KR101562038B1 - Composition for effervescent tablet with reducing the agricultural manpower and preparing method thereof - Google Patents

Abstract

The present invention relates to a direct-applied tablet capable of exhibiting excellent and uniform drug efficacy even in a fresh water paddy field in which a large amount of other suspended substances are present due to excellent spreading and foaming durability. Also, the present invention relates to a tablet phase wettable powder having excellent foamability and collapsibility so that a user can dilute it in water in a short period of time, and has high hygroscopicity so that uniform chemical treatment can be performed. According to the present invention, since the composition of the foamable tablet for agricultural use which includes the direct spraying tablet and the tablet phase wettable agent is coated with a binder such as acid and carbonate, the storage stability is reduced even when stored at a high temperature and at a room temperature Does not occur. In addition, since the flowability and the pressing pressure of the plant are drastically reduced due to the granulation, the workability can be improved, which is a suitable manufacturing method for mass production.

Description

Technical Field [0001] The present invention relates to a composition for the production of effervescent tablets for labor for agricultural use and a method for preparing the same,

TECHNICAL FIELD The present invention relates to a method of manufacturing a labor-saving, effervescent tablet for agricultural use and a tablet produced thereby.

Foamable agricultural tablets are formulations in which tablets produced by appropriate combination of acids, carbonates and other materials are reacted in water to generate carbon dioxide gas, thereby causing breakdown of the tablets and diffusion of the active ingredient. More specifically, tablets for direct application (DT) are prepared by throwing tablets into deserted rice fields, and tablets are diluted in water according to dilution drainage, , Water dispersible Tablet). The direct spraying tablets, one of the expandable agricultural agricultural tablets, not only can reduce the labor of walking on a wide area by using heavy duster with 3kg of medicines per 10a in using conventional granules, Labor force can be drastically reduced. In addition, the use of conventional tabletting agents, wetting agents and the like can minimize the risk of exposure to the user due to the scattering of pesticides and dust, as well as the weight per tablet, so that the product can be metered in accordance with the dilution factor Can be eliminated.

However, such agro-effervescent tablets have associated problems because the acid and carbonate materials formed react with trace amounts of water to generate carbon dioxide gas. For example, water contained in the composition or moisture in the atmosphere in the manufacturing process causes expansion of the container during storage and distribution of the foamable tablet, and degradation of stability such as decomposition of the effective component of the product occurs. In addition, in the case of the direct-applied tablet, the foaming power is lowered and the diffusibility of the active ingredient is lowered, so that a weak point occurs at the treatment point or the drug efficacy is uneven. In addition, There is a problem such that the effect is insufficient or the nozzles of the sprayer are clogged during the treatment because the water or the aqueous solution is lowered.

On the other hand, Patent Document 1 discloses a preparation method for suppressing the reaction of acid and carbonate due to moisture by using ammonium anhydride as an inorganic acid in a conventional direct-spaying tablet composition in order to solve the aforementioned stability problem. However, in Patent Document 1, a large amount of ammonium anhydride alum is required, so that it is not suitable for producing foamable tablets in which a high content of active ingredient is introduced. Also, in the case of tablet formulations, it is important to prepare tablets that exhibit fast degradability, good hygroscopicity, and increased stability during storage when diluting tablets with water to enhance effective drug treatment and user convenience.

Therefore, as described above, a concrete method for increasing the stability during storage while retaining fast collapsibility and excellent hygroscopicity of the foamable tablet will be required.

(Patent Document 1) KR10-0418425 B1

The present invention provides a composition for manufacturing labor-saving foamable tablets and a method for producing the same, which solve the problems of low storage stability which may occur during storage of foamable tablets at high temperature and at room temperature.

It is another object of the present invention to provide a composition for manufacturing labor-saving foamable tablets and a method for manufacturing the same, by solving the problem of enhancing disintegrability and limiting the use amount of auxiliary materials in the production of foamable tablets having a high active ingredient content.

It is another object of the present invention to provide a composition of a direct spray tablet which satisfies the diffusion sustaining force required for a direct spray tablet and exhibits a uniform and excellent drug efficacy even in a fresh water paddy containing a large amount of suspended substances, and a method for producing the same.

It is still another object of the present invention to provide a composition of a tablet phase wettable powder which simultaneously satisfies both the rapid disintegration and the excellent hygroscopicity required for a tablet phase wettable powder and a method for producing the same.

