WO2009157214A1 - Aluminosilicate de magnésium non cristallin sphérique - Google Patents

Aluminosilicate de magnésium non cristallin sphérique Download PDF

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WO2009157214A1
WO2009157214A1 PCT/JP2009/002972 JP2009002972W WO2009157214A1 WO 2009157214 A1 WO2009157214 A1 WO 2009157214A1 JP 2009002972 W JP2009002972 W JP 2009002972W WO 2009157214 A1 WO2009157214 A1 WO 2009157214A1
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magnesium aluminate
spherical
amorphous magnesium
aluminate silicate
hydrochloride
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PCT/JP2009/002972
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English (en)
Japanese (ja)
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町村等
高堂銀優
大貫哲也
小泉晴佳
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富士化学工業株式会社
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Priority to JP2010517774A priority Critical patent/JPWO2009157214A1/ja
Publication of WO2009157214A1 publication Critical patent/WO2009157214A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B33/00—Silicon; Compounds thereof
    • C01B33/20—Silicates
    • C01B33/22—Magnesium silicates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/015—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B33/00—Silicon; Compounds thereof
    • C01B33/20—Silicates
    • C01B33/26—Aluminium-containing silicates, i.e. silico-aluminates
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09C—TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES ; PREPARATION OF CARBON BLACK  ; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS
    • C09C1/00—Treatment of specific inorganic materials other than fibrous fillers; Preparation of carbon black
    • C09C1/40—Compounds of aluminium
    • C09C1/405—Compounds of aluminium containing combined silica, e.g. mica
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/01—Particle morphology depicted by an image
    • C01P2004/03—Particle morphology depicted by an image obtained by SEM
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/30—Particle morphology extending in three dimensions
    • C01P2004/32—Spheres
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2006/00—Physical properties of inorganic compounds
    • C01P2006/12—Surface area
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2006/00—Physical properties of inorganic compounds
    • C01P2006/19—Oil-absorption capacity, e.g. DBP values

Definitions

  • the present invention relates to spherical amorphous magnesium aluminate silicate having high sphericity and particle strength, and a pharmaceutical preparation containing them.
  • nucleating agents As a means for controlling the release of long-acting pharmaceuticals, enteric dissolution, improving the stability of medicinal ingredients, or masking tastes, pharmaceuticals use granules having a multilayer structure centering on nucleating agents.
  • spherical particles having a uniform particle diameter and high sphericity As a nucleating agent, it is preferable to use spherical particles having a uniform particle diameter and high sphericity as a nucleating agent in order to increase the lamination rate and to uniformly laminate the thickness of each layer.
  • the properties required of the nucleating agent are required to be strength that does not break from the load applied during granulation, absorbability to absorb the spray solution, and stability that does not react with the drug.
  • spherical particles used as a nucleating agent are known as slightly spherical crystalline cellulose, purified white sugar spherical granules, mixed spherical granules of sugar / starch, lactose / crystalline cellulose spherical granules, and D-mannitol spherical granules. Although these particles had sufficient strength, the sphericity of the particle shape was not high, especially when the particle size was 100 ⁇ m or less, so that a uniform drug layer or coating layer was formed on the surface of the nucleating agent. Was enough performance. Moreover, since it consists of carbohydrates, there existed a problem that water absorption ability was low and granulation time was long.
  • Magnesium aluminate silicate is an amorphous substance represented by the following formula developed and manufactured by the present applicant in the 1955s.
  • Al2O3 ⁇ xMgO ⁇ ySiO2 ⁇ mH2O In the formula, x is 0.3 ⁇ x ⁇ 3.0, y is 1.0 ⁇ y ⁇ 3.0, and m is a number in the range of 0.1 ⁇ m ⁇ 7).
  • These are widely marketed under the name “Neusilin” (trademark, manufactured by Fuji Chemical Industry Co., Ltd., magnesium aluminate silicate).
  • Magnesium aluminate silicate is recorded in an external regulation, and has high antacid activity, moldability and specific surface area, and is used in pharmaceutical preparations as a pharmaceutical antacid, excipient, carrier and fluidizing agent. Further, since the primary particles are fine and the specific surface area is high, anti-caking agents, adsorbent carriers, and pulverized products are often used in the cosmetics and chemical products fields as fluidizing agents. As the form of the product, there are various products having different surface physical properties depending on the shape by a drying method such as an air dryer and a spray dryer and the synthesis method.
  • Spherical types include normal products (alkali type) and neutral products, both of which Al2O3 is 29.1 to 35.5% by weight, MgO is 11.4 to 14.0% by weight, and SiO2 is 29.2 to
  • the primary particles containing 35.6% by weight and having an average particle diameter of 0.01 to 1 ⁇ m are formed into spherical aggregates by spray drying, and the particle size distribution is 44 to 325 ⁇ m (Non-patent Document 1).
  • the pH of the 4 wt% slurry is 8.5 to 10.0 for normal products and 6.0 to 8.0 for neutral products, and the powder powder varies depending on the surface pH.
  • the normal product has a static specific volume of 2.7 to 3.4 ml / g, a specific surface area of 100 to 150 m 2 / g, an angle of repose of 25 to 32 degrees, an oil absorption capacity of 1.3 to 1.4 ml / g,
  • the neutral product has a static specific volume of 4.0 to 7.5 ml / g, a specific surface area of 250 to 300 m 2 / g, an angle of repose of 30 degrees, and an oil absorption capacity of 2.0 to 3.4 ml / g. .
