A new preparation method of pesticide effervescent tablets

Abstract

The present invention provides a new preparation method for pesticide effervescent agents. By applying the powder coating technology to the preparation method of pesticide effervescent agents, the problem of bag swelling caused by the reaction of acid source substances and base source substances in the pesticide effervescent agents to generate carbon dioxide gas can be solved.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticide formulation preparation, in particular to a preparation method of pesticide effervescent agents, and more specifically to the application of powder coating technology in the preparation method of pesticide effervescent agents. Background Art

[0002] Pesticide effervescent agents are one type of pesticide formulations and can be prepared into effervescent granules and effervescent tablets. The main components of pesticide effervescent agents include pesticide active ingredients, dispersants, wetting agents, binders, acid source substances, base source substances, fillers, etc. During the preparation process, each component is mixed evenly according to the formulation ratio, and is made into effervescent granules by extrusion granulation, or further pressed into effervescent tablets using a tableting machine, and then dried and packaged. When the effervescent agent is added to water, the acid source substance and the base source substance react to generate a large amount of bubbles (carbon dioxide), causing the granules or tablets to quickly disintegrate and disperse. Through the effervescent effect of the agent itself, the pesticide active ingredients are more evenly dispersed in the liquid medicine.

[0003] However, in traditional pesticide effervescent agents, the acid source substance and the base source substance are in direct contact. If there is residual moisture in the formulation or the formulation absorbs moisture in the air during storage, it is easy to have an acid-base reaction, generating carbon dioxide gas and causing the bag to swell, thereby affecting the product performance and shortening the shelf life of the product.

[0004] Therefore, it is necessary to develop a new preparation method to solve the problem of bag swelling caused by the reaction between the acid source substance and the base source substance in pesticide effervescent agents. Summary of the Invention

[0005] To solve the above technical problems, the present invention provides a new preparation method of pesticide effervescent agents. Specifically, the present invention applies powder coating technology to the preparation method of pesticide effervescent agents, which can solve the problem of bag swelling caused by the reaction between the acid source substance and the base source substance in pesticide effervescent agents.

[0006] Powder coating technology has developed from pharmaceutical film coating technology and refers to coating drug powders by physical and chemical methods or physical and mechanical methods. The present invention applies powder coating technology to the preparation method of pesticide effervescent agents. A specific organic solvent is used to dissolve the coating material, and then the base source substance is added and mixed evenly. With a specific solvent evaporation device and a specific evaporation temperature, the solvent quickly volatilizes, enabling the coating material to fully and evenly wrap on the surface of the base source substance, and the base source substance remains stable without being damaged, achieving the isolation of acid and base from each other and ensuring the stability of the product.

[0007] Unless otherwise specified, the ratios in the present invention are all weight ratios.

[0008] The preparation method of the pesticide effervescent agent of the present invention includes the following steps:

[0009] Step 1: Dissolve the coating material in an organic solvent, then add an alkali source substance and mix evenly, and spray-dry the coating.

[0010] Step 2: Mix the pesticide active ingredient, surfactant, filler, and acid source substance evenly in a certain proportion, pulverize by air flow, then add the alkali source substance after coating, mix evenly, granulate, and dry, or press into tablets with a tablet press after mixing evenly.

[0011] In a preferred embodiment, the specific process of Step 1 includes:

[0012] Process 1: After dispersing the alkali source substance powder in the coating solution, under stirring, atomize and evaporate the solvent at a certain temperature through a spray-drying device, so that the coating material precipitates on the surface of the alkali source substance powder to achieve coating of the material.

[0013] Or

[0014] Process 2: Add the alkali source substance powder into a fluidized bed with a high-speed rotating disk stirrer at the bottom. The bottom spray gun forms a certain angle with the material and is buried in the material, spray the coating solution on the material, and control the drying at a certain temperature.

[0015] In a preferred embodiment, the weight percentage contents of the components in the finally obtained pesticide effervescent agent are as follows: acid source substance 15 - 30%, coated alkali source substance 15 - 30%, pesticide active ingredient 1 - 30%, surfactant 1 - 30%, filler 1 - 80%. The sum of the weight percentage contents of the components is 100%.

