WO2007093370A1 - Fabrication de particuleS microscopiqueS de polymère, de substance active ou de polymère et de substance active par pulvérisation-broyage-séchage d'une solution dans un broyeur - Google Patents

Fabrication de particuleS microscopiqueS de polymère, de substance active ou de polymère et de substance active par pulvérisation-broyage-séchage d'une solution dans un broyeur Download PDF

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Publication number
WO2007093370A1
WO2007093370A1 PCT/EP2007/001219 EP2007001219W WO2007093370A1 WO 2007093370 A1 WO2007093370 A1 WO 2007093370A1 EP 2007001219 W EP2007001219 W EP 2007001219W WO 2007093370 A1 WO2007093370 A1 WO 2007093370A1
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Prior art keywords
particles
polymer
mill
active ingredient
grinding
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PCT/EP2007/001219
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German (de)
English (en)
Inventor
Andre Dammann
Thomas König
Martin Steinbeck
Dirk Triebe
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Bayer Technology Services Gmbh
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Publication of WO2007093370A1 publication Critical patent/WO2007093370A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A01N25/10—Macromolecular compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/12—Powders or granules
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring

Definitions

  • the present invention relates to a method for the production of microscale particles by a combined spray-mill-drying and the particles obtainable therewith and their use.
  • jet milling or grinding media mills are usually used in the comminution technique. It is known from the literature that jet mills which operate with high gas throughputs can be used in part for the after-drying of products (flow processes in comminution in jet mills, Muschelknautz et al., CIT42, 1, 1970). The complete drying of products from solutions, pastes, suspensions or emulsions or combinations using a jet mill with high gas flow rates is not yet named.
  • microparticles An important application of microparticles is a controlled release of an active agent that can be achieved by polymer-drug-matrix formulations.
  • the active substance or the active ingredients are crystalline or amorphous in the form of particles or amorphously dissolved in the polymer matrix.
  • a particular application of such particles is the sustained release of microscale particles over a long period of time.
  • Such long-term release formulations can be used, for example, in crop protection and horticulture (for example in seed dressing), in animal health or in human medicine, in the field of cosmetics and dermatology, in material protection / protection of wood, etc.
  • the target particle size can only be achieved inadequately, uneconomically or even not at all. This case is a well-known problem in the spray-drying and in a further process step, optionally followed by grinding during the particle formation of polymers or polymer-containing formulations (eg polymer-active matrix formulations with long-term release over weeks / months by long-chain polymers).
  • polymers or polymer-containing formulations eg polymer-active matrix formulations with long-term release over weeks / months by long-chain polymers.
  • EP 0400522 A2 Boehringer
  • an active substance or active ingredients and a biodegradable polymer are dissolved in an organic solvent, the mixture is dried with the aid of a spray drier and then ground in a jet mill.
  • Produced are ⁇ -scale particles for pharmaceutical sustained release with a release on the order of hours or days.
  • the jet mill is only for crushing and ggs. used for drying the product from the spray drying.
  • WO 94/09898 A1 (Schwarz Pharma AG) one or more active substances and a biodegradable polymer are each dissolved separately in a biodegradable solvent (or the active ingredient is suspended), the two solutions are then mixed and the resulting solution or suspension or emulsion is spray-dried.
  • the process is technically limited to polymers for forming the formulation matrix that are compatible with the spray-drying process and results in the production of more biocompatible ⁇ -scale formulations. Subsequent grinding in a jet mill does not take place.
  • the discharge of the spray dryer i. the spray dryer cyclone is coupled to the jet injector / injector. This avoids product handling between the spray tower and the cyclone with the aim of a hygienic process.
  • the jet mill is used only for crushing and ggs. for post-drying of the product from spray drying.
  • a major drawback of the process is the processing of highly flammable substances (e.g., organic solvents for polymers and active ingredients) in that a spray dryer with associated cyclone and filter is a large volume apparatus that must be operated explosion proof.
