Controlled release of biologically active agents for purposes of agricultural crop management

resources, conservation and recycling

ELSEVIER Resources, Conservation and Recycling 16 (1996) 289-320

Controlled release of biologically active agents for purposes of agricultural crop management

Marc Gregory Mogul ", Hanife Akin b, Nesrin Hasirci b,1, Debra J. Tranto lo c, Joseph D. Gresser c, Donald L. Wise "' *

a Department of Chemical Engineering, Center for Biotechnology Engineering, Northeastern University, Boston, MA 02115, USA

b Middle East Technical University, Department of Chemistry, Ankara 06531, Turkey c Cambridge Scientific, Inc., 195 Common St., Belmont, MA 02178, USA

A b s t r a c t

Increasing attention is being directed to reducing the amount of pesticides, herbicides, and other biologically active agents used in modern agricultural crop management. One method for reducing the amount of such agents, while still maintaining effectiveness, is to encapsulate or otherwise incorporate the active agent into some form of plastic. Such 'filled' plastics, usually prepared by certain techniques for standard broadcast methods used in agriculture, may be sprayed, dusted, or spread as needed. By being incorporated into the plastic, the active agent diffuses slowly, but continuously, from the plastic matrix. It has been found in numerous instances that this use of controlled release delivery systems results in using less amount of the active agent. Further, with increasing attention being directed toward biologicals, rather than organic chemicals, for use in crop management, this incorporation of the biologicals into plastic serves the role of protection of the biological, as well as providing for slow release. One method of preparing an encapsulated polymeric controlled release system will be reviewed in depth, as well as field results.

Keywords: Plastic; Agrochemical; Herbicide; Pesticide

1. I n t r o d u c t i o n

Agriculture represents one of the most important areas of international needs to health, nutrition and economic developments. The rapidly growing demand for food is

* Corresponding author. i Presently on Sabbatical as a Fullbright Scholar at MIT, Cambridge, MA 02139, USA.

0921-3449/96/$15.00 © 1996 Elsevier Science B.V. All rights reserved SSDI 0921-3449(95)00063- 1

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the main impetus behind the need for more efficient operation in both agriculture and industrial protection that afford higher yields and better quality. Agrochemicais are concerned with the utilization of chemicals to control either plant or animal life which are at a disadvantage and to improve production of crops both in quality and quantity. However, the potential hazards of the conventional agrochemicals to public health and wildlife result in greatly increasing stringent limitations on their use.

Depending on the method of application and climate conditions, as much as 90% of applied conventional agrochemicals never reach their objective to produce the desired biological response at the precise time and in the precise quantities required. The results of these inefficiencies are the nonspecific and periodic application of the active agents. Both factors, besides increasing the cost of the treatment, produce undesirable side effects either to the plant or to the environment. Recently controlled release technology emerged as an alternative approach which promises to solve problems accompanying the use of some agrochemicals while avoiding the possible side effects of the other.

The principal advantage of controlled release formulations is that they allow much less pesticide to be used for the same period of activity. Moreover, when the normal half-life of a potent pesticide is short, the release formulations are especially advanta- geous in comparison to conventional methods of application.

When applied by conventional methods, pesticides are invariably subject to leaching, evaporation and degradation (photolytic, hydrolytic, and microbial), all of which remove the active materials from their target before they can perform their function. If a pesticide is chemically combinded or dissolved or encapsulated in a polymeric material, its application to soil or any other medium would result in release of the active ingredient by hydrolysis or diffusion at a controlled rate. Therefore, the loss of the active agent by degradation, evaporation or leaching would be minimized. Application of such combinations would therefore result in a much more efficient use of the active agent per unit weight as well as a much longer period of protection for the same amount than if applied by conventional methods. Since the biocide would be encased in a polymeric cage, it would be less susceptible to attack by bacteria or fungi. Combinations designed to offer prolonged protection would thereby eliminate the cost of repeated and over applications.

Many of the pesticides which are readily biodegradable, and therefore desirable, are highly toxic. Because of their mobility in water and air, their application is also a danger to the surrounding wildlife. If these materials were chemically contained within a polymer, they should become much less toxic, since all of the active ingredient would not be released at one time. Moreover, the polymeric combination of pesticides, being solid and less toxic, could be easily handled and transported from one place to another. Furthermore the material could be processed and distributed by conventional machinery.

The large amounts of pesticides applied to achieve protection for a long time sometimes cause phytotoxicity. Since a controlled release formulation would not release the active ingredients all at once, this should not arise. Moreover, a combination of pesticide with polymer should minimize errors associated with measuring and diluting liquid concentrates. A polymer combination of a pesticide in the solid form should be easily deposited precisely where it will perform most efficiently, and thus minimize waste. Because the actual amount of pesticide needed for a biological response is small,

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the material released under controlled conditions would by substantially absorbed by the host or trapped and degraded in the soil. By eliminating the wide-spread distribution of large amounts of pesticides, saturation of the ecological environment would be avoided, and the leaching of pesticides by rain into waterways and subsoil should be alleviated. Some rather stable pesticides or their degradation products now find their way into potable water supplies and can end up in humans through food consumption, with the attendant possibility of health problems in the long term. If leaching could be minimized, herbicides could be used more safely near irrigation canals and near crops sensitive to some of these agents.

Solvent evaporation and organic phase separation are two processes by which microencapsulation can be readily performed in the laboratory without the need for specialized equipment. The major difference between the two procedures is that solvent evaporation is an aqueous system, whereas organic phase separation is nonaqueous. In this respect, the two processes are complimentary in that the limitation of one method may be circumvented by using the other. Therefore, many core materials can be microencapsulated using one of the two processes. Selecting the appropriate method requires consideration of the physicochemical properties of the core material in conjunc- tion with the characteristics of the process.

The term 'pesticides' is a convenient cover for all chemicals used for pest control although its terminal root implies that the pesticides should be toxic to the pest, whether the latter be plant or animal. A chemical pesticide may be defined as a substance which kills harmful organisms which are free-living at some stage in their life cycle. This substance is usually applied during the free-living period of the pest's life. They are thus distinguished from those drugs which are used to kill organisms which are endoparasitic throughout their life cycle.

Chemical pesticides are classified by referring to the type of pest they control, and thus we speak of insecticides, acaricides, nematicides, rodenticides, fungicides, and/or herbicides. Some chemicals fall into more than one of these catagories, parathion, for example, being an insecticide, an acaricide and a nematicide. Proceeding with the generalization concerning pesticides applied to the growing plant, the toxic chemical should possess certain other properties as well.

It must be effective at a concentration which causes no injury of economic importance to the host plant. The sensitivities of the plant to the pesticide will, in general, vary with its stage of development. The dormant plant will often tolerate materials which if applied to the foliage would cause defoliation.

The material, if poisonous to man, must be capable of use in a manner sate to the operator and to those in subsequent contact with the crop. This applies whether in harvesting or storage, or whether on food or fodder.

The use of the pesticides must not have an unfavorable effect on the biological environment of the treated crop. Such ecological effects increase vastly in importance as the area over which the material is used is increased and as the diversity of crops treated is reduced. Moreover, the risks increase with the stability of the pesticide and the biological activity of its metabolic products. The long and extensive use of the persistent organochlorine insecticides has created a world-wide contamination of the environment and has become a serious public concern.

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The pesticide should be used in a manner which gives the greatest economic protection in addition to reducing the risks of the selection of resistant pest strains. These hazards increase with the stability of the pesticide and its active metabolites, though they emerged with an insecticide as evanescent as hydrogen cyanide.

The pesticide should not be so stable that it leaves undesirable residues in food or soil, but it must remain long enough to control the pest. Stability in storage is, however, necessary. This problem is made more complicated by the necessity of formulating the material in some way. The active ingredient is very rarely used in the pure form, or merely mixed with water, but is almost always mixed with other materials that facilitate its dilution, application and retention. The resulting product must be stable both chemically and physically over a wide range of storage conditions. The storage environment may vary from those found in a rough hut in the tropics, to those of a modem air-conditioned storehouse.

It must kill a worthwhile number of different kinds of pests if a manufacturer is going to find it profitable to market. Speed of action is not usually important, unless damage must be checked quickly.

Finally, pesticides must be resonably cheap to manufacture. Few products are made in isolation. Pesticide manufacture is usually a small section of a large chemical company with by-products of one division being used as raw materials in others. Such integration allows the costs to be spread more widely.

Weed control appears, at first sight, to be intrinsically more difficult than most kinds of pest control as the pest is usually closely related to the victim. This relationship calls for a high degree of selective toxicity in the techniques used for weed control. This selectivity need not be biochemically based, because most weeds are not directly dependent upon their victims, but merely share the same habitat. The difficulties arise when they are sharing habitats at exactly the same time. It is then difficult to apply chemicals so that they affect only the weed plant.

There is no general rule as to the best system of herbicide classification. For the chemist, it is the structural formula and can be divided broadly into inorganic and organic. The organic chemicals are then subdivided into families such as aliphatic and aromatic acids and nitriles, amides, ureas and triazines where a chemical group is common to a number of herbicides.

Other classifications are based on use and mode of application. Herbicides are classified as selective when they are used to kill weeds without harming the crop, as non-selective when the purpose is to kill all vegetation. True selectivity refers to the capacity of a herbicide, when applied at the proper dosage and time, to be active only against certain species of plants but not against others. But, selectivity can also be achieved by placement. This occurs when a non-selective herbicide is applied in such a way that it contacts the weeds but not the crop.

All herbicides affect plants by contact or translocation. The contact herbicides kill the plant parts to which the chemical is applied. They are most effective against annual weeds, those that germinate from seeds and to maturity each year. Translocated herbicides are absorbed either by roots or above-ground parts of the plant and then moved within the plant system to distant tissues. Translocated herbicides may be effective against all weed types. Their greatest advantage is seen when used to control

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established perennial weeds, those that continue their growth from year to y,~ar. The herbicides are applied to the soil at one of three times: before the planting of the crop (pre-planting); before emergence (pre-emergence); after emergence (post-emergence).

2. Review of literature

The following review is based on the matrix material used and is then subdivided into the active agent being released.

