The document describes the DiscovIR-LC system, a hyphenated GPC-IR technique. It can be used for polymer, excipient, and materials analysis. Applications include excipient characterization and degradation analysis, copolymer compositional drift analysis across molecular weight distributions, polyolefin branching analysis, polymer blend ratio analysis, polymer additive analysis, and formulation analysis of products like motor oil lubricants. The technique provides both separation and identification capabilities for applications in process control, materials development, and quality analysis.

1. LC-IR Hyphenated Technology for
Polymer / Excipient Analysis
Ming Zhou, William Carson, Sidney Bourne,
David Dunn and Tom Kearney
Spectra Analysis, Inc.
Contact: ZhouM@Spectra-Analysis.com
Nov. 16, 2009
1

2. OUTLINE
LC-IR Hyphenated Technology
DiscovIR-LC System & Instrumentation
Features & Applications of DiscovIR-LC
Copolymer Compositional Analysis across MW Distributions:
e.g. Styrene/Butadiene, Excipient PVP/VAc Characterization
Excipient Degradation Analysis: HPMCAS, PEG
Polyolefin Branching Analysis by High Temp GPC-IR: Copolymers
Polymer Blend Ratio Analysis across MWD: EVA/PMMA
Polymer Additive Analysis: De-Formulation of Motor Oil Lubricants
Summary
2

3. Hyphenated Technologies
GC-MS GC-IR
LC-MS LC-IR
Separation Gas Phase & Liquid Phase
Chromatography
Detection Mass Infra Red
Spectroscopy Spectroscopy
DiscovIR-GC
DiscovIR-LC
Identification Data Acquisition & Analysis

4. LC-IR Hyphenated System
The DiscovIR-LCTM is a fully automated direct deposition LC-IR
analyzer used by chemists to identify unknown components in
complex mixtures. 4

5. How Does It Work?

6. How is the Solvent Removed?
Nitrogen Addition
Cyclone
Thermal Nebulization
From LC
Cyclone Evaporator
Evaporator
Air Cooled
Condenser
Patent pending:
PCT/US2007/025207
Chilled
Condenser
Particle Stream to DiscovIR
Waste Solvent

7. What is Direct Deposition FTIR?

8. Direct Deposition FTIR and Data Processing

9. LC-IR Hyphenated Technology for Polymer Analysis
9

10. Features of DiscovIR-LC
Online Fully Integrated System
Fully Automated Operation: No Fractionation
Multi-Sample Processing: 8-40 Hr ZnSe Disk Time
Microgram Sensitivity at Sample Injection Point
Real-Time Chromatography & Spectral Data
Solid Phase Transmission IR Spectra: High Quality w/ Purified Analytes
Database Search Capability & In-House Library Creation
Data Analysis: GRAMS for Chemometrics, 3D LC-IR, Functional Group
Chromatograms & Comparisons at any Wavenumbers or across Peaks
All LC Solvents: Water, ACN, Methanol, THF, Chloroform, HFIP
GPC/SEC: TCB @ High Temperature (150C)
HPLC: Isocratic or Gradient; Normal & Reverse- Phase
Compatible with LC-MS Set-Up in Parallel

11. LC-IR Applications
Excipient Characterization, Functionality & Degradation Analysis
Copolymer Composition Analysis across MW Distribution
Polyolefin Copolymer Branching Analysis by High Temp GPC-IR
Polymer Blend Ratio Analysis across MW Distribution
Polymer Additive & Impurity Analysis
De-Formulation for Polymers and Additives: Competitive Analysis
Process Control & Optimization
Reactive Polymer Analysis for Coating, Adhesive, Sealant & Elastomer
Plastics, Rubbers, Films, Fibers, Foams, Composites & Biopolymers
Isomer Analysis for Chemicals, Forensics & Pharmaceuticals
General Analytical Capability: Trouble Shooting
11

12. IR Spectrum of Styrene/Butadiene Copolymer
Cove this
The three bands filled in red arise from the styrene
comonomer (1605, 1495, and 698 cm-1)
The green filled band (968 cm-1) is
generated by the butadiene comonomer.
There is no significant overlap of any of these bands by the other comonomer species.

