This document discusses using size exclusion chromatography coupled with Fourier transform infrared spectroscopy (SEC/GPC-FTIR) to characterize pharmaceutical copolymer excipients. Specifically:
1. GPC-IR can analyze copolymer compositional drifts across molecular weight distributions by measuring functional group ratios.
2. It is useful for characterizing lot-to-lot and grade-to-grade variations in polymeric excipients from different manufacturing processes.
3. Case studies on copovidone and HPMCAS excipients show how GPC-IR detects compositional differences between samples and grades.
New LC-IR Technique To Characterize Polymeric Excipients In Pharmaceutical Fo...mzhou45
GPC-IR combined technique to characterize polymeric excipients for lot-to-lot variations and degradation/stability from thermal processing in drug formulations
New LC-IR Technique To Characterize Polymeric Excipients In Pharmaceutical Fo...mzhou45
GPC-IR combined technique to characterize polymeric excipients for lot-to-lot variations and degradation/stability from thermal processing in drug formulations
Cooperative learning in science education is addressed in this article. How students use a very relevant topic of anti-cancer agents, and the novel technique of (Heteronuclear single Quantum Correllation Spectroscopy )2D -HSQC FT-NMR to organize spectra data is shown. Here, undergraduates become familiar with making plots of 1H FT-NMR and 13C FT-NMR , learning FT-NMR data processing (spinworks) and also use Chemdraw NMR to present data take with a Varian 600 MHz FT-NMR spectrometer.
This product can provide synergistic processing and cured resin performance advantages relative to simple mixtures of polyetheramines (PEAs) and cycloaliphatic amines.
Application Note: A Rapid Procedure for Screening Transuranium Nuclides in Ur...PerkinElmer, Inc.
One of the most extensive tasks is the field of bioassay analysis is the determination of pure alpha- (and beta-) emitting radionuclides from the nuclear fuel cycle such as (234)U and (235)U, or anthropogenic (239)Pu and (241)Am in urine samples. However, any radiochemical method, which is applied to perform such analyses, has to be highly sensitive since even small amounts of incorporated radionuclides decaying by alpha emission may contribute to harmful doses to human organs.
Since alpha radiation has an extremely short penetration length in water and solid substances, direct counting of a salt residue of dry ashed urine is not possible. Therefore, complex radiochemical techniques have been developed for efficient separation of the transuranium elements from the bulk matrix. However, in addition to several purification steps, these methods require the production of almost weightless planar sources (e.g. via electrolytic deposition) in order to perform radioassays with proportional or surface barrier detector. In contrast to the extensive preparative techniques, fast methods using alpha/beta-LSC are of increasing interest. Due to the efficient detection of alpha emitters in a liquid scintillation cocktail, extensive radiochemical purification procedures are not necessary provided the sample is homogeneous in the liquid scintillation cocktail.
Deformulating Complex Polymer Mixtures By GPC-IR Technologymzhou45
GPC-IR to de-formulate complex polymer mixtures such as adhesives, coatingg, inks, additives to identify polymer components and find their specific raw material suppliers by IR database search. The presentation was given at American Coating Conference 2012 on May 7 in Indy.
Reaction Mechanism Generator: Cheminformatics for Kinetic ModelingRichard West
This is my 6-minute CINFlash Talk in the Cheminformatics session at the ACS Meeting in Boston, August 2010. For more about RMG visit http://facebook.com/rmg.mit or http://rmg.sourceforge.net/
LC-IR Applications In Polymer Related Industriesmzhou45
LC-IR Application Overview for Polymer Related Industries with Many Case Studies: characterize copolymer compositions across MWD and de-formulate complex polymer mixtures
Cooperative learning in science education is addressed in this article. How students use a very relevant topic of anti-cancer agents, and the novel technique of (Heteronuclear single Quantum Correllation Spectroscopy )2D -HSQC FT-NMR to organize spectra data is shown. Here, undergraduates become familiar with making plots of 1H FT-NMR and 13C FT-NMR , learning FT-NMR data processing (spinworks) and also use Chemdraw NMR to present data take with a Varian 600 MHz FT-NMR spectrometer.