In one embodiment of the present invention, there is provided a process for producing a powder, comprising: (a) mixing an active ingredient in a solid phase and a foaming agent, followed by pulverization to prepare a powder; (b) injecting the powder into a fluidized bed granulator to form a fluidized bed; And (c) granulating the binder solution and the liquid active ingredient, if necessary, into the fluidized bed, thereby granulating the foamed tablet. In the above specific example, the production of the foamable tablets for agrochemicals characterized in that at least one selected from the group consisting of surfactants, extenders, and glidants is further added to the solid active ingredient and the foaming agent of step (a) Method. In the above embodiment, the binder solution is a binder solution prepared by dissolving any one selected from the group consisting of polypyrrolidone, methyl cellulose, starch, gelatin, polyvinyl alcohol, and polyethylene glycol in water or an organic solvent By weight based on the total weight of the pesticidal composition. In the above embodiment, the foaming agent is composed of organic acid, alum and carbonate, and the organic acid is any one selected from the group consisting of citric acid, tartaric acid and maleic acid, Wherein the carbonate is at least one selected from the group consisting of sodium hydrogencarbonate, calcium carbonate, potassium hydrogencarbonate, potassium carbonate and sodium sesquicarbonate. In the above embodiment, the binder is 0.5 to 5.0 parts by weight of polypyrrolidone based on the weight of the binder solution. In the above embodiment, the present invention provides a method for producing an expandable agricultural pesticide tablets, wherein the solid active ingredient is an active ingredient of a herbicide, a bactericide, or an insecticide.

In one embodiment of the invention, there is provided an agrochemical effervescent tablet comprising from 0.1 to 50% by weight of active ingredient granulated, from 10 to 60% by weight of a blowing agent and from 0.5 to 5% by weight of a binder, based on the total weight of the tablet. In this embodiment, the binding agent is a solution in which any one selected from the group consisting of polypyrrolidone, methylcellulose, starch, gelatin, polyvinyl alcohol, and polyethylene glycol is dissolved. In the above embodiment, the foaming agent is composed of organic acid, alum and carbonate, and the organic acid is any one selected from the group consisting of citric acid, tartaric acid and maleic acid, Wherein the carbonate is at least one selected from the group consisting of sodium hydrogencarbonate, calcium carbonate, potassium hydrogencarbonate, potassium carbonate and sodium sesquicarbonate. In the above embodiment, the binder is 0.5 to 5.0 parts by weight of polypyrrolidone based on the weight of the binder solution. In the above embodiment, the present invention provides an effervescent tablet for agricultural chemicals characterized in that the solid active ingredient is an active ingredient of a herbicide, a bactericide or an insecticide.

In the present invention, the herbicide is selected from the group consisting of Bentazon, Penoxsulam, MCPA, Cyhalofop-butyl, Fenoxaprop-P-ethyl, Propanil, 2.4-D, Metamifop, Bispyribac- sodium, MCPB, Azimsulfuron, Flucetosulfuron, Propyrisulfuron, Butachlor, Pretilachlor, Oxadiazon, Oxadiargyl, Fentrazamide , Mefenacet, Cafenstrole, Indanofan, Pyriminobac-methyl, Fenoxasulfone, Benzobicyclon, Bromobutide, Mesotrione, Tefuryltrione, Triafamone, Metazosulfuron, Azimsulfuron, Pyrazosulfuron-ethyl, Halosulfuron-methyl, Bensulfuron-methyl, Imazosulfuron, Glufosinate, Glyphosate, Dichlobenyl, , MCPA, Pyraflufen-ethyl, Nicosulfuron, Dicamba, Rimsulfuron, Mesotrione, Mecoprop, Metamifop, Bifenox, Flucetosulfuron, Sethoxidim, Simazine, Imazaquin, Carfentrazone-ethyl, Clethodim, Trifloxysulfuron, Fenoxaprop-P-ethyl, Flasulfuron, Fluroxypyr, Flumioxazin, Fluazifop -P-butyl, Tiafenacil, Ipfencarbazon, Bicyclopyrone, and Halauxifen-Methyl. The original title.