  • the resulting particles are unfavorable, especially hard, impact-resistant, plastic and / or adhesive substances or mixtures are therefore ⁇ -scale particles, in particular drug-matrix formulations with a drug release over a long period of weeks / Months about the described method difficult or impossible to produce.
  • the present invention relates to a process for the production of particles, preferably of microscale particles from difficult-to-grind substances or formulations or of microscale particles of substances or formulations that difficult by pure spray drying are prepared, such as polymers, or polymer formulations, drugs or Wirkstoffforrnultechniken, optionally with the addition of. Fillers and / or other additives, as well as other soluble, suspendable or emulsifiable substances and the particles produced and their use.
  • the solution, suspension or emulsion a) is sprayed by means of a spray nozzle or several spray nozzles directly into the grinding chamber of a mill or a device according to the principle of a grinding media mill, and the dried shaped particles are discharged
  • the solution, suspension or emulsion a) is sprayed with the aid of a spray nozzle or several spray nozzles in a pre-chamber of a mill or a device according to the principle of a grinding mill, the liquid, wet or partially dried particles are introduced into the grinding chamber, in one dried and crushed combined process and the dried particles are discharged.
  • the relevant substance or substances for example polymers and / or active substances and, if appropriate, further auxiliaries and additives
  • the relevant substance or substances are dissolved, suspended or emulsified in a solvent or in a solvent combination.
  • a liquid or a suspension is emulsified into the solution, or solids are suspended as particles in the solution.
  • Suitable solvents or solvent combinations are preferably organic substances having a low enthalpy of vaporization and / or a low boiling point and, as far as possible, low toxicity, which are inert to the solutes or the individual components of the formulation. These can be, for example:
  • Alkanes such as methane, ethane, butane, propane, n-pentane and its isomers, cyclohexane, n-hexane and its isomers, cyclohexane, methylcyclopentane, n-heptane and its isomers, n-octane and its isomers
  • Halogenated alkanes such as chloromethane, dichloromethane, trichloromethane or carbon tetrachloride, chloroethane, dichloroethane, trifluoroethane, trichloroethane, dichloro-trifluoroethane, dichlorotetrafluoroethane, tetrafluoroethylene, bromomethane, dibromomethane, tribromomethane, tetrabromomethane,
  • Ethers such as, for example, dimethyl ether, methyl ethyl ether, diethyl ether, tetrahydrofuran, dioxane,
  • Alcohols such as methanol, ethanol, butanol, 1-propanol and 2-propanol,
  • Organic acids such as formic acid, chloroformic acid, acetic acid, chloroacetic acid and dichloroacetic acid,
  • Aldehydes such as formaldehyde and acetaldehyde
  • Ketones for example 2-propanone, 2-butanone, 2-pentanone, 3-pentanone, cyclohexanone or dioxane,
  • Esters such as, for example, methyl formate, methyl acetate, ethyl formate and ethyl acetate, n-butyl acetate, isobutyl acetate,
  • Nitriles such as acetonitrile
  • Aromatic carbon compounds such as benzene, toluene, o-xylene and p-
  • Phenols such as phenol and cresols
  • Inorganic acids in highly concentrated form or dissolved in water such as hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid,
  • Aromatic nitrogen compounds such as imidazole, methylimidazole or pyridine, Sulfoxides such as dimethyl sulfoxide,
  • salts such as sodium chloride, sodium sulfate, sodium nitrate,
  • acetone since this substance has a low enthalpy of vaporization and boiling temperature and, moreover, the toxic hazard potential is limited.
  • the resulting aqueous or nonaqueous solution, suspension or emulsion usually has, for the purpose of spraying with a nozzle, a dynamic viscosity of ⁇ 10000 mPas, preferably ⁇ 1000 mPas, particularly preferably ⁇ 100 mPas.
