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High Throughput Approach for Agricultural Formulation Optimization

P. F. Augusto, K. Harris, M. I. Michen, L. G. Madrigal, S.-S. Ng, L. B. Quencer, C. J. Tucker, J. Mu The Dow Chemical Company April 25th, 2013

High Throughput Research at Dow

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Sample

Preparation Properties Performance

70

60

50

40

30

Su

rfa

ce T

en

sio

n (

mN

/m)

0.001 0.01 0.1Concentration (wt%)

Tergitol A Tergitol B Tergitol C Tergitol D Tergitol E Tergitol F Tergitol G Tergitol H Tergitol I Tergitol J

Do

w C

lea

nin

g In

de

x

12

13

14

15

16

17

2-EH - 10% 2-EH - 15% 2-octanol - 10%2-octanol - 15%

Dowanol PnB - 10%Dowanol PnB - 15%

PnHex - 10%PnHex - 15%

Tide-Snow

Solvent

All PairsTukey-Kramer 0.05

RsquareAdj RsquareRoot Mean Square ErrorMean of ResponseObservations (or Sum Wgts)

0.3975770.3593280.82126914.49079

135

Summary of Fit

SolventErrorC. Total

Source 8

126 134

DF 56.08695 84.98491 141.07186

Sum of Squares 7.01087 0.67448

Mean Square 10.3944

F Ratio <.0001Prob > F

Analysis of Variance

2-EH - 10%2-EH - 15%2-octanol - 10%2-octanol - 15%Dowanol PnB - 10%Dowanol PnB - 15%PnHex - 10%PnHex - 15%Tide-Snow

Level 15 15 15 15 15 15 15 15 15

Number 14.4771 14.2851 15.2826 14.3529 14.2351 13.9370 13.3073 15.4482 15.0918

Mean0.212050.212050.212050.212050.212050.212050.212050.212050.21205

Std Error 14.057 13.865 14.863 13.933 13.815 13.517 12.888 15.029 14.672

Lower 95% 14.897 14.705 15.702 14.773 14.655 14.357 13.727 15.868 15.511

Upper 95%

Means for Oneway Anova

Oneway Anova

Oneway Analysis of Dow Cleaning Index By Solvent

Symyx XCM

Har

dwar

e S

oftw

are

• Catalysis, synthesis and polymerization (new materials) • Liquid formulations (agricultural, home and personal care, electronic materials) • Coatings and adhesives (water-borne and reactive) • Thermoset and thermoplastic formulation and application

Dow is a leading innovator in high throughput with an initial investment of > $100 million in the early 2000s

Combinatorial Design of Experiments

Formulation Constraints

Experimental Constraints

DOE: Understanding Reproducibility and

Modeling Needs

Library Studio

Experimental Variables

Design Parameters

Formulation Components

Equations

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Informatics Is Critical

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Dow has various information research groups that work to develop and integrate the best hardware and software options for HTR

Mining & Modeling

Combinatorial DOE

Automated Formulation

System

Data Collection & Processing

Data Analysis & Visualization

Phase Diagrams

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Other Screens Rheology, chemical/thermal stability, cleaning, solubility, cloud point, wetting, etc.

Instructed Volume

Experimental Design

Ternary Phase Diagram

Output • Number of phases • Volume fraction of

each phase • Optical clarity of each

phase

Visualization Software

Automated Liquid Handler Phase Characterization

Phase Identification and Characterization Apparatus

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• Heating/cooling programmable controller • Mixing capabilities: Variable time/speed control • Birefringence filters • Digital imagery with side and back lighting • Analyzes for optical clarity, color and uniformity • 6-plate deck (~45 min/ plate)

Vial Tray Deck Vortex mixer

Vial in gripper

Wrist shaker

Imaging Chamber

Temperature Scanning Turbiometry (TST)

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• Samples are video recorded and software detects opacity changes

• Device ramps 48 samples through a temperature sweep using various min/ max temperatures and adjustable heating rates

HTR Performance Evaluation Capabilities

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• Solubility/compatibility • Surface tension/CMC • Foam generation and stability • Wetting • Solubilization • Emulsion stability • Rheology • Freeze/thaw stability • Optical clarity • Application-specific screens