In the present invention, the fungicide may be selected from the group consisting of Probenazole, Mancozeb, Cymoxanil, Bitertanol, Chlorothalonil, Edifenphos, Pencycuron, Thiophanate-methyl, Iprodione, Hymexazol, Oxine-copper, Validamycin A, Flusilazole, Folpet, Isoprothiolane, Tecloftalam, Carbendazim, Iprobenfos , Bacillus subtilis DBB1501, Difenoconazole, Copper hydroxide, Fenarimol, Triadimenol, Fosetyl-aluminum, Boscalid, Tetraconazole Dichlofluanid, Propineb, Copper oxychloride, Fenbuconazole, Benalaxyl-M, Epoxiconazole, Dimethomorph, Fenhexamid, Dithianon, Procymidone, Benthiavalicarb-isopropyl, Carpropamid, Ferimzone, Tricyclazole, Streptomycin, Metalaxyl, Polyoxin B, Thiamime, Triadimefon, Prochloraz, Benomyl, Captan, Trifloxystrobin, Thifluzamide, Metalaxyl-M, Etridiazole, Ethaboxam, Tebuconazole, Oxadixyl , Siloxane, Iminoctadine tris (albesilate), Metrafenone, Fluquinconazole, Iminoctadine triacetate, Fluazinam, Dazomet, Orysastrob is selected from the group consisting of fungicides including fludioxonil, Tiadinil, Polyoxin D, Azoxystrobin, Cyproconazole, Zoxamide, Fenobucarb (BPMC), Isoprocarb, Methiocarb, Pyraclostrobin, Kresoxim-methyl, Tolylfluanid and Mandipropamid.

In the present invention, the insecticide may be selected from the group consisting of Organophosphates (Acephate, Azinphos-methyl, Cadusafos, Chlorpyrifos, Dimethoate, Ethoprophos, Fenitrothion, Fenthion, Fosthiazate, Methidathion, Monocrotophos, Omethoate, Phenthoate, Phorate, Phosphamidon, Phoxim, Pirimiphos- methyl, Prothiofos, Pyridaphenthion, Terbufos , Trichlorfon etc.), Carbamates (Benfuracarb, Carbaryl, Carbofuran, Carbosulfan, Fenobucarb, Methomyl, Thiodicarb etc.) Pyrethroids (Acrinathrin, Bifenthrin, Cyfluthrin, Cypermethrin, Deltamethrin, Esfenvalerate, Etofenprox, Fenpropathrin, Fenvalerate, Permethrin etc.), Neonicotinoids , Clothianidin, Dinotefuran, Imidacloprid, Thiacloprid, Thiamethoxam, Sulfoxaflor), Spinosyns (Spinosad, Spinetoram), Benzoylureas (Bistrifluron, Diflubenzuron, Flucycloxuron, Flufenoxuron, Lufenuron, Novaluron, Teflubenzuron), METI acaricides and insecticides (Fenazaquin, Fenpyroximate, Pyridaben, Tebufenpyrad , Pyflubumide), Tetronic & Tetramic acid derivatives (Spirodiclofen, Spiromesifen, Spirotetramat), D is selected from the group consisting of insecticides selected from the group consisting of iamides (Flubendiamide, Chlorantraniliprole, Cyantraniliporle), Flonicamid, Pymetrozine, Abamectin, Emamectin-benzoate, Milbemectin, Lepimectin, Pyriproxyfen, Chlorfenapyr, Azocyclotin, Cyhexatin, Fenbutatin oxide and Buprofezin.

In the present invention, the "foaming agent" is a preparation used for causing collapse and diffusion of tablets while causing acid and carbonate to react with each other in water to generate carbon dioxide gas. As the acid, organic acids such as citric acid, tartaric acid, maleic acid and the like can be used, and alum can be used as anhydrous potassium alum. On the other hand, as the carbonate, sodium hydrogencarbonate, calcium carbonate, potassium hydrogencarbonate, potassium carbonate, sodium sesquicarbonate and the like can be used. Depending on the constitution of acid and carbonate, reactivity and foaming form in water are different. Therefore, they may be selected singly or in combination of two or more according to the quality required for the product.

"Surfactant" in the present invention is a formulation used to promote proper wetting and diffusion of an active ingredient during the reaction of tablet and water. Various kinds of surfactants may be used. Examples of wetting agents include poly-oxyethylene lauryl ether, sodium dodecyl sulfate, and sodium dialkysulfosuccinate. And the like. As the dispersing agent, a condensate of naphthalene sulfonate, an acrylic polymer material, or the like can be used. The use of some surfactants with a certain degree of cohesion increases the strength of tablets during tableting and increases the disintegration time in water. Therefore, it is important to select an appropriate surfactant.

"Extender" in the present invention is a formulation used to provide a suitable volume to make tablets of the desired size. Mineral substances including diatomaceous earth, kaolin and talc, or a mixture of two or more kinds of thickening agents selected from the group consisting of calcium chloride, ammonium sulfate, sodium sulfate, urea, lactose, mannitol, microcrystalline cellulose and the like.

