Solid microspheres for agriculturally active compounds and process for their production

Microspheres containing an agriculturally active material are produced by mixing a liquid phase containing the agriculturally active material and optionally an emulsifying agent and an aqueous phase containing polyvinyl alcohol and adding a material selected from clays, silicas, starch, and starch derivatives, followed by spray drying.

BACKGROUND AND PRIOR ART 
This invention relates to the production of solid microspheres for use in 
controlled release of agriculturally active materials, particularly liquid 
materials. 
There are a number of techniques available in the art for providing 
controlled-release formulations of such materials. Among those are 
procedures for encapsulating compounds in shells comprised of various 
polymers. The capsules may contain the agriculturally active materials in 
various physical forms. In some processes the capsules are formed by 
producing an emulsion of a liquid active ingredient (which may be in the 
form of the ingredient per se in liquid form or a solution of it in an 
appropriate solvent) in a second phase in the presence of one or more 
monomers or pre-polymers followed by processing steps to produce a shell 
of a polymer surrounding the emulsified droplets of active liquid 
material. In other embodiments, the active liquid ingredient may be 
present as an emulsion, in a solution, or as a suspension of smaller 
microspheres, within the capsule formed by the polymer. 
One technique for producing controlled release formulations in the form of 
microspheres involves dispersing a liquid, water-insoluble active 
ingredient (which may be the ingredient per se or a solution of it in a 
water-immiscible solvent) in an aqueous phase containing polyvinyl 
alcohol, and then forming the microcapsules or microspheres by 
spray-drying this dispersion to remove the solvent and the water. Such a 
process is disclosed in general, in U.S. Pat. No. 4,244,836 of Frensch et 
al. 
Modifications or improvements of this process are disclosed in U.S. Pat. 
Nos. 5,073,191 and 5,160,530 (the former being a division of the latter) 
of Misselbrook et al. In the process as described in those patents, a low 
melting agriculturally-active material, in molten form, is combined with 
an aqueous solution of a water-soluble film-forming polymer such as 
polyvinyl alcohol, at a temperature sufficient to maintain the active 
material in the molten state. The active material is then dispersed or 
emulsified in the aqueous solution and the resulting dispersion or 
emulsion is then spray-dried at a temperature of between approximately 
50.degree. and 220.degree. C. so as to produce either microcapsules or 
microspheres containing the active ingredient. Additives such as 
plasticizers, wetting agents and anti-caking agents may be included in the 
aqueous phase for modification of the nature of the polymeric wall of the 
microcapsules or microspheres. The patent states that the product produced 
by this process is a dry, free-flowing powder or granule. However, 
problems occurred when the techniques of the Misselbrook et al. patents 
were applied in an attempt to produce microcapsules or microspheres 
containing the low-melting insecticide lambda-cyhalothrin, 
[.alpha.(S*),3.alpha.(Z)]-(.+-.)-cyano-(3-phenoxybenzyl)-3-(2-chloro-3,3,3 
-trifluoro-1-propenyl)-2,2-dimethyl cyclopropane carboxylate. While the 
microsphere product produced by this technique appeared to be of good 
quality, it did not disperse well when mixed with water for spraying; 
because of the low melting point of the active ingredient, the material 
tended to melt, stick together, and plug up the spray nozzels. 
The present invention, therefore, is directed to a process for production 
of microcapsules or microspheres containing an agriculturally active 
material (e.g. a molten low melting solid, a liquid active ingredient, an 
emulsion or a solution) which forms good quality microspheres and which 
disperses well in water for spraying. 
SUMMARY OF THE INVENTION 
This invention comprises a process for production of microspheres 
containing an agriculturally active material comprising the steps of (a) 
preparing a liquid phase comprising an agriculturally active material; (b) 
mixing said liquid phase with an aqueous phase comprising from about 1 to 
about 25 percent by weight of polyvinyl alcohol; (c) adding to this 
mixture of step (b) from about 5 to about 40 percent by weight, based on 
the mixture, of a particulate material selected from clays, silicas, 
water-soluble starches, starch derivatives and combinations thereof; and 
(d) spray-drying the resulting suspension to encapsulate the active 
material in polyvinyl alcohol. 
