Solid bulk composition of the carrier for the active substance in water dispersible solid dosage form, the way of obtaining and solid dosage form


(57) Abstract:

Purpose: solid dosage forms of medicines and plant protection products. The inventive composition is a carrier for active substances comprising microcrystalline cellulose and urea or ammonium salt, or a mixture, in a weight ratio of 2: 1-1: 5, respectively. The composition may additionally contain 1% natrocarbonatite as a suspending agent. The method of obtaining this composition is that all of the above ingredients are mixed with water to obtain a homogeneous slurry which is spray dried to a residual moisture content of 1 to 3 wt. %. Solid dosage form obtained by pressing or by extrusion, which contains an effective amount of biologically active substances, soluble in water, so pl. 100oC, adjuvants and 28 - 63 wt. % the above media. 3 s and 5 C.p. f-crystals, 6 PL.

The invention relates to the combination tonkoizmelchennyj particles used as carriers for active substances, these substances are used for dispersion or dissolution in aqueous media.

In addition, the invention relates to solid dosage f the substance, in which the dosage form rapidly disintegrates in an aqueous environment for release of the active substance.

The active substance in combination with carrier particles in solid dosage forms, are available for a wide pharmaceutical and industrial use. In many areas of solid dosage forms such as tablets, have an advantage over liquid systems and mixtures of particles or agglomerates of active substances and particulate media. They have great convenience in the handling of drugs and security (in relation to both human and environmental), allow for better control of the amount of their consumption and to experience fewer problems during their transport in containers (because the minimum contact of the active substance from the container).

Despite this, the solid dosage form is not used in the production of chemicals for agriculture, such as gibberellins and pesticides, and use of active substances in some other cases, industrial farming due to the lack of suitable carrier materials that provide good binding, compressibility (in the case of a compact form, such as tablets) and would be suitable desint RMI for agriculture and other industrial applications must possess sufficient strength for their preservation in the packaging and handling without damage or liming. They should also disintegrates to the desired extent in the aquatic environment, including cold water. Forming a suspension in an aqueous medium (for example, in the tank sprinkler installation), the material of the carrier with the active substance should remain in the water in suspension without settling to the bottom in sufficient time allowed for its use (agriculture), to the place of its application.

Microcrystalline cellulose (MCC) is well known as the carrier particles or the environment for pharmaceutically active drugs, alone or in combination with other material media, in solid dosage forms (tablets, pills, beads and the like) that has been shown in the U.S. patents NN 517381; 4816064; 4249938 and the Japan patent 72/37012 approved in 1872, on an application filed June 9, 1970

MCC is used to shape swelling foods, although these forms are not dosed forms in the usual sense, because they are not designed to release the expected quantitative units of the active substance (see Lejlicksman, Food Hydroevlloids, Vol. III, 1986, CRC Press, Jnc. , 34 - 42). As described in U.S. patent N 4744987, MCC has excellent properties for the preparation of solid dosage forms, and these solid form b is as a carrier for active substances, other than pharmaceuticals, especially active substances, which are used in too large areas, as in the case of chemicals for crops, such as herbicides and pesticides. It is therefore desirable to dilute the ICC sonosite in order to reduce the price, but without excessive reduction benefits of the MCC. However, the use of consicely with low price should not be lower compressive properties, as well as the rapid disintegration of the compact compositions at low temperatures often encountered when using chemicals for crops, or under conditions that may arise in such circumstances, the other using them.

Urea is known to be a carrier for herbicides, as described in U.S. patents NN 4517381; 4186064 and 4249938. Although these patents also referred to the ICC, there was no indication or suggestion that these materials can be used in combination as carriers in solid dosage form. Urea is well known as a plant fertilizer and fertilizer and as a food additive for ruminants. It is also used in pharmaceutical preparations as a diuretic and to reduce intracranial pressure.

Itself the urea GIHR is effectively and evenly distributed on the soil as fertilizer. This mass also tends to slow dissolution. In U.S. patent N 3558299 disclosed a method of preparation of the crystalline non-caking particles of urea coating them with a mixture of inert substances and urease. Disclosed inert substances are tonkoizmelchennye clay (talc, mica) or powdered materials such as walnut shells, or powdered rods corn cobs. MCC or solid dosage forms, such as pellets or tablets that are not mentioned.

Japanese published patent application N 59/82303, filed November 2, 1982, and published may 12, 1984, discloses a chemical composition for crops, which rapidly disintegrates in water. The composition includes is able to wet the powder from:

a) agrochemically (fertilizer, herbicide, and others),

b) an inorganic powder (calcium silicate),

C) fine powdery resin which swells when adsorbs water (stitched Solimar cellulose, polyacrylate and other), urea, MKC and/or solid dosage form is not explicitly detected.