In the present invention, "binder" is a preparation for simultaneously coating an acid and a carbonate through a granulation process through a fluid bed granulator to block the chemical reaction due to residual moisture in the product and form granules of the pulverized raw material . The granules formed through the granulation process improve the fluidity within the facility and ensure that the tablet is well-pressed at low pressures of the tablet machine. When granulating, an organic solvent such as water or ethanol is used, so that conventional binders dissolved therein can be used. Examples of the specific binder include polypyrrolidone, methylcellulose, starch, gelatin, polyvinyl alcohol and the like. Depending on the type of the solvent used, they may be used alone or in combination of two or more.

The term "lubricant" in the present invention can be used to prevent powder from adhering to the fluidized bed granule wall during the granulation process through the Fluid Bed Granulator, and after the granulation the lubricant is attached to the surface of the granule Thereby improving the fluidity of the granules. This causes the granules to flow well into the tablet die and increase the filling rate, which reduces friction between tablets and punch and die walls when tableting, thereby reducing the occurrence of poor tablets, including capping. Further, the surface of the tablets to be tableted is smoothed so that an excellent appearance can be formed. The lubricant may be used alone or in combination of two or more kinds of lubricants selected from the group including magnesium stearate, magnesium oxide, magnesium carbonate, disodium lauryl sulfate and the like.

Since the whole composition of the foamable tablet according to the present invention is coated with a binding agent, storage stability does not deteriorate even when stored at room temperature and high temperature for a long time. In addition, since the tablet is granulated, the fluidity of the tablet is excellent, so that it is suitable for mass production and the tableting pressure for securing the appropriate hardness of the tablet is remarkably low. Therefore, even in the production of the foamable tablet containing a high content of active ingredient, Collapse property can be ensured. Due to the advantages described above, the direct-spray tablet, which is one of the expandable tablets, can exhibit uniform and superior drug efficacy even in a fresh water paddy having a large amount of suspended substances due to its excellent foaming durability, It exhibits high disintegration and high hygroscopicity and can exhibit convenient pharmaceutical treatment and uniform drug efficacy.

1 is a test chart for measuring the diffusibility of a direct-applied tablet prepared according to the present invention.

Hereinafter, the components and technical features of the present invention will be described in more detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention and are not intended to limit the scope of the invention.

Manufacture of Direct Spray Tablets

Directly sprayed tablets were prepared as described in Table 1 below.

Unit (wt%) division ingredient Example 1.1 1.2 1.3 Active ingredient Azimusulfuron 0.3 0.3 0.3 Benzobicyclone 4.0 4.0 4.0 Phenoxhlam 0.5 0.5 0.5 mountain Tartaric acid 23.0 23.0 23.0 lead carbonate
Sodium hydrogencarbonate 30.0 30.0 30.0 Sodium carbonate 5.0 5.0 5.0 Surfactants
Condensation product of naphthalene sulfonate 5.0 5.0 5.0 Sodium dioctylsulfosuccinate 3.0 3.0 3.0 Lubricant
Magnesium oxide 3.0 3.0 3.0 Magnesium stearate 0.3 0.3 0.3 extender Ammonium sulfate 21.9 21.9 21.9 Binder Polypyrrolidone 4.0 4.0 - Polyvinyl alcohol - - 4.0 menstruum water - 36.0 36.0

Example 1.1

Of the constituents of Table 1,

1) Step 1: 0.3% by weight of azimersulfuron, 4.0% by weight of benzoicycloine, 0.5% by weight of phenoxolam, 23.0% by weight of tartaric acid as an acidic substance, sodium hydrogenphosphate as a basic substance , 5.0% by weight of sodium carbonate, 5.0% by weight of sodium carbonate and 5.0% by weight of a surfactant naphthalenesulfonate condensate, 3.0% by weight of sodium dioctylsulfosuccinate, 3.0% by weight of magnesium oxide as a lubricant and 21.9% by weight of ammonium sulfate as an extender were mixed in a ribbon mixer And pulverized to an average particle size of 0.5 to 20 mu m using a jet mill.

2) a second step; 4.0% by weight of the binder polypyrrolidone was re-mixed in the ribbon mixer together with the milled mixture in one step in the original powdery state without dissolving in water or an organic solvent.

3) a third step; 2 process powder and 0.3 wt% magnesium stearate as an additional lubricant were re-mixed in a ribbon mixer.

4) fourth step; In the third step, the mixed powders were transferred to a tablet machine and tableted at a pressure of 100 kg / cm 2 to prepare tablets having a weight of 25 g and a diameter of 5 cm and packed in an aluminum laminate bag in an amount of 250 g.

