PHYSICAL STABILITY OF AGROCHEMICAL … STABILITY OF AGROCHEMICAL FORMULATIONS From Suspension to...

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 info@crystallizationsystems.com

This webinar will last 45 minutes

This webinar is being recorded and will be made available

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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