[0016] The present invention selects a specific coating material to isolate the contact between acid and alkali in the coated state, avoiding the generation of flatulence due to acid-base reaction, and at the same time can quickly dissolve in water to release the material and generate acid-base reaction. The coating materials that can be used include: one or a combination of more than one of hydroxypropyl methylcellulose, polyvinylpyrrolidone, sodium carboxymethyl starch, polyvinyl alcohol, acrylic resin, ethyl cellulose, polyethylene glycol 4000, polyethylene glycol 6000, urea-formaldehyde resin, sodium octenyl succinate starch, cellulose acetate phthalate, gum arabic, etc. Preferred coating materials include: one or a combination of more than one of polyvinylpyrrolidone, polyethylene glycol 4000, polyethylene glycol 6000, etc. The optimal coating material is polyethylene glycol 6000.

[0017] The present invention selects specific organic solvents, which are volatile, green and environmentally friendly, can dissolve the coating material, and form a uniform film on the material to be coated after drying. The organic solvents that can be used include: one or a combination of more of absolute ethanol, isopropanol, acetone, tetrahydrofuran, cyclohexanone, dimethylformamide, n-propyl bromide, ethylene glycol propyl ether, etc. Preferred organic solvents include: one or a combination of more of absolute ethanol, isopropanol, dimethylformamide, etc. The optimal solvent material is absolute ethanol.

[0018] The ratio of the coating material to the organic solvent in the present invention is 0.01-0.5:1, preferably 0.1-0.3:1.

[0019] The drying temperature in the present invention is 40-60 °C, preferably 45-55 °C, and most preferably 50 °C.

[0020] The acid source substances that can be used in the present invention can be organic acids and inorganic acids, including: one or a combination of several of tartaric acid, citric acid, fumaric acid, succinic acid, adipic acid, malic acid, etc.

[0021] The base source substances that can be used in the present invention include: one or a combination of several of sodium bicarbonate, sodium carbonate, calcium carbonate, potassium carbonate, potassium bicarbonate. The base source substance particles are 100-300 mesh. Among them, the ratio of the coating material to the base source substance is 1:3-5.

[0022] The active ingredients of pesticides that can be used in the present invention are not particularly limited, and can be insecticides, fungicides, nematicides, herbicides, plant growth regulators and mixtures thereof, including: trichlorfon, monocrotophos, parathion, methyl parathion, phoxim, isocarb, triazophos, methylphosphate, phorate, profenofos, terbufos, isoprocarb, fenbutylcarb, carbofuran, pirimicarb, methomyl, butiocarb, endosulfan, dimethoate, dimethoate, tetramethrin, allethrin, fenthrin, methylthrin, methoxythrin, chlorpyrifos, permethrin, cypermethrin, fenvalerate, cypermethrin, deltamethrin, bromothrin, cyfluthrin, cypermethrin, buprofezin, imidacloprid, diflubenzuron, dicofol, pyridaben, Bacillus thuringiensis, nuclear polyhedrosis virus, avermectin, thiram, mancozeb, rice blast, and isothiocarb. net, pentachloronitrobenzene, thiophanate-methyl, carbendazim, seed dressing, triadimefon, tricyclazole, procymidone, sclerotium net, rice blast, prochloraz, Jinggangmycin, 2,4-D butyl ester, 2,4-D sodium salt, 2-methyl-4-chloro, alachlor, acetochlor, butachlor, dicamba, glyphosate, atrazine, benzylsulfuron-methyl, pyrazosulfuron-methyl, sulfamethoxam, bensulfuron-methyl, dichloroquinoline, mefenacet, Cyclohexine, diazinon, diuron, oxadiazine, diclofenac, hexazinone, metsulfuron-methyl, quizalofop-ethyl, chlorsulfuron, chlorimuron-methyl, imazethapyr, bentazone, promethazine, acifluorfen, safflower, sodium pentachlorophenol, simazine, avenanthrone, isoproturon, isoclomazone, indoleacetic acid, triacontanol, biju, chlormequat, naphthylacetic acid, gibberellin, brassinolide, sodium nitrophenol, paclobutrazol, uniclobutrazol, etc.

[0023] The surfactants that can be used in the present invention include: alkyl naphthalene sulfonates, sodium dodecyl sulfate, pull-open powder, fatty alcohol polyoxyethylene ether, lignin sulfonates, alkylphenol polyoxyethylene ether, alkyl naphthalene formaldehyde condensates, succinic acid sulfonates, dodecylbenzene sulfonates, polycarboxylates, fatty alcohol polyoxyethylene ethers, and ethylene oxide propylene oxide block copolymers, or a combination of several of them.