In accordance with the present invention a combination of tonkoizmelchennyj MCC particles and at least one nitrogen-containing compounds, such as the ode or the ability to swell in water, such that they quickly dispersed in aqueous medium, the composition of the ICC: nitrogen-containing compound in a weight ratio of from 10:1 to 1:10 with medium which is miscible with the active substance, and formed so as to form an effective solid dosage form.

The medium may additionally include a hydrocolloid, such as sodium carboxymethyl cellulose (Na), in order to help the formation of MCC suspension, when the solid dosage forms of the invention are dispersed in the aquatic environment.

Solid dosage forms of the invention is rugged enough to withstand packaging and work with them without destroying or liming. Moreover, the solid dosage forms rapidly disintegrate in water even at low temperatures, and disintegrated, suspended particles are not mixed and not compacted when you are in a calm state, over an extended period of several days or more long. When the active substance is a substance that can be toxic when working with it indoors, such as a herbicide or pesticide, solid dosage form improves the way R is whether the ICC in solid dosage forms - achieved the ability to release active substances in cases of use, when the price of the media is an important factor.

This is achieved along with an amazing improvement in properties, including rapid disintegration, and no deterioration of the properties inherent in the MCC. The property of rapid disintegration even at low ambient temperatures (such as dew point in the environmental agriculture environment) reduces toxicity to birds, when the active substance is of a type that represents such a risk, if the dispersion is carried out in the range of lateinamerika granules or kabananukye forms. In addition, because the carrying capacity of a media composition of the present invention is very high and is 65% or more by weight of active substance in some cases, evaluation of the effectiveness of the composition is enhanced.

MCC is a purified, partially depolimerizovannogo natural cellulose, used first as a medium for drugs in pharmacology. Its popularity is due to the outstanding characteristics of compressibility, leading to good binding and disintegration properties in comparison with other media for the pills, such is ina road, as the way of its reception. This led to the restriction of its successful use in cost-sensitive markets chemicals for crops.

In accordance with the present invention is the price of MCC opposed to combining cells with one or more water soluble or swellable in water containing a neutral substance which is compatible with the active substance and differs from it, in order to prepare the mixture of particles. The active substance is then mixed with carrier particles, and the combination is formed by traditional methods in solid dosage form. The obtained formed the mass can vary widely in shape and size. It can be ordered or disordered appearance, and can be round, disc-shaped, flat or oblong in shape.

Different solid forms described as tablets, pills, beads, balls, cakes, CDs, granules, strips, pellets and the like. Form can not only be compression molded, but can be molded by extrusion, pelletizing, granulating, stamping, briquetting, or may be formed in any other way.

Materials from MCC used in this other trademarks. The particle size of the carrier to obtain optimal results depends on the way the ICC combined with sonosite, the desired value of the disintegration of the solid dosage form is created with a mixture of MCC/mixture of consicely, and the stability of the aqueous suspension depends on the disintegration of the solid dosage forms. For example, if the combination of carrier and active ingredients compressed as dry powder in teletrauma machine, the smallest particles will flow at a low speed in the car and in the feed chute or the transmitting mechanism can be formed obstacle. Accordingly, when the composition is formed by compression of a dry powder, it was determined that the effective particle size of the carrier is primary due to particle size of MCC. Suitable average particle size of MCC ranges from 20 to 90 μm, preferably, variations in size were from 30 to 70 μm, and most preferred particle size of 50 microns.

Soluble or swelling in water containing conoidal can be any substance that is chemically inert, neutral and stable system carrier in this invention will not be subjected to hydrolysis or destroyed in other ways. With the society, but to be effective for the intended use of solid dosage forms. While conoidal acts as an amplifier for the ICC, it is necessary also to reduce the price of the total composition of media, it also acts as a "trigger" mechanism and contributes to the disintegration of the composition of the medium in the water. This enhanced disintegration is inherent in the MCC and improves the properties of the suspension when the final disintegration of the solid dosage forms.

The magnitude of disintegration can be reduced or controlled in other ways in order to achieve the desired values, it is necessary to increase the proportion of cells in the mixture of the carrier and also adding a gelling component in the mixture. Various gel-forming substances are well known and include polyacrylamide and other forming a gel hydrocolloids.

Disintegration of the solid dosage forms and the subsequent magnitude of release of the active substance primarily dependent on the water solubility of the active substance and the quantity of the active substance in solid dosage form. In General, the greater the load the active substance reduces the disintegration of tablets and the release of the active substance. Effective the third.