Example 1.2

Of the constituents of Table 1,

1) a first step; The procedure of Example 1.1 was repeated.

2) a second step; 4.0% by weight of polypyrrolidone as a binder was stirred with 36.0% by weight of water in a mixing bath to prepare a binder solution having a concentration of 10.0%.

3) a third step; In the first step, the pulverized powder is introduced into the fluidized bed granulator to form a fluidized bed at a superficial velocity of 0.4 to 0.5 m / s. The binder solution prepared in the second step is sprayed at a rate of 70 ml / min to powder circulated up and down by the formed fluidized bed to form granules. At this time, the supply temperature is set to 110 ° C or more so that the binder solution is sprayed, and all the water used as the solvent is evaporated to be removed. The finished granulate is mixed in a ribbon mixer with 0.3% by weight of magnesium stearate, a lubricant.

4) fourth step; The granules formed in step 3 were transferred to a tablet machine in the same manner as in Example 1.1.

Example 1.3

Of the constituents of Table 1,

1) a first step; The procedure of Example 1 was repeated.

2) a second step; And 4.0% by weight of polyvinyl alcohol as a binder were used as the binder.

3) a third step; Was carried out in the same manner as in Example 1.2.

4) fourth step; Was carried out in the same manner as in Example 1.2.

Preparation of purified water-wetting agent

Tablet water-solubilizing agent was prepared as shown in Table 2 below.

Unit (wt%) division
ingredient
Example 2.1 2.2 2.3 Active ingredient
Captain 50.0 50.0 - Boss Khalid - - 47.0 mountain Citric acid 12.0 12.0 13.0 lead carbonate
Potassium hydrogencarbonate 12.0 12.0 13.0 Potassium carbonate 3.0 3.0 3.0 Surfactants
Condensation product of naphthalene sulfonate 3.0 3.0 3.0 Sodium dioctylsulfosuccinate 2.0 2.0 2.0 Lubricant
Magnesium oxide 2.0 2.0 2.0 Magnesium stearate 0.3 0.3 0.3 extender Potassium chloride 13.7 13.7 13.7 Binder
Polypyrrolidone 2.0 2.0 3.0 Polyvinyl alcohol - - - menstruum ethanol - 18.0 27.0

Example 2.1

Of the constituents of Table 2,

1) a first step; 50% by weight of capsaicin, 12% by weight of citric acid, 12.0% by weight of potassium hydrogen carbonate and 3.0% by weight of potassium carbonate, 3.0% by weight of a surfactant naphthalenesulfonate condensate, 2.0% by weight of sodium dioctylsulfosuccinate, 2.0% by weight of magnesium oxide as a lubricant, and 13.7% by weight of potassium chloride as an extender were mixed in a ribbon mixer and pulverized to an average particle size of 0.5 to 20 μm using a jet mill.

2) a second step; 2.0% by weight of the binder polypyrrolidone was re-mixed in the ribbon mixer together with the milled mixture in one step in the original powdery state without dissolving in water or an organic solvent.

3) a third step; 2 process powder and 0.3 wt% magnesium stearate as an additional lubricant were re-mixed in a ribbon mixer.

4) fourth step; In the third step, the mixed powder was transferred to a tablet machine, and the tableting pressure capable of producing tablets having a weight of 6.7 g, a diameter of 3 cm and a hardness of about 200 N was measured. Tablets were prepared with the tableting pressure measured and packed in 250 g of aluminum laminate bag.

Example 2.2

Of the constituents of Table 2,

1) a first step; The procedure of Example 2.1 was repeated.

2) a second step; 2.0% by weight of polypyrrolidone as a binder was mixed with 18.0% by weight of ethanol in a mixing bath to prepare a binder solution having a concentration of 10.0%.

3) a third step; In the first step, the pulverized powder is introduced into the fluidized bed granulator to form a fluidized bed at a superficial velocity of 0.4 to 0.5 m / s. The binder solution prepared in the second step is sprayed at a rate of 30 ml / min to powder circulated up and down by the formed fluidized bed to form granules. At this time, the supply temperature is set to 70 ° C or more so that the binder solution is sprayed, and all the ethanol used as the solvent is evaporated to be removed. The finished granulate is mixed in a ribbon mixer with 0.3% by weight of magnesium stearate, a lubricant.

4) fourth step; The granules formed in step 3 were transferred to a tablet machine in the same manner as in Example 2.1.