[0024] The fillers that can be used in the present invention include: one or a combination of kaolin, bentonite, attapulgite, corn starch, sepiolite, microcrystalline cellulose, talc, diatomaceous earth, white carbon black, magnesium stearate, and lactose.

[0025] By adopting the above technical solution, the present invention has the following beneficial effects:

[0026] (1) The present invention determines a specific ratio of coating material and organic solvent so that the coating solution has an appropriate viscosity, which is not only conducive to spraying through the equipment, but also has good film-forming properties and can be evenly coated on the surface of the alkaline source substance.

[0027] (2) The present invention determines the ratio of a specific coating material to an alkali source substance, enabling the coating material to form a film layer with uniform thickness on the surface of the alkali source substance. Eventually, the coated alkali source substance particles formed have uniform particle sizes and good fluidity.

[0028] (3) The present invention solves a series of problems such as the reaction between acid and base during the storage of effervescent agents, resulting in gas swelling and poor disintegration properties, improves the quality of the product, and extends the shelf life of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] To more clearly illustrate the preparation method of the pesticide effervescent agent of the present invention, a flowchart shown in the accompanying drawings is provided. However, this is not a limitation to the preparation method of the present invention. For those of ordinary skill in the art, without creative efforts, other preparation method processes can also be obtained according to the said drawings, without departing from the spirit and scope of the content of the present invention.

[0030] Figure 1 It is a flowchart of the preparation method of the pesticide effervescent agent of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0031] The technical solutions of the present invention will be clearly and completely described below in conjunction with specific embodiments. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention.

[0032] I. Screening of the ratio of coating material to organic solvent

[0033] Test method: Dissolve polyethylene glycol 6000 in absolute ethanol at different ratios, and use a viscometer to measure the viscosity. Add a red dye for easy observation, and then use a coater to apply the solution on a glass plate with a thickness of 50 microns and place it in an oven to dry at 50 °C for 1 minute. Observe the film-forming situation under a microscope, and the results are summarized in Table 1 below.

[0034] Table 1

[0035]

[0036] It can be seen from the above test data that when the ratio of polyethylene glycol 6000 to absolute ethanol is 1:1, the viscosity of the solution is relatively high. During drying, the film layer is unevenly heated, resulting in fracture, local shrinkage of the film layer, and uneven film thickness. When the ratio of polyethylene glycol 6000 to absolute ethanol is 0.1 - 0.3:1, the film-forming thickness is uniform and the film layer has no fracture.

[0037] The same test was conducted on polyvinylpyrrolidone and polyethylene glycol 4000, and similar situations were also observed.

[0038] II. Formulation Examples

[0039] Example 1, 16% Acetochlor + Bensulfuron-methyl Effervescent Granules

[0040] Mix polyethylene glycol 6000 and absolute ethanol in a ratio of 0.25:1, stir until completely dissolved, then add sodium bicarbonate with a particle size of about 100 mesh. The ratio of polyethylene glycol 6000 to sodium bicarbonate is 1:3. Spray-dry and coat under stirring, with a drying temperature of 50°C, to obtain coated sodium bicarbonate.

[0041] Then, mix 13 g of acetochlor, 3 g of bensulfuron-methyl, 10 g of silica white, 8 g of alkylnaphthalenesulfonate, 2 g of sodium dodecyl sulfate, 20 g of citric acid, and 16 g of kaolin uniformly, grind them to 44 μm by air flow, and then add 28 g of coated sodium bicarbonate, mix uniformly and granulate and dry.

[0042] Comparative Example 1-1

[0043] Prepare according to the formula and preparation method of Example 1, except that sodium bicarbonate is not coated with a coating material.

[0044] Comparative Example 1-2

[0045] Prepare according to the formula and preparation method of Example 1, except that polyethylene glycol 6000 and absolute ethanol are mixed in a ratio of 1:1.

[0046] Comparative Example 1-3

[0047] Prepare according to the formula and preparation method of Example 1, except that the drying temperature is 70°C.

[0048] Example 2, 17% Pretilachlor + Pyrazosulfuron-ethyl Effervescent Tablets

[0049] Mix polyethylene glycol 6000 and absolute ethanol in a ratio of 0.1:1, stir until completely dissolved, then add sodium bicarbonate with a particle size of about 100 mesh. The ratio of polyethylene glycol 6000 to sodium bicarbonate is 1:4. Spray-dry and coat under stirring, with a drying temperature of 50°C, to obtain coated sodium bicarbonate.

