encapsulation in double emulsions fundamental analysis of ... · experimental setup for...
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Encapsulation in double emulsions Fundamental analysis of stability
S. Nachtigall, C. Holtze, A. Laurenzis, S. Bachmann, M. Vranceanu, G. Oetter, F. Runge (BASF SE)V. Götz, S. Hosseinpour, W. Peukert (FAU Erlangen)N. Leister, H. P. Karbstein (KIT Karlsruhe)
Formula X I Manchester I 24-27th June 2019
Potential applications - Encapsulation of… …enzymes, proteins or peptides for detergents …hydrophilic bioactive ingredients (e.g. vitamins) for
cosmetic and food applications …hydrophilic crop protecting agents and active
ingredients in pharmaceuticals
Double emulsions: promising structures to encapsulate hydrophilic active ingredients
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Inner aqueous phase (W1)including active ingredients
Outer aqueous phase (W2)
Hydrophobic shell material (liquid or solid)
W/O-emulsifierO/W-emulsifier
Benefits Stability/protection of active ingredients Triggered or retarded release Taste/smell masking Drift and washing-out prevention
Double emulsions – example “Hollow microcapsules”
200 µm
Curing
Closedcapsule
Activeloading
Porous capsule
Concept Filling of empty, porous capsules with active
material Pores of capsules to be closed after filling
Benefits Universal capsules for various active ingredients Biodegradable capsule matrix
@BASF @customer
200 µm
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Lipophilic surfactant (W/O-emulsifier) High energy input (e.g. gear rim
dispersing device)
Polymer and solvent
H2O
FiltrationDistillation of solvent
Washing
Step 1: W1 in O emulsification Step 2: (W1/O) in W2 emulsification
Hydrophilic surfactant (O/W-emulsifier) Low energy input (e.g. stirred vessel)
Double emulsions – example “Hollow microcapsules”
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Double emulsions: challenges
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Advantages Various different applications
Preparation with common equipment
DiffusionCoalescence
BUT Big challenge to keep active inside
No guidelines for process and product development
Double emulsions: challenges Analysis of coalescence- and diffusion phenomena in W1/O/W2-double emulsions
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New analytical approaches for investigating instability mechanisms
Influence of process parameters
Identification of structure/property-relationships
Guidelines for faster formulation and process development
Formulation and process development based on molecular understanding
W/O-emulsifierO/W-emulsifier
Diffusion and coalescence at interfaces: single drop experiments & interfacial tension measurements
Characterization of interfaces via nonlinear spectroscopy (SFG, SHG)
Supported by molecular modeling (BASF)
Analysis of double emulsions in different scales
Methods to investigate instability mechanisms
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tcoalescence tdiffusion*
*S. M. Neumann, CC BY
Diffusion and Coalescence Time Analyzer*Influence of emulsifier systems
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*S. M. Neumann, U. van der Schaaf, H.P. Schuchmann: The Diffusion and Coalescence Time Analyzer (DCTA): A novelExperimental setup for investigating instability phenomena in double emulsions. Food Structure 12 (2017) 103 – 112.
OW2
Water - MCT TO8 - MCT TO8 - PGPR Water - PGPR0
15
30
45
60
Coa
lesc
ence
tim
e in
s
>300 sOil phase: Miglyol® 812O/W-emulsifier: Lutensol® TO8, 0.1 wt%W/O-emulsifier: PGPR, 0.1 wt.%
Without emulsifier
+ Lutensol TO8 ®
+ PGPR+ PGPR+ Lutensol®
TO8
> 300 s
Diffusion and coalescence at interfacesInfluence of emulsifier system
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1E-7 1E-6 1E-5 1E-4 0,001 0,01 0,1 10
10
20
30 10-6wt%TO8 10-3wt%TO8 10-1wt%TO8
IFT
in m
N/m
PGPR concentration in wt%1E-7 1E-6 1E-5 1E-4 0,001 0,01 0,1 1
0
10
20
30
IFT
in m
N/m
PGPR concentration in wt%
Oil phase: Miglyol® 812W/O-emulsifier: PGPRO/W-emulsifier: Lutensol® TO8tcoal = 5 s
tcoal = 35 s
tcoal > 300 stcoal = 30 s
tcoal = 25 s
tcoal = 23 s
0
OW2
O/W-emulsifier disturbs stability
Analysis of emulsifier diffusionInterfacial tension measurements
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1 wt% 0.1 wt%
10 100 1000 10000 1000000
2
4
6
8
10
12
14
16
18
20
IFT
in m
N/m
Time in seconds
Oil phase: Miglyol® 812O/W-emulsifier: Lutensol® TO8
Determination of emulsifier diffusion via interfacial tension
Characterization of interfaces Nonlinear spectroscopy (SFG, SHG)
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Experimental SFG setup
Planar setup Scattering setup
Experimental SHG setup
Fundamental analysis Learning about systems
Analysis of real emulsions
Interfacial emulsifier composition
Second Harmonic Generation (SHG): amount of molecules at interface (intensity)
Sum Frequency Generation (SFG): type and orientation of molecules (spectra)
2800 3000 3200 3400 3600
SFG
nor
m. s
igna
l (a.
u.)
IR Wavenumber (cm-1)
water MCT on water
Characterization of interfaces Planar SFG spectra I Influence of O/W-emulsifier
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Distinction between Miglyol® 812 and Lutensol® TO 8 is possible
Lutensol ® TO 8 dominates at interface
Ordered and covering layer of surfactant
Detection of O/W-emulsifier at interface
2800 3000 3200 3400 3600
SFG
nor
m. s
igna
l (a.
u.)
IR Wavenumber (cm-1)
water MCT on water 0.1 wt% Lutensol TO 8 in water
2800 3000 3200 3400 3600
SFG
nor
m. s
igna
l (a.
u.)
IR Wavenumber (cm-1)
water MCT on water 0.1 wt% Lutensol TO 8 in water MCT + 0.1 wt% Lutensol TO 8 on water
Water spectrumWater I Miglyol® 812Water + 0.1 % Lutensol® TO8Water + 0.1 % Lutensol® TO8 I Miglyol® 812
Characterization of interfaces Scattering SHG analysis I Adsorption of Malachite green
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0 2 4 6 8 10 12 14 16 18 20
4000
8000
12000
16000
20000
24000
28000
MCT-SDS (0.3 mM, 190 nm)
Hexadecane-SDS (0.3 mM, 180 nm)
MCT-Texapon (24 mM, 182 nm)
SHG
cou
nts
Malachite green (µM/l)
Miglyol® 812 I Texapon® NSO(24 mM, d = 182 nm)Miglyol® 812 I SDS (0.3 mM, d = 190 nm)Hexadecane I SDS (0.3 mM, d = 180 nm)
Emulsion production: UltrasoundDispersed phase: Miglyol® 812 (φ=1 %)Continuous phase: water + surfactantAddition of malachite green
Different types of adsorption depending on emulsion properties
Surfactant molecules: replacement, binding on, relocation…
Double emulsions - Summary & Outlook
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Advantages Various different applications
Preparation with common equipment
Challenges Keeping the active inside → stability issues
No guidelines for process and product development
Analysis of instability mechanisms New technical approaches to analyze instability mechanisms and for the characterization of interfaces
Applicability of analytical approaches shown
Next steps: screening of different emulsifiers and transfer of gained knowledge to real systems