Example 2.3

Of the constituents of Table 2,

1) a first step; 47% by weight of boschalide, 13% by weight of citric acid as an acidic substance, 13.0% by weight of potassium hydrogen carbonate as basic substance and 3.0% by weight of potassium carbonate, 3.0% by weight of a surfactant naphthalenesulfonate condensate as a tableting water- , 2.0% by weight of sodium dioctylsulfosuccinate, 2.0% by weight of magnesium oxide as a lubricant, and 13.7% by weight of potassium chloride as an extender were mixed in a ribbon mixer and pulverized to an average particle size of 0.5 to 20 μm using a jet mill.

2) a second step; Was performed in the same manner as in Example 2.2.

3) a third step; 2 was sprayed at a rate of 50 ml / min to form granules. The procedure of Example 2.2 was repeated except that the binder solution prepared in Step 2 was sprayed at a rate of 50 ml / min.

4) fourth step; The procedure of Example 2.1 was repeated.

Physicochemical Effects of Foaming Tablets

Example 3.1. Storage stability test

The tablets prepared according to Examples 1 and 2 were sealed in an aluminum laminate bag and stored in an incubator at 40 ° C. and 54 ° C. for 24 weeks at room temperature, 12 weeks at 40 ° C., and 6 weeks at 54 ° C. After storage, the packaged container was examined for swelling and the degradation rate of the active ingredient was measured at 54 ° C over a 6-week period. The results are shown in Table 3 below.

unit(%) division ingredient Example 1.1 1.2 1.3 2.1 2.2 2.3 Container expansion

Room temperature, 24 weeks ○ × × ○ × × 40 ℃, 12 weeks ○ × × ○ × × 54 ℃, 6 weeks ○ × × ○ × × Effective Component Decomposition Rate



Azimusulfuron 6.8 7.5 7.1 - - - Benzobicyclone 0.7 0.5 0.5 - - - Phenoxhlam 0.4 0.6 0.1 - - - Captain - - - 0.3 0.5 - Boss Khalid - - - - - 0.8

1) x: not inflated, o: inflated

2) Subsequent degradation rate (%): (A-B) / A x 100 (%)

* A: pesticide effective ingredient content of the tablet after manufacture, B: pesticide effective ingredient content of the tablet after the completion of aging

As can be seen from Table 3, Examples 1.2, 1.3, 2.2 and 2.3, in which the binder was coated on the entire composition by using a fluidized bed granulator different from Examples 1.1 and 2.1 which were composed of the same composition but simply mixed, The storage stability at high temperature was excellent. In particular, no problems occurred even when stored at 54 占 폚 for 6 weeks, so that the foamability and collapsibility of the tablet could be maintained for a long time, and the problems such as expansion of the container during storage and storage of the tablet did not occur. In addition, since the degradation rate of the active ingredient is within the allowable range according to the content of the active ingredient, even after the completion of the aging test at 54 ° C for 6 weeks, good quality can be maintained even during the 3-year drug effect.

3.2. Diffusion Test of Direct Spray Tablets

In order to measure the diffusibility of the directly sprayed tablets prepared according to Examples 1.1 to 1.3, test pieces having a width of 10 m and a length of 10 m were provided as shown in Fig. 1, The tablets of Examples 1.1 to 1.3, which had a weight of 25 g in appearance, were thrown at the center point of the test sphere. The samples (water) were taken at 4m left, 2m left, 2m right, 4m right and 4th throw from the center point after 3 hours, 6 hours, and 24 hours after throwing, The diffusion residual concentration was analyzed by liquid chromatography mass spectrometer (HPLC / MS / MS) and is shown in Table 4 below.

Example
Elapsed time
Residual Concentration of Benzodicycline in Water by Sampling Point (ppm) Left 4m Left 2m Throw point Right 2m Right 4m 1.1

3 hours 0.03 0.14 0.10 0.04 0.01 6 hours 0.03 0.08 0.12 0.05 0.01 24 hours 0.01 0.01 0.01 0.01 0.01 1.2

3 hours 0.02 0.03 0.77 0.00 0.01 6 hours 0.02 0.09 0.44 0.18 0.00 24 hours 0.04 0.06 0.12 0.07 0.02 1.3

3 hours 0.03 0.21 0.26 0.23 0.02 6 hours 0.05 0.17 0.18 0.17 0.03 24 hours 0.02 0.02 0.02 0.02 0.01

As can be seen from the above Table 4, the direct sprayed tablets according to the present invention have a relatively high diffusion residual concentration in benzo bicyclo in comparison with Example 1.1, which is simply mixed with the same composition, have.