Various nitrogen-containing components must have an affinity for the surface of the particles of the ICC in order to facilitate the interaction with particles MCC (through hydrogen bonding or otherwise), when subjected to the shaping forces such as compression, but which are also soluble at an energy lower than the energy required for communication with the MCC particles after disintegration of the solid dosage forms in the aquatic environment. Under these conditions, MCC particles originally and tightly contacted with the active substance, but quickly separated in the water and desagregirutee to create a huge surface area and release the active ingredient when the solid dosage form is added to the aquatic environment.

Among the nitrogen-containing compounds are effective in this regard are compounds containing amide, ammonium salts and nitrates of the metal. Amesterdam compounds include any water-soluble organic compound containing a carbonyl or amide functional group adjacent or existing separately from the carbon chain. Such substances can be simple amides (-NHCOR, where R is an aliphatic or cycloaliphatic education, consisting of Saedinenie (such as benzamide) are also included for to lengthen the time of dissolution in water or swelling, they must be compatible with the active substance. Especially preferred simple amides, such as acetamide", she and amesterdam substances and other compounds containing urea group (-NHCONH), such as urea, thiourea, dimethyloxetane, tetraethylsilane and propermotion.

Ammonium salts, derivatives of inorganic or organic acids include ammonium sulfate, ammonium phosphate, ammonium nitrate, ammonium carbonate and ammonium citrate.

The nitrates of the metals include nitrates of metals of periodic table groups IA, IB, IIA, IIB and other metals: Mn, Fe, Co, Ni, Al, Su, Pb, Sb, Bi. Mainly nitrates should be nitrates of alkali metals, such as nitrates of sodium and potassium.

Nitrogen-containing substances can be used alone or in mixture of two or more substances. The selection of nitrogen-containing substances produced on the basis of both their effectiveness as sonorites, but based on the price. In this regard, raw material type, nitrogen-containing compounds, such as urea, ammonium salts, nitrates, metals (including mixtures of them), it is preferable to use in those cases, the CC, for the formation of the composition of different media should be mixed with the active substance. They must be particles of small size and flow freely to the formation of homogeneous mixtures with MCC. When urea is used as conoidal, it is necessary to consider that the standard urea industrial production varies by size: 2,36 up to 2.0 mm (8-10 mesh by American technical standard ATS) - rough material, or 1.40 mm - 600 µm (14-30 mesh ATS) - thin material. Particles of small size (about 10-200 μm) get a well-known method, including crystallization, freeze drying, various crushing as the individual components of the carrier, and a mixture of media after dry milling. If the composition of the media is a wet granules with the active substance, to form the final dosage forms containing soocial will dissolve in MCC. In this case, the particle size of sonorites plays no role.

The ratio of MCC to the nitrogen-containing compound in the medium along with the particle size of the carrier is affected by the hardness (measured by the force of the tension) solid dosage forms prepared with the carrier, and the hardness has a feedback effect on the value detente is their use, and at the same time they must be ready to disintegration in the aquatic environment. Tablets with a tension of 2 to 25 kg/cm2will resist damage during their use, but will quickly disintegrate in the aquatic environment. Most preferably, the tensile force was 3 - 10 kg/cm2. A suitable ratio of the amount of MCC: nitrogen-containing compound for the manifestation of such properties shall be from 10:1 to 1:10 by weight, preferably from 5:1 to 1:5. Most preferably the ratio of 1:1.

Components of the carrier are combined in any way, to get dry, tonkoizmelchennye mixture of particles or powder. The technique of preparing such mixtures or powders are well known and include: education of the dry mixture or granulation, the moisture of the granules, followed by drying and dispersing in water, followed by spraying. Dosage forms can be prepared from the composition of the carrier and the active substance by any known method, including direct compression and/or compaction by flattening dry mix, wet granulation followed by compression and/or spheronization.

When tableting carried out by a method suitable for obtaining twizala or spray drying can be used for the preparation of compositions media for tableting. The choice of method depends primarily on the active substance, the ability of the mixture of carrier and active ingredients to freely flow through tabletiruemuju machine or embossed and binding properties of ingredients. If the active substance can be mixed with a carrier to form a free flowing dense powder, the mixture can be directly subjected to compression. In the dry granules dry powder mixture of carrier components and the active substance is squeezed to pieces, if you use a tablet press. Alternatively, the dry powder compact is rolled into a plate. Pieces or plates of powder is then put through a sieve (for example, the size of the sieve of 1.7 mm, 1.4 mm or 1.18 mm, i.e. 12, 14 and 16 mesh on ATS, respectively) in order to form solid pellets for the final stage tableting.

In the same way wet granulation water is added to a mixture of MCC and sonorites to form a wet granulated material. The amount of water depends on the ratio of MCC and sonorites. A higher ratio of MCC: soocial weight will require more water, which is valid to add. Basically 1/3 of the mixture of MCC, media and water predstavlaet sieve (hole sieve of 2 mm; 10 mesh on ATS), dried and again passed through a sieve (for example, with openings of 850 μm; 20 mesh on ATS). Receive granules, ready for mixing with the active substance and other ingredients for tableting.