  • the particle size of the powder for microscale matrix particles is usually in the range of d 50 ⁇ 30 ⁇ m, preferably in the range of d 50 ⁇ 10 ⁇ m, particularly preferably in the range of d 50 ⁇ 5 ⁇ m.
  • suspension or emulsion particles are produced by spraying in a (possibly modified) mill, in an integrated spray-mill-drying process, dried and ground.
  • the target size of the resulting particles is usually at a diameter of d50 ⁇ 100 microns, preferably d50 ⁇ 30 microns, more preferably d50 ⁇ 10 microns.
  • the particles are produced by spraying the solution, suspension or emulsion directly into the mill or by introducing the particles preformed directly in front of the mill in a preform chamber into the mill.
  • Particles particularly suitable are mills with high gas throughput, preferably jet mills and in particular spiral jet mills (eg spiral jet mill type Bayer LSM) with a subsequent separation of the particles (eg via a cyclone / filter arrangement) and a Exhaust gas purification (eg scrubber, combustion, A-carbon filter).
  • Spiral jet mills are on the one hand typical for crushing in the finest range d50 ⁇ 10 microns and on the other hand are particularly suitable in terms of explosion protection.
  • Spiral jet mills have namely because of their high energy density on a small enclosed space and also have no ignition sources by rotating or other moving parts, so that on the one hand, the volume of an explosive mixture and the risk of ignition sources are low.
  • mills or grinding systems for fine or very fine comminution such as other jet mills (eg fluidized bed counter-jet mills, counter-jet mills or oval tube jet mills) and grinding media mills (eg vibrating mills, ball mills, attritors) or according to the principle of Mahl stressesmühlen operated devices (MahlSystem Messengere by Movement of a MahlSystem commonlyung), in which, however, the drying then possibly not done as in the jet mills convective by the gas flow, but must be made according to the principle of contact drying via Vakuumabsaugung the solvent vapors and heat.
  • high-speed rotor impact mills can be used, as far as they provide a sufficiently high stress for the desired target particle size.
  • the spray directly in front of the mill e.g. take place in an antechamber before the injector entry of a spiral jet mill.
  • the target particle size of the process is already sought.
  • the solvent already partially evaporated so that even in the prechamber shaping by the spraying and possibly superficial drying takes place.
  • small compact, possibly superficially dried drops are optionally produced with intermediate threads or thin superficially dried threads or thread structures, which are entered after Vorform documentation with a gas flow consisting of the Verdüsungsgasstrom and possibly already evaporated solvent in the milling chamber.
  • a gas flow consisting of the Verdüsungsgasstrom and possibly already evaporated solvent in the milling chamber.
  • the grinding gas causes a combined crushing and drying, by convective drying and impact / friction in jet mills or contact drying (vacuum / hot surfaces) and impact / friction in media mills, and depending on the type of mill subsequent classification before or after the exit of Particles from the grinding chamber.
  • the particles produced and in particular microscale particles are usually deposited after leaving the mill or the integrated or downstream classifier by conventional separation apparatus such as cyclone and / or filter.
  • the comminution during the drying process can have an advantageous effect on the residual solvent contents of the particles produced since the comminution increases the surface area of the solid and thus the heat and mass transfer surface for the drying.
  • the particles are already stressed when they have not yet reached their final strength, i. if they are at least partially liquid, soft and correspondingly deformable compared to the solvent-free polymer.
  • the gas stream for atomization and / or the grinding gas volume flow can be added to the apparatus for better drying of the resulting particles heated.
  • this heating may be disadvantageous for the comminution due to the increasing elasticity of the products, so that this parameter must be adapted individually to the respective product.
  • the nozzle type and the nozzle geometry eg a two-fluid nozzle in nitrogen operation
  • an operating parameter set emission pressure of liquid and optionally gas, throughput of liquid and possibly gas
  • the nozzles and their operating parameters are also adapted to the following mill and its operating parameters, as well as the periphery of the mill (cyclone and / or particle separation filter, solvent separation condenser, eg scrubber, incinerator, A-carbon filter for exhaust air purification, etc.) , If it is necessary to dry the particles prior to entry into the mill, the necessary energy can be supplied by preheating the liquid solution, suspension or emulsion and / or by adding the (possibly warm) atomizing gas.