  • This spherical type magnesium aluminate silicate is synthesized by spraying and drying aluminum aluminate, magnesium salt, silicate by adjusting the reaction conditions such as the order of addition in the solvent, pH, temperature, etc.
  • Patent Documents 1, 2, and 3 Conventional magnesium aluminate silicate has been porous and spherical particles by spray drying, but the particle strength is not sufficiently high and the specific volume is relatively large.
  • Patent Document 4 There is also a granule obtained by spray-drying 30% by weight or more of magnesium aluminate metasilicate, silicic anhydride and water insoluble powder. Even when a large amount of moisture is present, the strength is weak enough to maintain the strength and shape. For example, in a shaking test, at least about 20% is destroyed. There is a powder composition obtained by spray drying magnesium aluminate silicate and sugar (Patent Document 5). It is an excipient for intraoral quick disintegrating tablets and its strength is not clarified.
  • the inventors of the present invention smashed amorphous magnesium aluminate silicate to several ⁇ m or less, and spray-dried heavy amorphous spherical magnesium aluminate silicate excellent in particle strength, sphericity, and water absorption ability. It was found that it can be obtained.
  • the present invention has the following configuration. (1) It is composed of amorphous primary particles having an average particle size of 0.01 to 0.5 ⁇ m, a particle strength of 50 to 1000 g / mm 2 , an average particle size of 1 to 500 ⁇ m, and a sphericity of 0.8 or more.
  • the spherical amorphous magnesium aluminate silicate according to (1) having a particle strength of 100 to 1000 g / mm 2 and an average particle size of 5 to 300 ⁇ m, (3) Specific surface area of 10 to 500 m 2 / g, static specific volume of 1.0 to 7.0 ml / g, oil absorption of 0.5 to 5.0 ml / g, water absorption of 0.5 to 5.
  • a granular composition comprising an active ingredient layer around the spherical amorphous magnesium aluminate silicate according to any one of (1) to (5), (7) A pharmaceutical composition comprising the spherical amorphous magnesium aluminate silicate according to any one of (1) to (5).
  • the spherical amorphous magnesium silicate aluminate having high particle strength according to the present invention has high specific surface area and high adsorption performance, and is useful for use in pharmaceutical preparations such as adsorption and mixing of core particles and active substances.
  • FIG. 4 is a SEM photograph (1 memory 5 ⁇ m) of spherical amorphous magnesium aluminate silicate of Example 2.
  • 2 is a SEM photograph (1 memory 5 ⁇ m) of spherical amorphous magnesium aluminate of Comparative Example 1.
  • 4 is a SEM photograph (1 memory 5 ⁇ m) of spherical amorphous magnesium aluminate of Comparative Example 2.
  • 4 is a SEM photograph (1 memory: 10 ⁇ m) of granules of Example 3.
  • FIG. 4 is a SEM photograph (1 memory: 200 ⁇ m) of spherical amorphous magnesium aluminate of Example 4.
  • 6 is a SEM photograph (1 memory: 200 ⁇ m) of crystalline cellulose of Comparative Example 4. It is a table
  • magnesium aluminate silicate is represented by the following composition formula (I).
  • Al 2 O 3 .xMgO.ySiO 2 .mH 2 O (I) (In the formula, 0.1 ⁇ x ⁇ 3.0, y is 0.5 ⁇ y ⁇ 5.0, and m is a number in the range of 0.1 ⁇ m ⁇ 10)
  • the Al 2 O 3 .xMgO.ySiO 2 may be in a range that can maintain a non-crystalline state and form fine primary particles, and 0.1 ⁇ x ⁇ 3.0, y is 0.5 ⁇ y ⁇ 5.0, preferably 0.2 ⁇ x ⁇ 2.0, y is 0.5 ⁇ y ⁇ 3.0, more preferably 0.5 ⁇ x ⁇ 1.5, and y is 1. 4 ⁇ y ⁇ 2.1.
  • the non-crystalline state can be confirmed from the absence of a crystal peak by X-RD.
  • the spherical amorphous magnesium aluminate silicate of the present invention is an aggregate of primary particles of amorphous spherical magnesium aluminate silicate having an irregular shape.
  • the finer the primary particles the more cohesive and the higher the strength. Aggregates are easily formed, and the average particle size is 0.01 to 1.0 ⁇ m, preferably 0.01 to 0.5 ⁇ m.
  • the spherical amorphous magnesium aluminate silicate of the present invention has an average particle size of 1 to 500 ⁇ m, preferably an average particle size of 1 to 300 ⁇ m, more preferably 1 to 200 ⁇ m.
  • the spherical amorphous magnesium aluminate silicate of the present invention has a particle strength of 50 to 1000 g / mm 2 , preferably 100 to 1000 g / mm 2 .
  • commercially available spherical type amorphous magnesium aluminate silicate (Neusilin (trademark) SG1, NS2N, etc.) cannot be measured with a particle hardness measuring device because the particle strength is small (50 g / mm 2 or less).
  • the spherical amorphous magnesium aluminate silicate of the present invention has a sphericity of 0.8 or more, preferably 0.85 or more, more preferably 0.9 or more.
  • Ordinary spherical particles can not reduce the unevenness derived from the raw material, the smaller the particle diameter, the greater the proportion of those unevenness, the shape becomes distorted and the sphericity decreases, the spherical non-crystal of the present invention
  • Magnesium aluminate silicate has a feature that the sphericity does not change even when the particle diameter is reduced.
  • the spherical amorphous magnesium aluminate silicate of the present invention has a particle size as small as nano-order, and the particles themselves are porous agglomerates of porous amorphous magnesium aluminate silicate with small inter-particle voids. It is believed that there is.
