CA1057192A - Method of preparing pesticide formulation by freeze drying - Google Patents

Abstract

A B S T R A C T
Process for the preparation of a pesticide formulation containing at least 80% by weight of pesticidally toxic material, which comprises freezing an intimate mixture containing the pesticidal toxicant, at least one surface-active agent and a sublimable liquid medium, reducing the pressure above the frozen mixture to below the triple point pressure of the liquid, and removing the medium as a gas whilst maintaining the pressure below that at which the medium can exist in a liquid form.

Description

- 2 ~ 1 O 57 1 9 2 This invention relates to the preparation of improved pesticide formulations containing very high concentrations of the pesticidally active ingredient.
The active component of most pesticides is a well-de~ined chemical compound, but in agricultural applications it is usually impracticable to apply this compound directly because of the problems inherent in securing uniform distribution over large areas of the small amounts required (typically 1 kg per hectare). Hence, in practice the compound is generally diluted with relatively large volumes of water to facilitate spray application over these large areas. However, in most instances the low water solubility of the active ingredient makes it difficult for the user to prepare such spray solutic)ns by direct dissolution or suspension, and therefore the product is normally formulated with carefully selected carriers and surface-active agents to ensure that the formulation will rapidly disperse in water to give a product having good spraying characteristics.
The development and production of such a ~ormulated product which will not only have the necessary physical properties but also a satisfactory stability under field conditions allied with good biological performance requires a high level of expertise and quality control, and it is therefore rarely practicable for each end-user to purchase the active ingredient, carrier and surface-active agent

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in order to produce his own formulation on the spot.
Accordingly almost all pesticides are sold as formulations containing carrier and surface-active agent in addition to the active ingredient, which can be applied either directly (e.g. with granule~) or after suitable dilution with water (e.g. wettable powders, emul'sifiable concentrates, suspension concentrates, etc.) The ~inal choice of formulation type will be dictated by the intended application of the product and the physical properties of the active ingredient, for example granules being chosen for localized application whilst dilute sprays are used for treatment of large , areas.
In order to provide a formulation having acceptable physical properties it is normally necessary to include not only surface-active agents but also a carrier, which may be a liquid, as in the case of an emulsifiable concentrate, or solid as in the case of a wettable powder. Without the use of such a carrier severe technical problems can arise in producing an acceptable formulation; ~or example any attempt to prepare a wettable powder without a solid carrier, or filler, results in an inadequate mix of the surface-active ingredients with the active ingredient, overheating of the mill with smearing of the toxicant over the mill surfaces and inadequate

4 -attrition leading to insufficiently small particle size. However, the presence o~ this carrier inevitably increases both raw material and transport costs although it has no intrinsic value to the customer.
Clearly it would be advantageous if the quantity of carrier could be substantially reduced or even eliminated, and it has now been found according to the subJect o~ the preæenb invention that this can be achieved by preparing formulatio~sin the presence o~ a liquid which is then removed by sublimation.
The present invention therefore provides a process for the preparation of a pesticide formulation containing at least 80% by weight o~ pesticidally toxic material, which comprises ~reezing an intimate mixture containing the pesticidal toxicant, at least one sur~ace-active agent and a sublimable liquid medium, reducing the pressure above the ~rozen mixture to below the triple point pressure o~ the liquid, and removing the medium as a gas whilst maintaining the pressure below that at which the medium can exist in liquid form. It should be appreciated that the pestioidally ef~ective material may contain other components in addition to the toxicant designed to enhance the biological ef~ect o~ the toxicant, ~or example an oil may be added to facilitate herbicidal activity or a synergist to enhance insectioidal

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activity. Also polymers may be added to control the release o~ toxicant.
The es~ential criterion required of the liquid medium is that it possesses a triple point at which gas, liquid and solid are in equilibrium and at pressures below that Or the triple point it exists solely in the solid and gaseous phases, since it is then possible at suitably reduced pressure to remove the medium from the ~rozen mixture via the gas phase without the medium melting into a liquid phase. Under these conditions, the removal of the medium can be ef~ected without destroying the intimate association of the toxicant and surface-active agent, and thereby can yield a carrier-free product having acceptable physical properties. The removal o~ the medium from the frozen mixture is accomplished by allowing it to gain heat, whilst maintaining the pressure below that at which the medium can exist in the liquid state, and maintaining a condensing surrace near to the ~rozen mixture at a temperature below that Or the mixture. Under the~e condition~
the medium evaporates rrom the frozen mixture as a gas and iB collected as a solid on the condensing surrace. The rate at which this gas phase transfer f medium ~rom rrozen mixture to condensing surrace takes place is dependent primarily on the pressure