Nonionics Tested StructureA 2-Ethyl-hexyl- (PO)2(EO)4B 2-Ethyl-hexyl- (PO)3(EO)7C 2-Ethyl-hexyl- (PO)1(EO)8D 2-Ethyl-hexyl- (PO)9(EO)9E 2-Ethyl-hexyl- (PO)11(EO)11F Undecyl-(PO)1.5(EO)7G Undecyl-(PO)2(EO)7H Undecyl-(PO)3(EO)7I TERGITOL NP-9J TERGITOL 15-S-9

70

60

50

40

30

Sur

face

Ten

sion

(mN

/m)

0.001 0.01 0.1Concentration (wt%)

TERGITOL ATERGITOL BTERGITOL CTERGITOL DTERGITOL ETERGITOL FTERGITOL GTERGITOL HTERGITOL ITERGITOL J

Nonionics Tested StructureA 2-Ethyl-hexyl- (PO)2(EO)4B 2-Ethyl-hexyl- (PO)3(EO)7C 2-Ethyl-hexyl- (PO)1(EO)8D 2-Ethyl-hexyl- (PO)9(EO)9E 2-Ethyl-hexyl- (PO)11(EO)11F Undecyl-(PO)1.5(EO)7G Undecyl-(PO)2(EO)7H Undecyl-(PO)3(EO)7I TERGITOL NP-9J TERGITOL 15-S-9

70

60

50

40

30

Sur

face

Ten

sion

(mN

/m)

0.001 0.01 0.1Concentration (wt%)

TERGITOL ATERGITOL BTERGITOL CTERGITOL DTERGITOL ETERGITOL FTERGITOL GTERGITOL H

TERGITOL ATERGITOL BTERGITOL CTERGITOL DTERGITOL ETERGITOL FTERGITOL GTERGITOL HTERGITOL ITERGITOL J

100

80

60

40

20

0

Clo

ud p

oint

(°C

)

1.00.80.60.40.20.0Concentration (M)

Na2SO4

S-7S-9S-12S-15S-20S-30S-40

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0.0

Cla

rity

(vol

ts)

1086420Na2SO4 concentration (wt %)

S-7S-9S-12S-15S-20S-30S-40

1% TERGITOL 15-S

Agrochemical Formulation Development

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When traditional formulation approaches are limited… High throughput methods speed up new formulation development • Reformulation to meet new regulatory requirements • Aromatic solvent replacement • Multi-active compatibility • Tank mix compatibility • Customized projects

Example: Reformulation of Emulsifiable Concentrate

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Example of a failed emulsion: Example of a good emulsion:

Hei

ght

Hei

ght

Opacity Opacity

Height level 1

Height level 2

Height level 3

Uniform opacity at different height levels

Different opacity at different height levels

CIPAC MT36

40% AI 51% Solvent 9% Emulsifier

96 formulations

in 45 min

Items Room Temp

0ºC, 1wk

54ºC, 2 wks

Active content (%) 30.31 30.30 30.18

Phase separation (%) 0 0 6.0 (water separation)

Viscosity (mPas) 186.7 147.5 124.2 Emulsion stability (diluted

200 times,1h) qualified qualified qualified

Persistent foaming (mL) 0 0 0 Particle Size (d50), µm 1.41 1.90 1.64

0 2 4 6

DOW EO/PO butyl ether copolymer

DOW EO/PO copolymer

phosphate ester

polyether

Particle size (µm)

Stability of EW 30% Chlorpyrifos

54ºC, 2 weeks

0ºC, 1 week

Initial

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Chlorpyrifos 30%

Solvent Oil 150# 15% DOW EO/PO butyl ether copolymer

4%

Defoamer 0.5% Propylene Glycol 5% Xanthan Gum 0.2% Water ~100

Typical EW Formulation

Summary

• High throughput formulation tools are utilized to accelerate research in a variety of application areas

• High throughput technique allows formulators to cover more experiments addressing unpredictability associated with active ingredients characteristics

• When traditional agrochemical formulation approaches fail, high throughput formulation strategies allow large scale, systematic screening of additives in a short time period

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