  • process parameters such as pressures, temperatures, product viscosities and throughputs must be set in such a way that wall adhesions are avoided.
  • post-drying for example by vacuum drying
  • ⁇ -scale particles having an average diameter d 50 ⁇ 100 ⁇ m, preferably d 50 ⁇ 30 ⁇ m, particularly preferably d 50 ⁇ 10 ⁇ m, are produced.
  • the microparticles are usually measured by the method of laser diffraction (Malvern Mastersizer, possibly with previous ultrasound treatment) and also assessed microscopically (eg, SEM). Depending on the substance system and the particle size range, it is also possible to determine the particle sizes. driving (wet screening, air jet screening), sedimentation (eg sedimentation scale), ultrasonic methods, quantitative methods of image analysis, etc.
  • polymers such as:
  • Homopolymers with C-C main chain linkage for example polyethylene, polypropylene, polyvinyl chloride, polymethyl methacrylate, polyvinylpyrrolidone, polystyrene, polyacrylonitrile,
  • Copolymers having C-C main chain linkage with at least two different monomers for example two or more of ethylene, propylene, styrene, vinyl chloride,
  • Polyesters of at least one aromatic dicarboxylic acid for example terephthalic acid, isophthalic acid
  • one or more components from the group of aliphatic dialcohols for example diethylene glycol, butanediol, cyclohexane-1,4-dimethanol, 1-3 propanediol, hexanediol
  • Polyamides such as polyamide 6, polyamide 66, polyamide 4, polyamide 11, polyamide 12,
  • Aromatic homo- or copolycarbonates for example based on bisphenol A (2,2-bis (4-ydroxyphenyl) propane, bisphenol TMC (4,4 '- (3,3,5-trimethylcyclohexylidene) bisphenol), bisphenol M (4,4 '- (1,3-phenylenebis (1-methylethylidene) bisphenol), bisphenol Z (4,4'-cyclohexylidene bisphenol)
  • Polyesteramides e.g. from the monomers ethylene glycol, butanediol, caprolactam,
  • Adipic acid hexadimethylenediamine, terephthalic acid
  • Polyesters containing portions of aliphatic dicarboxylic acids for example, succinic, oxalic, malonic, adipic, glutaric, maleic, fumaric
  • aromatic dicarboxylic acids e.g., terephthalic, phthalic
  • polyhydric alcohols eg, diethylene glycol, butanediol, cyclohexane-1,4-dimethanol, 1 -3 propanediol
  • Cellulose and cellulose derivatives for example methylcellulose, hydroxypropylcellulose, cellulose acetate, etc., Starch and its derivatives,
  • Polyurethanes based on polyfunctional isocyanates such as diisocyanate-toluene, diphenylmethane-isocyanate, hexamethylene-diisocyanate, isophorone-diisocyanate and polyhydric alcohols, such as diethylene glycol, butanediol, cyclohexane-1,4-dimethanol, 1-3 propanediol, hexanediol, glycerol .
  • polyfunctional isocyanates such as diisocyanate-toluene, diphenylmethane-isocyanate, hexamethylene-diisocyanate, isophorone-diisocyanate and polyhydric alcohols, such as diethylene glycol, butanediol, cyclohexane-1,4-dimethanol, 1-3 propanediol, hexanediol, glycerol .
  • Polymers with C-O main chain for example polyoxymethylene,
  • copolymers prepared by reactive extrusion of at least two of the polymers mentioned in points 3 to 11.
  • particles are produced from polymers which, on the one hand, permit release to be delayed for a sufficiently long time but, on the other hand, degradation products which occur have sufficiently biocompatible properties (biodegradable or biocompatible polymers).
