Pest Management Science Pest Manag Sci 57:129±132 (2001)

Delivery of biological performance viamicro-encapsulation formulation chemistry †

Ian M Shirley,1* Herbert B Scher,2 Robert M Perrin,1 Philip J Wege,1

Marius Rodson,2 Jin-Ling Chen2 and Allen W Rehmke2

1Zeneca Agrochemicals, Jealott’s Hill International Research Centre, Bracknell, Berkshire RG42 6ET, UK2Zeneca Ag Products, Western Research Centre, Richmond, California 94804, USA

(Rec

* CoE-ma† Bason b

# 2

Abstract: Lambda-cyhalothrin micro-capsules have been prepared by a novel in situ procedure.

Manipulation of the chemistry has led to slow- and fast-release formulations. The latter has a bio-

logical performance comparable to commercial lambda-cyhalothrin emulsi®able concentrates, but

exhibits a signi®cantly improved toxicological pro®le over EC, WP and WG formulations. Micro-

encapsulation technology satis®es many of the drivers towards the safer use of pesticides.

# 2001 Society of Chemical Industry

Keywords: lambda-cyhalothrin; controlled release; micro-capsule; manufacture

1 INTRODUCTIONWhile new chemistries for crop protection are often

perceived primarily as the preparation of biologically

active agents, formulation chemistry plays a vital role

in determining the ®nal performance of the latter, and

recent years have seen great advances in this area. The

development of a satisfactory formulation requires an

understanding of many disciplines ranging from

polymer synthesis and colloid science through mam-

malian toxicology to application technology and

biological performance.

For many years the main purpose of the formulation

was to facilitate the transport of the active ingredient to

its target, and the formulators' concern was largely

with the physico-chemical properties of the formula-

tion in bulk and when dispersed in the carrier medium,

usually water. This could be achieved satisfactorily

with a range of relatively simple formulations, but

considerable limitations became apparent. For exam-

ple, emulsi®able concentrates have been extensively

used for the delivery of many pesticides. The

formulations are generally simple to make, have high

biological activity, are chemically stable and suit many

actives, due to solubility matching. However issues

related to phytotoxicity, acute operator toxicity and

`green' pressures to minimise the impact of solvents on

the environment have driven the industry to develop

alternative formulation types.

In addition, such formulations offered little cap-

ability for controlling the activity of the pesticide,

either in respect of its direct action on the target or of

undesirable side-effects such as toxicity or phytotoxi-

eived 19 June 2000; revised version received 15 August 2000)

rrespondence to: Ian M Shirley, Zeneca Agrochemicals, Jealott’s Hillil: ian.shirley@aguk.zeneca.comed on a paper presented at the symposium ‘New Chemistries for Cro

ehalf of the Bioactive Sciences and Crop Protection Groups of the SC

001 Society of Chemical Industry. Pest Manag Sci 1526±498X/2

city. In recent years major advances in controlled

delivery technology have led to the development of

novel and more sophisticated formulation techniques

which have allowed these limitations to be addressed.

One of the most important of these is micro-

encapsulation.

Micro-encapsulation technology satis®es many of

the drivers for an improved formulation in that it

enables the manufacturer to deliver reduced toxicity

and controlled activity, reduced evaporative losses,

reduced phytotoxicity, controlled environmental de-

gradation, reduced leaching into groundwater and,

consequently, reduced levels in the environment.

The agrochemical is contained in a polymer micro-

capsule, generally less than about 40 microns, and

typically about 10 microns, in diameter. Such particle

sizes avoid blockages of screens and ®lters in spray

applicators. Solids contents of the order of 50% w/w,

and AI (active ingredient):polymer ratios of 9:1 are

readily achievable making the technology very eco-

nomical. Many liquid AIs, or solutions of solid AIs,

may be encapsulated provided that the liquid or

solution has low solubility in water and provided that

the AI does not react with the wall-forming materials.

Although micro-capsules may be dispersed in either

aqueous or organic continuous phases, carriers for the

delivery of agrochemicals usually use water. This in

itself offers advantages in safety over ECs. Colloidal

stability is maintained by surface-active agents ad-

sorbed on the surface of the capsule walls. The walls of

the micro-capsules provide a barrier designed to

control the release of the pesticide. The solubility of

International Research Centre, Bracknell, Berkshire RG42 6ET, UK

p Protection’, organised by Dr L Copping and the late Dr J DingwallI and held at 14/15 Belgrave Square, London, UK on 19 June 2000

001/$30.00 129

IM Shirley et al

the pesticide in water is usually so low that the water

itself provides a supplementary barrier until after

application and drying. Unless so designed1,2 the

capsule walls do not rupture or degrade in use.

