From active substance to product – the formulation is the key - Bayer ...

From active substanceto product – theformulation is the keyCrop protection isn’t simplya question of using theright active substance: thesuccess of a product alsodepends on deliveringthe active substance inthe right formulation*.The science of Formulation Technologyinvolves incorporating the active substanceinto a final product that is the most practicalfor the user, and which guarantees thata small amount of active substance is distributedevenly over a large treated area.An important consideration is whether thecrop protection agent will be applied byspraying, irrigation or broadcasting, orwhether treatment should be in the form ofa seed-coating. This article discusses thevarious factors that have to be taken intoaccount when developing the right formulationfor a particular active substance. Itwill also introduce the formulation typesthat have been developed for the mostcommonly used types of spray application.High demands made offormulationsThe choice of formulation is determinedby the type of use, the crop to betreated, the cultural methods most commonlyused in the region, and any specificrequirements on the part of the user. Butthe wide range of formulation types thathave been developed also follows fromvariation in the physico-chemical propertiesof the active substances themselves.Among these, melting point, solubility andchemical stability are important factors.Another determinant is whether the activesubstance shows systemic redistribution,or only contact activity. A particularlyimportant aspect of the formulation is thatit should aim to optimize factors such asretention, penetration, rain-fastness andspreadability, so that the active substancecan express its full biological activity.The development of a formulation alsoinvolves testing further important criteriasuch as crop compatibility, environmentalbehaviour, and toxicity. Moreover, it isimportant that the product, once sold,remains stable in storage under variousconditions, retaining its activity for at leasttwo years.Being able to meet these challengesrelies on the availability of a selection ofdifferent formulation types: EC, EW, SL,SC, WG, and more recently, CS, SE andOD. Special products, such as slug pelletsand several other application types, arealso available – for example for use in gardens.Solution, Emulsion,Suspension or GranuleOne of the most important considerationsfor the user in the field is that thecrop protection product should remain in astable mixture with water in the spray tank.This presents formulation technologistswith a real challenge, because there arevery few products that are fully soluble inwater. For this reason, many formulationsare prepared in the form of concentratedemulsions or suspensions in readiness foruse. Other formulations are sold as organicsolvents or granules that form an emulsionor suspension only after being diluted withwater in the spray tank. Emulsions containwater. Because the larger droplets reflectlight, macro-emulsions appear as typicalmilky-white spray mixtures.The importance of the solventThe development of an EC-formulationstarts with the search for a suitable solventor mixture of solvents that meets the followingcriteria: it must be toxicologicallyand ecotoxicologically safe, and shouldhave low flammability. According to thedemands the formulation and the activesubstance have to meet, further substancesmay be introduced, for example to optimizethe spreadability of the spray mixtureor to promote the penetration of the activeDiluting an emulsifiable concentrate (EC) in water produces an emulsion.the active substance dissolved in finelydistributedoil droplets, whereas suspensionscontain the active substance in theform of finely-distributed solid particles.Emulsifiable concentrates (EC)ECs have long been, and remain one ofthe most important formulation types forapplying crop protection agents to cereals.The farmer buys a liquid product, in whichthe components of the formulation comprisea homogeneous solution. An emulsionis formed only after dilution withwater. This might, for example, be a microemulsionwith droplet sizes of between0.01 and 0.1 µm. Apart from a slight bluishshimmer resulting from light dispersion(the so-called Tyndall-Effect), the microemulsionappears to the user as a clearsolution, because the individual dropletscannot be seen with the naked eye.However, most EC-formulations comprisea macro-emulsion with a droplet size ofbetween 0.1 and 10 µm when diluted withsubstance into the plant. Finally, the appropriateemulsifier system must be selected,so that the emulsion remains sufficientlystable for spray application following dilutionwith water.The challenge of stabilityOnce prepared by the user, an emulsionmust remain stable for at least 24 hourswithout forming significant amounts ofdeposits in the form of oil, cream, or sediment.It is also vital to avoid crystallizationof the active substance in the spray mixture,because this could lead to blockage ofthe spray nozzles or the pump filter duringapplication.What used to be considered an acceptabledegree of crystallization is no longerthinkable for a modern EC-formulation.On the one hand, the demands made by theuser have sharply increased; on the other* The preparation called the „formulation“ is identicalto the product as sold.1/05 COURIER 7