In different processes wet granulation of MCC can "interact" with nitrogen sonosite according to the method described in U.S. patent N 4744987, where nitrogen-containing component is substituted for the calcium carbonate. In the interaction of cells with sonosite common source solution MCC and conoidal form a good mixing and liquid is evaporated any effective way. The spray drying is preferred. The ratio of MCC: soocial may be the same as in other methods of mixing, and the resulting particles can be passed through a sieve in order to obtain the distribution of the particles in the desired size. Oprocentowany material carrier can then be combined with the active substance in the same manner as described above, with further drying or wet granulation and direct compression.

Wet granulation or extrusion (die) can be used to prepare the composition of the media for all activeresource otherwise, when mixed with a carrier.

According to another aspect of this invention, it is possible to prevent the precipitation of the ICC, when the solid dosage form of the invention dispersed in an aqueous solution, using the introduction of the media minimal amounts of hydrocolloid compatible with MCC and effectively help wet (hydrating) MCC. These substances act so that the suspended cells, and are characterized by water solubility and binding with MCC or otherwise adhesion to the ICC. They can be natural or synthetic and are generally a polymerized hydrocarbons.

Typical of suspendida substances are derivatives of cellulose such as sodium carboxymethyl cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose and methylcellulose; adhesive substances such as seaweed extracts (agar, carrageenan, alginate), plant extracts (pectins, low methoxyphedrine), exudates from plants (Arabicas, tragakant, karaya, ghatti), extracts from seeds of a plant (sarangee beans, kvar) and microbial enzymatic bonding agents (dextran, xanthan gum); starches, including pregelatinization and modified the P CLASS="ptx2">

Mainly suspendresume substances are salts such as sodium carboxymethyl cellulose. At the same time, it is not entirely clear why I believe that the best suspendisse action comes from repelling particles forces, due to the ionic composition of such materials.

Suspendresume substances are used in small quantities of about 0.05 to 25% by weight of the ICC, mainly about 0.5 - 10% by weight, taken in accordance with the molecular weight, and correlate with the viscosity of the substance. In the case of substances having an advantage over the other, sodium carboxymethyl cellulose, medium or high viscosity materials are preferred due to the stronger hydration of these materials, while materials with low viscosity are more easily dispersed.

Suspendresume substances can be mixed with MCC and sonosite any effective way and in appendices do not need. If the composition of the carrier prepared in liquid form, for example, by wet granulation or spray drying, suspendisse substance is usually added after mixing the ICC and sonorites in the aqueous medium by stirring for formation of the mixture.

Lubricants contribute to removing the compact form of the drug from the cavities of the stamp. They can also reduce the friction (sliding) and to prevent sticking of materials, due to the stamping surface properties of ANTIEPILEPTICS). A typical lubricant is talc; long chain esters of fatty acids or their salts such as stearic and palmitic acid, stearates of magnesium and calcium; and other materials such as hydrogenated animal oils, glycerylmonostearate, glycerinated and polyethylene glycol 6000. Using glide the impact such materials, as airborne silica, evaporating dioxide silicone and silicone hydrogel. The typical number of used lubricants and glidants is about 0.25 - 5% by weight for each of them, based on the total weight of solid dosage forms.

Incremental disintegrator may be added in the composition of the medium in order to increase the dissolution of solid dosage forms in a liquid medium, especially at low temperatures. Typical disintegrators are: starch (corn, potato, amelody), glycolate sodium-starch, alginic acid, synthetic polymers, such as styrenedivinylbenzene, acrylic ion exchanger or an adsorbent resin, crosspovidone and polysaccharides of soybean. Preferential cage - croscarmellose and cross-linked sodium carboxymethyl cellulose sold under the brand name AK-Di-Sol". Disintegrator are usually used in amounts of 1-5% of the total weight of dosage form.

The active substance can be released from the solid carrier of the present invention that includes any liquid or solid compound or mixtures thereof, which have been under certain circumstances, dispersed or dissolved in a liquid medium or to cook in is in place (for example, for use in an industrial process or waste waters, in the water of rivers or lakes, in the fluid layer, in pools for swimming, vessels with oil, body fluids, water, reaching for drinking, food additives, pharmacy and so on). Of course, the active substance must not react with components of the medium, which can reduce or interfere with the functions of the media. Media and solid dosage form of the invention, moreover, are widely used in various fields and products, including agricultural products and preparations for veterinary medicine, pharmacy, nutrition of humans and animals, to add to the water of the swimming pools in the industry for obtaining oil in bottles, there are other areas of use: in the production of cosmetic substances, household pesticides and other manufacturing fields.