3. Synthetic polymeric delivery vehicles

3.1. Herbicides

Monomeric herbicides of diethanolamine derivatives were prepared from diethanolamine, 2,4-D, and 4-chloro-2-methylphenoxyacetic acids [1]. The melt polycon- densation reactions of the monomeric diethanolamine derivatives with dicarboxylic acids afforded the corresponding herbicide polyesters. However, the solution polycondensa- tion technique was used in the preparation of the herbicide-polyurethane derivatives. The reaction was carried out by using diethanolamine derivatives with HMDI. Introduction of different ratios of crosslinking into the linear polymers was achieved by subjecting them to reactions involving different ratios of HMDI (5 and 10%). The results of these reactions created a swellable polymeric material. Furthermore, the preformed amine polyester of hydroquinol-diacetic acid was also modified with 2,4-D. The produced monomers, polyesters, and polyurethanes were characterized by various physical techniques. The hydrolysis of 2,4-D from polymeric herbicides was carried out under different simulated conditions. The amounts of the released herbicide were evaluated by measuring the ultraviolet absorbance of the supernatant solutions at different periods of time.

A series of polymeric microsphere formulations were prepared and tested for their ability to control the release of a particular herbicide, Dicamba (Da; 3,6-dichloro-2- methoxybenzoic acid) [2]. Microspheres were produced from ethylcellulose, polyarylsulfone, or a combination of the two. The desired size range of the microspheres ranged from 20 to 40 microns, and were created by solvent evaporation or spray drying. Generally, polyarylsulfone microspheres could be loaded with more Dicamba (up to nearly 50 wt%) than could the ethylcellulose (maximum loading obtained was 23 wt%). Ethylcelluiose microspheres released Dicamba at a greater rate than did comparable polyarylsulfone microspheres under both sonication and soil column irrigation release tests. The release rate of Dicamba from the ethyl cellulose microspheres could be controlled using different viscosity grades. For example, higher viscosity ethylcelluiose led to a lower Dicamba release rate. Furthermore, the release rate of Dicamba from microspheres was also controlled by using a combination of ethylcellulose with polyarylsulfone. Overall, microspheres prepared from ethylcellulose, polyarylsulfone or ethylcellulose with polyarylsulfone show promise as controlled release formulations for herbicides.

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The preparation and characterization of polymeric herbicides at different degrees of crosslinking are described [3]. The product specifically consists of 2,4-D and 4-chloro- 2-methylphenoxyacetic acid covalently or ionically bound to oligoethylenoxylated styrene/divinylbenzene (St /DVB) resins. Herbicide binding was attained by nucle- ophilic displacement on chloromethyl groups, by esterification of hydroxyl groups and by ion exchange. Herbicide release from polymer beads loaded with 0.3-1.5 mmol of herbicide per g of dry polymer was monitored in aqueous solutions at pH 4, 7, and 9. In covalently bound herbicides, a release of 20-30% at best was detected after 3 months under acidic and neutral conditions. Alternatively, much faster rates and higher extents of release were detected at pH 9. The ionically bound herbicide systems appeared to be less affected by pH. Apparently, no regular trend of the herbicide release can be associated with structural parameters such as the length of the oligo(oxyethylene) segment, the degree of crosslinking of the St /DVB resin, the loading, and the nature of the herbicide. The release profiles can be fitted by a bi-exponential kinetic treatment, implying the occurence of two processes differing by three-orders of magnitude in their absolute rates.

A slow release herbicide system (Biobarrier) was tested by Dosskey et al. [4] for its ability to act as a barrier to plant root growth into buried hazardous waste. A layer of trifluralin-releasing pellets, bonded to polypropylene fabric, was placed between the topsoil and the gravel drainage layer. The system consisted of 100 and 200 i containers which were planted in bahiagrass, bamboo, and lobiolly pine. After 3 years, sampling has revealed almost no growth of roots below the treated fabric. However, roots have grown closer to the barrier than expected, and rhizomes appear less affected than roots. The extent to which elevated soil temperatures influenced the effectiveness is uncertain, although longevity is likely to be reduced. Adequate soil depth over the fabric is important for good health of the associated cover vegetation.

Controlled release compounds are comprised of an aqueous dispersion of a water insoluble matrix and the disperse phase containing a herbicide, insecticide, fungicide or nematocide. The matrix is made up of a viscous oil, such as bitumen, or materials containing abietic acid (ester) or a carboxylic acid (ester) [5]. The compound also comprises a nonionic or an anionic surfactant, with a HLB of 8-20. An aqueous dispersion had as the oil phase a mixture of trifluralin 144, bitumen 264, xylene 72, Ca dodecylbenzenesulfonate (68% in BuOH) 16, and alkyl polyoxypropylene polyoxyalky- lene 16. The formulation was less phytotoxic to wheat than a conventional trifluralin emulsion concentration.

A polymeric device to control root growth is sometimes referred to as a biobarrier. A trifluralin releasing polymeric biobarrier under study had an estimated bioactive lifetime at 13°C of approx. 100 years and underwent field tests for more than 7 years [6]. To evaluate its biobarrier performance subplots of the field test plots were evacuated. This procedure was necessary in order to quantitatively document the change in herbicide content of the device as well as changes in the herbicide soil profile concentrations over an extended period of time. This evacuation included the retrieval of the releasing devices, and soil samples were taken over a seven year period following initiation of tests. Due to a less than expected soil overburden and a lack of soil moisture at the site, the average temperature at the level of the devices was significantly greater than 13°C.

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Based of the results of the final field sampling, the bioactive lifetime determined remained close to the lifetime predicted when the devices were first laid down. This fact is due to the lifetime being a function of the average annual temperature of the controlled release devices at the site; the vertical profile of trifluralin in the soil appeared to stabilize within a few months of placement of the biobarrier devices, with diffusion of trifluralin from the site not being detectable. The results of the field validation tests indicated that the device was trully a long-term controlled release device that functions as originally predicted.

Van Voris et al. [7] presented data on several biobarrier-based commercial products and indicated that a maximum effective bioactive lifetime on the order of 100 years can be achieved. Commercial products tested were: ROOT-SHIELD, a root-repelling sewer gasket for concrete, clay, and PVC sewer lines; BIOBARRIER, a spun-bonded polyproylene geotextile fabric with biobarrier nodules evenly spaced on the geotextile, developed to prevent root growth from invading septic tanks, penetrating under road- ways, and along the edge of sidewalks, airport runways, and tennis courts, and for landscaping; and ROOT-GUARD, an impregnated plastic drip irrigation emitter designed to protect burried drip irrigation systems from being plugged by roots. When placed in a layer of soil, the biobarrier system will prevent roots and shoots from penetrating through that layer without harming the overlying vegetation. It was found that equilibrium concentrations in the soil could be adjusted by varying the type of dinitroaniline, the type and crystallinity of the polymer, the structure and percentage trifluralin of the device (i.e., wall thickness for Fickian diffusion), the type and quantity of the carrier used, and the geometric pattern or spacing on which the biobarrier devices are placed.

Field, greenhouse, and laboratory studies were conducted by Chalmers et al. [8] to evaluate the performance of starch xanthide (SX), sludge polymer (SP), and conventional formulations containing (CF) of benefin, oxadiazon and prosulfalin. These compounds are used for the control of large crabgrass (Digitaria sanguinalis) in Kentucky bluegrass (Poa pratensis) turf. Turf injury was greatest with SP oxadiazon and prosulfalin formulations, while SX formulations of oxadiazon and prosulfalin caused decreased and/or delayed injury. In addition, the aforementioned provided control comparable to conventional formulations. Coarse SX granules containing prosulfalin caused less turf injury than fine granules, while the opposite effect sometimes occurred with SX oxadiazon. Differences in control were observed in the greenhouse when SX benefin formulations, which varied in crosslinking agent and/or degree of substitution, were compared to the conventional formulation on sandy and silt loam soils. SX benefin formulations also demonstrated controlled release properties, which improved large crabgrass control when compared to the conventional formulation in the greenhouse. This effect was short lived on silt loam but persisted on sand. SX granules crosslinked with Fe 3+ extended benefin activity longer than H202 crosslinked materials on sandy soil only. Release of ~4C-labeled benefin from SX matrixes was altered by the extent of water imbibition, solvent characteristics, and granule size.

Slow release formulations of s-triazine derivatives (desmetryn and terbutyrn), were prepared by extrusion of ethylene-vinyl acetate copolymer with the two derivatives [9]. Diffusion coefficients of the compounds in the matrix were measured for desmetryn as

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D O = 3.99 × 10 - l° cm2/s and for terbutym as D O = 8.1 × 10 -~° cm2/s. Slow release formulations of terbutyrn showed a strong herbicidal activity with a long duration in controlling Lemna minor in a laboratory flow system as well as Eichornia crassipes, Salvinia molesta, and Pistia stratiotes under outdoor conditions.

N,N-Diacryloyl metribuzin (DAMB) was synthesized by acylation of metribuzin with acryloyl chloride and then polymerized using free-radical initiation to obtain the polymer-bound herbicide as a candidate for hydrolytic controlled release applications [10]. The diacrylamide structure allowed cyclopolymerization resulting in polymers having cyclic imide units along the chain. Copolymerization with acrylamide (AM) and acrylic acid (AA) were conducted in order to increase hydrophilicity. Reactivity ratios indicated DAMB to be the more reactive comonomer. Both the DAMB/AM and DAMB/AA systems produced random copolymers. The later, however, showed less tendency for blockness. Studies in aqueous buffer systems indicated that hydrolysis of the labile bond to release metribuzin was occurring at low rates. The rates increased with increasing pH of the medium or hydrophilic content of the polymer.

A trifluralin releasing device was developed by Burton et al. [11] with an effective lifetime of approx. 100 years. Herbicide released from the device in soil will prevent root penetration through the soil layer without harming the overlying vegetation. Equilibrium concentrations of trifluralin in soil can be adjusted (together with the theorectical life of the device) to suit specific needs. Based on results from field trials, concentrations of trifluralin sufficient to prevent root elongation were maintained in the soil with minimal diffusion out of the immediate area.

New polymer compounds containing pendant herbicide substituents were developed by Harris [12] as effective, economical, and environmentally safe controlled release aquatic herbicides. The synthesis of one of the most promising controlled release systems, a hydroxy-terminated, low-molecular weight poly GMA adduct of 2,4-D, was successively scaled-up to commercial levels. However, the processing of the adduct solution as obtained from the reaction mixture was difficult. A method to remove the solvent was required before the procedure could be used to prepare material for field tests.

