Irradiated with 20 and 40 kGYs

A Carbonyl Index Can be Defined to Measure this Oxidation

Statistical Results for Micro-FTIR Dosimetry of Gamma vs ControlThe Micro-FTIR Method is Accurate, Precise, and Robust

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X = Thickness of slice (area of 1304 cm-1 Absorbance)

Area of C=OAbsorbancedivided 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.

Stability of Fina Syndiotactic and IsotacticPolypropylenes to Cobalt Radiation

and Accelerated Aging

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.

Stereostructure of Isotactic Polypropylene

Hydroperoxide Formation by “Backbiting” Oxidation

Strings of Close, Unstable, Pendant Hydroperoxides

Free Radical Degradation of Isotactic Polypropylene

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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.

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Syndiotactic Polypropylene Before and After 38 kGy & 17 Days @ 70 C

The Syndiotactic Polymer exhibits very little Rad-induced Oxidation

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IPP & SPP: 38 kGy & 70 C Aging StudyAccelerated Aging Increases IPP Oxidation

but has Very Little Effect on SPPIPP @ 70 C: 17 Days 88 Hrs 16 Hrs 0 Hrs

IPP 0 Dose

SPP 0 Dose

SPP @ 70 C:0 to 17 Days

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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 Oxidationbut has Very Little Effect on SPP

Carrier Gas Flowpath to Mass Spec Detector

Pure He flowing throughglass lined steel tubethat contains sample.

Tube is injected intoGC Inlet and heated.

Volatiles separate oncolumn and are analyzedby the MS.

Radiation SterilizedSyndiotactic PolypropyleneGenerates an Order ofMagnitude Less Volatilesthan an Equal Mass ofIrradiated Isotactic Polypropylene

THDSB/GC/MS Analysesof Post-Rad Volatiles

The Close, Unstable, Pendant Hydroperoxides Explode Like a String of Firecrackers

CO2acetaldehyde

acetoneacetic 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

Thermally Degraded Post Rad Isotactic PolypropyleneEmits Low Mass Scission Products Based on C-C-O Units …

Air & WaterDesorbed OutOf Tube

Acetone

Acetic Acid

… Because Similar Oxidized Structures Degrade into Similar Volatiles

THDSB/GC/IR Analyses of Post-Rad Volatiles

Thermally Degraded Post Rad Syndiotactic PolypropyleneEmits a Far More Random Mix of Scission Products …

Air & WaterDesorbed OutOf Tube

2-Hydroxy-Propionic Acid

3-Methyl-2,4-Pentanediol

4-Butyl-Gamma-Octanolactone

… Because a More Random Dispersion of Oxidized Structures Yieldsa More Random Mix of Volatile Degradation Products

THDSB/GC/FTIR Analyses of Post-Rad Volatiles

Phenolic Antioxidants Protect Against Radiation Damage by Scavenging the Free Radicals Formed in the Polymer by Radiation

Part 7: Additives; their Analysis and Issues

But Phenolic Antioxidants Turn Plastic Yellow When Irradiated

Hindered Amine Light Stabilizers Form Cytotoxic Hydroxylaminesas they Protect the Polymer from Radiation Damage

Without Discoloration

Millad 3988 Clarifies PolypropyleneMolding Heat Causes Hydrolysis, Releasing Benzaldehyde Derivatives

This Causes the Polymer to Emit a “Cherry Candy” SmellMillad makes Polypropylene more brittle

Clarified Polypropylene Crystallized at 130 C from the MeltNucleation Determines Morphology

ClarifiedNot Clarified

Sublimation depletes Boundary of MilladPolypropylene Spherulites grow

Millad preventsSpherulite growth

Millad Forms Thermally Unstable Precipitate if it is Overheated DuringInjection 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

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.

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

Thin Layer Chromatography (TLC) can Separate Chemical Mixtures that theGC/MS can’t: Chemicals that are non-Volatile or Thermally Unstable

Liquid carries chemicals in spot of extract up the plate, separating them

>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

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Measuring Durometer of FINISHED (competitive) Devices:FTIR of DEHP Plasticized PVC Device vs Pure PVC

Pure PVCDEHP

Part 8: Tricks of the Trade

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FINISHED Device: Measuring Plasticized PVC Durometer

Hard Endotracheal Tube

Soft Nasogastric Tube

DEHP

PVC

Spectra “normalized” for equal plasticizer (DEHP) content showthat the harder PVC has a higher PVC to Plasticizer RatioSuch a test can tell the Durometer used by a Competitor

HigherPVC

conc.

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Reverse engineering competitive cathetersMicro-FTIR Spectrum of Pellethane

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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

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Micro-FTIR Spectrum of Tecothane

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Micro-FTIR ID: FINISHED Device Tecothane Durometer

74A

85A

55D

75D

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Micro-FTIR Spectrum of Tecoflex with 20% BaSO4

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Micro-FTIR ID: FINISHED Device Tecoflex Durometer

80 A

85 A

100 A

65 D

60 D

NOTE:This method is more accurate than themanufacturer’s ability to control or measuretheir Durometer. The Hardness Pucks thatwere supplied by the manufacturer (aftermeasuring Durometer with a Hardness Tester)and were supposed to be 60 D were insteadHARDER than the supposed 65 D pucks.

HIGH-GLOSSABS CRACKS

LOW-GLOSS ABSRESISTS CRACKING

FTIR Shows Why High-Gloss ABS Has Less ESCR Than Low-Gloss ABS

More Styrene/Butadiene Rubber dispersed in the Acrylonitrile matrixyields High Gloss ABS with less resistance to Environmental Stress Cracking

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.

The film contains K-Resin…

…and the stretched Heat Seal Ply is EVA

Device package bottom web wascryo-fractured with liquid N2 andthe heat seal ply was stretched over aluminum sheet.

Device package bottom web wascryo-fractured with liquid N2 andthe protruding and overhangingplys show a Surlyn center plysandwiched in EVA heat seal plys.

Surlyn center plyprotruding fromfractured laminatedfilm

Surlyn ply and EVA heatseal ply together

Device package bottom web wascryofractured with liquid N2 andthis two ply film separated intoa K Resin ply and a more flexibleEVA heat seal ply.

K Resin ply is stiffer

EVA heat seal ply