This product can provide synergistic processing and cured resin performance advantages relative to simple mixtures of polyetheramines (PEAs) and cycloaliphatic amines.
Application Note: A Rapid Procedure for Screening Transuranium Nuclides in Ur...PerkinElmer, Inc.
One of the most extensive tasks is the field of bioassay analysis is the determination of pure alpha- (and beta-) emitting radionuclides from the nuclear fuel cycle such as (234)U and (235)U, or anthropogenic (239)Pu and (241)Am in urine samples. However, any radiochemical method, which is applied to perform such analyses, has to be highly sensitive since even small amounts of incorporated radionuclides decaying by alpha emission may contribute to harmful doses to human organs.
Since alpha radiation has an extremely short penetration length in water and solid substances, direct counting of a salt residue of dry ashed urine is not possible. Therefore, complex radiochemical techniques have been developed for efficient separation of the transuranium elements from the bulk matrix. However, in addition to several purification steps, these methods require the production of almost weightless planar sources (e.g. via electrolytic deposition) in order to perform radioassays with proportional or surface barrier detector. In contrast to the extensive preparative techniques, fast methods using alpha/beta-LSC are of increasing interest. Due to the efficient detection of alpha emitters in a liquid scintillation cocktail, extensive radiochemical purification procedures are not necessary provided the sample is homogeneous in the liquid scintillation cocktail.
Deformulating Complex Polymer Mixtures By GPC-IR Technologymzhou45
GPC-IR to de-formulate complex polymer mixtures such as adhesives, coatingg, inks, additives to identify polymer components and find their specific raw material suppliers by IR database search. The presentation was given at American Coating Conference 2012 on May 7 in Indy.
Reaction Mechanism Generator: Cheminformatics for Kinetic ModelingRichard West
This is my 6-minute CINFlash Talk in the Cheminformatics session at the ACS Meeting in Boston, August 2010. For more about RMG visit http://facebook.com/rmg.mit or http://rmg.sourceforge.net/
LC-IR Applications In Polymer Related Industriesmzhou45
LC-IR Application Overview for Polymer Related Industries with Many Case Studies: characterize copolymer compositions across MWD and de-formulate complex polymer mixtures
AAPS2011 Oral--Analytical Techniques To Characterize Excipient Stability &...mzhou45
AAPS2011 Oral Presentation at Hot Melt Extrusion Symposium on Oct. 26, 2011 in Washington DC Titled "Analytical Techniques to Characterize the Stability & Degradation of Polymeric Excipients from Hot Melt Extrusion Processing
Analysis based Method development & Validation projects will be providedanaloglabs
1. ICH Guidelines
2. Assay , Dissolution, Content Uniformity & Related substances Validation
3. Cleaning Validation
4. Preparation of Protocol & Report
5. How to submit Thesis
6. Calculation all parameters
7. Explanation of entire project process for mini projects (B.Pharmacy), Major Projects (M.Pharmacy and M.Sc) and Phd thesis for presentation and paper submission
Analog Labs- Analytical validation and Method development Training in AR&Danaloglabs
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3. Method validation by HPLC - Assay, Dissolution, Content Uniformity & Related substances Validation
4. Cleaning Validation
5. Preparation of Protocol & Report
6. Interview based training
II. Analytical Method Development & Validation by HPLC short term (only for groups i.e. min 5 students): Fee Rs.1500/- [Theory , Interview Orient Material , Certificate] – 2 days (Mon – Tues)
1. Concept & Method development by HPLC
2. ICH Guidelines
3. Method validation by HPLC - Assay, Dissolution, Content Uniformity & Related substances Validation
4. Cleaning Validation
5. Preparation of Protocol & Report
6. Interview based training
Analog Labs - SAS IN PHARMA INDUSTRY & Basic CDM:analoglabs
SAS – Basic Training & Complete Material short term 1 day training – Rs 1500/-
Following Material will be provided
1. SAS interview Questions and answers
2. Certification eBooks & Training material
4. Software
5. Projects - Clinical, market research & Finance
6. Sample programmes & Tutorials (cDISC)
7. Resumes tips & Assignments for Practice
This high performance liquid chromatograph (HPLC) is the first-ever instrument designed specifically for quantitative determination of cannabinoid content. Ready for use after one day of installation and testing, it provides a choice of three different HPLC methods and a dedicated user interface for a simplified workflow.