[0050] Then, mix 15 g of pretilachlor, 2 g of pyrazosulfuron-ethyl, 10 g of silica white, 8 g of alkylnaphthalenesulfonate, 2 g of sodium dodecyl sulfate, 20 g of tartaric acid, and 18 g of kaolin uniformly, grind them to 44 μm by air flow, then granulate by dry method and add 25 g of coated sodium bicarbonate, mix uniformly and press into tablets by a tablet press, with a tablet weight of about 2.0 g.

[0051] Comparative Example 2-1

[0052] Prepared according to the formulation and preparation method of Example 2, except that uncoated sodium bicarbonate is not used.

[0053] Comparative Example 2-2

[0054] Prepared according to the formulation and preparation method of Example 2, except that the ratio of polyethylene glycol 6000 to sodium bicarbonate is 1:8.

[0055] Comparative Example 2-3

[0056] Prepared according to the formulation and preparation method of Example 2, except that the coating drying temperature is 75°C.

[0057] Example 3, 18% Quinclorac·Bensulfuron-methyl Effervescent Tablets

[0058] Mix polyethylene glycol 4000 and absolute ethanol in a ratio of 0.3:1, stir until completely dissolved, then add sodium bicarbonate with a particle size of about 100 mesh into a fluidized bed with a high-speed rotary stirrer at the bottom. The bottom spray gun forms a certain angle with the material and is buried in the material, and spray the coating solution onto the material. The ratio of polyethylene glycol 4000 to sodium bicarbonate is 1:5, and the drying temperature is 50°C.

[0059] Then mix 16 g of quinclorac, 2 g of bensulfuron-methyl, 10 g of microcrystalline cellulose, 8 g of alkyl naphthalene sulfonate, 2 g of sodium dodecyl sulfate, 20 g of tartaric acid, and 18 g of kaolin uniformly, grind them by air flow to 44 μm, then granulate by dry granulation and add 24 g of coated sodium bicarbonate, mix uniformly and press tablets with a tableting machine. The tablet weight is about 2.0 g.

[0060] Example 4, 31% Quinclorac·Bensulfuron-methyl Effervescent Granules

[0061] Mix polyvinylpyrrolidone and absolute ethanol in a ratio of 0.2:1, stir until completely dissolved, then add sodium bicarbonate with a particle size of about 100 mesh into a fluidized bed with a high-speed rotary stirrer at the bottom. The bottom spray gun forms a certain angle with the material and is buried in the material, and spray the coating solution onto the material. The ratio of polyvinylpyrrolidone to sodium bicarbonate is 1:4, and the drying temperature is 50°C.

[0062] Then mix 28 g of quinclorac, 3 g of bensulfuron-methyl, 8 g of alkyl naphthalene sulfonate, 2 g of sodium dodecyl sulfate, 20 g of citric acid, and 14 g of kaolin uniformly, grind them by air flow to 44 μm, then add 25 g of coated sodium bicarbonate, mix uniformly and granulate and dry.

[0063] III. Preparation Performance Testing

[0064] Test 1 Technical Indicators and Their Testing Methods

[0065] (1) Test for flatulence after heat storage:

[0066] Put 20 g of the sample into an aluminum foil bag, evacuate and seal it, then place it in a constant temperature oven at (54 ± 2) °C for 14 days. Take it out and cool it to room temperature to check if the package is bloated.

[0067] (2) Test for disintegration rate:

[0068] For effervescent tablets, take 1 tablet or for effervescent granules, take 2 g and place them in a 250 ml beaker (containing 200 ml of water at a temperature of 20 °C ± 5 °C). Then start timing. A large number of bubbles will be released. When the gas stops escaping around the tablet or fragments, the preparation dissolves or disperses in water and there are no remaining aggregated granules, stop timing. Repeat the test 5 times and take the average value.

[0069] (3) Test for suspension rate:

[0070] Test according to the suspension rate standard for water dispersible granules in GB / T 14825-2006.

[0071] The test data obtained are summarized in Table 2 below.