This invention further comprises microspheres produced by the above 
process. 
DETAILED DESCRIPTION OF THE INVENTION 
The process of this invention is used to prepare polymeric microspheres 
enclosing an agriculturally active material. 
In the process of this invention, the agriculturally active material, if 
not already in liquid form, is converted to a liquid. Liquid forms of the 
active material which may be used in this process include molten forms of 
low-melting solids, agricultural materials which are liquids at 
temperatures of normal use, emulsions, dispersions, and solutions in water 
or organic solvents. 
The agriculturally active material which is enclosed within the 
microspheres of this invention may be either liquid or solid. Solids are 
first dissolved or suspended in a solvent for purposes of producing 
microspheres, but are contained in the final microsphere product in 
primarily the solid form due to evaporation of the solvent when the 
microspheres are formed. 
Agriculturally active materials which may be used in this invention include 
the insecticide lambda-cyhalothrin, other pyrethroid insecticides, and 
herbicides such as sulfosate (trimethylsulfonium salt of 
N-phosphonomethylglycine, napropamide 
(N,N-diethyl-.alpha.-naphthoxypropionamide), trifluralin 
(.alpha.,.alpha.,.alpha.-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine), 
paraquat (1,1'-dimethyl-4,4'-bipyridinium salts), thiocarbamate herbicides 
such as EPTC, butylate, and vernolate (optionally with a herbicide 
antidote), and the fumigant metam sodium (sodium N-methyldithiocarbamate). 
Sulfosate and paraquat, for instance, are water-soluble salts which are 
solids under normal temperatures, and which are dissolved in water for use 
in this invention. 
In the use of the process of this invention for production of microspheres 
containing materials which are not water-soluble, organic and aqueous 
phases are prepared. For purposes of convenience, the invention will be 
described primarily in terms of such a two-phase system. 
If an organic solvent is utilized, it is chosen on the basis of three 
properties. First, the solvent must dissolve the active ingredient as well 
as any other components of the organic phase. Secondly, the solvent 
preferably should have a relatively low boiling point so as to be easily 
removed through spray-drying. The boiling point of the solvent thus should 
be at a maximum of about 220.degree. C. Thirdly, the solvent must be 
immiscible with water. Suitable solvents include hydrocarbons such as 
pentane, hexane, heptane, cyclohexane, and the like, chlorinated solvents 
such as dichloromethane, N-alkylpyrrolidones, gamma-butyrolactone, 
cyclohexanone, methylcyclohexanone, methanol, fatty acid esters and 
isophorone. 
The organic phase will also contain an emulsifier, which may be any of a 
number of types known to cause emulsions to form when organic and aqueous 
phases are mixed. Typical emulsifiers include surfactants such as 
polyethylene glycol ethers of linear alcohols, ethoxylated nonylphenols, 
napthalenesulfonates, alkali metal/alkyl sulfates and other salts, and the 
like. One preferred emulsifier is the anionic/nonionic blend sold as Atlox 
3409F. Other additives such as dispersants and wetting agents may be 
contained in either phase. Typical dispersants include 
naphthalene/formaldehyde condensates, lignosulfonates and naphthalene 
sulfonates. A preferred dispersant is Soprophor S/40P (a blend of 
ethoxylated tristyrylphenols). Wetting agents include naphthalene 
sulfonates, sulfated alkyl carboxylates and sulfosuccinates; a preferred 
wetting agent is Stepwet 95 (sodium lauryl sulfate). 
The organic phase will typically contain from about 10 to about 95, 
preferably from about 30 to about 95, weight percent of the agriculturally 
active substance, and from about 1 to about 20, preferably from about 2 to 
about 4 weight percent emulsifier (if the emulsifier is present in the 
organic phase). If the agriculturally active substance is dissolved in a 
solvent, the solvent will comprise from about 10 to about 90, preferably 
from about 40 to about 70 weight percent of the organic phase. 
Dispersants, if used, will be present in from about 1 to about 20 weight 
percent; wetting agents, if used, in from about 0.5 to about 5 weight 
percent. 