Lambda-cyhalothrin is a particularly active pyre-

throid insecticide3 which has been marketed in a

number of delivery systems, including emulsi®able

concentrates, oil-in-water emulsions, water-dispersi-

ble granules and water-dispersible powders. In con-

ventional formulations, however, it may have side-

effects of eye toxicity and paraesthesia (subjective

facial sensation).4 In this paper we describe the

development of micro-capsule formulations of lamb-

da-cyhalothrin which minimise these side-effects, and

which allow us, by varying the chemistry, to control

the availability and hence the performance of the AI.

2 EXPERIMENTAL METHODMicro-capsules may be made by a number of methods

including phase separation5 (coacervation) and inter-

facial polymerisation6 processes. Preparation by inter-

facial polymerisation is now a well-established

commercial process. In a widely used approach6 the

oil containing one or more monomers is emulsi®ed,

and a further monomer(s) is/are then added to the

aqueous phase whence it/they diffuse(s) to the oil-

water interfaces and polymerise(s) with the mono-

mer(s) in the oil. Suitable oil-phase monomers include

dicarboxylic acid chlorides, di-isocyanates, bis(chloro-

carbonates) and bis(sulfonyl chlorides) which may be

polymerised as appropriate with, for example, dia-

mines or diols added through the aqueous phase.

Polyurea capsule walls result from the polymerisation

of di-isocyanates and diamines.

We have developed a novel in situ procedure7 for

polyurea micro-capsules where all of the wall-forming

monomers, which are typically tolylene di-isocyanate

(TDI) and polymethylenepolyphenylene isocyanate

(PMPPI), and the materials to be encapsulated are

mixed to form an `oil'. PMPPI is an oligomeric

material which has an isocyanate functionality >2

and is used for cross-linking (Fig 1).

For lambda-cyhalothrin micro-capsules, the materi-

als to be encapsulated typically comprise a solution of

the AI in an aromatic solvent. The oil is dispersed at

ambient temperature and under appropriate shear

conditions into an aqueous phase, usually containing

an emulsi®er and a colloid stabiliser. The droplet size

is controlled by the degree of shear and the amount of

Figure 1. Tolylene di-isocyanate (1) and polymethylenepolyphenyleneisocyanate (2).

130

emulsi®er. Under these conditions there is generally

relatively little hydrolysis of the aromatic isocyanates.

The temperature of the emulsion is raised to about

50°C when some of the isocyanate molecules at the

water-oil interface are hydrolysed to carbamic acids

which decarboxylate to give amines. The free amines

then rapidly react with unchanged isocyanates to

generate the polyurea wall at the interface. A range

of lambda-cyhalothrin micro-capsules having a poly-

urea wall system have been made by this process.

The nature of the polymerisation process leads to

the formation of an asymmetric membrane having a

high-density outer skin which is believed to dominate

the control of the release rate of pesticide from the

capsule. The more diffuse inner portion contributes to

the mechanical integrity of the wall.

3 DISCUSSIONThe development of a commercially successful micro-

capsule formulation extends far beyond the polymer

chemistry of wall formation. While the choice of

micro-capsule construction affects biological perfor-

mance through, for example, release rates and adhe-

sion of the capsule to a particular substrate, the

formulation must also be designed to be robust in use.

The type and amount of surfactant employed can

affect the particle size, the propensity for particle

growth during the wall-forming step and the tank-mix

compatibility. On completion of wall formation,

suspending agents are usually added at an optimised

level to enhance storage stability by inhibiting settling,

and to aid dispersion, mixing and drainage from

containers.

Most agricultural micro-capsules operate by release

by Fickian diffusion. The release rate is a function of

the particle size, ie surface area (4prori) the concentra-

tion gradient from the inside to the outside of the

capsule (CiÿCo), the wall thickness (roÿ ri) and the

permeability (P) of the encapsulated material through

the wall, and can be described by the equation:

dM

dt� release rate � �4�rori�P�Ci ÿ Co�

ro ÿ ri

Permeability is a function of the solubility and

diffusion coef®cients for the core materials through

the wall and can be controlled by the monomer

composition and the cross-link density.

Manipulation of these parameters in the polyurea

wall system enables control over a wide range of

release rates and thus the delivery of biological

performance. The performance and properties of two

different lambda-cyhalothrin polyurea micro-capsule

wall compositions may be illustrated by comparison of

one against the other and/or against an EC formula-

tion.

Relatively slow release rates (up to 3 months) are

required for certain products such as those sold into

the public health and urban markets under the trade-

names of Icon1 10CS and Demand1 10CS. However

Pest Manag Sci 57:129±132 (2001)

Table 1. Typical properties of lambda-cyhalothrinmicro-capsule formulations

Property Fast-release 25CS Slow-release 10CS

AI content (g litreÿ1) 250 100

(% w/w) 22.8 9.7

Density (gmlÿ1) 1.095 1.031

pH 5.0 5.0

Average particle size (mm) 2.6 12.0

Viscosity at 50sÿ1 shear rate (mPa sÿ1) 140 80

Table 2. Control of Helicoverpa zea (cotton bollworm) in US cotton withcapsule and EC formulations of lambda-cyhalothrin applied at 33gAI haÿ1

Formulation

Reduction in square damage (%) a,b

3 DAA (12.6) 7 DAA (23.6) 14 DAA (51.0)

EC 79 97 91

Zeon capsules 92 91 96

a ()=% Square damage in untreated plots.b DAA= days after application.

