FR2867025A1 - Stable, dust-free, solid tablet formulations of agrochemical active agents, e.g. insecticides or fungicides, containing effervescent couple, hydrophilic super-disintegrant and directly compressible filler - Google Patents

Abstract

A new solid formulation (I), in tablet form, comprises (by weight) (a) 0.1-80% agrochemical active agent (solid at room temperature), (b) 0.1-10% effervescent couple, (c) 0.5-10% hydrophilic super-disintegrant and (d) 1-60% directly compressible, water-soluble or hydrophilic filler.

Description

1 2867025

  The present invention relates to novel agrochemical compositions, especially tablets.

  The present invention more particularly relates to solid forms, stable, and may contain active principles sensitive to hydrolysis or heat-sensitive.

  In agriculture, the cost of agrochemicals is an essential aspect that distinguishes it from pharmaceuticals.

  Indeed, the quantities used in agriculture are important given the surfaces to be treated, which requires minimizing the cost of formulation.

  Already known active ingredients formulated in the form of powders but have the disadvantage of emitting dust, which causes a risk of inhalation of the product by the user when it pours it into a sprayer.

  To solve this drawback, essentially there are dispersible granules generally manufactured by atomization, fluidized air bed or extrusion. There are also water-soluble sachets pre-dosed filled with a powder of active ingredients.

  It would be desirable to have solid, inexpensive, non-pulverulent formulations which may have the advantage of being pre-dosed into active ingredients, which may be large in size.

  It would also be desirable to have solid formulations for incorporating active ingredients sensitive to acids or bases.

  It would also be desirable to have solid formulations capable of being stored over relatively long periods with the minimum of precautions.

  It would be equally desirable to have solid formulations that are easy and economical to manufacture and that are particularly suitable for direct compression of powders.

  However, after much research, the Applicant has discovered satisfactory formulations.

  This is why the present application relates to a solid formulation, in particular pre-dosed in tablets, characterized in that it comprises, by weight, - 0.1 to 80% of a solid agrochemical active ingredient at ambient temperature, - 0, 1 to 10% of an effervescent couple, 0.5 to 10% of a hydrophilic super-disintegrant, 1 to 60% of a hydrosoluble or hydrophilic filler for direct compression, and optionally 0.5 to 10% of a a binder, up to 40% of an insoluble charge for direct compression.

  In the present application and in the following, the term of one or one means at least one unless the context shows that the term means only one.

  For example, an agrochemical active solid at room temperature may be an insecticide, a herbicide, a fungicide or a pheromone.

  The insecticidal active ingredient may be, for example, a natural or synthetic pyrethroid, such as deltamethrin, lambda-cyalothrin, betacyfluthrin, esfenvalerate or tau-fluvalinate, an organohalogen such as endosulfan, or a chloronicotinil such as imidacloprid or Acetamiprid, thiametoxam or thiacloprid The insecticidal active ingredient may be in particular a natural or synthetic pyrethroid, such as deltamethrin, lambdacyhalothrin or beta-cypermethrin, and particularly the latter.

  The active ingredient insecticide can also be an association of active ingredients, prepared or not in advance.

  The term insecticidal active ingredient also refers to the related active ingredients such as nematicides or acaricides.

  Examples of herbicides that may be mentioned include aryloxyphenoxypropionates (fops) such as cyhalofop-butyl, clodinafoppropargyl, or diclofop, or cyclohexane-dione oxime such as clethodim or hydroxybenzonitriles such as bromoxynil or ioxynil, or biscarbonates such as phenmedipham or desmedipham, or sulfonylureas such as mesosulfuron-methyl, tribenuron-methyl, flazasulfuron or nicosulfuron.

  The term herbicidal active ingredient also refers to related active ingredients such as growth regulators.

  The fungicide may be for example various heterocycles including azoles such as tebuconazole, cyproconazole, diniconazole, epoxyconazole or difenoconazole or strobilurins such as trifloxystrobin, azoxystrobin or kresoxim-methyl.

