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Presentation slides at Eastern Analytical Symposium on Nov. 16, 2009 about LC-IR analytical technology for polymer & excipient analysis.
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LC-IR Hyphenated Technology for
Polymer / Excipient Analysis
Ming Zhou, William Carson, Sidney Bourne,
David Dunn and Tom Kearney
Spectra Analysis, Inc.
Contact: [email protected]
Nov. 16, 20091
OUTLINELC-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
Summary2
Hyphenated Technologies
Gas Phase & Liquid PhaseChromatography
MassSpectroscopy
Infra RedSpectroscopy
Separation
Identification
DiscovIR-GC
DiscovIR-LC
Detection
Data Acquisition & Analysis
GC-MS GC-IRLC-MS LC-IR
4
The DiscovIR-LCTM is a fully automated direct deposition LC-IR analyzer used by chemists to identify unknown components in complex mixtures.
LC-IR Hyphenated System
How Does It Work?
How is the Solvent Removed?
CycloneEvaporator
Thermal NebulizationFrom LC
Nitrogen Addition
ChilledCondenser
Waste Solvent
Particle Stream to DiscovIR
Air CooledCondenser
CycloneEvaporator
Patent pending: PCT/US2007/025207
What is Direct Deposition FTIR?
Direct Deposition FTIR and Data Processing
LC-IR Hyphenated Technology for Polymer Analysis
9
Features of DiscovIR-LC
Online Fully Integrated SystemFully Automated Operation: No FractionationMulti-Sample Processing: 8-40 Hr ZnSe Disk TimeMicrogram Sensitivity at Sample Injection PointReal-Time Chromatography & Spectral DataSolid Phase Transmission IR Spectra: High Quality w/ Purified AnalytesDatabase Search Capability & In-House Library CreationData Analysis: GRAMS for Chemometrics, 3D LC-IR, Functional Group Chromatograms & Comparisons at any Wavenumbers or across PeaksAll LC Solvents: Water, ACN, Methanol, THF, Chloroform, HFIPGPC/SEC: TCB @ High Temperature (150C)HPLC: Isocratic or Gradient; Normal & Reverse- PhaseCompatible with LC-MS Set-Up in Parallel
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
IR Spectrum of Styrene/Butadiene Copolymer
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.
Cove this
Styrene/Butadiene CopolymerChemical Composition Across Molecular Weight Distribution
Styrene in eluted polymer - ratio of (styrene) 1495cm-1 / (butadiene) 968 cm-1
Bulk Average – 10% Styrene
Excipient Characterization IR Spectrum of Copovidone VP/VAc Copolymer
Peak 1680 cm-1 from VP comonomer
Peak 1740 cm-1 from VAc comonomer
GPC-IR Chromatogram Overlay with Comonomer Ratios
Excipient Copovidone Compositional Drift with MW Distributions Vs. Bulk Average
Abs. Peak Ratio: AVA / AVP = (k1*b*MVA) / (k2*b*MVP) = k (MVA / MVP) ~ Comonomer Ratio
(Molecular Weight Distribution)
Bulk Average
Excipient Functionality Characterization by LC-IR
16
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
Degradation Study of Excipient HPMCAS in Hot Melt Extrusion Process by GPC-IR
HME Processing Temperatures: (Lowest) A < B < C (Highest)
Excipient HPMCAS Degradantin Hot Melt Extrusion Process
IR Database Search Result: Succinic Acid (Degradant)
Degradation Study of HPMC-AS Excipient in Hot Melt Extrusion Process by GPC-IR
Fig. A Schematic Structure of HPMC Derivatives, Cellulose Ethers & Esters
Detected Degradant: Succinic AcidDetected Functionality Ratio Change: Hydroxyl Vs. CarbonylHelp Understand Excipient Degradation MechanismStudy Excipient / API Interactions
Excipient HPMCAS Degradationin Hot Melt Extrusion Process
Functional Group Ratio Changes from High Temp Process (C)
Excipient Characterization with LC-IRin 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. 6The 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).
Degradation Study by HPLC-IR for Degraded PEG-1000 Excipient
Three Chromatographic displays generated from one time ordered set of FTIR Spectra
Identification of Homologous Series from Degraded PEG by Reverse Phase HPLC-IR
11.45 minutes
4.93 minutes
1.50 minutes
Na+ or K+ Cation Carboxylate Salt
1607
Aldehyde1719
Proposed Mechanism of PEG Air OxidationSupported by LC-IR Data
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).
Polyolefin Branching Analysis by GPC-IR
Copolymer Compositional Drift ~ CH3 Branching ~ Peak Ratio A1378/A1468
GPC-IR Chromatogram of PE/PP Copolymer Overlaid with Peak Ratio Abs1378/Abs1468
(Molecular Weight Distribution)
Area Ratio = Area (2940-3100cm-1) / Area (2940-2800cm-1)
Polyolefin Branching Analysis by ChemometricsGPC-IR Chromatograms Overlaid with Area Ratios
(Molecular Weight Distribution)
Area Ratio = Area (Peak 1375 cm-1) / Area (Peak 1465 cm-1)
Branching Levels (Area Ratios) with a GPC-IR Chromatogram
(Molecular Weight Distribution)
GPC-IR Branching Analysis of Dow ENGAGE® Polyolefins
Polymer Blend Ratio Analysis by GPC-IRfor EVA / PBMA Mixture
IR spectral bands of EVA & PBMA are closely overlapped. The 1152 and 2852 cm-1 bands selected for minimal convolution.
Polymer Blend EVA/PBMA Ratios with MWD Determined by Spectral Peak Ratios
(Molecular Weight Distribution)
Calibration Curve: Y = 1.6162 X-0.2149 by Flow Injection Method w/o LC SeparationY is Mass Ratio, X is Peak Ratio Abs(2852)/Abs(1152)
y = 1.6162x - 0.2149
0
0.5
1
1.5
2
2.5
3
3.5
4
0 0.5 1 1.5 2 2.5
absEVA(2852)/absPBMA(1152)
mEV
A/m
PBM
A
Polymer Additive Analysis withGPC-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).
Polymer Additive Analysis withGPC-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.
Polymer Additive AnalysisPolyDiMethyl Siloxane in THF/H2O
PDMS is Difficult to be Detected by UV or RI.IR is an Universal Detector for Organics
De-Formulation of Motor Oil LubricantGPC-IR 3D View for Additive Analysis
SAE 15W-40 Heavy Duty Oil in THF
Low MW Mineral Oil Diverted after 12.2 min
Wavenumber, cm-1
Elution Time
(Min. & MW)
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
SUMMARYDiscovIR-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