In agricultural areas of application active substances include herbicides, plant growth regulators and all types of biocides such as pesticides. Pesticides include atrazine, bentazon, trifluralin, propanil, metribuzin, alachor, butachlor, bromanil, clomazone, oxadiazon, lorsban, bifenox, aldicarb, monocrotophos, propoxur, diflubenzuron, carbofuran, permethrin, carbaryl, cypermethrin, endosulfan.

The process of shaping in addition to the pelletizing can be used for preparing solid dosage forms of the present invention, equipment and accessories for such well-known works. These processes include the preparation of pills, punching weight, agglomeration and giving a spherical shape and is described in detail in textbooks and publications on this issue.

In the composition of the media of the present invention is allowed considerable flexibility in connection with the purpose of dosage forms. For example, the compressed forms such as tablets, can be produced in two-section or multi-section form, so that they can be separated by hand or machine, and are designed to release the fractional amounts of the active substance. Such pills are especially used successfully for the release of pesticides, herbicides and other agro-chemicals for the home and garden, villas, etc., and are used in rural areas without loss of bioeffectives. Moreover, chemically incompatible activity, such as a tablet, containing several different pesticides or combination of herbicides and pesticides, can be separated in solid dosage form of education is the AI of the invention. Used here, the sizes of the sieves indicated in the ATC Standard E 11-87.

Example 1.

The method of preparation of the dry mix.

Microcrystalline cellulose (MCC) (AVICEL PI h 105, average particle size 20 microns; We FMC) and milled granules of urea, passed through a sieve with openings of 850 - 250 mcm (20 - 60 mesh ATS), mixed in a dry state in the RK-mixer with the formation of 5 mixtures with different proportions (table. 1). 4 g of each mixture used to prepare tablets with a diameter of 2.54 cm in tabletirujut press Carver, creating pressure 923 kg/cm2with a moisture content of 3%. Measure the thickness of each tablet, determine the time of disintegration, immersing the tablet in the vessel 400 ml of water at room temperature. The results are presented in table. 1. You can see that compared with the control, the disintegration time is significantly reduced in the presence of urea.

Example 2.

The way to obtain wet granules.

Urea (particle size is the same as in example 1) and microcrystalline cellulose (AVICEL PI h 105; MCC, 150 g) are mixed in a system of Hobart for 5 min in a 1 : 1 ratio urea/MCC. Add approximately 150 ml of tap water is a sieve with holes of 2 mm (10 mesh ATS). The obtained granulated material is dried at 50oC to a moisture content of 3%. The dry granular material is passed through a sieve with openings of 850 μm (20 mesh ATS). These pellets are used to produce tablets of 0.5 g using a tablet press model Stoker 52 and a 1.11 cm (7/16 inch) standard concave shtam. The hardness of the tablets was measured using Schleuniger Hardness tester. The disintegration time of the tablets is determined by immersing each tablet 400 ml of water at room temperature; the results are shown in table. 2, which shows that solid tablets (pressure of 10.5 kg/cm2) not disintegrable during the time for which getintegervalue more soft tablets (pressure 6 kg/cm2), and that the increase in hardness significantly slows down or prevents the disintegration of the tablets.

Example 3.

Tablets with herbicide prepared by dry granulation.

A mixture of 4,15 kg of the herbicide atrazine, to 45.4 g of AC-DI-SOL croscarmellose (disintegrant) (FMC Corporation), 226,8 g anionic dispersant chemical-sodium lignosulphonate, to 45.4 g of surface-active substances alkylarylsulfonate and 68 g aerated synthetic silica are mixed in RK-mixer for 10 minutes the mixture rasmol the second material (1.34 kg) is transferred into the mixer and add 228 g of microcrystalline cellulose Avicel PI h 101 (50 µm - the average particle size; FMC Corporation), 571,5 g of urea (the same as in example 1) and an increase of 22.7 g croscarmellose AK-DI-SOL (disintegrant). The resulting mixture was stirred for 5 minutes Talc (40,4 g) and magnesium stearate (4,48 g) added as a lubricating material (lubricant), and the mixture is stirred 5 min, then passed through the feeder to vibratory sieve and served in tablet press (Colton 250) using the stamp of 4.6 cm (1 and 13/16 inches) with a smooth cutting surface of the stamp. Extruded material is ground in the mill fitza equipped with a 1.7 mm sieve (12 mesh ATS) that produce granular material. These granules were compressed on a tablet press Stokes model P with a speed of 16 tablets per minute. The diameter of the tablets was to 6.67 cm (2 5/18 inch). When falling from a height of 4 feet onto a hard surface obtained 60 mg tablets remained intact, indicating that the high hardness of the tablets. Tablets getintegervalue fully in 2-2,5 min after immersion in 4 l of tap water at room temperature, demonstrating the value of disintegration acceptable to drug suspensions herbicides for aerosol use.