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and the temperature ~ the frozen mixture, lower pressures and higher temperatures increasing the rate of transfer.
For reasons of practical convenience it is preferred to use as the sublimable liquid medium a material which is liquid at room temperature and which can be ~rozen by the use of readily available materials such as solid carbon dioxide or other conventional re~rigerants. Thu~ water i9 a particularly convenient sublimable liquid medium, although organic liquids such as benzene and dioxane can also be used under appropriate conditions. When water is used the ~reezing is suitably effected by a mixture of solid carbon dioxide and, for example, acetone, and the water removal (freeze-drying) is generally carried out at a pressure below 1 Torr (the triple point pressure of water being 4,6 Torr) using a condenser cooled to below minus 30C and allowing the frozen mixture to warm to above 0C, preferably around room temperature or even hlgher.
The surfaoe-active agent may be an emulsi~ying agent or a dispersing agent or a wetting agent;
it may be nonionic, ampholytic, cationic or anionic.
Any o~ the surface-active agents usually applied in ~ormulating herbicides or insecticides may be used. Examples of suitable surface-active agents .

are the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids, the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide and/or propylene oxide; fatty acid esters of glycerol, sorbitan, sucrose or pentaerythritol;
condensates of these with ethylene oxide and/or ~opylene oxide, condensation products of fatty alcohols or alkyl phenols for example p-octylphenol or p-octylcresol, with ethylene oxide and/or propylene oxide; sulphates or sulphonates of these condensation products; alkali or alkaline earthmetal salts, preferably sodium salts, of sulphuric or sulphonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulphate, sodium secondary alkyl sulphates, sodium salts of sulphonated castor oil, and sodium ; alkylaryl sulphonates such as sodium dodecylbenzene sulphonate; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide.
The toxicant used in the process of this invention may be any pesticide which i~ solid under normal temperatures (e~g. 20-25C) and atmospheric pressure, and its intimate mixture with the sublimable liquid medium and surface-active agent may be accomplished in a variety o~ ways. Thus in one embodiment the medium may be chosen so that it is one capable of dissolving the toxicant, when the requisite intimate admixture is readily achieved sirlply by stirring the resulting solution. This procedure may be applied using either water or a suitable organic liquid as the sublimable solvent, but in either case it is desirable for the solution to be frozen rapidly in order to minimize the growth of large crystals which would require crushing prior to subliming o~f the liquid medium.
,10 In a second embodiment the medium may be chosen so that the toxicant dissolves to only a limited extent, water usually being the medium of choice since the majority of pesticides are insoluble ~or only slightly ~oluble) in water. In this embodiment the solid toxicant is mixed with the water (or other medium) and appropriate sur~ace-active agents and then subjected to a suitable milling process (e.g.
in a slow or high speed stirrer grinder) which ensures that the solid particles of toxicant are su~ficiently small to permit their regular coating by the sur~aoe-aotive agents present in the mixture. Pre~erabl,y the par~ticle size should be reduced to below 100 microns, and desirably below 10 microns. The amount of water present during the milling process is not critical, because effectively all the water is removed lOS7~92 during the subsequent freeze-drying step. However, if the water content of the slurry produced by milling is less than 50%, it is sometimes found that the freeze-dried product forms as a crust which requires further milling to yield an acceptable product.
Therefore it i8 preferable to adjust the proportion of water to minimize the crust formation during drying.
When the slurry formed by milling solid toxicant with a non-solvent medium and surface-active agents is frozen, the dispersed ~olid particles are locked into place in the resultant ice matrix. Thus, when the pressure is reduced and the water sublimes away, the toxicant particles, together with the surface-active agent, do not agglomerate as the volume of mixture i i8 reduced. The resulting dry, powdery product containing only toxicant and ~urface-active agents, is termed a "Technical ~Concentrate", and possesses physical properties closely resembling those of a conventional wettable powder, although having no solid filler and therefore a much higher toxicant content.
This retention Or the spatial relationships Or the slurry components during the freeze-drying makes possible a rurther a~pect of this second embodiment or the invention, namely the production Or a freeze-dried suspension concentrate which can be reconstituted - lo - 1057192 without loss of physical properties merely by addition of water. According to this aspect of the invention, the toxicant is milled together with water which may contain, in addition to the more conventional surface-active agents, a suspending agent, such as a protective colloid or thixotropic agent, and optionally also dissolved organic solidsor inorganic salts to raise the density of the suspending liquid and thereby assist in preventing sedimentation, the resulting mixture is frozen and the water removed therefrom at a pressure sufficiently low to preclude the formation of liquid water. With suitable choice of the ingredients, the milling can yield a stable, non-sedimenting, flowable product containing up to 50-60% of toxicant. It is normally impracticable to use a lesser amount of water (or other suspending medium) without impairing the physical properties of the suspension concentrate, whilst any attempt to remove the water subsequently by conventional means results in a similar detrimental ePfect. However, the removal of the water by ~reeze-drying, according to the process of the present invention, yields a dry powdery product which retains latent the physical properties required to produce a stable 9uspension and can therefore be reconstituted by addition of water into acceptable suspension concentrates :