  • polymer-active ingredient-matrix-microparticles are produced.
  • active ingredients are agrochemical active ingredients such as fungicides, bactericides, insecticides, acaricides, herbicides, plant growth regulators, plant nutrients and repellents, drugs, as well as flavors and fragrances possible.
  • both pure active substance particles can be processed as well as formulation containing from 0.1 to 99.9%, preferably from 1 to 90%, particularly preferably from 5 to 50% active ingredient.
  • microscale polymer-active substance matrix particles can be produced by the process according to the invention which, despite their small particle size, show sustained release of the active ingredient over days / weeks or months.
  • fungicides such as: 2-anilino-4-methyl-6-cyclopropyl-pyrimidine; 2 ', 6'-dibromo-2-methyl-4'-trifluoromethoxy-4-trifluoromethyl-1,3-thiazole-5-carboxanilide; 2,6-dichloro-N- (4-trifluoromethylbenzyl) benzamide; (E) -2-methoxymino-N-methyl-2- (2-phenoxyphenyl) -acetamide; 8-hydroxyquinoline sulfate; Methyl (E) -2- ⁇ 2- [6- (2-cyanophenoxy) pyrimidin-4-yloxy] -phenyl ⁇ -3-methoxyacrylate; Methyl (E) -methoximino [alpha- (o-tolyloxy) -o-tolyl] -acetate; 2-Phenylphenol (OPP), Aldimorph, Ampropyl-pyrimidine; 2 '
  • Cyproconazole Cyprofuram, Carpropamid, Dichlorophene, Diclobutrazole, Dichlofluanid, Diclomezine, Dicloran, Diethofencarb, Difenoconazole, Dimethirimol, Dimethomorph, Diniconazole, Dinocap, Diphenylamine, Dipyrrithione, Ditalimfos, Dithianone, Dodine, Drazoxolone, Edifenphos, Epoxyconazole, Ethirimol, Etridiazole, Fenamidone, Fenarimol, fenbuconazole, fenhexamide, fenfuram, fenitropan, fenpiclonil, fenpropidin,
  • Fenpropimorph fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoromides, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminum, fthalide, fuberidazole, furalaxyl, furmecyclox, fenhexamid, guazatine, hexachlorobenzene, hexaconazole, Hymexazole, imiazalil, imibenconazole, iminoctadine, Iprobenfos (IBP), iprodione, isoprothiolane,
  • Iprovalicarb kasugamycin
  • copper preparations such as: copper hydroxide, copper naphthenate, copper oxychloride, copper sulfate, copper oxide, oxine-copper and Bordeaux mixture, mancopper, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methasulfocarb, methfuroxam, metiram, Metominostrobin, Metsulfovax, Myclobutanil, Nickeldimethyldithiocarbamate, Nitrothal-isopropyl, Nuarimol, Ofurace,
  • Thicyofen thiophanate-methyl, thiram, tolclophos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, trichlamide, tricyclazole, tridemorph, triflumizole, triforin, triticonazole, trifloxystrobin, validamycin A, vinclozoline, zineb, ziram, and 2- [2- (2- 1-chloro-cyclopropyl) -3- (2-chlorophenyl) -2-hydroxypropyl] -2,4-dihydro- [1,2,4] triazole-3-thione.
  • bactericides such as bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furancarboxylic acid, oxytetracycline, probenazole, streptomycin, tecloftalam, copper sulfate and other copper preparations.