  • the sphericity is a value obtained by dividing the minor axis of a spherical particle by an SEM photograph or an optical microscope by the major axis, as will be described later.
  • the spherical amorphous magnesium aluminate silicate of the present invention has a specific surface area equivalent to that of commercially available spherical amorphous magnesium aluminate silicate, and is 20 to 500 m 2 / g, preferably 40 to 400 m 2 / g, more preferably. Is 60 to 300 m 2 / g.
  • the spherical amorphous magnesium aluminate silicate of the present invention has a static specific volume equivalent to that of commercially available spherical amorphous magnesium aluminate silicate, and is 1.0 to 7.0 ml / g, preferably 1.0 to The amount is 5.0 ml / g, more preferably 1.0 to 4.0 ml / g.
  • the spherical amorphous magnesium aluminate silicate of the present invention has an oil absorption equivalent to commercially available spherical amorphous magnesium aluminate silicate, and is 0.5 to 5.0 ml / g, preferably 1.0 to 5. 0 ml / g.
  • the spherical amorphous magnesium aluminate silicate of the present invention has a water absorption equivalent to that of commercially available spherical amorphous magnesium aluminate silicate, and is 0.5 to 5.0 ml / g, preferably 1.0 to 5. 0 ml / g.
  • amorphous spherical magnesium aluminate silicate of the present invention there are two types of amorphous spherical magnesium aluminate silicate of the present invention, a normal product (alkali type) and a neutral product (neutral type), each having different physical properties depending on the surface hydroxide of the primary particles.
  • the alkali type refers to magnesium aluminate silicate having a 4% slurry pH of 8.5 to 11.0, which will be described later
  • the neutral type refers to magnesium aluminate having a 4% slurry pH of 5.5 to 8.5, which will be described later.
  • the 4% slurry pH is a pH value measured by a pH meter after weighing 2 g of a sample and adding water to make a total volume of 50 ml, stirring for 2 minutes.
  • the amorphous spherical magnesium aluminate silicate of the present invention is produced by pulverizing amorphous magnesium aluminate silicate suspended in a solvent into fine particles and spray drying.
  • the amorphous spherical magnesium aluminate silicate of the present invention can be produced commercially or can be produced by a known method disclosed by the present applicant.
  • Japanese Patent Publication No. 34-513, Japanese Patent Publication No. 34-514 And JP-B-34-618, JP-B-36-23163, JP-B-42-7719, JP-B-52-16078, and JP-B-57-17845 can be produced commercially or can be produced by a known method disclosed by the present applicant.
  • Japanese Patent Publication No. 34-513 Japanese Patent Publication No. 34-514 And JP-B-34-618, JP-B-36-23163, JP-B-42-7719, JP-B-52-16078, and JP-B-57-17845.
  • the method for producing amorphous magnesium aluminate silicate has desired physical properties by appropriately selecting mixing conditions such as order of addition of aluminum salt, magnesium salt, and silicate in a solvent, pH, temperature, and the like.
  • the amorphous magnesium aluminate silicate can be produced. These dried products or undried products after wet synthesis are used.
  • pulverization method either wet pulverization or dry pulverization may be used.
  • wet pulverization Nanomizer (product name, manufactured by SGS Engineering Co., Ltd.), Starburst (product name, manufactured by Sugino Machine Co., Ltd.), Ultimateizer (product) Name, Karasawa Fine Co., Ltd.), high-pressure homogenizers such as microfluidizer (product name, manufactured by Mizuho Kogyo Co., Ltd.), bead mill, disk mill, homomixer, etc.
  • the pulverization conditions may be any conditions as long as the desired average particle diameter can be obtained.
  • the slurry concentration that can be pulverized is adjusted, and a plurality of passes at a pressure of 100 MPa or more can be selected as appropriate.
  • the bead mill the bead system, the flow rate, the rotation speed, and the slurry concentration can be appropriately selected so as to obtain a desired average particle size.
  • spherical particles produced by, for example, ordinary spray drying of these secondary agglomerated particles have a large gap with few contact points of constituent particles, a large specific volume, and a low particle strength.
  • the spherical amorphous magnesium aluminate silicate of the present invention is dispersed and pulverized by pulverization of the amorphous magnesium silicate aluminate forming the secondary agglomerated particles to secondary agglomerated particles having small intergranular voids, Adjust to the desired average particle size.
  • the average particle size in the pulverization is 0.01 to 10 ⁇ m, preferably 0.05 to 6 ⁇ m, more preferably 0.01 to 3 ⁇ m.
  • the dry-milled amorphous magnesium aluminate silicate is suspended in a solvent, and the wet-milled amorphous magnesium aluminate silicate is adjusted to adjust the concentration if necessary.
  • the solvent may be any solvent that does not affect the properties of the particles, and examples thereof include hydrophilic solvents such as water, ethanol, methanol, and acetone, preferably water.
  • the dispersion can be prepared by a known method, for example, ordinary stirring, colloid mill, high-pressure homogenizer, ultrasonic irradiation, etc., but any method capable of highly dispersing particles in an aqueous dispersion. That's fine.
  • the concentration of the suspension may be in a range that can be sprayed into the air layer, that is, the solid content is 1 to 40% by weight, preferably 5 to 30% by weight.
  • an additive capable of changing physical properties to be described later can be added to adjust the desired physical properties.
  • Drying is performed by spraying the suspension of amorphous magnesium aluminate silicate into the air layer.