Akelah et al. [13] followed the hydrolytic release of phenoxyacetic acids from Amberlite IRA-401 (a styrene macroreticular copolymer) and linear polystyrenes containing quaternary ammonium groups over 200 days. The linear polymers were characterized by a rapid initial release in the first few hours, followed by a more gradual rate lasting several days. The crosslinked systems had much lower release rates with little initial release. The hydrophilicity of the ammonium salt groups was a major factor governing the rate of hydrolysis. The increased rates were attributed to intramolecular interactions of neighboring ammonium salt groups generated during the hydrolysis. The concentrations of herbicide delivered with time were investigated at pH 4, 7 and 10. In general, all systems showed faster release in basic media. The rates in acidic and neutral media were similar.

Compounds comprised of an active ingredient, porosigen and/or porosity-modifying constituent, and a thermoset polymer or polymer combination constitute controlled release herbicide systems. Thus, systems comprised of polyethylene, ethylene-propylene copolymer (Vistalon 702), Zn stearate, diuron, and various combinations of CaCO 3,

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(NH4)2SO4, SiO 2, and ethylene glycol were described for controlling aquatic plant species [14]. Varying the porosigen and porosity-modifying constituents changed the herbicide release rate and modified plant control over various periods of time.

Thiocarbamate herbicides were also incorporated into granular carders and the granules were coated with unsaturated glycerides or their copolymers with cyclopentadiene to give slow release products [15]. Thus, Trusorb granules are impregnated with 10% molinate and coated with CPL-70 (cyclopentadiene-linseed oil copolymer). Co napthonate was added as a siccative. In model rice culture experiments, the formulation (0.84 active ingredient/ha) gave better post-flooding control of Echinochloa crus-gaUi than the corresponding noncoated granules.

Four herbicides, alachlor, metachlor, oxadiazon, and oryzalin were formulated as slow release tablets were evaluted for weed control on container grown nursery crops. Metachlor tablets at 40 kg /ha exhibited 120 days of excellent weed control [16]. Less injury was evident on border forsythis (Forsythia intermedia Spectasbilis) and cranberry cotoneaster (Cotneaster apiculatux) when herbicide applications were made using tablets in comparison to an equivalent amount of granular material.

Biodegradable polysaccharides for controlled release of pendant herbicides were prepared by McCormick et al. [17]. Such polysaccharides as chitin, cellulose, amylose, or dextran were reacted with carbamate or ester derivatives such as metribuzin iso- cyanate and 2,4-dichlorophenoxyacetate chloride in 5% LiC1/DMAC (N,N-dimethyl- acetamide) at 30-120°C. Formation of the pendent herbicide was demonstrated by the infrared spectra of the carbonyl group formed. To study the degree of substitution (DS) with reaction temperature, the model cellulose carbanilate was prepared at several temperatures. This demonstrated increased substitution with temperature (30-120°C) and reaction time (0-40 h). In release studies with chitin carbanilate, the absolute amount of aniline released was greater with the greater DS over a given period, and the percent available remained constant for a longer period. Data for the effects of particle size and pH on the release of aniline were also given.

Foret and Barry [18] tested three controlled release chemical herbicide formulations in outdoor pools for control of several aquatic plant species. The chemicals were formulations of 2,4-D, copper sulfate, and fenac. The plant species used were waterhy- acinth, Egeria, Eurasian watermilfoil, Hydrilla, and coontail. Although preliminary, the results showed a general decrease in normal plant growth. Conclusive results could not be determined due to various problems that arose during the conduct of the study. It was recommended that small-scale field trials of these controlled release formulations be continued.

3.2. Pesticides

James et al. [19] did research on controlled release insecticide devices for protection of sheep against head strike caused by Lucilia cuprina. The effectiveness of polymer matrix tags containing (w/w) 8.5% cypermethrin, 7.5% flucythrinate, 13.7% tetrachlorvinphos or 20% diazinon in protecting sheep against head strike by the sheep blowfly (Lucilia cuprina Wiedemann) was investigated in larval implant, fly cage and field studies. Tags impregnated with cypermethrin reduced the total number of egg

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masses deposited on the heads of sheep in fly cage studies over a 6 week period by 73.3%, compared with no treatment. Tags impregnated with flucythrinate reduced the number of egg masses by 25.3% over 21 weeks, but there was no significant differences between treated and untreated sheep at individual exposures. Egg masses were found on the majority of tagged sheep and no protection was provided against implants with first instar L. cuprina larvae by either cypermethrin or flucythrinate tags. Tags impregnated with diazinon gave longer protection than treatment with a liquid formulation containing 400 ppm diazinon in larval implant, fly cage and field studies. Most strikes in the diazinon tagged sheep occurred at sites which were not contacted by the tags. Tags impregnated with tetrachlorvinphos reduced the number of strikes in comparison with no treatment in larval implant and fly cage studies, but the results were inconsistent and not as good as those from diazinon tag. They concluded that well-designed controlled release devices that reliably contact the wool on the heads of sheep at sites of flystrike risk and which are able to withstand damage from rams fighting may be able to give prolonged protection against head strike.

Domb and Maniar [20] prepared solid, water insoluble lipospheres which contain drugs such as vaccines and anesthetics, as well as other biologically active agents including insecticides and repellants, fertilizers and pesticides. The controlled release lipospheres have several advantages. They include emulsions and vesicles, both of which are stable for an extended period of time. A mixture of lidocaine, tristearin and lecithin with a buffer solution was shaken vigorously. Then, the solution was immediately cooled, and immersed in a dry ice-acetone bath to give lipospheres containing lidocaine. The wide uses of the lipospheres are shown.

Gupta and Rutledge [21] investigated controlled release repellent formulations on human volunteers under three climatic regimens. Two controlled release repellant formulations containing 33% (3M) and 42% (Biotek) deet and an Army repellant containing 75% deet were evaluated in three different climatic regimens (tropical forested, tropical open and basic hot environments). All these repellants provided similar protection for different time periods after application under all three climates against Aedes aegypti, Aedes taeniorhynchus and Anopheles stephensi.

Polymeric hydrogels based on polysaccharides, hyroxyethylcellulose and dextran, were attained by crosslinking with epichlorohydrin [22]. The crosslinked polymer beds were loaded with 2,4-D by direct esterification in the presence of carbonyldiimidazole. Loads ranging between 0.5 and 2.2 mol of 2,4-dichlorophenoxyacetyloyl groups per glucose unit were obtained. The release of the 2,4-D herbicide was investigated in buffered solutions to different structural parameters. These included the nature of the polymer mixtures, crosslinking extent and herbicide loading. A fairly slow release, ranging from 10 to 25% after 4 months, was recorded under neutral and acidic conditions. However, at a pH of 9, an initial burst in the release profile was observed. Moreover, 90% of 2,4-D loading was determined to be released. In the majority of the cases, the release kinetics are reproduced by the combination of the two exponential .decay processes, that differ by about three-orders of magnitude in their absolute rates.

Greene and Meyers [23] developed microcapsules containing selected pesticides which utilize the unique release characteristics of Intelimer polymers. In response to soil or air temperature, the active ingredient is released at the temperature corresponding to

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the onset of the pest. The release point may be selected throughout the normal biological temperature range. A variety of agrochemicals including diazinon and trifluralin have been successfully microencapsulated using this technology. Greenhouse studies indicate that microencapsulating trifluralin dramatically reduces its phytotoxicity to corn and allowed a 50% reduction in the amount of active ingredient needed for weed control in cotton. In field trials, triflualin microcapsules at an application rate of 0.55 kg /ha provided equivalent 90 day control of weeds to an 1.1 kg /ha treatment of the commercially available formulation Treflan 4 emulsifiable concentration (EC). Further- more, bioassay results have demonstrated the decrease in phytotoxicity.

A series of polymeric hydrogels containing different oxyethylene oligomers were prepared by Issa et al. [24]. The reaction entailed radical polymerization of oligo(oxyethyl) methacrylate monomers in the presence of different amounts of N,N'- methylenebiscrylamide as crosslinking agent or acryamide as hydrophilic comonomer. Systemic herbicides, such as 2,4-D and 4-chloro-2-methylphenoxyacetic acid, were covalently supported on the polymeric hydrogels by esterification of the side chain hydroxyl groups. Swelling in water depended mainly on the length of the oligo(oxyethylene) side chains, the content of hydrophilic comonomer and, to a minor extent, on the degree of crosslinking. Herbicide loading produced a substantial drop in the water uptake by the polymer. The release of herbicides, investigated at room temperature in water at different pH values, was very much affected by alkylanity and to a lesser extent by the polymer structure.

Singh and Khosla [25] discovered that a slow release 2,4-D lac formulation (17.7% active ingredient) was lethal to Hordeum vulgare and Achyranthes aspera in bioassays at a lower concentration (1200 ppm) than were standard formulations of 2,4-D or 2,4-D Na salt. Weed control in wheat (Trificura aestivum) by 2,4-D lac was comparable to the standard formulations. However, selectivity against dicots was maintained. Yield increases with 2,4-D lac were 6-12%, but the reduction of wheat height was apparent at a concentration of 3000 ppm. In addition, there was no indication of residual effects in a subsequent crop of Abelmoschus esculentus.

Bahadir and Korte [26] prepared granule, strip, and film shaped controlled release formulations of selected pesticides in LDPE and EVA copolymers by extrusion at 150-170°C. Pesticides were made up of chlorinated hydrocarbons, organophosphates, carbamates, derivatives of triazines and other chemical classes. Migration of active ingredients from the matrix into water, and further into the vapor phase, were studied. Values of diffusion coefficients were obtained in the range of Do= 10-8-10 -12 (cmE/s). Kinetic models for different pathways of release were evaluated. Several formulations were tested under laboratory and field conditions. Desmetryn formulation covering films showed a significant growth supression of weeds in field trials for cultivation of vegetables. Herbicidal granules inhibited growth of duckweed in a simulated running water system. The steady-state concentrations of approx. 20 ppb terbutryn, and endosulfan containing blue-colored film formulations had a high effectiveness in controlling tsetse and Mediterranean fruit flies.

Laminated articles are provided which comprise one or more layers containing pesticides and pest attractants. This allows the controlled release of the pesticides from within the laminate to the surface of the laminate, so as to maximize efficiency against


target species. The laminated structure also permits prolonged, controlled release of pesticides and properly timed combinations of pesticides, that might otherwise be prematurely dissipated, decomposed, or inefficiently applied. Various combinations of polymers and active agents and a number of different laminated structures are utilized to optimize efficient use of the pesticides. A vinyl dispenser was prepared by coating a 0.004 inch PVC film, with plastisol containing malathion, and placing onto the plastisol a nylon scrim as well as a second 0.004 inch PVC film [27]. This combination of materials was bonded by pressing at 290°F, a corresponding pressure of 1.2 psig, for a period of 15 s. The amount of plastisol applied was sufficient to provide 5% malthion based on the total weight of the laminate.