13. Styrene/Butadiene Copolymer
Chemical Composition Across Molecular Weight Distribution
Bulk Average – 10% Styrene
Styrene in eluted polymer - ratio of (styrene) 1495cm-1 / (butadiene) 968 cm-1

14. Excipient Characterization
IR Spectrum of Copovidone VP/VAc Copolymer
Peak 1680 cm-1 from VP comonomer
Peak 1740 cm-1 from VAc comonomer

15. Excipient Copovidone Compositional Drift
with MW Distributions Vs. Bulk Average
GPC-IR Chromatogram Overlay with Comonomer Ratios
Bulk Average
(Molecular Weight Distribution)
Abs. Peak Ratio: AVA / AVP = (k1*b*MVA) / (k2*b*MVP) = k (MVA / MVP) ~ Comonomer Ratio

16. Excipient Functionality Characterization by LC-IR
Copolymer Compositional Analysis with MW Distributions
• Comonomer Ratio Drift (Functional Groups) vs. Bulk Average
• Hydrophilic/Hydrophobic Ratio Drift vs. Phase Separations
• Morphology Effects on Excipient (/Drug) Dissolution Rate
• Excipient Lot-to Lot Variations
• Quality by Design (QbD) Studies
• Excipient Performance & Functional Group Correlations
Various Excipient Copolymers & Terpolymers
• Copovidone: PolyVinyl Pyrrolidone / Vinyl Acetate – PVP/VAc
• Methacrylate Copolymers: Eudragit
• SoluPlus Terpolymer: PEG / PCL / PVAc
Cellulose Derivatives (Lot-to-Lot Variations)
• Hypromellose: HPMC, HPMC-AS, HPMC-P
• HydroxyPropyl Cellulose: HPC, HEC
• Cellulose Esters: CAB, C-A-P 16

17. Degradation Study of Excipient HPMCAS
in Hot Melt Extrusion Process by GPC-IR
HME Processing Temperatures: (Lowest) A < B < C (Highest)

18. Excipient HPMCAS Degradant
in Hot Melt Extrusion Process
IR Database Search Result: Succinic Acid (Degradant)

19. Degradation Study of HPMC-AS Excipient
in Hot Melt Extrusion Process by GPC-IR
Detected Degradant: Succinic Acid
Detected Functionality Ratio Change: Hydroxyl Vs. Carbonyl
Help Understand Excipient Degradation Mechanism
Study Excipient / API Interactions
Fig. A Schematic Structure of HPMC Derivatives, Cellulose Ethers & Esters

20. Excipient HPMCAS Degradation
in Hot Melt Extrusion Process
Functional Group Ratio Changes from High Temp Process (C)

21. Excipient Characterization with LC-IR
in Drug Formulations
• Polymeric Excipient Characterization
• Degradation in Process (Hot Melt Extrusion)
• Excipient / API Interactions
• Forced Degradation in Shelf Life Study
December 1, 2008: Vol. 5, No. 6
The cover cartoon illustrates a solid dispersion assembly that is composed
of entangled polymer chains with drug molecules embedded in the form of
single molecule, small clusters, and/or large aggregates (amorphous).

22. Degradation Study by HPLC-IR
for Degraded PEG-1000 Excipient
Three Chromatographic displays
generated from one time ordered
set of FTIR Spectra

23. Identification of Homologous Series from
Degraded PEG by Reverse Phase HPLC-IR
Na+ or K+ Cation
Aldehyde Carboxylate Salt
1719 1607
11.45 minutes
4.93 minutes
1.50 minutes

24. Proposed Mechanism of PEG Air Oxidation
Supported by LC-IR Data

25. High Temp GPC-IR for Polyolefin Branching Analysis
Polyethylene Sample with & without TCB Solvent
DiscovIR-LC Removes TCB Completely and Gives Clean IR Spectrum (Blue).

