physical stability of agrochemical … stability of agrochemical formulations from suspension to...
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PHYSICAL STABILITY OF AGROCHEMICAL FORMULATIONSFrom Suspension to emulsion
Presented by: Dr. Martin Viertelhaus, BASF SE
13th June 2017
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Your Speaker
Dr. Martin Viertelhaus is Research Scientist Crystalline Materials and Polymorphism atBASF SE, Ludwigshafen, Germany.
His expertise is in the field of solid state development and physicochemicalcharacterization of active ingredients: e.g. agrochemical, pharmaceutical andperformance chemicals. During his professional career, he worked for pharmaceuticaland chemical companies as well as for a service provider.
Dr. Martin Viertelhaus
The audience is muted and send the questions to [email protected]
This webinar will last 45 minutes
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TECHNOBIS CRYSTALLIZATION SYSTEMS Privately owned company 50 employees Located in Alkmaar, The Netherlands Leader in 3 major markets: Pharma, Agro
and Fine Chemicals
Portfolio 3 products for: formulation,
process optimization andcrystallization related research
Products
Discover• Early stage salt, polymorph screening• Single crystal growth
Screen• Solubility, MSZW• Phase diagrams• Selecting solvents• Polymorphs, Salt and Co-crystals
screening
Optimize• Form control• Habit control• Particle size• Process optimization• Formulation
Working volume:0.5 – 1 ml
16 reactors
Working volume:2.5 – 5 ml8 reactors
Working volume:0.06 – 0.1 ml32 reactors
150 Jahre
Dr. Martin Viertelhaus
Physical Stability of Agrochemical FormulationsFrom Suspension to Emulsion
5
Overview
solid state properties
agrochemicals and their formulations
two active ingredients …
… plus formulants
re-crystallization
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 6
Solid State Properties
solid state properties depend on the crystal form
knowledge about (meta)stable solid forms of active ingredients (AIs) is important for production formulation storage application
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 7
lead optimization development registration production marketing/
sales IP protectionnew
generation products
Formulation and Solid State of Active Ingredient
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 8
Agrochemicals
indications fungicides (F)
herbicides (H)
insecticides (I)
product application
formulated concentrate
dilution in water(compatibility with water)
application to fields
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 9
Agrochemical Formulation
formulation development high active loading
low viscosity (liquid)
easy to dissolve/disperse (solid) storage stability 2 years at ambient temperature 2 weeks @ 54°C (accelerated)
application stability
robustness in biological tests
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 10
Formulation Stability
production mixing properties viscosity
storage sedimentation, re-suspension agglomeration, crystallization
dilution and application mixing crystal growth
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 11
crystalline active on leaf surface
Agrochemical Formulation
63 different classifications of formulations
active is
solid in solid mixture suspended in liquid dissolved in water or solvent
solid state properties of active of interest in formulation
after dilution
during application on the plant
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 12
int. code description
EC emulsifiable concentrate
SL soluble concentrate
DC dispersible concentrate
SC suspension concentrate
SE suspo-emulsion
OD dispersion in oil
EW emulsion, oil in water
ME micro-emulsion
CS capsule suspension
WG water dispersible granule
WP wettable powderCropLife International, Technical Monograph n°2
Agrochemical FormulationActive x Active
the majority of agrochemical formulations include more than one active ingredient
up to four actives ingredients
less resistance building
broader application window
cooperative effects
stronger curative effect
13Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus
soybean rust
Two Active Ingredients
2 solid actives:
pre-formulation
active 1+
active 2
mixtureof AIs
eutecticmelt co-crystal
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 14
Active I – Active IIEutectic
15Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus
40.00
50.00
60.00
70.00
80.00
90.00
100.00
110.00
120.00
40
50
60
70
80
90
100
110
120
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
T / °CT / °C
x Active II
Tm/°C
Tm(AI form II)/°C
Tm(AII)/°C
Tm(AI form I)/°C
melting points of separate actives above 80°C
mixed actives: eutectic melting at 62.6°C
Suspension Stability Experiment
pre-formulation or final formulation
further reduction of „melting point“conversion point from suspension to emulsion
mixture of active ingredients and solvents/blank formulations stirring temperature rise pictures
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 16
Photos taken with Crystalline PV
Active I – Active IIFormulation Development
AI I : AI II (g/g)
Crystalline PV: T ramp 20°C/h, bottom stirred
17
54.1°C 54.2°C 54.3°C 54.4°C 54.5°C 54.6°C 54.7°C 54.8°C 54.9°C 55.0°C 55.1°C 55.2°C
58.2°C 58.4°C 58.6°C 58.8°C 59.0°C 59.2°C 59.4°C 59.6°C 59.8°C 60.0°C 60.0°C 60.0°C
solvent A
solvent B
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus
Photos taken with Crystalline PV
Final Formulation
solids: eutectic melting at 62.6°C
eutectic melting temperature reduced to 59°C in solvent A 55°C in solvent B
formulation physically not stableagglomeration, sedimentation
decision:no suspension concentrate
18Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus
Two Active Ingredientsplus Liquid Formulants
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 19
active 1+
active 2mixtureof AIs
liquid plus solid(e.g. eutectic +excess solid)
eutecticmelt co-crystal
active 1+ active 2
+ formulants
mixture of AIsin formulation
(SC)
liquid plus solid(excess solid
active) emulsion
co-crystalin liquid
formulation (SC)
solution
Re-Crystallization
temperature cycling to enhance the chance to crystallize
crystal size
crystal morphology
individual experiments and temperature programs
20Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus
experiment: Crystalline PV, T ramp -7.5°C/h, bottom stirred
28.3°C 28.0°C 27.8°C 27.6°C 27.3°C 27.0°C 26.9°C 26.5°C 26.3°C 26.0°C
Photos taken with Crystalline PV
Physical Stability of Agro Formulations
investigation regarding solid state properties of actives model formulations final formulation
can explain observation of farmers/users in final formulation
can avoid running for the wrong formulation type
21Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus
dissolution
re-crystallization
phase transformation
Acknowledgement
Agrochemical Formulation, Suspension, Emulsion, M. Viertelhaus 22
Martin ViertelhausBASF SE
Ludwigshafen
Christian Sowa
Rolf Hellmann
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