Controlled release and hydrolysis resistant pentachlorophenol pesticides were prepared by incorporation of pentachlorophenol via ester groups in carboxy-containing polymers [28]. Poly(pentachlorophenyl acrylate), poly(pentachlorophenyl methacrylate), poly(pentachlorophenyl p-vinylbenzoate), pentachlorophenyl acrylate-styrene copolymer, pentachlorophenyl acrylate-4-vinylpyridine copolymer, pentachlorophenyl methacrylate-styrene copolymer, pentachlorophenyl methacrylate-4-vinylpyridine copolymer and pentachlorophenyl p-vinylbenzoate-styrene copolymer were prepared by conventional polymerization and copolymerization. Techniques and the rate of release of pentacholorophenol was determined as a function of pH, hydrolysis medium and temperature. The rates of release of pentacholorophenol were more rapid from polymers containing a hydrophilic moiety. More specifically, pentachlorophenyl acrylate-4-vinylpyridine copolymer was hydrolyzed more than twice as fast as poly(pentacholorphenyl acrylate), which had a higher hydrolysis rate than pentachlorophenyl acrylate-styrene copolymer. Also, the release rate was more in an alkaline medium and at higher temperatures.

Bhattacharya et al. [29] initially converted 2,4-D to a polymerizable derivative, a diolamide of 2,4-D. This diolamide was copolymerized with a number of dicarboxylic acid/anhydrides to give polymeric herbicide formulations in which the backbones are completely biodegradable by hydrolysis. Crosslinking reaction of these polymers with vinyl and acrylic monomers gave partially degradable polymeric herbicides. Release characteristics of these formulations were studied in neutral, alkaline, and acidic media.

Castor oil and its polyol derivatives were used as a matrix to prepare controlled release 2,4-D formulations [30]. Their release characteristics were studied both in vivo and in vitro. The initial release rate was dependent on the hydrophilicity of the formulations. The pH of the hydrolysis also strongly affected the release characteristics; the release rate increased sharply in the alkaline range (pH 10). Crosslinking via carbamate linkage retarded the release rate. Compared to formulations based on natural or synthetic polymer matrices, such castor oil-based preparations are likely to be more suitable for agricultural applications requiring a shorter release period of the toxicant.

A one-phase, solid, controlled release pesticidal compound was prepared. The product contains a pesticide in combination with crosslinked SMA 3000 A (maleic .anhydride-styrene copolymer) [31]. Thus, a mixture of methomyl 1240, SMA 3000 A 1525, and m-phenylenediamine 186 g was heated at 82°C. The melt was then cooled to give a dusty crumb composition containing 41% methomyl. The ground crumb was then mixed with Na laurylsulfate, Na lignosulfonate, and fused silica to give a controlled

M.G. Mogul et a l . / Resources, Conservation and Recycling 16 (1996) 289-320 301

release pesticidal formulation. Other pesticides such as metribuzin, cymoxanil, and oxamyl were used in a variety of formulations.

Granular compounds consisting of a pesticide containing solid core and a membrane- like coating are an example of a slow release pesticide. The membrane-like coating is formed from an adduct to a conjugated diene with an approximate stoichiometric amount of unsaturated fatty acid radicals, which is provided by a lipid [32]. Thus, soil placement of granules comprised of 0.2% carbofuran applied over a fertilizer, coated with a copolymer of 38% dicyclopentadiene and 62% linseed oil, provided progressive control of green peach aphids on crysanthemums in pot experiments.

Pesticides in homogeneous combination with a crosslinked copolymer prepared from hydrophobic monomers form one-phase, solid controlled release compounds. Use of hydrophobic monomers such as styrene, a-methyl styrene, and carboxylic acid-containing monomers, was reported by Wysong [33]. Wynsong charged a jacked stainless steel sigma blade mixer with 1240 g methomyl, 1525 g poly(styrene-maleic anhydride) (SMA 3000A), and 186 g m-phenylenediamine. The dry mixture was mixed and heated with steam in the jacket to a melt temperature of 82°C. When the temperature reached the melt temperature the steam was discontinued. With continued mixing, the temperature rose to 103°C at which point cooling water (5°C) was applied to the jacket. As the temperature decreased, the elastomeric mixture hardened and formed a dusty crumb. At 46°C, the polymer crumb was unloaded. Dispersion containing 0.01% of the product at an average particle size of 11 microns completely controlled southern armyworm larvae on excised bean leaves after 2 days in laboratory tests. Furthermore, 0.005 and 0.0025% of the product gave 95% control.

Fathead minnows were exposed to three encapsulated slow release pesticide formulations and three corresponding technical grade products used in their manufacture. Jarvinen and Tanner [34] indicated increased toxicity with time for encapsulated methyl parathion, diazinon and their technical grades using static 4-day median lethal concentration (LCso) values derived from aged stock solutions. The technical grades, however, were more toxic than the encapsulated. Encapsulated Dursban was less toxic with time, whereas toxicity remained similar with time for the technical grade. Flow-through 4-day LCso values for methyl parathion, Penncap-M, Dursban, Dursban 10 CR, and diazinon are 5.36, 6.91, 0.14, 0.12 and 6.9 mg/1, respectively. In general, long-term toxicity was similar for both pesticide forms. The amount of growth (wt.) which was determined as weight increase was the most sensitive parameter measured in the 32 day embryo-larval tests, except for the Dursban 10 CR study where it was equally as sensitive as survival. Growth effects occurred at > 0 . 3 1 - < 0.38, > 0 .38 -< 0.59, > 0 .0016-< 0.0032, > 0.002- < 0.0048, > 0.050- < 0.090 and > 0.040- < 0.076 mg/1 for methyl parathion, Penncap-M, Dursban, Dursban 10 CR, Diazinon, and Knox Out 2 FM, respectively. Water solubilities were slightly lower for the encapsulated compounds. Estimated half-lives were 18 days for methyl parathion and 15 days for Penncap-M; 41 days for Dursban and > 200 days for Dursban 10 CR, and approx. 30 days for diazinon and > 230 days for Knox Out 2 FM.

Adhemet controlled release pesticides are prepared from carbinol-containing organic polymers crosslinked by hydrolyzable silanes, hydrolyzable organic Ti compounds, and pesticides [35]. Thus, a plasticized polyester-titanate-silane solution was prepared from a


saturated ethylene glycol-propylene glycol-adipic acid polymer. Dipropylene glycol dibenzoate, tetraisopropyl titanate, tetraethyl silicate, and pyrethroids were added as well. This controlled release pesticide controlled cockroaches over a 7-day period. The control was ineffective at day 7.

Young et al. [36] comprised compounds of a carbinol-containing organic polymer, a crosslinking agent consisting of a hydrolyzable Ti compound, or a partial hydrolyzate, as well as a pesticidally active ingredient and adherent controlled release pesticides. Thus, a polyol-titanate solution comprised of pyrethoids 0.1, piperonyl butoxide 0.5, petroleum distillate 0.4, Niax LG-56 0.33, tetra-2-ethylhexyl titanate 0.165, dipyropylene glycol dibenzoate (Benzoflex 9-88) 0.495, and xylene 98.01% was uniformly applied to a glass panel which was subsequently conditioned for 24 h at 78°F with 42% relative humidity. Exposure to German cockroaches to treated panels after 7 days resulted in 60% mortality as compared with no mortality for control panels lacking polyol-titanate constituents.

Slow release, low mammalian contact-toxicity formulations are prepared by coating granules containing organophosphorus pesticide with acrylic polymers. Thus, montmorillonite granules (78.5 g) are treated with 15.5 g O,O-di-Et S-[[(1,1- dimethylethyl)thio]methyl]phosphorodithioate and 4 g di-, tri-, and tetraethyleneglycol mixture. The above preparation is coated with Rhoplex B-85 acrylic resin [37]. The coated granules, applied at 4 mg/950 mg soil were active for 131 days against Diabrotica undecipunctata and showed no dermatological toxicity to rabbits.

Adherent controlled release pesticides are given containing a hydrolyzable silane, or an organopolysiloxane containing an hydrolyzable silane group, a hydrolyzable organic Ti compound, and a pesticide [38]. Thus, a compound was given, containing pyrethroid 0.1, piperonyl butoxide 0.5, petroleum distillate 0.4, tetrabutyl titanate 0.75, TESEPS (triethoxysilyethylated methylhydrogenpolysiloxane) 0.25, DC-200 (dimethylpolysilo- xane) 4, and perchloroethylene 94% by weight. When tested on glass panels, the formulation showed longer residual toxicity to Blattella germarmica than similar preparations without the Ti compounds and the siloxanes.

3.3. Other

Polymeric molluscacides containing a niclosamide moiety have been prepared by Rehab and Akelah [39] utilizing a chemical reaction of commercially available polymers. The reactants involed are poly(chloromethylstyrene) (2% DVB; Labalit) and Amberlite IR-120 (8% DVB) with Bayluscide. The resulting polymers contain the Bayluscide active group either via a covalent bond or through physical interaction with the diethanolamine groups of the modified polymers. The release rates of the niclosamide were determined in different pH media by ultraviolet spectrophotometric analyses. The hydrolysis data showed that the release rates are strongly dependent upon the pH of the medium, as well as the structure and composition of the polymers. More specifically, the linkage between the polymer and the niclosamide moiety also appeared to be an important factor affecting the rates of release. This interaction can be explained by the relative effects of covalent bonding against physical interaction of the molluscicide to a polymer substrate. In support of this, experimental data have demonstrated the resulting differences in the release rates from the different polymeric systems.

M.G. Mogul et a l . / Resources, Conservation and Recycling 16 (1996) 289-320 303

Emara [40] has devised a simple method for the preparation of slow release compositions of niclosamide, the active ingredient of Bayluscide. The compositions, as monolithic discs, were prepared by insolubilizing gelatin by crosslinking treatments with 25% glutaraldehyde. Discs of six different extents of crosslinking containing molluscicide (w/w) were made. Evaluation of these compositions was carried out under both short-term hydrodynamic conditions (flow-through method), and long-term static conditions, using dechlorinated tap water. The results proved that the release profiles, mechanical stability, and swelling ratios of the compositions varied depending on the crosslinking treatment periods (CTP). The release mechanism of the crosslinked compositions was found to approach zero-order release behavior for all the compositions. The release rate constants of different formulations ranged from 0.09 to 1.42 ~ g / c m 2 min -~. The percent degradation of the crosslinked gelatin matrices was considerably affected by CTP, ranging from 5.5 to 82.0%. Bioassays were carried out using Biomphalaria alexandrina, the snail vectors of schistosomiasis. A daily 100% snail mortality prevailed for 52 and 73 days with the non-crosslinked and crosslinked matrices (CTP = 0.25 h), respectively.