[0072] Table 2

[0073]

[0074]

[0075] It can be seen from the above test data that the effervescent agents prepared by the preparation method of the present invention do not show flatulence after 14 days of heat storage, and the acid and alkali do not react during the shelf life. In Comparative Examples 1-1 and 2-1, sodium bicarbonate was not coated, and carbon dioxide would be gradually released during heat storage, causing the bag to swell. In Comparative Example 1-2, the ratio of polyethylene glycol 6000 to absolute ethanol was 1:1, which was not within the scope of the present invention. At this ratio, the coating solution was relatively viscous. After adding sodium bicarbonate, incomplete or uneven coating of some sodium bicarbonate powder occurred during spray drying, which would also form a swollen bag; in Comparative Example 2-2, the ratio of polyethylene glycol 6000 to sodium bicarbonate was 1:8, which was not within the scope of the present invention. The dosage of polyethylene glycol 6000 was too low, resulting in incomplete or thin coating of some sodium bicarbonate powder, forming a swollen bag. In Comparative Examples 1-3 and 2-3, the temperature was too high during spray drying coating of sodium bicarbonate, causing sodium bicarbonate to decompose. In the above comparative examples, due to the loss of sodium bicarbonate, the disintegration time was significantly longer than that of the present invention. Moreover, after the loss of sodium bicarbonate, the reaction with acidic substances was not intense enough, which also affected the suspension rate of the active ingredient.

[0076] Experiment 2 Microscopic observation

[0077] The morphological observations of the coated sodium bicarbonate particles in the examples and comparative examples were carried out under a microscope, and the observation results are summarized in Table 3 below.

[0078] Table 3

[0079] Particle morphology Example 1 Relatively regular circular shape, complete film layer Comparative example 1-1 Irregular particles Comparative example 1-2 Some particles adhere, the film layer is relatively thick, and there are depressions Comparative example 1-3 Relatively regular circular shape, complete film layer Example 2 Relatively regular circular shape, complete film layer Comparative example 2-1 Irregular particles Comparative example 2-2 Some particles are not coated or the coating is incomplete Comparative example 2-3 Relatively regular circular shape, complete film layer Example 3 Relatively regular circular shape, complete film layer Example 4 Relatively regular circular shape, complete film layer

[0080] Finally, it should be noted that the above examples are only used to illustrate the technical solutions of the present invention, not to limit them; although the present invention has been described in detail with reference to the foregoing examples, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing examples, or perform equivalent replacements for some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A preparation method of a pesticide effervescent agent, characterized in that, It includes the following steps: Step 1: Dissolve the coating material in an organic solvent, then add the alkali source substance, and perform spray drying coating. The drying temperature is 40 - 60 °C; Step 2: Mix the pesticide active ingredient, surfactant, filler, and acid source substance evenly according to a certain ratio, perform air-flow pulverization, then add the alkali source substance after coating, mix evenly and granulate and dry, or mix evenly and then press into tablets by a tableting machine; Among them, the coating material in Step 1 is one or a combination of polyvinylpyrrolidone, polyethylene glycol 4000, and polyethylene glycol 6000, and the organic solvent is anhydrous ethanol; the ratio of the coating material to the organic solvent is 0.1 - 0.3:1; the ratio of the coating material to the alkali source substance is 1:3 - 5; the particle size of the alkali source substance is 100 - 300 mesh, and the particle size of each substance after air-flow pulverization is 100 - 300 mesh.

2. The preparation method of the pesticide effervescent agent according to claim 1, wherein The acid source substance is one or a combination of tartaric acid, citric acid, fumaric acid, succinic acid, adipic acid, and malic acid; the alkali source substance is one or a combination of sodium bicarbonate, sodium carbonate, calcium carbonate, potassium carbonate, and potassium bicarbonate.

3. The preparation method of the pesticide effervescent agent according to any one of claims 1 to 2, characterized in that, The specific process of Step 1 includes: Process 1: After dispersing the alkali source substance powder in the coating solution, under stirring, through a spray drying device at a certain temperature, atomize and evaporate the solvent, so that the coating material precipitates on the surface of the alkali source substance powder to achieve coating of the material; Or Process 2: Add the alkali source substance powder into a fluidized bed with a high-speed rotating disk stirrer at the bottom. The bottom spray gun forms a certain angle with the material and is buried in the material, spray the coating solution onto the material, and control the drying at a certain temperature.

4. The preparation method of the pesticide effervescent agent according to claim 1, characterized in that, In Step 2, each component is mixed according to the following weight percentage content: acid source substance 15 - 30%, coated alkali source substance 15 - 30%, pesticide active ingredient 1 - 30%, surfactant 1 - 30%, filler 1 - 80%, and the sum of the weight percentage contents of each component is 100%.

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