of any convenient toxicant concentration, or alternatively directly into sprayable suspensions Additionally, a ~chnical concentrate can be reconstituted into a suspension concentrate by mixing with water containing the appropriate extra ingredients needed to make a stable suspension concentrate.
; Alternatively, if the toxicant r~quires the addition of an oil for optimum activity, for example, in the post-emergence use of triazine herbicides, the technical concentrates can be mixed directly with an emulsion of the oil in water.
It will be appreciated that the process of this invention is applicable to the preparation of products containing mixtures of toxicants. These may be toxicant materials which are either both soluble or both substantially insoluble in the sublimable li~uid medium, or it may often be convenient to prepare a product containing, for example, both a soIuble and an insoluble pesticide. In the last situation, the proc~re followed is precisely that described earlier for the formulation of insoluble toxicants except that the sublimable liquid medium in which the insoluble toxicant is milled contain8 additionally a dissolved quantity of the soluble toxi¢ant.
The invention is further described in the following ex~mples.

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Example I Preparation of Technical Concentrates A blend comprising 190g. "Gardona"'insecticide (technical material containing 98.5% wt. 2-chloro-1-(2, 4, 5-trichlorophenyl) vinyl dimethyl phosphate), 5g. Orota~731 SD (sodium salt of condensed aryl sulphonic acid), 5g. Vanisperse-:-CB (sodium lignin sulphonate) and 200g. water was charged to an attritor and ground until the particle size was in the range of 1-2 microns. After blending, the slurry was run out of the attritor into a round-bottomed 2 litre flask, which was rotated in a solid carbon dioxide/
acetone freezing bath ~til the slurry formed a uniform coating of frozen solid over the entire internal surface of the flask.
The flask was then connected by a manifold connector to a freeze-drying unit, evacuated to a pressure of about 0.5 Torr and exposed to ambient temperature (20C) whilst the condenser in the freeze-drying ~it was maintained at about -35~C. About 6 hours is required to complete the drying of a 500g. batch of slurry, and the completion of the drying stage can be recognized by the external surfaces Or the flask reaching room temperature (during the drying the heat uptake required to sublimate the water maintains a cooling effect on the flask). The flask was then removed from the drying unit and the resultant technical concentrate was poured out as a free flowing powder, "Trademark ~ - 13 - 1057~9Z

Follo~ling a similar procedure, technical concentrates were also prepared with the following toxicants:-"Torque"-~(trineophyl tin oxide/hydroxide) 97Z wt.
(98% pure technical material) Marasperse7~CBOS-3 1.5% wt.
(Sodium lignosulphonate) DuponaI'ME 1.5% wt.
(Sodium lauryl sulphate) "Bladex't`(Cyanazine - 99% pure technical) 96% wt.
Aerosol OTB~ 2% wt (Sodium dioctyl sulpho-succinate) Vanisperse-`~CB 2% wt.
Bladex~ 13%
MCPA 82%
Vanisperse'~CB 2.0%
Empice~ LZ 2,0%
(Sodium lauryl sulphate) The physical properties of three o~ these technical concentrates are summarized in the following Table l.