Biological performance of micro-encapsulated formulations

fast release (within hours) is desired for other products

(Karate1 with Zeon technology1 25CS) which are

designed to have a knock-down performance similar to

that of a lambda-cyhalothrin EC. Illustrative formula-

tion data for fast- and slow-release capsules are

summarised in Table 1. In this paper the notation

10CS and 25CS pertain speci®cally to the products

de®ned above.

The very different release rates between the two

capsule formulations are accomplished principally by

varying the micro-capsule size and the ratio of

TDI:PMPPI monomers. The delivery of biological

performance is thus achieved via formulation chem-

istry.

The average capsule size in the 10CS slow-release

formulation is about 12 microns, while that in the

25CS fast-release formulation is about 2.6 microns.

The ratio of TDI:PMPPI is much higher in the 25CS

than in 10CS formulation, resulting in a much higher

cross-link density in the latter product. The higher

level of cross-linking, coupled with a thicker wall,

greatly reduces the release rate.

Upon application and dry-down, the robust 10CS

micro-capsules maintain their integrity and release

Table 3. Toxicological properties of lambda-cyhalothrin formulations

Property

10CS

(slow release)

EPA

toxicity a

Oral LD50 (rat) (mg kgÿ1) >5000 (M) IV

>5000 (F)

Dermal LD50 (rabbit) (mg kgÿ1) >2000 (M, F) III

Inhalation LC50 (rat) (mg litreÿ1) >4.62 (M) III

>4.63 (F)

Eye irritation (rabbit) Mild irritant III

Skin irritation (rabbit) Slight irritant IV

a EPA toxicological categories: I (most toxic)±IV (least toxic).b Contains 13.1% w/w lambda-cyhalothrin, 86.9% w/w inerts (solvent and emulsi®e

Pest Manag Sci 57:129±132 (2001)

slowly so that residual activity is maintained over

several months.

By contrast, the relatively fragile 25CS micro-

capsules release rapidly upon application and dry-

down. The larger capsules (which are relatively few in

number) at the high tail of the particle-size distribution

tend to collapse on drying, affording instant release of

the capsule contents. The smaller capsules, present as

the majority, remain intact but rapidly release lambda-

cyhalothrin by virtue of their thin walls and their very

high surface area. This behaviour results in rapid

knock-down times for this formulation. From statis-

tical analysis of 146 ®eld trials on 16 crops in North

America from 1994 to 1997 it was concluded that the

ef®cacy of such capsule formulations was as good as or

in some cases better than that of EC formulations. The

control of Helicoverpa zea (Boddie) is illustrated in

Table 2.

The differences and bene®ts of formulation type are

further illustrated by comparing the toxicological

properties of lambda-cyhalothrin formulations (Table

3). Comparison of the toxicological data for the EC

and for 25CS micro-capsules shows that the latter

exhibit marked improvements in all areas of acute

toxicity. The micro-capsule formulation causes less

eye irritation, appreciably less skin irritation and has

signi®cantly lower inhalation toxicity. The improve-

ment is all the more impressive given that the

comparisons are made between 13.1 and 25% w/w of

active ingredient in the EC and capsule formulation

respectively.

4 CONCLUSIONSIn summary, micro-capsule suspensions retain the

ease of handling associated with EC and WG

25CS

(fast release)

EPA

toxicity a

l-Cyhalothrin EC b

(immediate release)

EPA

toxicity a

245 (M) II 64 (M) II

180 (F) 101 (F)

>2000 (M, F) III >2000 (M, F) III

3.72 (M) IV 0.315 (M) II

3.12 (F) 0.175 (F)

Mild irritant III Moderate irritant II

Mild irritant III Extreme irritant I

r).

131

IM Shirley et al

formulations, while conferring such advantages as (1)

the need for less protective clothing, due to lower

toxicity hazards, (2) reduced paraesthesia or `sub-

jective facial sensation', (3) safer storage, due to

reduced ¯ammability and volatility, (4) lower packa-

ging and transport costs for higher strength products

containing up to 250g AI litreÿ1, and (5) less odour

and damage to paint and other surfaces from solvents.

In addition fast-release micro-capsules have biological

activity equivalent to that of the best commercial

emulsi®able concentrates.

ACKNOWLEDGEMENTSThe authors would like to thank the many chemists

and biologists within Zeneca who have contributed to

the current development and understanding of this

unique technology.

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Pest Manag Sci 57:129±132 (2001)