  • the drying method by spraying in the gas layer can be performed by any known method for forming spherical particles.
  • spray drying, fluidized bed drying, rolling bed drying, stirring It can be performed by grain drying, freeze drying or the like.
  • spray drying is easy to form the porosity by instantly removing the solvent component, easy to form particles with high sphericity by cohesive drying while maintaining a liquid spherical shape, uniform particle size
  • it is most suitable for the production of spherical particles because the production setting of fine particles is easy.
  • the spray drying conditions are not particularly limited, it is preferable to use a disk-type or nozzle-type spray dryer as the spray device.
  • the inlet temperature is preferably about 120 to 400 ° C.
  • the outlet temperature is preferably about 80 to 300 ° C.
  • Spherical amorphous magnesium aluminate silicate can change or impart particle strength, disintegration, moldability, etc. by blending an additive capable of changing physical properties in addition to amorphous magnesium aluminate silicate.
  • the additive capable of changing the physical properties can be added in the range of 1 to 99% by weight, preferably 10 to 90% by weight, based on the whole spherical particles.
  • the particle strength can be further increased by blending a substance having low melting point or solvent solubility.
  • the pores of amorphous magnesium aluminate silicate are filled, the specific surface area, oil absorption, and water absorption are reduced.
  • a water-soluble additive or disintegrant disintegration can be imparted by contact with water.
  • the additive capable of changing physical properties is a substance generally corresponding to an excipient, a disintegration aid, and a binder in the field of pharmaceutical preparations, but is not particularly limited to these uses. Two or more additives whose physical properties can be changed can be blended in the range of 0 to 89% by weight, respectively.
  • excipient in the present invention examples include starch acrylate, L-aspartic acid, aminoethylsulfonic acid, aminoacetic acid, candy (powder), gum arabic, gum arabic powder, alginic acid, sodium alginate, pregelatinized starch, and inositol.
  • Ethyl cellulose ethylene vinyl acetate copolymer, erythritol, sodium chloride, olive oil, kaolin, cacao butter, casein, fructose, pumice granules, carmellose, carmellose sodium, hydrous silicon dioxide, dry yeast, dry aluminum hydroxide gel, dry sodium sulfate , Dried magnesium sulfate, agar, agar powder, xylitol, citric acid, sodium citrate, disodium citrate, glycerin, calcium glycerophosphate, sodium gluconate, L-glutamine, clay, clay -Grain, croscarmellose sodium, aluminum silicate, synthetic aluminum silicate, hydroxypropyl starch, crystalline cellulose, calcium silicate, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, cinnamon powder, crystalline cellulose, crystalline cellulose Carmellose sodium, microcrystalline cellulose, pearl millet, synthetic aluminum silicate, synthetic hydrotalcite,
  • disintegrant in the present invention examples include adipic acid, alginic acid, sodium alginate, pregelatinized starch, erythritol, fructose, sodium carboxymethyl starch, carmellose, carmellose calcium, carmellose sodium, hydrous silicon dioxide, agar, xylitol, guar gum , Calcium citrate, croscarmellose sodium, crospovidone, synthetic aluminum silicate, low-substituted hydroxypropyl cellulose, crystalline cellulose, crystalline cellulose carmellose sodium, wheat starch, rice starch, cellulose acetate phthalate, dioctyl sodium sulfo Succinate, sucrose fatty acid ester, magnesium magnesium hydroxide, calcium stearate, polyoxyl stearate, sesquiolein Sorbitan, gelatin, shellac, sorbitol, sorbitan fatty acid ester, talc, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate,
  • binder in the present invention examples include, for example, ethyl acrylate / methyl methacrylate copolymer emulsion, acetylglycerin fatty acid ester, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, aminoethylsulfonic acid, candy (powder).
  • Coating agents include hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, starch paste, pregelatinized starch, polyvinyl pyrrolidone, gum arabic, sugar syrup, sodium carboxymethylcellulose, pullulan, polyvinyl alcohol, polyethylene glycol, ethylcellulose, acrylic copolymer Examples include coalescence, hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate, carboxymethylethylcellulose, cellulose acetate, hydroxypropylmethylcellulose acetate succinate, shellac, and silicone resin.
  • Surfactants include sodium lauryl sulfate, lauric acid diethanolamide, sucrose fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, polyethylene glycol fatty acid ester, stearyl alcohol, cetanol, polyoxyethylene polyoxypropylene glycol, polysorbate, polyoxy Examples include ethylene hydrogenated castor oil and phospholipid.
  • the spherical amorphous magnesium aluminate of the present invention can be used as a core particle for producing a granule (granulated particle, fine particle) composition. It is suitable for a controlled-release preparation for gastrointestinal absorption such as bitterness masking for oral disintegrating tablets, sustained release and rapid release.
  • This granular composition consists of an active ingredient layer centering on the spherical amorphous magnesium aluminate of the present invention. If necessary, a coating layer can be formed outside the active ingredient layer.
  • the granular composition comprises 0.01 to 500 parts by weight, preferably 0.1 to 200 parts by weight of the active ingredient per 100 parts by weight of spherical amorphous magnesium aluminate silicate.
  • the active ingredient may be supported on an excipient and granulated with a binder.
  • the blending amount of the coating component is 0.01 to 100 parts by weight with respect to 100 parts by weight of spherical amorphous magnesium aluminate silicate.
  • a binder, a coating agent, an excipient and the like can be blended in the active ingredient layer and / or the coating layer.
  • a water-soluble substance, a plasticizer, a stabilizer, a colorant, a surfactant, a fluidizing agent, etc. for adjusting the dissolution rate may be added as necessary.
