Fingerprinting Emulsions and Micro-emulsions using ......Fingerprinting Emulsions and...
Transcript of Fingerprinting Emulsions and Micro-emulsions using ......Fingerprinting Emulsions and...
Fingerprinting Emulsions and Micro-emulsions using Solvent NMR
Relaxation and Diffusion measurements
15th AIChE Annual Meeting Salt lake City, UT, November 9th 2015
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David Fairhurst, PhD. and
Sean Race XiGo Nanotools, Inc.
Characterization of Emulsions: Limitations of Current Techniques
Though widely used, traditional techniques have limitations that make them unsuitable for analysis of many emulsion systems Light Microscopy, Image Analysis, Confocal Scanning Microscopy q Small sample size - Time consuming – Can distort droplet shape and size - Cannot
measure nano- and micro-emulsions
Laser Light Scattering q Dilution step disrupts many emulsions - Cannot distinguish between droplet and
suspended solid particle - Droplet clusters are estimated as large droplets - Cannot measure micro-emulsions
Electrozone Sensing q Requires dilution - Large number of droplets need to be measured individually -
Limited to O/W emulsion systems - Cannot measure micro-emulsions Acoustic Attenuation q Signal attenuates drastically with high solid-content samples and the presence of air XIGO Nanotools 2015 2
Micro-emulsions Increase in use in major industrial applications q enhanced oil recovery q drug carriers Thorough characterization of colloidal (nano) systems essential q problems with study of micro-emulsions
q form spontaneously at specific Oil/Water compositions q thermodynamically stable q destroyed on dilution or alteration of composition q study is difficult – few techniques available
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Practical Advantages of NMR Relaxation and Diffusion measurements
q any liquid (with at least one H atom) q includes mixtures of (miscible) liquids
q wide internal phase concentration range: 1% to 70+% (HIPE) q no dilution, no sample preparation
q rapid measurements (typically minutes) q small samples (typically 0.1mL; as little as 200µL) q non-invasive, non-destructive
q samples can be stored and re-measured
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NMR Gradient Coils
Relaxation: Fixed Uniform field Diffusion: Variable Field Gradient
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NMR Relaxation Free Induction Decay
Spin-echo relaxation: T2 method
Spin-lattice relaxation: T1 method
Choice of T1 or T2 depends on specific application
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CPMG pulse sequence
Inversion Recovery pulse sequence
Emulsions
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Regular emulsions are two phase systems: O/W or W/O Each phase has an intrinsic relaxation time → composition dependent Single exponential (blue line) to the relaxation data (red dots) not appropriate Requires a double exponential fit → two resultant relaxation times: short T and long T
NMR relaxation can clearly distinguish between the two phases
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Emulsions: Rheology data*
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For each emulsion pair: (a) as Viscosity ↑ the long T2 ↓ (b) as Yield ↑ the short T2 ↓
0.01000 0.1000 1.000 10.00 100.0 1000shear stress (Pa)
0.1000
1.000
10.00
100.0
1000
10000
1.000E5
1.000E6
1.000E7
visc
osity
(Pa.
s)Sample 1_O-W lotion_050415-0001f, Steady state flow stepSample 2_O-W emulsion_050415-0006f, Steady state flow step
Emulsion pair 1
NMR relaxation correlates well with emulsion viscoelastic characteristics
Sample Viscosity (Pa.s)
Yield (Pa)
Short T2 (ms)
Long T2 (ms)
Jergens 93,640 20 80 302
Generic** 66,790 10 278 541
Aveeno 280,170 100 256 497
Generic 450,040 170 148 337
Gold Bond 233,700 60 77 251
Generic 280,400 110 47 244
*TA Rheometer Model AR 1000
** Studio 35, Walgreens
Jergens
Generic
Model Micro-emulsions
Formulation Water Composition 1. 47% oil, 53% water 4% surfactant, 2.0% NaCl, 2.5% co-solvent 2. 62% oil, 38% water 4% surfactant, 2.0% NaCl, 5.0% co-solvent 3. 44% oil, 56% water 4% surfactant, 2.2% NaCl, 5.0% co-solvent 4. 77% oil, 23% water 4% surfactant, 1.7% NaCl, 5.0% co-solvent
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Oil= n-decane Co-solvent= 2-butanol
Micro-emulsions 1
Oil-rich phase Microemulsion Water-rich phase
1
2 3 4
Relaxation plot for Sample #2 model micro-emulsion
At high magnetization values (short time) single exponential fit (blue line) to the data (red dots) is not good → indicates two phases
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** Sudan Red Dye Soluble in oil