Examples 4-18.

Tablets of other herbicides of pregnacey, the forces of compression and different proportions MCC, urea and various additives in the media. The data (table. 3) show that as the hardness (the upper value of the voltage), and softness (lower value of the power voltage) of the tablets could be obtained using the compositions of the media of the present invention, but the disintegration time (dissolution) was similar in these tablets under the influence of different amounts of added MCC and urea and under the influence of variable quantities of lubricants and/or glidants (compare examples 4, 6, 7, 9 and 10). Examples 10 to 14 show the effect of varying magnitude compression forces in the preparation of tablets disintegration time. It will be shown that a lower hardness (power voltage) leads to the shortening of the time of disintegration, and Vice versa (see tab. 3).

A. Lubricants consisting of talc and/or magnesium stearate.

1 = 2,0% talc/0.3% magnesium stearate;

2 = 2,0% talc/0.6% magnesium stearate;

3 = only magnesium stearate;

4 = 1% talc/0.2% magnesium stearate.

B. Glidant (synthetic silicates).

1 = airborne silicate;

2 = volatile silicate;

3 = 3% of airborne silica/1% volatile silica.

C. Surface is sulfonate sodium.

D. Calculated as in example 2,

that is, Measured as in example 2.

W. AK-DI-SOL croscarmellose.

Example 19.

Pharmaceutically active beads obtained by the method of extrusion/spheronization.

Quickly dezintegriruetsja balls hydrochlorothizide (active substance) get on the next recipe (see tab. 4).

Ingredient MCC/urea accompanying material prepared by dissolving urea in water, using dispensatory mixer, add the ICC in the form of moist pellets at a ratio of MCC/urea 1:2, dispersed cells in a solution and sprayed dried mixture to obtain a powder containing 2% moisture.

Polyfon H surfactant (Westvaco) is an anionic dispersant sodium lignosulphonate. Celatum OP 4 diatomite is a diatomaceous earth (Eagle Picher). Ingredients 1-5 are mixed in a mixer with a volume of 2 quarts (Hobart mixer) for 2 min at speed 1. Water (140 ml) is added gradually over a further 3 min at speed set on the 1st. The wet mass is mixed over 1 min at speed set at 1, and then a lot of hands passed through a sieve of 1.18 mm (16 mesh ATS) and the pre is>/P>The wet granulation of MCC/ammonium sulfate.

Microcrystalline cellulose (Avicel PI h 105; MCC), 500 g and 300 g of ammonium sulfate are mixed in a Hobart mixer at low speed for 5 minutes Add portions solution consisting of 180 g of ammonium sulfate and 375 g of water for 1 min with constant stirring. The focus was on preventing solid formations of growth on the sides and the blades of the mixer. The wet granulated material obtained by mixing with a mixture of MCC/ammonium sulfate (1: 1). This material is passed through a sieve 2.0 mm (10 mesh ATS). Then it is put on a tray and dried by a current of air for 6 hours at a temperature of 50oC to the humidity was 2-3%. The dry granular material is passed through a sieve of 850 μm (20 mesh ATS). To add grease (lubricant) dry, passed through a sieve granules are first placed in a V-shaped mixer and mixed for 5 min with 10 g (1 wt. %/wt. ) stearate, representing the lubricant. Just get a small tablet containing urea and sulfate, as consicely.

The dry granular material, not necessarily containing a lubricating substance, used for the cooking of an inch). The hardness of the tablets was measured using Slaunger tester. The disintegration time of the tablets is determined by immersing each tablet in 700 ml of water at room temperature in a USP-disintegrity apparatus. The test results are given in table. 5 below, in comparison with urea as sonosite. Good ability to compression and disintegration time of tablets prepared with composition MCC/ammonium sulfate, showed that the composition of the tablets is an effective environment for tabletting active substances, such as agro-chemicals.

Example 21.

The way to obtain wet granules with MCC/ammonium phosphate.

Microcrystalline cellulose Avicel, Peach 101 in the amount of 500 g is passed through a 425 μm sieve (40 mesh ATS). Then MCC and 300 g of ammonium phosphate are mixed at low speed in a Hobart mixer. In the process of stirring the solution containing 200 g of ammonium phosphate in 500 ml of water for 2 min and additionally stirred for 2 minutes Get wet granular material from MCC/ammonium phosphate (1 : 1). This material is passed through a sieve of 1.7 mm (12 mesh ATS), placed on a tray and dried at 50oC for 6 h to achieve a moisture content of 2-3%. Adding masiva edalat not USP method and visually, after immersion of the pellets in 250 ml of water. The results of this analysis are shown in table. 5, data from which was concluded that the composition containing MCC/ammonium phosphate is an effective environment for tabletting active substances, such as agro-chemicals.