  • the active ingredient is not particularly limited, and drugs for central nerves such as agents for peripheral nerves, antipyretic analgesic / anti-inflammatory agents, hypnotic sedatives, and agents for peripheral nerves; drugs for peripheral nerves such as skeletal muscle relaxants and autonomic nerve agents; Cardiovascular agents such as cardiotonic agents, arrhythmic agents, diuretics, vasodilators; respiratory organ agents such as bronchodilators and antitussives; gastrointestinal agents such as digestives, intestines, antacids; hormones, antihistamines, vitamins Metabolic drugs such as drugs; anti-ulcer agents; antibiotics; chemotherapeutic agents; herbal extracts;
  • Examples include active ingredients for cold medicine and active ingredients for rhinitis.
  • active ingredient for cold medicine include antipyretic analgesic / anti-inflammatory agents, bronchodilators, antihistamines, antitussives, antiseptics, antiseptic antiseptics, vitamins, and herbal medicine extracts.
  • active ingredient for rhinitis include sympathomimetic agents, parasympathetic nerve blockers, antiallergic agents and antiinflammatory agents, and the like.
  • Antipyretic analgesic and anti-inflammatory agents include, for example, pranlukast hydrate, acetaminophen, phenacetin, levetamine hydrochloride and other aniline derivatives, etenzamide, sazapyrine, methyl salicylate, phenyl salicylate, sodium salicylate, choline salicylate, aspirin, aspirin aluminum Salicylic acid derivatives, etc., pyrazolo derivatives such as isopropylantipyrine, sulpyrine, phenylbutazone, ketophenylbutazone, antipyrine, aminopyridine, propionic acid derivatives such as ibuprofen, ketoprofen, oxacyprozin, naproxen, fenoprofen calcium, thiaprofenic acid, etc.
  • bronchodilators examples include ephedrine hydrochloride, dl-methyl ephedrine hydrochloride, dl-methyl ephedrine hydrochloride saccharinate, isoprenaline hydrochloride, isoproterenol sulfate, methoxyphenamine hydrochloride, orciprenaline sulfate, chlorprenalin hydrochloride, trimethoxy hydrochloride Ol, salbutamol sulfate, terbutaline sulfate, hexoprenaline sulfate, formoterol fumarate, fenoterol hydrobromide, procaterol hydrochloride, pluterol hydrochloride, clenpterol hydrochloride, mabuterol hydrochloride, aminophylline, theophylline, dibrophyrin, proxyphylline, xanthine derivatives, odor And anticholinergic agents such as flutropium
  • Antihistamines include, for example, ethanolamine antihistamines such as diphenhydramine, propylamine antihistamines such as dl-chlorpheniramine maleate and chlorpheniramine maleate, alimemazine tartrate, isothipentyl hydrochloride, promethazine hydrochloride, and phenothiazine hydrochloride.
  • Examples include antihistamines, diphenylpyralin, carbinoxamine maleate, clemastine fumarate, iproheptin hydrochloride, homochlorcyclidine hydrochloride, cyproheptadine hydrochloride, dimethindene maleate, triprolidine hydrochloride, olopatadine hydrochloride, and the like.
  • Antitussives include, for example, codeines such as codeine phosphate, dihydrocodeine phosphate, dextromethorphan hydrobromide, cloperastine, noscapine dimethylmorphane, oxerazine, pentoxyberine citrate, eprazinone hydrochloride, clobutinol hydrochloride, citric acid
  • codeines such as codeine phosphate, dihydrocodeine phosphate, dextromethorphan hydrobromide, cloperastine, noscapine dimethylmorphane, oxerazine, pentoxyberine citrate, eprazinone hydrochloride, clobutinol hydrochloride, citric acid
  • codeines such as codeine phosphate, dihydrocodeine phosphate, dextromethorphan hydrobromide, cloperastine, noscapine dimethylmorphane, oxerazine, pentoxyberine citrate, eprazinone hydro
  • Examples of the desalting agent include potassium guaiacol sulfonate, carbocysteine, cysteine derivatives such as L-ethylcysteine hydrochloride, L-methylcysteine hydrochloride, acetylcysteine, bromhexine, ambroxol hydrochloride, and the like.
  • Examples of antitussive removers include guaifenesin, tipipedin, oxymethebanol, aroclamide hydrochloride, carbetapentane phenate, trimethquinol hydrochloride, methoxyphenamine hydrochloride, and the like.
  • the medicinal component exemplified as the antitussive agent, antifouling agent, and antitussive exfoliating agent may sometimes exhibit an antitussive action and / or an antifouling action.
  • Examples of psychotropic drugs include chlorpromazine and reserpine.
  • Examples of the anxiolytic drug include tofisopam, zolpidem tartrate, alprazolam, chlordiazepoxide, diazepam and the like.
  • Examples of the antidepressant include tricyclic drugs such as isipran, tetracyclic drugs such as maprotiline hydrochloride, SSRI (selective serotonin reuptake inhibitor) such as sertraline hydrochloride, and SNRI (serotonin noradrenaline such as milnacipran hydrochloride). Reuptake inhibitors).
  • Examples of the hypnotic sedative include estazolam, nitrazepam, diazepam, perlapine, phenobarbital sodium and the like.
  • Examples of antispasmodic agents include scopolamine hydrobromide, papaverine hydrochloride, diphenhydramine hydrochloride, and the like.
  • Examples of central nervous system drugs include citicoline.
  • Examples of the antiepileptic agent include phenytoin and carbamazepine.