Skin absorption of benzoyl peroxide from a topical lotion containing freely dispersed drug was compared with that from the same lotion in which the drug was entrapped in a controlled release styrene-divinylbenzene polymer system [41]. In an in vitro diffusion system, statistically significant differences were found in the content of benzoyl peroxide in excised human skin and in percutaneous absorption. In vivo, significantly less benzoyl peroxide was absorbed through rhesus monkey skin from the polymeric system. This controlled release of benzoyl peroxide to skin can alter the dose relation that exists between efficacy and skin irritation. Corresponding studies showed reduced skin irritation in cumulative irritancy studies in rabbits and human beings. In vivo human antimicrobial efficacy studies showed that application of the formulations containing entrapped benzoyl peroxide significantly reduced counts of Propionibac- terium acnes and aerobic bacteria and the free fatty acid/triglyceride ratio in skin lipids. These findings support the hypothesis that, at least for this drug, controlled topical delivery can enhance safety without sacrificing efficacy.

Volatile substances" in combination with a number of additives were mixed and used as air fresheners, microbicides, insecticides, cosmetics, and pharmaceuticals. The containers were not deformed as the content of volatile substances evaporates into the air. Takahashi et al. [42] mixed by weight 3,5-di-tert-butyl-l-4-hydroxytoluene (0.05 parts, by weight) and a fruit fragrance (10.0 parts), and added it to a slow release plastic film container which was subsequently sealed. The fragrence was slowly released over a 2-week period without altering the shape of the container.

Saito [43] mixed chemicals containing plastic particles with a plastic powder that does not contain chemicals having a higher melting point or softening point than that of the chemicals containing plastic particles. The mixture is treated by microwave heating to soften the chemicals containing plastic particles. The plastic powder that does not contain chemicals is then used to coat the softened particles. Ethylene-vinyl acetate copolymer particles were soaked in 10% white rose fragrance. The fragrance containing particles were mixed with powdered polypropylene (200 mesh). The mixture was heated in a microwave oven. The particles were collected by sifting. The particles did not


aggregate at 70 ° for a time period of 24 h. Furthermore, the particles were fragrant 6 months after manufacturing.

Saleh [44] prepared three poly(vinyl chloride) (PVC) formulations of malathion and tested them as controlled release formulations against mosquito larvae (Culex pipiens). Nonexpanded formulations gave effective control, with 100% larval mortalities, for 23-51 days, followed by expanded (16-33 days) and foamed (14-27 days) formulations. Increasing the percentage of active ingredient in the formulations increased their effectiveness against mosquito larvae for longer periods. Larval treatments with these formulations of malathion led not only to mortality, but also to a decrease in the reproductive potential. In addition, the treatments decreased the longevity of mosquito adults which survived the controlled release of malathion.

Messiha and Ikladious [45] investigated the antifouling performance of some new organotin polymers in the Mediterranean and Red Sea. Three new organotin polymers with built-in organotin moieties were prepared from tributyltin acrylate and methacrylate with other vinyl monomers. The tin content of the prepared polymers was 19.5-22.5%. The antifouling performance of the polymers was tested as unpigmented and pigmented coatings by raft exposure to the local fouling-intensive marine environment in the harbors of Alexandria and E1-Ghardaqua. Formulations based on tri-n-butyltin methacrylate, methyl methacrylate, acrylonitrile and tri-n-butyltin acrylate showed good antifouling efficiency for more than 22 months.

Three PVC formulations of fenitrothion were prepared and tested as controlled release plastic pellets against A. aegypti larvae [46]. Based on both T50 (capacity to kill 50% of the larvae during a 24 h exposure) and T90 (capacity to kill 90% of the larvae by the end of the experiment), the nonexpanded formulation (PVC ÷ dioctyl pthalate + fenitrothion) was more effective than the expanded formulations of (PVC + diocty pthalate + Triton X-100 + (NH4)2CO 3 + citric acid + water + fenitrothion). The addition of a surfactant (Triton X-100) or a surfactant plus a blowing agent (CO 2, produced by the reaction of citric acid with (NH4)2CO3)), may have increased the amount of fenitrothion released per unit time compared with the nonexpanded formulation.

Controlled release formulations of temephos and fenthion (organophosphorus insecticides) were developed by Kalyanasundaram et al. [47]. The process involved impregnat- ing the insecticides in polyvinylchloride dioctylphthalate polymers. These pellets were effective against Aedes and Culex mosquito larvae for longer than 30 days. The concentration of the insecticide released during a 24 h period was well within the safety level.

Hitchcock et al. [48] studied thermoplastic, also known as ethylene-vinyl acetate copolymer or ethylene-propylene copolymer, formulations of chlorpyifos which exhibited suitable release characteristics to provide a 3 year control of soil insects in sugarcane. Release of chlorpyrifos from rubber formulations was too slow. Terbufos was released rapidly from controlled release granules. In addition, the controlled release formulations of chlorpyrifos (2-6 kg/ha) were effective against grubs with l- and 2-year life cycles in sugarcane.

A controlled release formulation of Abate was prepared by Das et al. [49] in the form of floating pellets. The preliminary treatment consisted of polyethylene dissolved in benzene or toluene followed by uniform mixing with 10% talc. This solution was


suspended in a stream of air, and sprayed with a 1% solution of Abate in benzene or toluene. This formulation (5 ppm) was sufficient to kill mosquito (Aedes aeggpfi) larvae. The maximum concentration of Abate released into water after 24 weeks was 0.01452 ppm.

Sherman [50] studied the mechanism of release of tributyltin fluoride (TBTF) from Ecopro 1370 (a commerically available larvicide containing 20% TBTF in low density polyethylene and with a theoretical life of 3.7 years) in water and yields a strange type of IB release curve. The studied release indicated an initial peak after 10 days, a minimum release at 13 days, and steady-state release after 24 days. The release was inhibited as water diffuses into the matrix where it reacted with TBTF to form immobile tributyltin hydroxide. The latter dehydrates to bis(tributyltin) oxide which diffuses into the aqueous layer to yield the steady-state system. A model containing three reaction zones can be used to explain these phenomena.

Compounds containing a solid polysiloxane containing hydroxyl groups and pyrethroids are adherent controlled release insecticides. Young et al. [51 ] demonstrated that pyrethroids had little effect on the retention (90%) of the solid silanol X2-5056 on glass slides. Additionally, when adult cockroaches were exposed to glass panels treated with a compound containing pyrethroids 0.1, piperonyl butoxide 0.5, petroleum distillate 0.4, X2-5056 0.5, and perchloroethylene 98.5%, mortalities of 100 and 15% were observed after 7 and 10 days residue, respectively.

Upatham and Sa-Nguankul [52] tested the controlled release formulation 7.2% Ecopro 1707 (Temephos) against three species of medically important mosquito larvae, as well as snails and their eggs in the lab. The effects were expressed in lethal concentration (LCs0) values in m g / l and in lethal time (LTs0, LTIo o) values in days. The LCso values of Anopheles dirus, Aedes aegypti, and Culex quinquefasciatus exposed to Ecopro 1707 were 0.2507, 0.0646, and 0.0525 mg/1, respectively. The LTso and LTto o values for mosquito larvae exposed to Ecopro 1707 were 4 and 8 days, respectively, at 0.014 mg/ l , and 2 and 6 days, respectively, at 0.150 mg/1 for Anopheles dirus; 2 and 9 days, respectively, at 0.014 mg/ l , and 1 and 7 days, respectively, at 0.150 for Aedes aegypti; and 5 and 19 days, respectively, at 0.014 m g / 1 and 4 and 6 days, respectively, at 0.015 m g / l for C. quinquefasciatus. The LCso values for Bithynia siamensis siamensis, lndoplanorbis exustus, and Lymnaea rubiginosa exposed to Ecopro 1707 were 68.8970, 14.2743 and 3.4810 mg/1, respectively. The LTso and LTIo o values for snails were 11 and 21 days, respectively, at 3.2 mg/1, and 7 and 12 days, respectively, at 32.0 mg / l for B. siamensis siamensis; 11 and 28 days, respectively, at 3.2 mg/ l , and 7 and 12 days, respectively, at l0 mg/1 for 1. exustus; and 10 m g / l for L. rubiginosa. The LCso values for 1 and 3 day-old eggs of L exustus and L. rubiginosa were 14.0933 and 45.2620 mg/ l , and 2.0038 and 2.7876 mg/1, respectively. The dosage of Ecopro 1707 required to control mosquito larvae would not affect either snails or their eggs.

Sherman and Jackson [53] prepared 20 and 100 ppb solutions of tributyltin fluoride (TBTF) and LCso for Aeries aegypti larvae occurred within 2 days, whereas in a 200 ppb solution LCso occurred in 7 days. Larval development was partially blocked at 20 ppm (12% pupated vs. 50% at 0 ppm) and totally blocked at 100 and 200 ppb. In leaching studies with ECOPRO 1320 (20% TBTF in a natural rubber base) pellet, TBTF


concentration in soltuions was initially high (18%), then declined to 2% remaining at this level for approx. 130 days before increasing to 15%. Kinetics studies with the ECOPRO 1320 formulation demonstrated that TBTF was hydrolyzed to TBT(OH) which hydrated mistributyltin oxide (TBTO) within the formulated pellet. Leached TBTO is proposed to be the primary biocide of the formulation and responsible for the 1000 day larvicidal properties of ECOPRO 1320.

4. Naturally-occurring polymeric delivery vehicles

4.1. Herbicides

Gala et al. [54] prepared an alginate-kaolin based controlled release formulation of the herbicide thiobencar, TCR-1. The distribution, bioaccumulation and persistence of the thiobencarb from this formulation were compared to those from commercial granular formulation, 10 G. The systems consisted of a flooded paddy soil under controlled conditions, a simulated aquatic system, and a rice paddy/fish system under greenhouse conditions. Persistence of the total residues and thiobencarb parent increased; 32.5% of the applied herbicide was recovered as the parent from the soil treated with TCR-1. This is compared to only 15.2% from the soil treated with 10 G. In addition, slower release into water and less accumulation in fish tissues were found in the simulated aquatic system treated with TCR-1. A lower concentration was detected in the paddy water in the simulated rice paddy/fish system treated with TCR-1 over the duration of a 66-day greenhouse experiment. Fish and rice plants accumulated less residues from the system treated with TCR-1 than that with commerical formulation 10 G. Thus, the persistence of thiobencarb in the controlled release formulation was prolonged in water and soil. Concurrently, the potential impact on non-target components such as rice plants and fish was reduced.