  • insecticides for example, insecticides, acaricides and nematicides such as: abamectin, acephate, acetamiprid, acrinathrin, alanycarb, aldicarb, alphamethrin, amitraz, avermectin, AZ
  • Fonophos Formothion, Fosthiazate, Fubfenprox, Furathiocarb, HCH, Heptenophos, Hexaflumuron, Hexythiazox, Imidacloprid, Iprobenfos, Isazophos, Isofenphos, Isoprocarb, Isoxathione, Ivermectin, Lambda-cyhalothrin, Lufenuron, Malathion, Mecarbam, Mevinphos, Mesulfenphos, Metaldehyde, Methacrifos, Methamidophos, Methidathione, Methiocarb, Methomyl, Metolcarb, Milbemectin, Monocrotophos, Moxidectin, Naled, NC
  • nitenpyram omethoate, oxamyl, oxydemethon M, oxydeprofos, parathion A, parathion M, permethrin, phenthoate, phorate, phosalone, phosmet, phosphamidone, phoxim, pirimicarb, pirimiphos M, pirimiphos A, profenophos, promecarb, propaphos, propoxur, prothiophos , Prothoate, pymetrozine, pyrachlophos, pyridaphenthione, pyresmethrin, pyrethrum, pyridaben, pyrimidifen, pyriproxifen, quinalphos, salithion, sebufos,
  • herbicides such as: anilides such as diflufenican and propanil; Arylcarbonates such as dichloro-picolinic acid, dicamba and picloram; Aryloxyalkanoic acids such as 2,4-D, 2,4-DB, 2,4-DP, fluroxypyr, MCPA, MCPP and triclopyr; Aryloxyphenoxyalkanoic acid esters, such as, for example, diclofopmethyl, fenoxapropethyl, fluazifop-butyl, haloxyfopmethyl and quizalofop-ethyl; Azinones, such as chloridazon and norflurazon; Carbamates such as chlorpropham, desmedipham, phenmedipham and propam; Chloroacetanilides such as alachlor, acetochlor, butachlor, metazachlor, metolachlor, pretilachlor and propachlor; Dinitroanilines such as oryzalin, pen
  • plant growth regulators such as chlorocholine chloride and ethephon.
  • plant nutrients are common inorganic or organic fertilizers for the supply of plants with macro and / or micronutrients
  • repellents are diethyl-tolylamide, ethylhexanediol and buty-pyronoxyl.
  • insecticides which may preferably be present in the powder formulations according to the invention are imidacloprid, thiacloprid, thiamethoxam, acetamiprid, clothianidin, betacyfluthrin, cypermethrin, transfluthrin, lambda-cyhalothrin and azinphosmethyl.
  • herbicides which may preferably be present in the powder formulations according to the invention are propoxycarbazone-sodium, flucarbazone-sodium, amicarbazones and dichlobenil and also phenyluracils of the formula in which the substituents R 1 , R 1 and R 2 have the meanings given below.
  • fungicides which may preferably be present in the powder formulations according to the invention are bitertanol, carbendazim, carpropamide, cyproconazole, cyprofuram, carpropamide, edifenphos, fenamidone, fenhexamide, fluoxastrobin, fluquinconazole, fosetyl-aluminum, iprodione, iprovalicarb, metominostrobin, pencycuron , Prochloraz, Propamocarb, Propineb, Prothioconazole, Pyrimethanil, Spiroxamine, Tebuconazole, Tolyfluanid, Triadimefon, Triadimenol, Trifloxystrobin.
  • the polymer-active-matrix-microparticles produced preferably consist of:
  • ggs From 0 to 50% by weight, preferably from 0.1 to 30% by weight, more preferably from 1 to 20% by weight, of organic or inorganic additives,
  • Suitable fillers are substances which can be incorporated in proportions, preferably in high proportions, into thermoplastic polymers, are chemically inert, increase the temperature stability of the formulation, are themselves thermally stable, improve the granulability, improve the grindability of the formulation or a allow suitable release of the active ingredient from the polymer matrix or influence them in a suitable manner, are ecologically safe and also as inexpensive as possible.
  • suitable organic or mineral fillers are:
  • Oxides e.g. Zinc oxide
  • glass structures e.g. Glass fibers, glass beads, glass powder or quartz sand
  • hydroxides e.g. Magnesium hydroxide or aluminum hydroxide
  • silicates in particular phyllosilicates, e.g. Mica
  • silicic acids especially with nanoscale structures such as e.g.