  • Examples of the sympathomimetic agent include isoproterenol hydrochloride.
  • Examples of peripheral neuropathy agents include epalrestat and mecobalamin.
  • Gastrointestinal drugs include, for example, healthy gastrointestinals such as diastase, sugar-containing pepsin, funnel extract, cellulase AP3, lipase AP, and cinnamon oil, and intestinals such as berberine chloride, resistant lactic acid bacteria and bifidobacteria.
  • the antacid include magnesium carbonate, sodium hydrogen carbonate, synthetic hydrotalcite, precipitated calcium carbonate, magnesium oxide and the like.
  • the anti-ulcer agent include teprenone, famotidine, lansoprazole, omeprazole, rabeprazole, cimetidine, ranitidine hydrochloride and the like.
  • antihypertensive agents examples include carvedilol, olmesartan medoxomil, benidipine hydrochloride, telmisartan, amlodipine besylate, delapril, captopril, hydralazine hydrochloride, labetalol hydrochloride, manidipine hydrochloride, candesartan cilexetil, methyldopa, perindopril erbumine, etc. It is done.
  • the vasoconstrictor examples include phenylephrine hydrochloride.
  • vasodilator examples include nicorandil, carbochromene hydrochloride, molsidomine, perapamil hydrochloride, cinnarizine and the like.
  • arrhythmic agent examples include procainamide hydrochloride, propranolol hydrochloride, pindolol and the like.
  • cardiotonic agent examples include caffeine and digoxin.
  • diuretic examples include isosorbide, furosemide, hydrochlorothiazide and the like.
  • hyperlipidemia agents examples include ethyl icosapentate, cerivastatin sodium, simvastatin, pravastatin sodium, pitavastatin calcium, atorvastatin calcium hydrate, and the like.
  • Antibiotics include, for example, vancomycin hydrochloride, cefdinir, itraconazole, clarithromycin, cefcapene pivoxil hydrochloride, cephalexin, cefaclor, amoxicillin, pipmecillin hydrochloride, cefotium hexetyl hydrochloride, cefadroxyl, cefixime, cefditren pivoxil, cefterampyrix And cephem compounds such as cefpodoximiproxetil, synthetic antibacterial agents such as ampicillin, cyclacin, nalidixic acid, levofloxacin, enoxacin, monobactams such as carmonam sodium, penems and carbapenems.
  • the chemotherapeutic agent include sulfamethizole.
  • Examples of the agent for diabetes include tolbutamide, voglibose, pioglitazone hydrochloride, glibenclamide, troglidazone and the like.
  • Examples of antispasmodic agents include meclizine hydrochloride and dimenhydrinate.
  • Antirheumatic drugs include methotrexate, bucillamine and the like.
  • Examples of hormone agents include liothyronine sodium, dexamethasone sodium phosphate, prednisolone, oxendron, leuprorelin acetate, and the like.
  • Alkaloid narcotics include opium, morphine hydrochloride, throne, oxycodone hydrochloride, opium alkaloid hydrochloride, cocaine hydrochloride, and the like.
  • sulfa drugs include sulfisomidine and sulfamethizole.
  • anti-gout drugs include allopurinol and colchicine.
  • blood coagulation inhibitor include dicumarol.
  • Examples of the antineoplastic agent include 5-fluorouracil, uracil, mitomycin, manidipine hydrochloride, voglibose, candesartan cilexetil, pioglitazone hydrochloride and the like.
  • active ingredients include, for example, tamsulosin hydrochloride, donepezil hydrochloride, oseltamivir, limaprost alphadex, loxoprofen sodium, sarpogrelate hydrochloride, ursodeoxycholic acid, alacepril, brotizolam, berberine hydrochloride or tannate, loperamide hydrochloride, ebastine, etc. Is mentioned.
  • Nutritional ingredients include proteins, carbohydrates, lipids, vitamins, minerals and other beneficial ingredients.
  • vitamins include carotenoids such as astaxanthin, vitamin A, ⁇ -carotene, lutein, zeaxanthin, fursultiamine, fursultiamine hydrochloride, prosultiamine, octothiamine, thiamine disulfide, bisbutyamine, bisbuthiamine Vitamin B1 such as bisibutiamine, benfotiamine, cetotiamine hydrochloride or a derivative thereof or a salt thereof, riboflavin, sodium riboflavin phosphate, sodium flavin adenine dinucleotide, a riboflavin vitamin B2 or a derivative thereof, or a salt thereof, Vitamin C derivatives such as ascorbic acid, ascorbic acid glucoside, L-ascorbyl palmitate, L-ascorbic acid phosphate, tocopherol, tocopherol acetate, co Click tocop
  • adenylic acid derivatives such as adenosine triphosphate, adenosine monophosphate and their salts, ribonucleic acid and its salts, guanine, xanthine and their derivatives and their derivatives.
  • Nucleic acid-related substances such as salt; Serum deproteinized extract, spleen extract, placenta extract, chicken crown extract, royal jelly extract, etc .; yeast extract, lactic acid bacteria extract, bifidobacteria extract, ganoderma extract Extracts from microorganisms such as foods; extracts from plants such as carrot extract, assembly extract, rosemary extract, buckwheat extract, garlic extract, hinokitiol, cephalanthin; ⁇ - or ⁇ -linolenic acid, Eicosapentaenoic acid and their derivatives, succinic acid and its derivatives and their salts, estradiol And derivatives thereof, and salts thereof, glycolic acid, lactic acid, malic acid, citric acid, salicylic acid and other ⁇ -hydroxy acids and derivatives thereof and salts thereof, glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid, phenylbutazone, indomethaci
  • the production of the granular composition using the spherical amorphous magnesium aluminate silicate of the present invention is carried out by using the spherical amorphous magnesium aluminate silicate of the present invention as a nucleating agent, fluidized bed granulation, stirring granulation, rolling layer. It can carry out by well-known wet granulation methods, such as granulation, spray-drying granulation, and extrusion granulation, These conditions can be performed by a conventional method.