  The active principle (or mixture of active ingredients) may represent from 0.1 (for active principles at a very low dose, such as sulphonylureas) to 80% of the solid formulation, in particular from 1 to 60%, preferably from 1% to 50%, especially from 1% to 40%.

  It is of course possible to use a single active principle or an association of active principles as we have seen.

  The effervescent couple may represent from 0.1 to 10% of the solid formulation, preferably from 1% to 10%, especially from 2% to 10%, particularly from 2% to 8%.

  An effervescent couple conventionally comprises a preferably organic acid such as tartaric acid or citric acid and a base, in particular an alkaline carbonate or hydrogencarbonate such as sodium hydrogencarbonate.

  Each of the elements of the pair can represent from about 1 to about 10% of the solid formulation, preferably from 1% to 7%, especially from 2% to 6%, especially from 3% to 6%, all of the two couple elements representing less than 10%.

  The hydrophilic super-disintegrant is preferably a disintegrant, low-binding and very swelling, for example of the carmellose crosslinked type (cross-linked carboxymethyl cellulose), preferably cross-linked povidone (polyvinyl pyrrolidone after PVP -crosslinked) or cross-linked carboxymethyl starch or conventional disintegrants of the type native corn starch. There may be mentioned for example the super disintegrant marketed by BASF under the name Luvicross or Kollidon CL.

  Particularly preferred are crosslinked polyvinyl pyrrolidone, crosslinked carboxymethyl starch and conventional native corn starch disintegrators.

  The hydrophilic super-disintegrant may represent from 0.5 to 10% of the solid formulation, preferably from 1% to 5%, especially from 2% to 4%.

  The hydrosoluble or hydrophilic feedstock for direct compression may be, for example, a derivative or mixture of derivatives of starches, sugars or polyols, preferably a polyol, sorbitol, mannitol, maltodextrin, lactose or pregelatinised starch type compound. Mention may be made, for example, of the product marketed by Roquette under the names Pearlitol, Neosorb or Starlac, which is a compound excipient comprising lactose and starch.

  The hydrosoluble or hydrophilic feedstock for direct compression may represent from 1 to 60% of the solid formulation, preferably from 3% to 50%, especially from 5% to 30%, particularly from 5% to 20%.

  Under preferred conditions of practice of the invention, the solid formulation above contains a binder.

  The binder may be, for example, a starch, sugar, polyol, cellulose, vinyl or acrylic derivative, preferably an adhesive strength binder which may be chosen from a range of adhesive strength, for example a binder of the carmellose or povydone type. linear. For example, the binder marketed by BASF under the name Luvitec K30 may be mentioned.

  The binder may represent from 0.5 to 10% of the solid formulation, preferably from 1% to 8%, especially from 2% to 6%.

  Under preferred conditions of implementation of the invention, the solid formulation above contains a lubricant. This may represent from 0.1 to 4% of the solid formulation pre-dosed in tablets, preferably from 0.2% to 3%, especially from 0.5% to 2.5%.

  The lubricant may be hydrophilic sucroester or lipophilic type such as magnesium stearate.

  In other preferred conditions of implementation of the invention, the solid formulation above also contains an insoluble filler for direct compression. This may represent up to 40% of the solid formulation in tablets, in particular pre-dosed, preferably from 5% to 40%, especially from 10% to 25%.

  The insoluble filler for direct compression may be, for example, a derivative of calcium salts, celluloses or starches, preferably a wicking disintegrating compound and particularly microcrystalline celluloses of various densities and granulometries and the resulting compound excipients. especially the type Avicel or Microcel. In the context of the invention, are classified in this class of excipients silicates and more particularly kaolins.

  In still other preferred conditions of implementation of the invention, the solid formulation above contains a slip agent to facilitate the flow in the compression matrix during implementation.