  • Particularly preferred mineral fillers are kaolin, calcium carbonate, finely divided silica, zeolite, activated carbon, glass or talc.
  • inorganic or organic additives can be used.
  • additives typical formulation additives from the group of wetting agents, dispersants / emulsifiers, lubricants, lubricants, defoamers, stabilizers, preservatives, antifreeze agents, antioxidants, dyes, or additives that influence the release of the active ingredient (s) can be added.
  • the prepared microscale polymer-drug-matrix particles can usually show a sustained-release of the active ingredient over> 3 weeks to a few months.
  • FIG. 3 Release curve Example 1 (homogenization by shaker)
  • FIG. 4 Release curve Example 2 (homogenization by shaker)
  • FIG. 5 Particles from example 1, scanning electron microscopy
  • FIG. 6 Particles from example 2, scanning electron microscopy
  • FIG. 7 Particle size distribution Example 1; Laser diffraction with Malvern Mastersizer 2000
  • FIG. 8 particle size distribution Example 2; Laser diffraction with Malvern Mastersizer 2000
  • A polymer-active substance-filler solution / suspension / emulsion
  • NTN / SAN / zeolite 30/60/10 drug-polymer-filler matrix formulation
  • a spiral jet mill Bayer LSM 100 (1) was modified according to Figure 1 so that the injector of the jet mill was removed and instead a Vorsprühhunt (4) was connected to the entry opening of the jet mill.
  • a two-substance nozzle (2) was mounted in the cover of the pre-spraying chamber.
  • the particles showed a release of active ingredient of ⁇ 10% over> 3 weeks, whereby homogenization was achieved by means of a horizontal shaker.
  • the release of the active ingredient was determined as follows: Depending on the active substance content, a quantity of sample was weighed into a 100 ml glass bottle and deionized water was added to give a concentration of about 1000 ppm of the active ingredient. The bottles were stored on a horizontal shaker (laboratory shaker Fa. IKA) and shaken at a frequency of 150 l / min (or, depending on the application, with a stirrer bar (20 mm stirrer bar, 400 rpm)) homogenized during the release time. The sampling took place at different time intervals. For this purpose, 2 mL sample was taken with the aid of a disposable syringe, filtered through a 0.20 ⁇ m syringe attachment filter (Sartorius MINISART) and placed in an HPLC vial.
  • NTN / SAN 30/70 drug-polymer-matrix formulation
  • a spiral jet mill Bayer LSM 100 (1) was modified according to FIG. 1 so that the injector of the jet mill was removed and instead of this a pre-spraying chamber (4) was connected to the opening of the jet mill.
  • a two-substance nozzle (2) was mounted in the cover of the pre-spraying chamber.
  • an acetone solution, (A), (85% solvent) of the insecticidal active ingredient imidacloprid (4.5% active ingredient) and a thermoplastic copolymer of styrene and acrylic nitrile (10 , 5% polymer) into the described spray chamber (4) sprayed and then introduced by the gas stream of atomizing nitrogen (B) and the partially evaporated solvent in the spiral jet mill LSM100 (1), which also with nitrogen (grinding gas (C), form approx. 7 bar_ü) was operated.
  • the particles showed a release of active ingredient of ⁇ 10% over> 3 weeks, whereby homogenization was achieved by means of a horizontal shaker.
  • the release of the active ingredient was determined as follows:
  • a quantity of sample was weighed into a 100 ml glass bottle and deionized water was added to give a concentration of about 1000 ppm of active ingredient.
  • the bottles were stored on a horizontal shaker (laboratory shaker from DCA) and shaken at a frequency of 150 l / min (or, depending on the application, with a stirrer bar (20 mm stirrer bar, 400 rpm)) homogenized during the release time. The sampling took place at different time intervals. For this purpose, 2 mL sample was taken with the aid of a disposable syringe, filtered through a 0.20 ⁇ m syringe filter (Sartorius MINISART) and placed in an HPLC vial.