Atrazine and metribuzin were microencapsulated within five different polymers by solvent evaporation process using two different emulsifiers. There were a total of 20 formulations. Herbicide efficacy studies by Dailey et al. [55] on Florida beggarweed, small flower morning glory, tall morning glory, and Palmer amaranth were conducted in the greenhouse. Nine of the ten atrazine formulations were at least as effective as a common dry flowable formulation, and five exhibited superior herbicidal activity and controlled release properties for over 32 weeks after initial treatment. The polymers demonstrating the most efficacy were cellulose acetate butyrate and ethylcellulose. Five of the ten metribuzin formulations had activities comparable to or slightly less than the common formulation and exhibited controlled relase properites. Furthermore, the other five had moderate to low herbicidal activity.

Unmodified starch is an effective matrix for encapsulating solid and/or liquid active agents such as herbicides. Gelatinization of starch in the presence of water and herbicide via continuous twin-screw extrusion processing followed by particularization to desirable mesh size yields slow release herbicide products. Rate of release can be controlled by varying extruder conditions, particle size and the addition of other chemical additives


to the starch matrix. Wing et al. [56] presented data to show efficacy of weed control and reduction of ground water contamination by various herbicide formulations.

Controlled release systems for hydrophobic, hydrolysis-susceptible herbicides comprise suspensions of herbicides, incorporated into polymer particles in an aqueous phase are discussed by Dorman and Meyers [57]. The suspensions are prepared by absorption of the herbicide into the particles from solutions in water-immiscible volatile solvents, followed by solvent removal. A solution of 10 g tridiphane in 8 ml hexane was strirred into a matrix of 20.6 g itaconic acid-stabilized polystyrene latex, 1 g Triton X-100, and 25 ml water. The herbicidal latex dispersion was then subsequently created by the evaporation of hexane in a vacuum.

Experimental controlled release starch granules containing 5.3% active ingredient (w/w) norflurazon or 6% active ingredient (w /w) simazine retarded the leaching of both herbicides in loamy sand soil colums. The release profile investigated by Boydston [58] was compared to common formulations of norflurazon (80% (w /w ) dry flowable) or simazine (90% (w/w) water dispersible granule). Barley bioassays indicated norflurazon and simazine remained in the surface depth of 15 cm when applied as common dry formulations and leached with 6 cm of water. Controlled release starch granules placed on pre-wetted soil columns began to release norflurazon by 7 days at 25°C, or 14 days at 15°C. Subsequent leaching moved norflurazon beyond the top 2.5 cm of the soil column.

Hussain et al. [59] prepared controlled release formulations of 14C-labeled thiobencarb herbicide in calcium alginate. Kaolin was used as an inexpensive filler. The rates of release of the herbicide from the prepared formulations as well as from common granular formulations were studied. The herbicide was released in static distilled water contained in both open and closed vessels. The rate of release of the herbicide was much higher in the common formulation than from the controlled release formulations. Furthermore, increasing the proportion of kaolin to calcium alginate in controlled release formulations reduced the rate of release of the herbicide. In addition, there was a significant loss of thiobencarb-related radioactivity from the water solution when exposed to sunlight and left uncovered. The loss of the herbicide seemed to be due to a chemical degradation as well as the physical process of evaporation.

A study was conducted by Vollner et al. [60] to evaluate slow release formulations of herbicides in aquatic systems. Laboratory, greenhouse and field experiments in a rice paddy were carried out to determine the behavior and fate of 2,4-D, dichlorobenil, glyphosphate, propanil and terbutryn after application of new formulations. Carbon-14 labeled materials were used of the experiments. The release rates into water and the residues in the plant and soil were determined. As formulating agents, natural polymers, like alginate, latex, latex-starch and modified cellulose were used to minimize the introduction of additional xenobiotics into the environment. This procedure mitigates the chance of negative effects on the environment by toxic or non biodegradable properties of the polymer. Hydroxyethyl cellulose (Natrosol), crosslinked with resin (melamine- formaldehyde 1%), was a promising agent for required formulations.

Shasha and Trimnell [61] combined urea pellets with herbicides entrapped in starch to reduce herbicide volatility and to increase safe handling. One method involved coating the pellets with a dispersion of herbicide in gelatinized starch to render the herbicide immediately available upon dissolution of urea. In another, a solution of polystyrene

308 M.G. Mogul et aL / Resources, Conservation and Recycling 16 (1996) 289-320

containing suspended encapsulated herbicide was used. This mixture was applied to urea pellets to provide a product with rate of release of herbicide proportional to the square root of time.

Pfister et al. [62] investigated the usefulness of Ca alginated as matrix material for controlled release formulations with the herbicides (1), desmetryn (2), chloridazon (3), atrazine (4), MCPB (5), simazine (6) and chloroxuron (7) as active ingredients. Release rates of these substances were measured from hydrated and dried gel beads. The results obtained indicate that the release from both gel types correspond to the water solubilities of the active ingredients. Sufficient retardation of herbicide release up to several months could be attained with the hydrated and dried Ca alginate formulations of 6 and 7 (water solubilities 5 and 3.7 ppm, respectively) and the dried formulations of 4 and 5 (water solubilities 70 and 44 ppm, respectively).

Wise [63] incorporated 2,4-D into polylactic acid and cast into thin films of approx. 5 microns in thickness. The thin film of herbicide/polymer was placed in a test tube between granular packing to maintain a continually moist environment. The test tube has a small opening cut in the bottom to permit throughput of water. Data were obtained by percolating sucessive portions of water, twice weekly, through the test tubes containing the herbicide source and then applying the extract to petri dishes in which mustard seedlings were cultured. The amount of water passing through the herbicide/polymer system and through the control (herbicide absorbed on filter paper was used) was calculated to be equivalent to that of approx. 4 inches of irrigation per week. The degree of growth reduction in the mustard seedlings served as a measurement of the effectiveness of the supply of herbicide. Specifically, the stem lengths of the longest of 50 seedlings were measured. On the basis of this test it was seen that the polylactic acid/herbicide source prolonged herbicide delivery significantly. Based on the success of the feasibility tests using films of herbicide/polymer, samples of polymer and 2,4-D on granular clay were prepared and tested. The overall object of preparing the clay/polymer/herbicide system was that such a system is immediately suitable for conventional broadcast application techniques. A weighed amount of polymer, herbicide, and 24- to 48-mesh clay granules were blended together with a solvent (acetone). The solvent was flashed off as the system was gently turned to permit uniform penetration and coating of the clay by the polymer/herbicide matrix. Overall, these results demonstrated the sustained release of herbicide from a practical conventional clay carrier when incorporated into a biodegradable polymer.

Connick [64] individually incorporated 2,4-D and dichlorobenil into 1.6-2.8 mm Na alginate gel beads using CaC12 and BaC12 as gellants. The release rate of each herbicide from the beads into water was greatly influenced by drying and the choice of gelled cation. Slowest release was obtained with dried samples that were gelled with BaC12. At the slowest rates, release of 2,4-D was complete in 14 days, whereas only 59% of the less-soluble dichlorobenil was released in 150 days.

A number of starch esters of various herbicides were prepared from an activated pregelatinized starch and the acid chlorides of the respective herbicides [65]. Picloram was released from aqueous suspensions of the ester, to which nonsterile soil was added, in sufficient amount to inhibit lettuce growth. Application of the supensions to sterile soil at a rate equivalent to 5 kg picloram/ha was phytoxic to lettuce for at least three

M.G. Mogul et aL/ Resources, Conseroation and Recycling 16 (1996) 289-320 309

seedings over 48 days. Similar results were obtained by incorporating the solid herbicide ester directly into nonsterile soil. In nonsterile soil pregelatinized starch picloram esters hydrolyze more readily than unmodified starch picloram esters.

4.2. Pesticides

Investigation of the physical entrapment of both biological and chemical pesticides was achieved by encapsulation of active ingredients within starch matrixes [66]. Starch is first gelatinized either physically using heat, or chemically using alkali or urea. Pesticide is then added followed by the crosslinking of starch. The final product is granular, ready to be used with conventional equipment. Electron microscope pho- tographs reveal the presence of a honeycomb matrix containing the pesticide. Sprayable formulations based on the entrapment within starch were also achieved. The sprayable material has a low and stable viscosity and can be used with conventional farm equipment. Upon application it dries to a thin film that does not dissolve in the presence of water.

Use of the poly(ethylene imine)-treated Ca alginate was investigated for the preparation of the slow release formulations of dichlobenil, propanil and carbofuran [67]. The release of pesticides from the alginate granules was markedly retarded by post-treatment of the Ca-algina~e beads with polyamine. The release profile depended on the post-treatment procedure; type of concentration of the polyamine, pH and the duration. Retarda- tion of the herbicide release up to 1 year was attained.

4.3. Other

Thermal analysis of controlled release formulations of fenthion was carried out by Prasad and Kalyanasundaram [68] using thermogravimetric analysis under accelerated storage conditions. The formulations were prepared by entrapment in crosslinked CM-cellulose and CM-cellulose-gelatin matrixes. Furthermore, thermograms of samples of sodium CM-cellulose, crosslinked polymer samples, and the formulations were studied. The thermogravimetric analysis showed improved heat resistance and retention of fenthion or its decomposition products in the formulated samples. The maximum decomposition of technical grade fenthion was 260°C. The corresponding weight loss was about 90%, whereas fenthion or its decomposition products appear to be retained in the fromulations to temperatures ranging from 400 to 500°C. Subsequent analysis indicated that the half-life of fenthion in the mechanical mixture with the carrier polymer was found to range from 19.92 to 29.98 days. Alternatively, the formulated retention times were found to range between 41.54 and 113.35 days.