How to Sales & before Sale Selling your Self !
Steps of Sales , This presentation ideal to learn more and follow steps of selling.
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Excipient Knowledge Management Mumbai 12 March 2015 Part 1 & 2Ajaz Hussain
Why attention to excipient knowledge management (specifically their functionality) is critical to mitigating risks (or to leverage opportunities) posed by the rapidly increasing complexity and uncertainty
Note: Knowledge management in the context of ‘intellectual property’ is not the focus of this talk
Plant hormones are of vital importance for normal functioning of plants that coordinate the growth and development of plants with response to the environment. Plant hormones are difficult to analyze because they occur in very low amounts in plant extracts which are very rich in interfering substances, especially secondary metabolites. To cope with this problem the plant extract must undergo several purification steps using unrelated separation mechanisms in order to increase orthogonality and purification efficiency (Dobrev et al., 2005). High performance liquid chromatography and Gas liquid chromatography are frequently used in the purification and quantification of plant hormones like Abscisic acid, Indole acetic acid etc.
A method for estimation of Abscisic acid in Arabidopsis thaliana includes an extraction of plant tissues with acetone/water/acetic acid (80:19:1, v/v), evaporation of the extracts and finally injection into the liquid chromatography-electrospray ionization tandem mass spectrometry (LC–ESI–MS–MS) system in multiple reaction monitoring (MRM) mode (Carbonell and Jáuregui, 2005).
A novel metabolic profiling approach to the analysis of acidic phytohormones and other metabolites based on a simplistic preparation scheme and analysis by chemical ionization-gas chromatography/mass spectrometry has also been developed (Schmelz et al., 2004). But Current metabolomic approaches are able to quantify highly abundant primary and secondary metabolites but do not perform well at detecting trace levels of phytohormones.
Separate profiling methods, with comparatively more elaborate sample preparation procedures, are now making phytohormone profiles accessible using trace analysis chemical ionization GC/MS techniques. Using LC/MS detection, a significant phytohormone profiling advance was recently achieved (Chiwocha et al. 2003).
Research Inventy : International Journal of Engineering and Scienceresearchinventy
Research Inventy : International Journal of Engineering and Science is published by the group of young academic and industrial researchers with 12 Issues per year. It is an online as well as print version open access journal that provides rapid publication (monthly) of articles in all areas of the subject such as: civil, mechanical, chemical, electronic and computer engineering as well as production and information technology. The Journal welcomes the submission of manuscripts that meet the general criteria of significance and scientific excellence. Papers will be published by rapid process within 20 days after acceptance and peer review process takes only 7 days. All articles published in Research Inventy will be peer-reviewed.
ISES 2013 - Day 2 - Professor John M. Dhaw (Professor, University of Albert...Student Energy
Game-Changing Technologies In The Oil and Gas Industry
How does the shale gas situation in the world change energy markets, are oil sands a part of the future and can subsea help provide the future with energy?
ISES 2013 - Professor John M. Shaw (Professor, University of Alberta) - Ener...Student Energy
How does the shale gas situation in the world change energy markets, are oil sands a part of the future and can subsea help provide the future with energy?