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Micro-emulsions 2 Sample Microemulsion
T2 relaxation time (ms)
Short T2 Long T2
1 925 1960
2 510 1400
3 940 1920
4 380 1100
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Short T2 Relaxation Times
NMR short T2 relaxation times track directly with % Oil in microemulsions
0 100 200 300 400 500 600 700 800 900
1000
#1 47% Oil #2 62% Oil #3 44% Oil #4 77% Oil
Double exponential fit to the relaxation curve results in two T2 values
Micro-emulsions 3
Sample 6: Original aqueous phase used to prepare Sample 2: 4% surfactant; 2% NaCl; 5% co-solvent Sample 10: Aqueous phase extracted from 3-phase system of Sample 2
NMR relaxation useful new tool to study the formulation of micro-emulsion systems
0
500
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3000
2% NaCl Sample #6 Sample #10
T2 Relaxation times
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NMR Diffusion
Signal echo is attenuated as droplets diffuse under the influence of an increasing field gradient
Signal Echo Attenuation and Drop Size
Increasing drop size
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.4 µ .5µ .6µ
Validation of NMR Technique Fundamental Measurement is Diffusion
0.01
0.10
1.00
20 200
Diffu
sion/10-
9 /m
2 s-1
Mw/g
Diffusion data for an homologous series of eight n-Alkanols Solid line – literature values Red dots ● Acorn Drop
Methanol
Decanol
Heptanol Pentanol Hexanol
Octanol
Butanol
Ethanol
Comparison Of Droplet Size Monodisperse PDMS-in-Water Emulsions
20µm 74µm
Nominal Size (µm) Visual
Measured Size (µm) NMR
20 19.8 40 38.9 51 49.9 64 62.7
74 71.8
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q Does not require any dilution step, or other pre-treatment prior to measurement q Bulk measurement of opaque or colored samples q Highly viscous, semi-solid emulsion systems (butter, asphalt….) q Presence of solid particles is not misinterpreted as droplets q Wide range of droplet sizes can be quantified including nano- and micro-
emulsions
Advantages of TD-PFG* NMR
q Measure self-diffusion coefficients of molecules q Emulsion formulation development and performance characterization q Quantify emulsification efficiency q Determine emulsion stability kinetics q Study accelerated aging under controlled (e.g. ICH) guidelines
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*Time Domain Pulse Field Gradient
Practical Uses of NMR Diffusion
Oil-in-Water Emulsions
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Comparison of six commercial lotions Sample Diffusion (m2 s-1)
Jergens 4.01 x 10-10
Generic* 4.46 x 10-10
Aveeno 1.98 x 10-10
Generic* 2.57 x 10-10
Gold Bond 2.12 x 10-10
Generic* 1.04 x 10-10
Attenuation
* Studio 35™, Walgreens, USA Micrograph Image
Virtually impossible to determine a precise droplet size from microscopy or light scattering
NMR easily tracks relative compositional differences
O/W Microemulsions
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0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
1
0 0.5 1 1.5 2 2.5
Sample 1
Sample 2
Sample 3
Sample 4
Attenuation functions
13 2
4
Sample Diffusion Coefficient (m2 s-1)
1 9.54 x 10-10
2 6.46 x 10-10
3 8.73 x 10-10
4 8.44 x 10-10
Symbols are experimental data points; lines are the fit Sample 1 and Sample 2 are markedly different Samples 3 and 4 are virtually identical
NMR can be used to easily fingerprint microemulsions
Conclusions q Controlling and understanding the relative affinities
of components critical for development of useful microemulsion systems
q NMR measurements can be used to fingerprint
preparation of emulsions and micro-emulsions q used at any step from R&D through QC and Process
control q provides insights into complex formulations
q NMR is non-invasive and non-destructive
q samples can be stored and re-measured
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Acorn Area™
q Patented*, low-field** (13MHz) NMR device q R&D and QC/QA laboratory use
q Batch mode q Time mode q Two temperature control options
Acorn Flow™
q Flow-thru option for the Acorn Area q Continuous sampling, addition of reactants, etc
q Heterogeneous and/or settling suspensions
Acorn Drop™
q Measures droplet size of emulsions without dilution q Two ranges: 1µm to 100µm (2Q 2015) and 1nm to 500nm (2016)
Acorn Chek™
q Production and process control in manufacturing (2016) * Patents issued in US, EU, China and Japan
** C.L. Claves et al, Surface Area Determination via NMR: Fluid and Frequency Effects, Powder Technology, 54(4) 261 (1988)
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Thank you
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