Example 22.

Composition of media suspendresume auxiliary materials.

In this typical case, the suspension was obtained by the sequential mixing 80 gallons of distilled water, of 46.77 kg (102 lb) urea, 2.1 lbs coarse fodder MCC (viscosity of 25 to 50 CP at a concentration of 2%, the degree of substitution of 0.7) and the 115.2 kg (254 lb) mashed MCC in the form of a filtered wet mass (pellet) (39% MCC in water). This mass was passed once through the mill for colloids until complete dispersion of solid particles before drying spray. The conditions of spray drying are selected so as to obtain a final particle size of about 30 to 50 μm and a water content of 2-3%. The resulting powder was tabletirujut by the wet granulation and determine the time of disintegration, as described in example 2. The disintegration time of 5 min or less is considered optimal. The dispersion of the suspension assess CIPAC way M which I suspendida auxiliary materials, immediately disintegrate in water and have a coefficient of suspension 0.

The test results are presented in table. 6. It is seen that as urea and MCC necessary for the formation of a good suspension and that the best product (the rate of disintegration and good suspension) obtained in recipe 3.

1. Solid bulk composition of the carrier for the active substance in water dispersible solid dosage form comprising microcrystalline cellulose (MCC), characterized in that it further contains a substance (P) selected from the group of urea, ammonium sulfate, ammonium phosphate, or a mixture when the mass ratio of MCC and (P) 2 : 1 - 1 : 5.

2. The composition according to p. 1, characterized in that it further comprises suspendisse-based agent derivative of cellulose in an amount of 1 wt.%.

3. The composition according to PP.1 and 2, characterized in that it contains MCC and urea in a weight ratio of 2 : 1 to 1 : 3.

4. The composition according to PP.1 to 3, characterized in that it contains cells with particle size of 20 to 50 μm.

5. The composition according to PP.2 to 4, characterized in that as a derivative of cellulose contains Na-carboxymethylcellulose.

6. The method of obtaining the granular composition of the medium on which acheinu, suspendisse agent and microcrystalline cellulose are mixed until a homogeneous slurry which is spray dried to a residual moisture content of 1 to 3 wt.%.

7. Solid dosage form obtained by pressing or by extrusion, comprising an effective amount of biologically active substances with Tpl.> 100oC, soluble in water, adjuvants and carrier, characterized in that as the carrier contains a composition according to PP.1 and 2 in the amount of 28.9 - 63,15 wt.%.

8. Form under item 7, characterized in that the biologically active substance containing herbicide.


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The invention relates to metering devices (metered tool)

The invention relates to the field of plant protection, in particular, to methods for producing insecticidal composition based on cypermethrine, which can be used to combat plant pests as such or after tabletting

The invention relates to agriculture, namely, to the means of protection of plants against diseases, in particular, compositions for immunizing plants against various phytopathogens

The invention relates to stabilised solid compositions containing S, S' - [2-(dimethylamino)trimethylene]bis-benzothiazolone(bensultap), more precisely to a stabilised solid compositions containing S, S'-[2-(dimethylamino)trimethylene] bis-benzothiazolone and at least one connection oxides, selected from the class consisting of titanium dioxide, zinc oxide, magnesium oxide and boron oxide

FIELD: agriculture and food-processing industry, in particular, composition used in the process of storage and transportation of roots, fruit products and raw plant material.

SUBSTANCE: composition comprises potassium or sodium pyrosulfite 93-96 wt%, binder such as polyethylene glycol with mean molar weight of 4,000 - 3.6 wt%, polyethylene glycol with mean molar weight of 400 - 1-2 wt%. Composition creates medium destructive for various kinds of phytopathogenic fungi, mold, malignant bacteria and dangerous Arthropods.

EFFECT: increased efficiency in protecting fruits and vegetables during storage and postharvest transportation.

1 tbl

FIELD: sanitary treatment of agricultural objects.

SUBSTANCE: invention provides bactericidal sulfur aerosol generating pyrotechnic composition comprising elementary sulfur, flame-suppressing and burning-stabilizing additives, and pyrotechnic base in the form of ammonium nitrate-coal mixture.

EFFECT: achieved safe formation of easily inflaming sulfur aerosol at relatively low cost and being low-sensitive to various pulsed impacts.

FIELD: agriculture.