In this work, dynamic simulation of reaction kinetics at particle scale using COMSOL Multiphysics is carried out. It was observed that the reaction rate and kinetics inside the pores of the catalyst is of higher magnitude as compared to bulk of the liquid. When the reactant mixture is mixed with solid catalyst particles it becomes a uniform particulate-liquid suspension at sufficiently high mixing speed in a batch reactor. Keeping this as hypothesis for the determination of kinetics where each solid catalyst particle is surrounded by reactant mixture which is of equal volume for all the catalyst particles, a dynamic simulation is carried out using COMSOL Multiphysics which has solver for diffusion-reaction equation for both in liquid phase and inside particle. The intrinsic reaction rate constants for bulk liquid phase and the particle are obtained by solving the diffusion-reaction equation and optimization method. The model prediction of overall kinetics is presented.
HPLC2010 Pharmaceutical Copolymer Excipient Characterization By GPC-FTIR
1. HPLC 2010 Boston: P2062T
Pharmaceutical Copolymer Excipient
Characterization by SEC/GPC-FTIR
William W. Carson; David Dunn; Jim Dwyer;
Ming Zhou; Tom Kearney
Spectra Analysis Instruments, Inc.
June 20, 2010
Contact: CarsonW@Spectra-Analysis.com
1
6. Excipient Characterization by GPC-IR
Copolymer Compositional Analysis with MW Distributions
• Comonomer Ratio Drift (Functional Groups) vs. Bulk Average
• Excipient Lot-to-Lot Variations: QbD Studies
Excipient Performance & Functional Group Correlations
• Hydrophobic/Hydrophilic Ratio Drift vs. Phase Separations
• Effects on Excipient Dissolution Behavior
Reference
(1) Chemical Heterogeneity on Dissolution of HPMC,
EU J. of Pharma Sci., P392 (2009), A. Viriden et al.
(2) Comp Drift Effect on Dissolution of PMMA/MAA,
Materials Letters, P1144 (2009), E. Manias et al.
6
7. IR Spectrum of Copovidone Excipient –
VP/VAc Copolymer from GPC-IR
Peak 1680 cm-1 from VP comonomer
Peak 1740 cm-1 from VAc comonomer
8. Excipient Compositional Drift (IR Peak Ratios)
with MWD Vs. Bulk Average
GPC-IR Chromatogram Overlay with Comonomer Ratios
Copovidone
Bulk Average
(Molecular Weight Distribution)
Abs. Peak Ratio: AVA / AVP = (k1*b*MVA) / (k2*b*MVP) = k (MVA / MVP) ~ Comonomer Ratio
9. Excipient Compositional Drift (%VAc)
with MWD Vs. Bulk Average
.6
Copovidone: sample A 50
molecular weight
% acetate comonomer
.5
distribution
max. IR absorbance
45
.4
.3 Bulk Average comonomer composition 40
40% VAc distribution
.2
35
.1
0 30
106 105 104 103 102 Molecular Weight
10. Copovidone Compositional Drifts (%VAc)
from Different Manf. Processes
.6
Copovidone: sample A
50
sample B
% acetate comonomer
.5
sample C
45
.4
Molecular Weight
max. IR absorbance
Distribution Comonomer Composition
.3
Distribution
40
Bulk 40% VAc
.2
35
.1
0 30
106 105 104 103 102 Molecular Weight
Copovidone A gave clear tablets while Copovidone C led to cloudy ones.