Prasad and Kalyanasundaram [69] prepared controlled release formulations of the mosquito larvacide Fenthion as monolithic slabs by making sodium CM-cellulose insoluble. The slabs were created by the ionotropic crosslinking with ferric chloride under ambient conditions of temperature and pH. In addition, slabs containing 20% and 10% larvicide concentrations and three different extents of crosslinking were made. Evaluation of these formulations under static conditions in water was continued until the formulations started to erode extensively. The release profile and stability of the


formulations varied depending on the larvicide loads and crosslinking periods. Formula- tions with 48.0 h of crosslinking as well as 20% and 10% larvicide (FeF 3 and FeF 6) were evaluated for 21 and 27 weeks with the respective average release rates of 6.4766 × 10 - 7 and 2.5094 × 10 - 7 m g / c m 2 s. Among these formulations, FeF 2 exhibited maximum closeness to zero-order release behavior compared to the rest. Constant rate of release was observed after an initial high rate of release, due to the swelling and gradual hydrolytic erosion of the ionic crosslinks of Fe(III) CM-cellulose matrix. Erosion rate constants were calculated by assuming that the release of fenthion from these formulations is due to the erosion of the entrapping matrix.

5. Non-polymeric delivery vehicles

5.1. Herbicides

The release processess of benthiocarb and butachlor from corncob and alginate controlled-release formulations were studied [70]. Their dynamic equations were established using the release process as the hypothetical base. The theoretical results were then compared to the experimental data. The release process of benthiocarb from corncob granules into water was described as being thermodynamically controlled. More specifically, the release rate of the herbicide would be affected essentially by adhesive components at the surface. For present corncob formulations, the release of benthiocarb was quicker from the TA1 fromulation than that from TA2. It took 15 days for 95% of the initially incorporated herbicide to be released out of the TA1 formulation. While for TA2 the release duration was about 30 days. Alternatively, the release of both the herbicides from alginate granules was mainly governed by a diffusive process, and could be described with a corresponding diffusion equation. Aside from the influence of composition, the formulation release rates were mainly determined by the size of the granules. The release rate constant was found to vary with the inverse square of the granule radius. The bigger the granule was, the lower the corresponding release rate. In addition, the formulation with a high content of alginate has a quicker release rate than the formulation with a low content of alignate. However, the realization of this controlled release system may very well be determined by the cost of alginate itself. In practice, the alginate fast release formulation must be developed by reducing the size of the granule.

Metolachlor was released from dicalcium phosphate tablets over a 25-day period [71 ]. This is compared to 2 and 3 days for the commercially available emulsifiable concentrations and granular formulations, respectively. Approx. 25% of the napropamide (I) has been recovered from the tablets during the same period. Similarly, adding a surfactant to the I/dicalcium phosphate tablet mixture increased the recovery rate to a point where 55% of the napropamide (I) was recovered. Tablets containing 4% napropamide released greater amounts of herbicide at a single collection period then did tablets containing 1% napropamide. Furthermore, adding a surfactant to the napropamide tablet mixture significantly improved Italian ryegrass control.

Slow release tablets made of dicalcium phosphate containing a herbicide and a


surfactant were placed on the surface of or buried in Metro Mix 350 or a pine bark-peat moss-sand medium in containers seeded with weeds [72]. These containers were then subsequently placed under intermittent mist in the greenhouse or under sprinklers outdoors. Up to 15 cm (6 in) diameter circular areas of weed control formed around a single tablet. Adding 1-2% surfactant to herbicides having a very low water solubility such as Gallery (isoaxaben), Surflan (oryzalin, Ronstar (oxadiazon), Goal (oxyflurfen), and for comparison, to Dual (metolachlor), markedly enhanced the release of herbicide and enlarged the area of weed inhibition. The surfactants that produced the best results were Triton X-100 and X-77. Initial release of herbicides from the tablets was rapid upon exposure to moisture and the area of activity became close to maximum within a few days after placing the tablet on the soil surface. Experimental observation revealed that tablets placed on the surface produced larger areas of activity than when buried. In addition, the tablets retained their shape after 3 months of outdoor exposure.

Riggle and Penner [73] used a pine craft lignin (PC940C) to control the release of [ 14C]chloroambin, [ 14C]metribuzin, and [lgc]alachlor as measured by the water leaching in soil columns. As more PC940C was used, a concentration effect was found with more of the three herbicides being retained in the top portion of the soil columns. Combina- tions of alachlor and metribuzin applied with PC940C did not alter the retention in the top portion of the soil columns of either metribuzin or alachlor compared to each herbicide applied with PC940C alone. Apparently, at the rate of PC940C used, there was no competition between either herbicide for the controlled release function of PC940C. The percentage of chloramben, metribuzin, and alachlor without PC940C reduced the mobility of both metribuzin and alachlor. Finally, [3H]PC940C was found to be immobile is soil columns leached with water.

2,4-D was chemically bonded as a pendant group to sawdust. The product was granulated, after adding a equal amount of free 2,4-D, with clay, glue, and lignin sulfonate [74]. Three years of field trials on crops have established the efficacy of the product as a cheap controlled release terrestrial herbicide.

Alachlor, chloramben, napthalam, and propachlor incorporated into di-Ca phosphate and plaster of paris slow release tablet formulations successfully controlled weeds for 16 weeks with no significant injury to cotoneaster (Cotoneaster dammed), euonymus (Euonymus fortuenei), forsythia (Forsythia intermedia), and privet (Ligustrum vicaryi) [75]. One tablet per container was applied, delivering 20 to 40 kg /ha active ingredient. Metolachlor was incorporated in the tablet formulations to deliver a rate of 40 kg /ha active ingredient per tablet to evaluate the area of weed control. Weeds were signifi- canlty reduced in containers treated with metolachlor tablets. An essentially weed-free area (7-8 cm radius) encompassing a single herbicide tablet was observed. Tablet formulations did not significantly differ in reduction of weeds in nursery containers.

5.2. Pesticides

Controlled release compounds are made by including title chemicals into biodegradable, microporous structures. Each microporous structure collapses upon drying but swells upon rewetting to allow the chemical entrapped in it to diffuse from the substrate. Never-dried wood pulp is a particularly desirable microporous structure because it has

312 M.G. Mogul et aL / Resources, Conservation and Recycling 16 (1996) 289-320

initially large pores and a large surface area, and swells. Allan [76] treated 2 g of 2,4-D in 60 ml 25% NH 3 solution with 3 g never-dried sulfite pulp. The composition was then followed by 25 min of washing and drying to give a sustained release profile.

Slow release systems are made of a drug or pesticide incorporated into a water soluble glass (m.p. < 320°F). The glass is ml(M1Aal): m2(M2ab2): m3(M3Ac3: .... (M1, M2, M3 = H, metal; A1, A2, A3 = carboxylate, nitrate, sulfate, bisulfate; a, b, c depend on the valencies of M and A; ml, m2, m3 are the same or different integer). The vitreous glass is optionally coated with a phosphate glass, having a predicted dissolution rate. Wardell and Duffy [77] incorporated biologically active lactones and esters into rods made of the carboxylate glass MeCO2Li:MeCO2Na (1.33:1). The rods were coated with the phosphate glass Na20:CaO:P205 (2:2:3).

Choudary et al. [78] has been presented for the first time a technique for controlled release of pesticides via complexation with metals in the interlamellars of montmorillonite, a smectite caly. This technique is an alternative method of controlled release which conventionally deals with the immobilization of pesticides in polymers. Diazinon, chlorpyrifos, carboxin, and carbendazim have been chelated with Cu /Co in the interlamellars of montmorillonite as evidenced by IR analysis, XRD, and ESR data. Chemical assay results indicate that the intercalated pesticides were released in small amounts over a period of 7-8 weeks. On the other hand, adsorbed pesticides were totally leached within 24 h from montmorillonite. The general and persistent toxicity tests for these complexes against housefly (Musca domesfica) demonstrate that the diazinon and chlorpyifos clay complexes showed 100% mortality for an extended period of 20-22 weeks. In contrast, the analogous conventional formulations exhibited 100% mortality only up to 4-8 weeks.

Controlled released pesticides are prepared by Stm~zcyk and Wrzesniewska-Tosik [79] using a ligninsulfonate carrier modified with aromatic acid chlorides, especially terephthaloyl chloride. The modified ligninsulfonates are reacted with pesticides containing CO2H groups (e.g., 2-4-D). Four weight parts lingninsulfonate was dissolved in DMSO 200 volume parts and pryidine 2.9 volume parts. The solution was stirred for 15 min at 30°C, and 3.484 weight parts of terephthaloyl chloride in 50 volume parts DMSO were added. This procedure was followed by 3.794 weight parts of 2,4-D in 50 mol parts DMSO being added to the solution. Then, the reaction mixture was heated for 4 h at 140°C, cooled, and precipitated in water. In addition, the precipitation was separated by filtration, washed further with water and MeOH, and dried using a pressure of 9.8-times 104 Pa, at a temperature of 60°C. This gave a final product which was 3.56 weight parts powder, consisting of the controlled release pesticide. In model experiments, 92% 2,4-D was released in a aqueous solution containing 40 mg product/l of water at a pH of 7, after a time duration of 36 days.

Struszczyk and Wrzesniewska-Tosik [80] prepared the controlled release pesticides on a liginsulfonate carrier modified by condensation with phenol and formaldehyde. The modified iiginsulfonates are reacted with pesticides containing COzH groups (e.g., 2,4-D). Four weight parts ligninsulfonate, 96% H2SO 4, 0.3 volume parts phenol and 33% aqueous formaldehyde solution, consisting of 7 volume parts were boiled for 4 h. After cooling to 30°C, 9.15 weight parts 2,4-D in 50 volume parts MeOH were added, followed by boiling the solution for 10 h. The resulting product was separated by

M.G. Mogul et aL / Resources, Conservation and Recycling 16 (1996) 289-320 313

filtration, copiously washed with water and MeOH, and dried at 60°C. The aforementioned steps give 3.2 weight parts controlled release pesticide powder. In model experiments, 81% 2,4-D was released in an aqueous solution containing 40 mg product/l of water, at a pH of 7 after 59 days. The product was successfully used for control of dicot weeds.

5.3. Other

Silica-shell microcapsules of insecticide were made from porous microbaloons of silica and chlorpyrifos [81]. The silica microbaloon (i.e., the shell material of the microcapsule), was made by an 'Interfacial Reaction Method.' The silica was formed by the reaction of a sodium silicate aqueous solution emulsified in an organic solvent with an ammonium salt aqueous solution. The mean particle diameter and specific surface area of the silica were 6.96 microns and 451 m2/g, respectively. The frequent pore size distribution ranged from 18 to 22 nm. The core material (i.e., chlorpyrifos), was impregnated in the core spaces of the silica ballooon through the micropores in the shell under vacuum conditions. The microcapsule was then prepared. The evaluation of biological activity of the microencapsulated chlorpyrifos paint and commerical pesticide paint was carried out against cockroaches for a period of 6 months. The residual activity of the pesticide in the inorganic microcapsule prepared by the interfacial reaction lasted longer than that of the commercial one. The microcapsules incorporated into the paint functioned as the controlled release device.