The aqueous phase comprises an aqueous solution of polyvinyl alcohol and 
optionally a buffer. It will typically contain from about 1 to about 25, 
preferably from about 2 to about 5 weight percent polyvinyl alcohol. If an 
emulsifier is used in the aqueous phase, it will comprise from about 2 to 
about 4 weight percent of that phase. 
The organic and aqueous phases are mixed and stirred to form an emulsion. 
The emulsification step is conducted at a temperature of from about 
10.degree. to about 100.degree. C., typically at ambient temperatures. If 
the organic phase contains an agriculturally active compound in molten 
form, temperature is maintained through the emulsification step 
sufficiently high so as to maintain that material in the molten state. 
The emulsification step is carried out with stirring. The size of the 
microspheres ultimately formed depends to a great extent on the speed with 
which the emulsion is stirred. The higher the stirring speed, the smaller 
the droplet of active ingredient plus polymer formed in the aqueous 
solution. In general, to obtain the microspheres of this invention, the 
stirring speed should be from about 500 to about 5,000, preferably from 
about 500 to about 2,500 rpm. The resulting microcapsules will have a 
diameter of from about 3 to about 200, preferably from about 3 to about 
10, microns. 
To the emulsion, with stirring, is added a particulate material selected 
from clays, silicas, water-soluble starches and starch derivatives. 
Suitable clays are those which are dispersible in water and which will 
combine with polyvinyl alcohol to form the microspheres of this invention 
and include, for example, attapulgite, kaolin, montmorilonite and 
diatomaceous silica. Silicas useable in this invention include hydrophilic 
and hydrophobic precipitated or fumed silicas. Water-soluble starches and 
derivatives include non-pre-gelled and pre-gelled starch, maltodextrins, 
and cyclodextrins. One such material is methylated .beta.-cyclodextrin, a 
water-soluble starch derivative, sold by Wacker-Chemie GmbH under the 
trademark Beta W7 M1.8. Combinations of various particulate materials may 
also be used. 
For use in this invention, the particulate material should have a particle 
size of about 0.1-30 microns, needle-or plate-shaped crystals, should be 
non-reactive with other materials used, non-hygroscopic and should 
contribute to viscosity. 
The particulate material is suspended in the emulsion. 
The suspension containing the agriculturally active material is then 
converted to controlled-release microspheres by spray-drying to remove the 
solvent and the water. Spray-drying is carried out at an inlet temperature 
of from about 100 to about 300, preferably from about 150.degree. to about 
220.degree. C. and an outlet temperature of from about 50.degree. to about 
100.degree., preferably from about 60.degree. to about 75.degree. C. The 
microspheres thus formed can, if desired, be further processed into other 
physical forms such as pellets, flakes, granules or powders. 
If the agriculturally active material is a water-soluble solid or 
water-miscible liquid, there is no need to form a two-phase system. One 
may either prepare two aqueous phases and mix them, or all the ingredients 
including the particulate material may be combined in a simple mixing 
step, with stirring, to produce a suspension. Such a single mixing step is 
considered equivalent to, and within the terms of, the two steps defined 
herein as preparing a liquid phase and mixing the liquid phase with an 
aqueous solution containing polyvinyl alcohol. 
The microcapsules of this invention demonstrate a quick release of the 
agriculturally active ingredient. Under microscopic examination, the 
microspheres formed small clusters and (compared to those of the 
Misselbrook et al. patents) disperse rapidly in water and do not tend to 
cause plugging of spray nozzles or other equipment. 
The following represent examples of the preparation of microspheres 
according to this invention. 
GENERAL PROCEDURE 
An organic phase was prepared containing either molten lambda-cyhalothrin 
or lambda-cyhalothrin dissolved in a solvent, as indicated. An aqueous 
phase was prepared which contained the polyvinyl alcohol. The two phases 
were combined, with stirring to form an emulsion, with an emulsifying 
agent either having been included in the organic phase or added in the 
emulsification step. Then, the particulate material was added, following 
which the suspension was spray-dried to produce the microspheres. 
The following tables show content of ingredients as starting materials and 
in the spray-dried microspheres. Polyvinyl alcohol was used in aqueous 
solutions of from 5-20% concentration; the amount of solution is 
indicated. Water was generally not present in the dried microspheres. 
Lambda-cyhalothrin was used in technical grade, 85.6% purity.