  • the binder-containing solution is continuously sprayed, and at the same time, an active ingredient and, if necessary, an excipient. Is supplied, and the powder is coated on spherical amorphous magnesium aluminate silicate and dried to form granules.
  • a solution in which the drug is dissolved or suspended in a binder-containing solution is sprayed, and the drug is applied to spherical amorphous magnesium aluminate silicate.
  • the powder containing is coated and dried to form granules. Subsequently, the coating solution or coating suspension is sprayed while the granules are flowing, and dried to form a film layer for the purpose of moisture proofing, bitterness masking, enteric properties, sustained release, sustainability, etc. Granules. Further, when the powder containing the drug is coated, a coating-containing solution or a coating suspension may be sprayed simultaneously. The order of granulation can be appropriately selected according to the type of drug.
  • the solvent of the above solution may be any pharmaceutically acceptable solvent without affecting these physical properties, and examples thereof include water, ethanol, methanol and the like.
  • the coating agent known excipients and the aforementioned coating agents can be used.
  • the spraying speed can be increased in the granulation process than the conventional organic nucleating agent, and the time required for the layer formation process Can be shortened.
  • the conditions vary depending on the granulator and the like, for example, in the case where an effect component is placed, the time can be shortened by 30 to 80%.
  • the layering can be completed in 10 to 20 hours. If it is light, the number of particles that are not sprayed by the wind is increased. However, since it is heavy, it is easy to apply the spray evenly with little wind.
  • the surface of the spherical amorphous magnesium aluminate of the present invention is a hydroxyl group and is not easily charged. It has better granulation operability than conventional carbohydrate-based organic nucleating agents.
  • the pharmaceutical preparation of the present invention can be in the form of a solid dosage form such as a tablet, a rapidly disintegrating tablet in the oral cavity, a capsule, a granule or a fine granule, or a liquid preparation of a suspension.
  • a solid dosage form such as a tablet, a rapidly disintegrating tablet in the oral cavity, a capsule, a granule or a fine granule, or a liquid preparation of a suspension.
  • the coating for releasability and bitterness masking can be listed uniformly, it is suitable for sustained release agents and oral rapid disintegrating agents that require release control.
  • the tablet is produced by mixing the granular composition of the present invention or the spherical amorphous magnesium aluminate silicate of the present invention with an additive component that can be blended with a pharmaceutical product by a method such as dry mixing or wet mixing, and then compression molding. .
  • a disintegrant such as F-MELT (trademark, manufactured by Fuji Chemical Industry Co., Ltd.), crospovidone, low-substituted hydroxypropylcellulose, sodium carboxymethyl starch, croscarmellose sodium, starch, etc. It can be a fast disintegrant.
  • the additive components that can be incorporated into the pharmaceutical preparation of the present invention include lubricants (sucrose fatty acid ester, magnesium stearate, talc , Sodium stearyl fumarate, etc.), acidulants (eg, citric acid, tartaric acid, malic acid, ascorbic acid, etc.), foaming agents (eg, sodium bicarbonate, sodium carbonate, etc.), sweeteners (sodium saccharin, dipotassium glycyrrhizin, aspartame, stevia) , Thaumatin etc.), fragrance (eg lemon oil, orange oil, menthol etc.), colorant (eg edible red No.
  • lubricants sucrose fatty acid ester, magnesium stearate, talc , Sodium stearyl fumarate, etc.
  • acidulants eg, citric acid, tartaric acid, malic acid, ascorbic acid, etc.
  • foaming agents eg, sodium bicarbonate, sodium carbon
  • the granule composition of the present invention and the pharmaceutical composition of the present invention can be used for foods, cosmetics, agricultural chemicals and the like in addition to pharmaceuticals. In particular, it is suitable for controlling the absorbability of functional food in the body.
  • spherical amorphous magnesium aluminate silicate of the present invention include high particle strength, sphericity, and high specific surface area, so column chromatography packing materials, various packing materials, various adsorption carriers, It can be used as a deodorant, a catalyst, a tooth abrasive, a release agent such as a film, a paint adhesion preventive or a matting material.
  • the average particle size of the dry powder was measured with a dry particle size distribution analyzer (LA-920, manufactured by Horiba, Ltd.).
  • a dry particle size distribution analyzer LA-920, manufactured by Horiba, Ltd.
  • the specific surface area was measured using a BET specific surface area measuring device (Monosorb MS-17, manufactured by Yuasa Ionics Co., Ltd.).
  • Water absorption was performed using linseed oil based on JISK5101.
  • Water absorption The amount of water absorption was based on JISK5101, using water instead of linseed oil.
  • Example 1 A suspension of 7.5 kg of amorphous magnesium aluminate silicate (also known as: magnesium aluminate metasilicate, trade name “Neusilin NFL2N”, neutral product, manufactured by Fuji Chemical Industry Co., Ltd.) in 50 L of water with a flow rate of 7 L / min. Then, using an optimizer pulverizer [Starburst Large Machine HJP-25080, manufactured by Sugino Machine Co., Ltd.], the powder was pulverized five times under the condition of a pressure of 245 MPa. The particle size distribution of the slurry after pulverization was 2.9 ⁇ m in terms of average particle size.