hand, modern application equipment andapplication methods require emulsions ofthe highest quality in order to allow thecrop protection agent to be distributedevenly across the treated field. A furtherconsideration is that the quality criteria forthe registration of new products havebecome significantly more stringent.Careful with mixtures!All formulation types have to be testedfor their miscibility with other crop protectionproducts, fertilisers and additives,because they must retain their biologicalactivity and crop compatibility in mixtureswith these products. Each individual formulationis a finely-tuned „system“ initself. Mixing formulations in the spraytank inevitably leads to various degrees ofunfavourable interaction between the inertingredients present in the different formulations.At worst, gel-formation, coagulationor sedimentation can make the spraymixture totally unusable. This places theonus on users to restrict themselves to mixturesthat have been fully tested and validated.Soluble liquids (SL)The water-soluble, liquid concentrates(Soluble Liquids), like the EC and EW,contain the active substance in dissolvedformulations. Nevertheless, localized concentrationof the product can lead to somedegree of crystallization if the spray mixtureis not properly stirred.Emulsions in Water (EW)EW-formulations are emulsions inwater. The emulsion can comprise a liquidactive substance, or otherwise one that hasbeen dissolved in solvents. This means thatconsiderably less solvent is applied to thecrop compared with EC-formulations.With an EW, the emulsion has already beenestablished in the sold product, and is onlydiluted in the spray mixture. EW-formulationshave the advantage that they show littletendency to form crystals in the spraymixture. EWs can also be in the form ofeither micro- and macro-emulsions.However, EW-formulations are uncommon,because few active substances areliquids or possess the suitable solubilityproperties.Suspension concentrates (SC)In SC-formulations, the active substanceis present as a solid that is finelydistributedin particles of between 1 and 4µm in size. The particles are held in suspensionin the water-based mediumthrough the addition of so-called dispersingagents; this effect involves mutualMixing a suspension concentrate (SC) with water produces a suspension. The active substance ispresent as finely-distributed particles.means that its biological availability islower than with EC, EW and SL formulations.This is why SCs are most suitablewhen a high degree of contact exposure ofthe host organism is the main aim.Water dispersible granules (WG)For insoluble active substances, wettablepowders (WP) used to be the preferredformulation type; however, thesetend to form dust and are difficult to doseout. Nowadays, these problems are solvedby choosing water dispersible granules.These are dust-free in practice, and allowthe inclusion of large amounts of activesubstance in the product, so WGs are particularlyuseful for active substances thatneed to be applied at high rates. In thisway, even if production costs are relativelyhigh, the cost per hectare can usually bekept down. WGs generally show good cropcompatibility, so they are often used formore sensitive crops, such as grapevine.Suspoemulsions (SE)A suspoemulsion is a combination of theSC and EW formulation types. The continuousphase comprises water, in which bothsolid particles and emulsion droplets arefinely distributed. This formulation type isespecially suitable wherever two activesubstances with starkly contrasting solubilityprofiles or melting points need to bemixed. The emulsion phase can also containadditives that promote the systemicactivity of the active substance.Oil dispersions (OD)Many (new) systemic active substancescannot be formulated as ECs because oftheir particular properties. Because theoptimal activity of these active substancesStirring water-dispersable granules (WG) into water makes them spread spontaneously.depends on their entering the plant, alternativesare needed in which the active substanceis present in solid form. TheFormulation Technology Unit at BayerCropScience has developed various conceptsinvolving oil dispersions (OD) inorder to achieve the required levels of biologicalactivity and crop compatibility. Inan OD, a solid active substance is suspendedin an oil. The oil also serves as acarrier for additives and/or a safener.Diluting the OD in water can produce variousspray mixtures: if the active substanceis itself water-soluble (as in many herbicides),then an emulsion results; if theactive substance shows low water solubility(as in many insecticides), a suspoemulsionresults.OutlookIn the context of the steadily increasingdemands of modern crop protection, new,optimized variations on existing formulationtypes – and of course new concepts –Dissolving a soluble concentrate (SL) in water results in a clear solution.form. However, SLs differ from ECs andEWs in that every component of the formulationis dissolved in the water-basedspray mixture – which is why the latter isalways a clear solution. This means thatSL-formulations can only be developed foractive substances that are sufficientlywater-soluble. A minimum spray mixturevolume is usually recommended for SL-repellency between the particles; and incombination with other substances thatform net-like structures, the dispersingagents also prevent sediments from forming.One disadvantage though is that theproduct’s high viscosity generally makes itmore difficult to empty the packagingcompletely. The fact that the active substanceis present in crystalline form alsoCapsule suspensions (CS)Capsule Suspensions are the best choiceif an active substance shows problems withstability, or needs to be released in theenvironment in a controlled manner. Theactive substance can be present within thecapsule either dissolved or dispersed in theliquid phase. The internal phase of the capsuleis usually a solvent. The capsule ispresent in the product and later, in thespray mixture, in suspension. A CS ismade from an emulsion that already containsthe active substance; the other componentis the capsule wall, the characteristicsof which determine the release kineticsof the CS formulation.Mixing an oil dispersion (OD) with water results in a suspoemulsion.will always be required. This is the taskassumed by the Formulation TechnologyUnit at Bayer CropScience. Formulationtechnology is an interdisciplinary scientificundertaking, with special relationships tothe disciplines of colloid chemistry andinterfacial physics, in which technicalchemistry plays an essential role.In one of the next issues of Courier, youwill be able to read about how efficientmodern spray applications can be, and howformulation technology can improve thedistribution of the active substances on,and within, the plant. ■8 COURIER 1/05 1/05 COURIER 9