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A,~-i .. _ _, . , . _ _ _ ... . . .. . , _ - 1 5 - ~057192 Example II Pre~aration of Freeze-Dried Sus~ension Concentrate 3 . 5 kg of 3/8~' diameter + 3.5 kg of 1/4~' diameter steartite media were charged to an attritor. t~ith the impeller rotating at 80 rpm, 10g Vanisperse7'CB, 3g Kelzan~
XC (a modified polysaccharide), 3g Orotan~ SN and water to 910g were added to the mill. After five minutes 450g BLADEX~was incorporated and the im~eller s~eed increased to 245 rpm and the milling continued for 4~ hours.
The mill was emptied whilst running at 80 rpm. The density of the formulation was determined ald found to be o.85 g/l indicating extreme aeration. After de-aeration, which was achieved with a Silverson stirrer fitted with an axial ~low head, the density was found to have increased to 1.07 g/kg.
The product was then divided into two equal portions, to one the requisite weight of mono-ethylene glycol (9%) was blended, this sample was then called 'Standard BLADE~'SC' and the physico-chemical properties examined.
The results were used as a standard a~ainst which a freeze dried and reconstituted suspension concentrate was compared. The remaining half of the SC was freeze-dried by the process described in Example I.
When dry the concentrate formed a crust which coated the internal surface of the flask. This crust broke into small piecea when the flask was ~ently tapped ~'Trademark and was reduced to a fine powder by a sin~le nass throu~h a hammer mi11. The free~e-dried concentrate was subsequently reconstituted by blending in the ratios 48% dried SC: 43% water and 9% mono-ethylene glycol using a Silverson stirrer fitted with an axial f'low head. The method of reconstitution ensured that any air entrapped in the dry powder was not retained in the SC.
The physico-chemical pro~erties of the reconstituted Bladex~SC were compared against those of the standard Bladex~SC, and the results are shown in Table 2.

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Exam,rle III
The biological activity of the Bladex'technical concentrate, Standard suspension concentrate and freeze dried suspension concentrate was assessed in comparative tests a~!ainst peas, rye grass and mustard, and comparisons Or standard Garden~75%
wettable r,owder with 94% technic~;l concentrate were made using Spodoptera Littoralis. The results of these tests are shown in the following tables 3 and 4, the standards being a wettable powder containing 50% by weight of Bladex~' ~Trademark 1~

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:7 Example ~V
A freeze-dried suspension concentrate of Bladex' was prepared followin~ the same procedure, and usin~
the same in~redients, as in Example II. A solution in water of the potassium salt of MCPA was also freeze dried, and 298~ of this product (equivalent to 250g MCPA acid) were mixed with 68~ of the dried Bladex`sus~ension concentrate, 3~ Kelzan7~XC and 3g Orota~SN to provide a formulation which could li be reconstituted by the addition of water into a sprayable formulation containing a mixture of Bladex~
:~ and MCPA.

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Claims (8)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. Process for the preparation of a pesticide formulation containing at least 80% by weight of pesticidally toxic material, which comprises freez-ing an intimate mixture containing the pesticidal toxicant, at least one sur-face-active agent and a sublimable liquid medium, reducing the pressure above the frozen mixture to below the triple point pressure of the liquid, and re-moving the medium as a gas whilst maintaining the pressure below that at which the medium can exist in a liquid form.

2. Process according to claim 1 wherein the pesticidal toxicant is substantially insoluble in the sublimable liquid medium, and the intimate mixture is obtained by milling together the toxicant, surface-active agent and liquid medium until the particles of toxicant are sufficiently small to permit their regular coating by the surface-active agent.

3. Process according to claim 2 wherein the milling is continued until the particle size of the toxicant is below 100 microns.

4. Process according to claim 1, 2 or 3, wherein the sublimable liquid medium is water.

5. Process according to claim 1 wherein the pesticidal toxicant is substantially insoluble in the sublimable medium and the intimate mixture is a suspension concentrate produced by milling together the toxicant, surface-active agent, liquid medium, a suspending agent and optionally also organic salts soluble in the liquid medium.

6. Process according to claim 1 wherein the intimate mixture contains at least two different pesticidal toxicants.

7. Process according to claim 6 wherein the intimate mixture is ob-tained by milling together the surface-active agent, a solution of at least one pesticidal toxicant in the liquid medium and at least one pesticidal toxicant substantially insoluble in the liquid medium until the particles of the substantially insoluble toxicant are sufficiently small to permit their regular coating by the surface-active agent.

8. Process according to claim 5, 6 or 7, wherein the sublimable liquid medium is water.