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  • Life Sciences & Earth Sciences (AREA)
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  • Health & Medical Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Agronomy & Crop Science (AREA)
  • Wood Science & Technology (AREA)
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Abstract

L'invention concerne un procédé de fabrication de particules par une combinaison de pulvérisation, de broyage et de séchage, qui est caractérisé en ce qu'il permet de réaliser conjointement le formage, le séchage et le broyage. Le procédé comprend les étapes suivantes : à l'étape 1, la substance ou la combinaison de substances est mise en solution, en suspension ou en émulsion dans un solvant ou une combinaison de solvants. A l'étape 2, la solution, la suspension ou l'émulsion de l'étape 1 est pulvérisée à l'aide d'une buse de pulvérisation ou de plusieurs buses de pulvérisation directement dans la chambre de broyage d'un broyeur ou d'un appareil qui fonctionne selon le principe d'un broyeur à corps de broyage et les particules ainsi façonnées et séchées sont extraites du broyeur. En variante, la solution, la suspension ou l'émulsion de l'étape 1 est pulvérisée à l'aide d'une buse de pulvérisation ou de plusieurs buses de pulvérisation dans la pré-chambre d'un broyeur ou d'un appareil qui fonctionne selon le principe d'un broyeur à corps de broyage, les particules liquides, humides ou séchées sont apportées dans la chambre de broyage, séchées et broyées et les particules façonnées et séchées sont extraites.
PCT/EP2007/001219 2006-02-14 2007-02-13 Fabrication de particuleS microscopiqueS de polymère, de substance active ou de polymère et de substance active par pulvérisation-broyage-séchage d'une solution dans un broyeur WO2007093370A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200610006618 DE102006006618A1 (de) 2006-02-14 2006-02-14 Herstellung mikroskaliger Polymer-,Wirkstoff-oder Polymer-Wirkstoff-Partikel durch Sprüh-Mahl-Trocknung einer Lösung in einer Mühle
DE102006006618.9 2006-02-14

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WO2007093370A1 true WO2007093370A1 (fr) 2007-08-23

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Publication number Priority date Publication date Assignee Title
WO2010100638A2 (fr) * 2009-03-04 2010-09-10 Celsius Property B.V. Amsterdam (Nl) Traitement de graine et composition pesticide
DK3837987T3 (da) * 2019-12-16 2022-11-14 Air Liquide Pulverisering af et stof, der omfatter et fedtstof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3971631A (en) * 1971-10-28 1976-07-27 J. M. Huber Corporation Pelletizing alkali metal polysilicates
EP0502325A1 (fr) * 1991-03-07 1992-09-09 Hoechst Aktiengesellschaft Procédé de préparation de silicates de sodium
DE19933832A1 (de) * 1999-07-20 2001-01-25 Bayer Ag Streugranulate
DE19928222A1 (de) * 1999-06-19 2001-05-17 Roland Nied Verfahren und Vorrichtung zur Herstellung eines Granulats
WO2003105584A1 (fr) * 2002-06-13 2003-12-24 Bayer Cropscience Aktiengesellschaft Formulations pulverulentes

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3971631A (en) * 1971-10-28 1976-07-27 J. M. Huber Corporation Pelletizing alkali metal polysilicates
EP0502325A1 (fr) * 1991-03-07 1992-09-09 Hoechst Aktiengesellschaft Procédé de préparation de silicates de sodium
DE19928222A1 (de) * 1999-06-19 2001-05-17 Roland Nied Verfahren und Vorrichtung zur Herstellung eines Granulats
DE19933832A1 (de) * 1999-07-20 2001-01-25 Bayer Ag Streugranulate
WO2003105584A1 (fr) * 2002-06-13 2003-12-24 Bayer Cropscience Aktiengesellschaft Formulations pulverulentes

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