26. Polyolefin Branching Analysis by GPC-IR
GPC-IR Chromatogram of PE/PP Copolymer Overlaid with Peak Ratio Abs1378/Abs1468
(Molecular Weight Distribution)
Copolymer Compositional Drift ~ CH3 Branching ~ Peak Ratio A1378/A1468

27. Polyolefin Branching Analysis by Chemometrics
GPC-IR Chromatograms Overlaid with Area Ratios
(Molecular Weight Distribution)
Area Ratio = Area (2940-3100cm-1) / Area (2940-2800cm-1)

28. GPC-IR Branching Analysis of Dow ENGAGE® Polyolefins
Branching Levels (Area Ratios) with a GPC-IR Chromatogram
(Molecular Weight Distribution)
Area Ratio = Area (Peak 1375 cm-1) / Area (Peak 1465 cm-1)

29. Polymer Blend Ratio Analysis by GPC-IR
for EVA / PBMA Mixture
IR spectral bands of EVA & PBMA are closely overlapped.
The 1152 and 2852 cm-1 bands selected for minimal convolution.

30. Polymer Blend EVA/PBMA Ratios with MWD
Determined by Spectral Peak Ratios
4
3.5
mEVA/mPBMA
y = 1.6162x - 0.2149
3
2.5
2
1.5
1
0.5
0
0 0.5 1 1.5 2 2.5
absEVA(2852)/absPBMA(1152)
(Molecular Weight Distribution)
Calibration Curve: Y = 1.6162 X-0.2149 by Flow Injection Method w/o LC Separation
Y is Mass Ratio, X is Peak Ratio Abs(2852)/Abs(1152)

31. Polymer Additive Analysis with
GPC-IR for ABS Plastic w/o Extraction Step
IR chromatogram and ratio plot for ABS sample. Ratio (green) of characteristic
IR absorbance bands for nitrile (2240 cm-1) and styrene (1495 cm-1).

32. Polymer Additive Analysis with
GPC-IR for ABS Plastic w/o Extraction Step
IR spectra at different elution times across the low MW peak of the SEC
analysis of ABS. Spectra indicate presence of multiple components.

33. Polymer Additive Analysis
PolyDiMethyl Siloxane in THF/H2O
PDMS is Difficult to be Detected by UV or RI.
IR is an Universal Detector for Organics

34. De-Formulation of Motor Oil Lubricant
GPC-IR 3D View for Additive Analysis
SAE 15W-40 Heavy Duty Oil in THF
Low MW Mineral Oil Diverted after 12.2 min
Elution
Time
(Min. & MW)
Wavenumber, cm-1

35. De-Formulation of Motor Oil Additives
with GPC-IR (Database Searchable)
De-Formulate Polymeric Additives in Motor Oil Lubricant
Additive #1 @ Retention Time 9.2 Min
•Styrene-Acrylate Copolymer (IR Database Search)
•Narrow MW Distribution ~ Average 600K
•Viscosity Index Improver
•No Comonomer Compositional Drift
Stable [700cm-1/1735cm-1] Band Ratio
Additive #2 @ Retention Time 10-12 Min
•Polyisobutenyl Succinimide (PIBS) (IR Database Search)
•Broad MW Range: 8-30K
•A Dispersant
•Small Comonomer Compositional Drift
[dimethyl (1367cm-1)/imide (1700cm-1)] Ratio Change <10%
Polymer Degradation Study – Oil Change Schedule

36. SUMMARY
DiscovIR-LC is a Powerful Tool for Polymer, Excipient & Materials Analysis
Excipient Characterization, Functionality & Degradation Analysis
Copolymer Compositional Drift Analysis across MW Distributions
Polyolefin Copolymer Branching Analysis by High Temp GPC-IR
Polymer Blend Ratio Analysis across MWD
Polymer Additive & Impurity Analysis
De-Formulation for Polymers, Excipients and Additives
Process Control & Optimization
Reactive Polymer Analysis for Coating, Adhesive, Sealant & Elastomer
Plastics, Rubbers, Films, Fibers, Foams, Composites & Biopolymers
Isomer Analysis for Chemicals, Forensics & Pharmaceuticals
General Analytical Capability: Trouble Shooting 36