3.3. Disintegration test of purified water-wetting agent

In order to measure the disintegratability of the tablet formulating agent prepared according to Examples 2.1 to 2.3, a test container having a size of 20 cm x 20 cm x 20 cm in width, height and height was prepared with a transparent acrylic plate. In order to measure the time required for the user to collapse and dilute the purified water-wetting agent into water, 5 liters of 3-degree hardness water having a temperature of 13 ° C, 18 ° C, and 23 ° C were placed in the above- After waiting until there was no solution, each tablets having a diameter of 3 cm and a weight of 6.7 g were cast, and the final disintegration time was measured. During the collapse, there was no further action such as shaking or stirring the vessel, and the experimental results for Examples 2.1 to 2.3 are shown in Table 5 below.

Measured water temperature Example 2.1 Example 2.2 Example 2.3 13 ℃ 8 minutes 00 seconds 4 minutes 00 seconds 3 minutes 40 seconds 18 ℃ 7 minutes 15 seconds 3 minutes 40 seconds 3 minutes 20 seconds 23 ℃ 6 minutes 30 seconds 3 minutes 20 seconds 3 minutes 05 seconds

As shown in Table 5, it can be seen that the disintegratability of Examples 2.2 to 2.3, which were granulated and tableted, than that of Example 2.1, which was not granulated by using a fluidized bed granulator, even though it was composed of the same composition, increased in water.

Biological effects of effervescent tablets

Example 4.1. Drug and Pharmacological Tests of Direct Spray Tablets

In order to measure the pharmacological effect and the weakness of the direct-sprayed tablets prepared according to Examples 1.1 to 1.3, perennial weeds such as water barrels, blood, and resistant tadpoles were treated with perennial weeds, After the migration, a test section having a width of 10 m and a length of 10 m was provided. On the 14th day after transplanting (14DAT: 14 days after transplanting), one tablet of each of Examples 1.1 to 1.3 having an outer shape of 5 cm in diameter and 25 g in weight was poured onto the central point of each test sphere, 20, 40 days of drug efficacy and weakness were investigated. The results of the pharmacodynamic and pharmacological test are shown in Table 6 below.

unit(%) Example
20 days after treatment, 40 days results Medicinal efficacy
Weak Resistant Water tiller blood A blast Processing point Outside processing point 1.1 74 62 81 77 98 93 75 65 84 77 2.0 0.0 0.0 0.0 1.2 97 85 98 94 99 95 93 82 98 91 0.0 0.0 0.0 0.0 1.3 95 84 98 94 98 93 91 81 97 91 0.0 0.0 0.0 0.0

As shown in Table 6, the direct-applied tablets according to the present invention can exhibit an excellent drug efficacy of 97% or more on average without weakness unlike the case of Example 1.1, which is simply mixed with the same composition.

Example 4.2. Drug Effects and Phytotoxicity Tests of Tablet Water-Solubilizing Agents

In order to measure the pharmacological effect and the weakness of the tablets prepared above according to Examples 2.1 to 2.3, firstly, test pouches in which the respective diseases occurred frequently were selected. In the selected test medium, the tablet formulating agent prepared by the above example was sufficiently diluted to meet the standard amount, and the diluted solution was applied to the target crops and treated with foliage. The treatments were 4 treatments at the intervals of 10 days from the beginning of June for apple spotted fallen leaves, apple brown patterned leaves, and persimmon leaves. The peach leaves were treated once before the germination and once before the flowering, Powdery mildew was treated 3 times at intervals of 10 days from the onset of onset. After treatment with the drug, the disease rate, the disease rate, and the degree of disease were investigated at the time of irradiation, and the efficacy and the weakness were evaluated. The results of the pharmacodynamic and pharmacological test are shown in Table 7 below.

unit(%) Example
Efficacy Weak
precipitate
Apple dotted leaves Apple brown pattern bottle Persimmon leaves Peach leaf orchid disease Melon powdery mildew 2.1 80.4 75.6 85.3 82.3 - 0.0 has exist 2.2 91.4 90.4 90.5 90.9 - 0.0 none 2.3 - 90.8 - - 94.9 0.0 none

As shown in Table 7, unlike Example 2.1, which is simply mixed with the same composition, the tablet formulating agent according to the present invention possesses excellent hygroscopicity without sediment, and can exhibit uniform and superior drug efficacy.