  The slip agent may be for example talc, colloidal silica, magnesium stearate, glycerol palmitostearate, sucroesters and preferably fumed silica. Mention may be made, for example, of the fumed silica marketed by Degussa under the name Aerosil 200.

  This may represent up to 2% of the pre-dosed solid formulation in tablets, preferably from 0.1% to 1.5%, most preferably from 0.3% to 1%.

  The excipients usually employed in these compositions, such as various wetting, dispersing, emulsifying, coloring or preserving agents, may also be incorporated into the above solid formulation.

  The unit weight of a solid formulation in tablets according to the invention may range from 0.01 g to 30 g depending on the nature and concentration of the active ingredient, and for many active ingredients from 1 g to 15 g.

  The phytosanitary tablet compositions of the present invention may be prepared according to methods known per se.

  The subject of the present invention is therefore still a process for the preparation of a composition described above, characterized in that the active ingredient (s) are mixed with the various excipients, and then the compression is carried out. direct preference of the mixture.

  Direct compression of the mixture means direct compression of a mixture of powders, including optionally the active principle (s), without prior granulation.

  In particular conditions of implementation of the method described above is carried out a granulation, preferably without wetting with water, before compression. To this end, it is possible to proceed by compacting and grinding. It is also possible to proceed by wet granulation in a mixer, preferably of the base type, for example Lôdige.

  In other preferred conditions of implementation of the method of the invention, the compression is performed using a rotary machine including forced feeding and particularly with pre-compression.

  The agrochemical compositions in particular pre-dosed tablets object of the present invention have very interesting properties and qualities.

  They make it possible in particular to have solid formulations pre-dosed in active principles economically compatible with agriculture, non-pulverulent and therefore limiting the risk of intoxication for the manipulator, size may be important therefore allowing the realization of pre-dosed forms.

  They allow in particular to have solid formulations of practical use with good suspensibility.

  They are versatile because they contain a reduced amount of acid and base, which improves the stability of the composition and particularly the active ingredient. A wide variety of active ingredients can be used.

  In addition, the amount of effervescent couple being reduced, the tablets are less sensitive to storage, especially in a humid atmosphere.

  The sensitivity of the formulations of the present invention is lower vis-à-vis moisture than that of formulations more strongly measured in effervescent pairs, which allows to dispense with certain precautions during their manufacture.

  The present invention can be implemented by direct compression (without prior granulation), which makes it possible to implement a simple and inexpensive method compatible with the prices practiced in the agrochemical field.

  The agrochemical compositions, in particular pre-dosed in tablets which are the subject of the present invention, even of large size, can disintegrate rapidly, in less than 3 minutes and even less than 2 minutes, while maintaining a good cohesion, which enables them to be packaged in bulk.

  These properties are illustrated below in the experimental part. They justify the use of the agrochemical compositions described above, in agriculture or gardening.

  This is why the invention also relates to the use of the above agrochemical compositions in the treatment of pests or parasites of vegetation or vegetation control particularly undesirable. In particular, it is possible to spray an agrochemical composition above after dilution in a sufficient quantity of water.

  The object of the invention is as much the provision of new agrochemical compositions as other compositions than those which may have been described in the state of the art. Therefore, those described in the literature are excluded.

  The preferred conditions of use of the agrochemical compositions described above also apply to the other objects of the invention referred to above, in particular to the processes for preparing them.

  The following examples illustrate the present application. EXAMPLE 1: Mancozeb Tablets Step A: A mixture for direct compression equivalent to about 36 tablets of 6.5 g is prepared with Turbula in the following proportions: Components g Mancozeb 85% + Surfactants (Dithane M 45) 250 Quality Crospovidone for disintegrating Croscarmellose sodium tablets 10 Microcrystalline cellulose pH 102 97 Mannitol for direct compression 70 Citric acid anhydrous 30 Sodium bicarbonate 20 Magnesium stearate 10 Amorphous pyrogenic silica 3 Stage B: The compression mixture of stage A was compressed on a device to compress alternative Frogerais uni-punch. A punch of 30 mm was used.