Controlled release formulations of fenthion, an organophosphorus larvicide, with easily biodegradable career materials like Jiggieth (the powdery gummy parts of plant material which acts as a binding agent), cork powder and plaster of paris was developed [82]. This formulation with 4 g of fenthion (82.5% EC) per pellet when released at the rate of 1 pellet/100 l of breeding habitat was effective for 32-37 days in cesspits, 37 days in soak pits and 27 days in septic tanks against Culex quinaquefasciatus. The release profile studied by HPLC indicated that the concentration of the insecticide could be maintained between 0.005 and 0.45 mg / l with an average release concentration of 0.2 mg/ l . This range is sufficient to produce 100% mortality against all the different vector species. The loss in the insecticide was reduced significantly by the additional incorporation of 0.2% of an antioxidant, 2,6-di-tert-Bu p-cresol.

Gresser [83] prepared and hardened samples of fish protein with 2 pph formaldehyde. These contained varying additives of Bayluscide at either 0.0 or 5.0 pph of the fungicide Dowicide at 0.05 pph level. Half of the samples of each type were post-treated with glutaraldehyde and then immersed for 8 weeks in pond water containing normal bacterial populations. Samples which had not been exposed to a postgelatin wash with glutaraldehyde showed degradative weight losses of between 50 to 75%. A clear difference was observed between these samples and those subjected to a postgelatin glutaraldehyde wash. The washed samples had lost only between 17 to 29% in the 8-week period. Samples hardened with 6.2 pph HCHO and washed with glutaraldehyde showed no significant improvement over those prepared with 2 pph HCOH, and similarly washed. The species Marisa cornu ariesta were exposed to preparations containing 0, 5, 10, and 25 pph Baluscide. All preparations containing 0.05 pph


Dowicide. No deaths were observed in tanks containing the controls (0 pph Baluscide, 0.05 pph Dowicide). The most rapid rate of death occurred at Bayluscide concentration, between 0.40 and 0.05 pph. Deaths occurred sooner among snails exposed to the more highly loaded preparations. The projected lifetime of the treated group is therefore between 200 and 330 days.

6. Experimental results

When a bioactive substance i s chemically combined, dissolved or encapsulated in a polymeric matrix, its application to soil or environment results in the release of the active ingredient at a decreased rate. This kind of release prevents the loss of the active agent by degradation, evaporation or leaching.

Bioerodible polymers are gaining attention in the area of controlled release applications. Considerable attention has been paid to the formation of nanoparticles f rom biodegradable materials. Candidate biodegradable polymers, such as gelatin, albumin, starch, poly(lactic-glycolide) copolymers and poly(di-lactide) have high novelty in these type of applications. In the release experiments, the microsphere structure offers advantages over other geometries because, the extremely small dimensions are obtain- able in a sphere.

A simple analysis of drug release was provided below by Sinclair and Peppas [84]:

M,/M® = kt n

Here, M, /M~ is the fraction of the initial drug released, t is time, k is a diffusional kinetic constant, and n is the diffusional exponent. The value of the exponent, n, is a good indication of the release mechanism. For release in spheres, the corresponding values for n are 0.43 for Fickian diffusion and 0.85 for Case-II release [85]. For values of n between these limits release is termed anomalous or non-Fickian. Diffusion coefficients can be calculated by using the two equations below. The relationships are derived from the Higuchi model by Baker and Lonsdale [86]. The release of a drug from a sphere of radius r, is given by two approximations:

Short time approximation is valid for Mt/M® < 0.4:

Mt/M~ = 6(D,t /r2~r) ' /2 _ (3D, t / r2 )

Long time approximation is valid for MI/M® > 0.6:

M,/M® = 1 - ( 6 / ~ - : ) e x p ( - ~r2O, t / r 2 )

In this study, a herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) was loaded into gelatin microspheres [87]. The microspheres were prepared by spraying hot gelatin solution into cold water containing the crosslinking agent glutaraldehyde. Loading of 2,4-D into the microspheres was carded out in aqueous solution and then some samples .were coated with a second layer of polymer, either with polyvinylalcohol or gelatin. The chemical, physical and thermal properties of the prepared microspheres were characterized with IR, SEM, DSC, TGA, as well as additional swelling experiments.

The microspheres with an average particle size of 1 micron were used. 2,4-D was not

M.G. Mogul et a l . / Resources, Conservation and Recycling 16 (1996) 289-320

Table 1 Loading conditions and amount of 2,4-D absorbed in the polymeric microspheres at different pH values

315

pH % Load Diff. D (cm 2/s) exponent (n) at M t/M® = 0.15

5 1.5 0.714 1.24X 10- 14 7 1.3 0.563 1.067 × 10-14 9 3.2 0.536 3.930× 10-16 11 4.6 0.515 2.871X 10-16

added into the medium during the preparation of gelatin microspheres because it could readily go into chemical reaction with glutaraldehyde. The microspheres were loaded later by soaking in a buffer solution containing 2,4-D. The variability in the solubility of 2,4-D in media with different pHs was the parameter that was influential on the extent of loading. The solubility of 2,4-D in the aqueous medium is on the order of ppm, but it increases in alkaline medium by salt formulation. Therefore, different buffer solutions of 2,4-D were used for loading. Loading conditions and the amount of 2,4-D absorbed in the polymeric microspheres at different pH values are given in Table 1. As seen from Table 1, the percent loading increased from 1.3 to 4.6 with increasing the pH from 5 to 11.

Gelatin is hydrophilic and erodes homogeneously. Drug release results indicate that matrix erosion contributes little or nothing to the drug release profile. Diffusion experientation indicates a 30 day release for the matrix loaded at pH 9 and 11, and 50 days for microspheres loaded in pH 5 and 7 media. The release experiments were carried out against distilled water and in all cases, three different release phases were distinguished. These consisted of an 'early burst' phase followed by a slow release and finally by a second burst due to erosion of the support material.

The mechanism of 2,4-D release from the microspheres was observed to have a combined diffusion-erosion type kinetics. Temperature affects both diffusion and erosion; therefore, in all cases the amount of released drug was increased with an increase in temperature. When the crosslink concentration increased from 4% to 24%, it caused an increase in crosslink density on gelation. This, in turn, effected the swelling properties and therefore resulted in a decrease in the diffusion coefficient from 10-14 cmE/s to 10 -16 cm2/s.

Double encapsulation of the microspheres decreased the permeability of 2,4-D significantly. The release rate of drug from the gelatin matrix had the highest value followed by the coated polyvinyl alcohol while the gelatin coated had the lowest release rate at three different temperatures (4, 25, 35°C).

With increasing loading the value of the diffusion exponent changes from anomolous behavior (with a t °'7 dependency) to that of Fickian diffusion (with a t °'5 dependency). Such transition can be considered as a change of relative importance of the diffusion process versus the polymer relaxation as a function of 2,4-D loading. At relatively low drug loadings, both the diffusion and the polymer relaxation appear to control the mode of drug penetration thereby giving rise to a penetration behavior between Case-II and Fickian extremes. However, at sufficiently high loadings of 2,4-D, diffusion is Fickian.

316 M.G. Mogul et al./Resources, Conservation and Recycling 16 (1996) 289-320

This is further supported by the evidence that the drug penetration rate increases with increasing drug level.

Since release was incomplete during the investigation time, diffusion coefficients were calculated by using only the short time approximation for Mt/M~ = 0.015 value. The diffusion coefficient values of microspheres, decreased from 1.246 × 10 - 1 4 to 2.87 × 10-16 cm2/s with increasing the percent loading from 1.5% to 4.6%, respectively.

The activation energy of diffusion, Ea, d, was calculated for all crosslinked matrices, by using Arrhenius rate law. Crosslinking caused an increase in Ea. d value from 1.45 J /mol to 3.91 J/mol. For coated PVA the Ea. d was found as 3.66 J /mol and for gelatin coated microsphere 8.06 J /mol .

7. Conclusions

Sustained release may be defined as a technique or method in which active chemicals are made available to a specific target at a desired rate for a specified period of time. In these systems a drug, pesticide or any other bioactive agent is incorporated into a carrier which is generally a polymeric material. The rate of release of the substance is determined by the properties of the polymer itself and also by the associated environmental factors. The formulations were first used in the agricultural industries for low molecular weight fertilizers, pesticides and antifoulants in the 1950s. However, in the 1970s formulations for large molecular weight drugs were designed [88]. During the last decade, increasing attention was paid to release of agricultural chemicals since they are excessively toxic. Also in conventional applications of agricultural chemicals, the concentration and persistence of the agent is decreased by biodegradation, chemical degradation, evaporation, surface runoff, and ground water leaching. However, almost 90% of the applied agent is uneffective and causes environmental contamination due to the aforementioned environmental effects. A question one could ask might be, if agricultural chemicals are directly responsible for 60% of production, why do we need controlled release formulations? The answer can be broken up distinctly into two parts. The first stems from the fact that agents are not used effectively. Ten billion dollars are spent annually in the US on pesticides. Yet pests still cause an estimated 30% loss in potential agricultural production. Secondly, although the US has a vast, fertile agricultural resource on which to draw upon, the overall surplus is estimated at only 6%. Furthermore, it takes 10-15 million dollars and 6-10 years to register a new insecticide, and there are only approx. 125 registered formulations.

Along the same lines, fouling on ships increases drag, fuel consumption (up to 50%), accelerates hull corrosion, interferes with sound devices, and clogs underwater pipes. Two hundred and fifty million dollars are spent annually in the US to remove fouling organisms. However, there is still 500 million dollars annual damage on permanent .structures along the US cost.

From an economic as well as an environmental standpoint, much basic research needs to be done in order to increase the effectiveness of the active agent without the harmful effects associated with exposing non-target areas. Characterizing the release mechanisms


along with developing new biodegradable matrixes will support the goal of controlled release. To effectively inhibit the damage that is caused from uncontrolled propagation of 'pests' in which the active agent is not otherwise harmful to the surrounding environment and/or wildlife.

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