11. IR Spectrum Difference of Two Grades of HPMC
(Type 2910 & 2208) from GPC-IR
-C-O-C-
OH CH2
HP
OCH3 CH2 CH3
12. HPMCAS Grade-to-Grade
Difference (LF, MF, HF) by GPC-IR
-C-O-C-
Backbone
HOOC-CH2-CH2-C=O Ether
AS A 1060
C=O Acetyl
1740 1235
CH3-C=O
HP
C/HP M
CH3
OH OCH3
1372
3470 2830
13. IR Band Identifications of HPMCAS Excipient
HOOC-CH2-CH2-C=O
CH3-C=O
Groups HP M C A AS Notes
CH3 1372 HP
OCH3 2830 M
OH 3470 (Unsub. OH & HP OH) OH
COCH3 1235 A
Total C=O 1740 AS
CH2 2935 2935 2935 2935 CH2
C-O-C 1060 BackBone
(BB)
17. Total C=O AS / Backbone Ratio Drifts of 2 HPMCAS
Samples with Elution Time (MWD)
ES1
SE2
18. To Find Succinic Acid Level on Backbone
(AS/Backbone)- k (A/Backbone) => S / Backbone
ES1
AS / BB Ratios
SE2
ES1
SE2 A / BB Ratios
Absorptivity Ratio k
Needs to be Calibrated
from Known Standards
21. To Find Unsubstituted OH on Backbone
(OH/Backbone)- k (HP/Backbone) => Unsub. OH / Backbone
Absorptivity Ratio k Needs to be Calibrated from
Known Standards
ES1
HP / BB Ratios
SE2
ES1
OH / BB Ratios
SE2
22. Methoxy / Backbone Ratio Drifts of 2 HPMCAS
Samples with Elution Time (MWD)
ES1
SE2
23. 2935cm-1 CH2 / Backbone Ratio Drifts of
2 HPMCAS Samples with Elution Time (MWD)
SE2
ES1
24. 2935 CH2 / BB & 2935 CH2 / AS Ratio Drifts of 2
HPMCAS Samples with Elution Time (MWD)
SE2
Peak 2935 / AS
ES1
Peak 2935 / BB
SE2
ES1
25. Small HP/AS Ratio Drifts of 2 HPMCAS Samples
with Elution Time (MWD)
SE2
ES1
26. Backbone/AS & HP/AS Ratio Drifts of 2 HPMCAS
Samples with Elution Time
SE2
BB / AS
ES1
SE2
HP / AS
ES1
35. GPC-IR Conclusions
GPC-IR Takes Snapshot IR Pictures of Polymer Excipients
for Compositional Drifts with MW Distributions
Many Ways to Analyze Functional Group Drifts w/ MWD:
Group vs. Backbone, Various Ratios among Groups, etc.
Useful to Characterize Lot-to-Lot, Grade-to-Grade and
Supplier-to-Supplier Variations of Polymeric Excipients
Understand Excipient Manufacturing Variables and QC
GPC-IR is a Powerful Tool to Analyze Compositional
Variations of Copolymers across MWD
37. Excipient Analysis 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).
38. GPC-IR Applications for Excipient Analysis
in Drug Formulations
Excipient Formulation Develop. Formulated Drugs
Manufacturing Drug Manufacturing Shelf Life Stability
• Process Control • Incoming QC • Stressed
• Lot-to-lot • Excipient Degradation
Variations Functionality
• CoA • Formulation • De-Formulate
Development Excipient Blends
• Novel Excipient • QbD
R&D • Trouble-Shoot
• Process Degradation Problem Drugs in
• Trouble Shooting (Hot Melt Extrusion) the Market
• Define Safe Process
Window / QbD
• Process Monitoring
• Trouble Shooting
Users: Excipient Pharma Co. Pharma Co.
Manufacturers HME Service Providers Generic Drug Co.
39. Excipient QbD Space
GPC-IR-Performance
Slide from USP International Excipient Workshop (July 2009)
Performance
GPC
IR
40. GPC-IR & HPLC-IR Applications
Excipient Characterization, Functionality & Degradation Analysis
Copolymer Compositional 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
Excipients, Plastics, Rubbers, Films, Fibers, Foams & Composites
Reactive Polymer Analysis for Coating, Adhesive, Sealant & Elastomer
Isomer Analysis for Chemicals, Forensics & Pharmaceuticals
General Analytical Capability: Trouble Shooting
40