  6.5 g of 50% mancozeb tablets with good cohesion were obtained.

  Example 2: Mancozeb Tablets Step A: The following constituents are compacted on a Frogerais reciprocating device and then crushed on an Erweka ribbon sizer to obtain particles of larger particle size.

  Components g Mancozeb 85% + Surfactants (Dithane M 45) 250 Quality Crospovidone for Tablet Disintegration Croscarmellose Sodium 5 Citric Acid Anhydrous 15 Sodium Bicarbonate 10 Magnesium Stearate 5 Amorphous Pyrogenous Silica 1.5 Stage B: The granular mixture of the stadium A was calibrated on an Erweka Oscillating Calibrator. Stage C: The 291.5 g of Stage B pellets were mixed with a Turbula drum mixer with the following components, to prepare a compression mix equivalent to approximately 77 tablets of 6.5 g: Components g Microcrystalline cellulose pH 102 47 Mannitol for direct compression 120 Crospovidone quality for tablet disintegration 5 Croscarmellose sodium 5 Citric acid anhydrous 15 Sodium bicarbonate 10 Magnesium stearate 5 Amorphous pyrogenic silica 1.5 Stage D: Compression mix stage C was compressed on a Frogerais uni-punch reciprocating tablet machine. A punch of 30 mm was used.

  6.5 g tablets of 50% mancozeb having good cohesion were obtained.

  Example 3: Copper hydroxide tablets Stage A: A mixture for direct compression equivalent to approximately 36 tablets of 14 g is prepared with Turbula in the following proportions: Components g Copper hydroxide 250 PVP crosslinked 25 Mixture lactose starch 75 Silicate hydrated aluminum 95 Citric acid anhydrous 17 Sodium bicarbonate 25 Amorphous pyrogenic silica 3 Magnesium stearate 10 Stage B: The compression mixture of stage A was compressed on a Frogerais uni-punch reciprocating machine. A punch of 30 mm was used.

  14 g tablets of 50% copper hydroxide having good cohesion were obtained.

  All the above tablets tested break up in less than 3 minutes without agitation, both in 500 ml of water and in 100 ml of water only.

Claims (10)

  1. A solid formulation in tablets, characterized in that it comprises by weight - 0.1 to 80% of a solid agrochemical active ingredient at ambient temperature, - 0.1 to 10% of an effervescent couple, 0.5 10% of a hydrophilic super-disintegrant, 1 to 60% of a hydrosoluble or hydrophilic filler for direct compression.   2. A solid formulation according to claim 1, characterized in that it comprises from 0.5 to 10% of a binder.   3. A solid formulation according to claim 1 or 2, characterized in that it comprises up to 40% of an insoluble charge for direct compression.   4. A solid formulation according to one of claims 1 to 3, characterized in that the effervescent couple is from 1% to 10% of said solid formulation.   5. A solid formulation according to one of claims 1 to 4, characterized in that the hydrophilic super-disintegrant is from 1% to 5% of the solid formulation.   6. A solid formulation according to one of claims 1 to 5, characterized in that the hydrosoluble or hydrophilic feedstock for direct compression represents from 3% to 50% of the solid formulation.   7. A solid formulation according to one of claims 1 to 6, characterized in that it contains an insoluble filler for direct compression representing from 5% to 40% of the solid formulation.   8. A solid formulation according to one of claims 1 to 7, characterized in that the effervescent couple is from 2% to 10% of said solid formulation.   9. A solid formulation according to one of claims 1 to 8, characterized in that the effervescent couple is from 2% to 8% of said solid formulation.   10. A solid formulation according to one of claims 1 to 9, characterized in that the hydrosoluble or hydrophilic feedstock for direct compression represents from 5% to 30% of the solid formulation.