Improved workability of foamable tablet

Example 5.1. Workability evaluation test

To determine the workability of the above example for continuous mass production, each powder and granule was transferred to a tablet machine for tableting. The flowability into the tablet die when the powder and granules are put into the hopper on the tabletop during the operation, the weight deviation which occurs when the tablets are continuously produced, and the capping caused by the friction between the tablets and the punch. And the required tablet pressures for producing the appropriate hardness of tablets (about 200 N) were measured and reported in Table 8 below.

division Item
Example 1.1 1.2 1.3 2.1 2.2 2.3 Tabulation
Workability


Flowability Bad Very good Very good Very good Good Good Weight deviation About 10% Less than 0.5% Less than 1% About 15% Less than 0.5% Less than 0.5% Poor purification
Incidence rate About 8% Less than 1% Less than 1% About 10% About 1% About 1% Required Static Pressure
(kg / cm2) 100
(The same pressure is applied) 90-100 5 to 10 5 to 10

1) Flowability:

* Good: Flows well to the die inside the hopper without clogging of the inner wall of the hopper or clogging of the injection part.

* Poor: It is difficult to work on the wall of the hopper or in the continuous operation.

2) Weight deviation: (maximum refill weight - minimum refill weight) / target refill weight × 100 (%)

3) Incidence of bad tablets: abnormal tablets production rate deviating from quality standard in continuous manufacturing using tablet machine.

4) Required static pressure: The required pressure of the tablet press to produce the appropriate hardness of the tablet (200N).

As shown in Table 8 above, Examples 1.2, 1.3, 2.2 and 2.3 prepared using a fluidized bed granulator compared to Examples 1.1 and 2.1, which were simply mixed with the same composition, showed improved flowability through the granulation Able to know. In addition, granulation is a suitable production method for mass production because it increases the productivity by decreasing the weight deviation of tablet and incidence of defective tablet during continuous tableting. Particularly, when preparing the tableting water-reducing agents as in Examples 2.1 to 2.3, it is possible to secure a sufficient hardness (200N) of the tablet even at a low pressure of 5 to 10 kg / cm 2, There is an advantage that the tablet can be produced at a high speed as well as reduced.

Claims (11)

(a) mixing an active ingredient in a solid phase and a foaming agent and pulverizing the mixture to prepare a powder;
(b) injecting the powder into a fluidized bed granulator to form a fluidized bed; And
(c) spraying a binder solution containing a binder to the fluidized bed at a rate of 30 to 70 ml / min to granulate the foamed tablet,
Wherein the foamable tablet comprises 0.1 to 50% by weight of the active ingredient, based on the total weight of the tablet; 10 to 60% by weight of a blowing agent; And 0.5 to 5% by weight of a binder. The method according to claim 1,
Wherein the liquid active ingredient is further mixed with the binder solution of step (c) and sprayed together. 3. The method according to claim 1 or 2,
Wherein the solid active ingredient and the foaming agent in step (a) are further mixed with at least one selected from the group consisting of a surfactant, an extender, and a glidant. 3. The method according to claim 1 or 2,
Wherein the binder solution is prepared by dissolving at least one binder selected from the group consisting of polypyrrolidone, methylcellulose, starch, gelatin, polyvinyl alcohol and polyethylene glycol. The method of claim 3,
The foaming agent is at least one selected from the group consisting of organic acid, alum and carbonate,
Wherein the organic acid is at least one selected from the group consisting of citric acid, tartaric acid, and maleic acid,
The alum is anhydrous potassium alum,
Wherein the carbonate is at least one selected from the group consisting of sodium hydrogencarbonate, calcium carbonate, potassium hydrogencarbonate, potassium carbonate and sodium sesquicarbonate. 3. The method according to claim 1 or 2,
Wherein the active ingredient is at least one selected from the group consisting of herbicides, bactericides and insecticides. A pharmaceutical composition which comprises 0.1 to 50% by weight, based on the total weight of the tablet, of an active ingredient prepared by the process according to any one of claims 1 or 2; 10 to 60% by weight of a blowing agent; And 0.5 to 5% by weight of a binder. 8. The method of claim 7,
Wherein the binder is at least one selected from the group consisting of polypyrrolidone, methylcellulose, starch, gelatin, polyvinyl alcohol, and polyethylene glycol. 8. The method of claim 7,
The foaming agent is at least one selected from the group consisting of organic acid, alum and carbonate,
Wherein the organic acid is at least one selected from the group consisting of citric acid, tartaric acid, and maleic acid,
The alum is anhydrous potassium alum,
Wherein the carbonate is at least one selected from the group consisting of sodium hydrogencarbonate, calcium carbonate, potassium hydrogencarbonate, potassium carbonate and sodium sesquicarbonate. 8. The method of claim 7,
Wherein the active ingredient is at least one selected from the group consisting of herbicides, bactericides and insecticides. delete

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