SUBSTANCE: claimed herbicidal agent comprises postemergence herbicide and carrier selected from group containing Fuller's earth, aerogel, high molecular polyglycoles and (met)acrylic acid-based polymers or copolymers thereof, with the proviso, that if as carrier Fuller's earth is used, herbicide is not Paraquat. This herbicide is used in weed controlling. Herbicidal agent of present invention may be applied prior weed growing out.

EFFECT: herbicidal agent with improved quality.

11 cl, 9 tbl

FIELD: preparations against rodents of murine type.

SUBSTANCE: the suggested rodenticide preparation contains a food basis, an attractant, flavorings, an aromatizing agent, a substance to prevent a man against the intake of the above-mentioned preparation, a dyestuff and an active substance, moreover, elements of food basis are designed to be of different geometrical shape made of baked product at addition of yeast being one of the attractant's components and thermally treated till the development of pronounced porosity, friability and at moisture content of not more than 10%, moreover, the preparation contains components at the following ratio, weight%: attractant 3-10%, flavorings 2-5%, aromatizing agent 0.1-1.0%, substance to prevent a man and domestic animals against the intake of the above-mentioned preparation being within 0.005-0.020% against the intake of food product, stabilizer against mold and oxidation 0.02-0.2%, preventive dyestuff 0.05-1.5%, active substance 0.005-1.5, food basis - the rest.

EFFECT: higher efficiency.

8 cl, 2 dwg, 2 tbl

FIELD: agriculture, in particular, deratization means.

SUBSTANCE: rodenticide composition comprises tetraphenacin, attractant such as sugar, non-refined vegetable oil, cocoa or dry milk, food base such as grain, cereal groats or combined feed, sulfaquinoxaline, and may contain colorant such as carmoisin, chlorophyll or ponceaux. Components are used in predetermined ratios.

EFFECT: reduced utilization time and enhanced activity of composition.

5 cl, 16 ex

FIELD: agriculture.

SUBSTANCE: wasp and hornet elimination means is bait adapted for placing into trap. Said means contains sugar, yeast, and filler, with wheat grits, ground bread hardtacks, flour or mixture thereof with fruit powder being used as filler and taken in the ratio of 1:1. Said means also contains surfactants such as sulfonol, sodium tripolyphosphate and the like. Toxic bait contains less than 1 wt% of diazinone. Method involves solving bait in effective amount of water; pouring in trap; hanging traps on plot, with number of traps constituting 1-2 pieces per 100 m2 of plot.

EFFECT: increased efficiency of wasp and hornet elimination means.

3 cl, 3 ex

FIELD: agriculture, in particular composition for rat controlling.

SUBSTANCE: claimed composition contains anticoagulant as active ingredient, attractant and food base, wherein as anticoagulant it contains zoocumarin and additionally sulfaquinoxaline in the next component ratio (mass %): zoocumarin 0.01-0.05; attractant 0.3-6.0; sulfaquinoxaline 0.025-0.1; and balance: food base. Rodenticide composition as attractant contains sugar; non-refined vegetable oil; cocoa, or desiccated milk; and as food base it contains corn, cereal grains, or compound feed; additionally it may contain 0.02-0.05 % of colorant such as chlorophyll, etc.

EFFECT: composition for effective rodent controlling.

5 cl, 15 ex

FIELD: agriculture.

SUBSTANCE: described is attractant composition for male elaters Crimean Agriotes tauricus (Coleoptera, Elateridae). Common attaractant composition used in agriculture for vermin protection of plants containing mixed 3,7-dimethyl-trans-2,6-octadiene-1-ol-3-methylbutanoate (40-68.0%), 2,6- dimethyl-trans-2, trans-6-octadiene-1,8-diol-di-(3-methylbutanoate) (18-55.5%), 3,7,11-trimethyl-trans-2, trans-6,10-dodecatrien-1-ol-3-methylbutanoate (4-10%), 3,7-dimethyl-cys-2,6- octadiene-1-ol-3-methylbutanoate (0.5-4.0%)) is added with ceresin at following component ratio, wt %: ceresin - 10.0-99.0; specified mix - 1.0-90.0.

EFFECT: production of attractant composition of long attractant activity.

3 tbl

FIELD: agriculture.

SUBSTANCE: herbicidal composition is made on the bases of 3.6-dichlorpyridine-2-carboxylic acid and substituted arylsulfonylheterylcarbamide. As a derivative of 3.6-dichlorpyridine-2-carboxylic acid it contains alcohol esters of C7-C10 356- dichlorpyridine-2-carboxylic acid or their mixtures, at the following components ratio, wt %: C7-C10 alcohol esters; 3,6-dichlorpyridine-2-carboxylic acid or their mixture - 40-75; substituted arylsulfonylheterylcarbamide - 1-5; surface -active agent 15-35; carrying agent - the remaining.

EFFECT: increases consistency of composition.

3 cl, 2 tbl, 12 ex