  • amorphous magnesium aluminate silicate also known as: magnesium aluminate metasilicate, trade name “Neusilin NFL2N”, neutral product, manufactured by Fuji Chemical Industry Co., Ltd.
  • an optimizer pulverizer Starburst Large Machine HJP-25080, manufactured by Sugino Machine Co., Ltd.
  • this pulverized liquid was prepared to a concentration of 11.6 w / w% and spray-dried using a centrifugal atomizer under the conditions of a rotational speed of 9000 rpm, a heat input temperature of 330 ° C., and an outlet temperature of 160 ° C., and spherical amorphous alumina silicate Magnesium acid was obtained.
  • FIG. 1 shows an SEM photograph
  • FIG. 7 shows an X-RD chart.
  • Example 2 Water is added to 80.4 g of sodium aluminate (Al 2 O 3 : 18.7%) to make a total volume of 500 ml. Water is added to 124.8 g of No. 3 sodium silicate (SiO 2 : 29.5%) to make a total amount of 250 ml. Magnesium chloride hexahydrate (MgO: 19.8%) 41.7 g and aluminum sulfate (Al 2 O 3 : 17.2%) 34.0 g are dissolved in water to make a total amount of 250 ml. Liquid A was placed in the reaction vessel, and liquid B was added at a rate of 10 ml / min with stirring. C solution was then added at approximately 25 ml / min.
  • the mixture was aged for 30 minutes, and then the product was filtered and washed with water.
  • the concentration was adjusted to 19 w / w%, and the mixture was pulverized 5 times under the conditions of a flow rate of 7 L / min and a pressure of 245 MPa using an optimizer pulverizer [Starburst Large Machine HJP-25080, manufactured by Sugino Machine Co., Ltd.].
  • the particle size distribution of the slurry after pulverization was 2.0 ⁇ m in terms of average particle size.
  • this pulverized liquid was prepared to a concentration of 14.9 w / w%, and spray-dried using a centrifugal atomizer under the conditions of a rotation speed of 9000 rpm, a heat input temperature of 330 ° C., and an outlet temperature of 160 ° C., and spherical amorphous alumina silicate Magnesium acid was obtained.
  • FIG. 2 shows an SEM photograph.
  • Example 2 Filtration, water washing, concentration adjustment (19 w / w%) suspension (average particle diameter 14.7 ⁇ m) obtained in Example 2 was rotated at 9000 rpm, heat input temperature 330 ° C., outlet temperature using a centrifugal atomizer. Spray drying was performed at 160 ° C. to obtain spherical amorphous magnesium aluminate silicate.
  • FIG. 4 shows an SEM photograph.
  • the spherical amorphous magnesium aluminate silicate of the present invention has high particle strength, sphericity, low specific volume, and exhibits characteristics not found in conventional spherical amorphous magnesium aluminate silicate. SEM photographs show that the spherical amorphous magnesium aluminate silicate of the present invention has finer particles densely aggregated.
  • Example 3 Manufacture of granules 100 g of spherical amorphous magnesium aluminate silicate of Example 1 was charged into a fluidized granulator / dryer (Freund Sangyo Co., Ltd., Flow Coater Mini FL), and hydroxypropylcellulose 8 367 g of purified water containing 3 g and 41.7 g of ground acetaminophen (200 mesh sieve product) was sprayed at a spraying speed of 1 to 4 g / min to obtain coated granules. The average particle size was 142 ⁇ m.
  • FIG. 5 shows an SEM photograph. A layer of hydroxypropyl cellulose and acetaminophen is uniformly wrapped around the spherical amorphous magnesium aluminate silicate of the present invention to form beautiful granules.
  • Example 3 Manufacture of granules 500 g of spherical amorphous magnesium aluminate silicate of Example 1 was charged into a fluidized granulation dryer (manufactured by Paulex, Multiplex MP-01 type SPC), and 100 g of hydroxypropylcellulose and pulverized 4400 g of purified water containing 500 g of acetaminophen (200 mesh sieve product) was sprayed at a spray rate of 2.2 to 9.6 g / min for 16 hours to obtain coated granules.
  • FIG. 7 shows an SEM photograph
  • FIG. 9 shows the relationship between the spray speed and the spray time.
  • the spherical amorphous magnesium aluminate of the present invention has a finer spherical shape than the nucleating agent made of crystalline cellulose, has a high spray rate, and greatly takes the time required for coating. It can be seen that it has been shortened.
  • Example 5 Manufacture of tablets 300 g of the granules of Example 3 were mixed with 200 g of excipient F-MELT [trademark, manufactured by Fuji Chemical Industry Co., Ltd.] for oral rapid disintegrant, 5 g of magnesium stearate, and 5 g of aspartame.
  • excipient F-MELT trademark, manufactured by Fuji Chemical Industry Co., Ltd.
  • a rotary tableting machine HT-AP18SS-II, manufactured by Hata Iron Works Co., Ltd.
  • a tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was tableted with a set hardness of 50 N to obtain an orally rapidly disintegrating tablet. It was possible to tablet well without capping or peeling.
  • the disintegration time in the pharmacopoeia disintegration test was 16 seconds. The bitterness of acetaminophen was not felt.

Abstract

Cette invention concerne une particule sphérique à cœur granulaire qui peut être utilisée à titre d'agent de nucléation pour la production de granules destinés à être utilisés dans des médicaments, des cosmétiques, des aliments et autres. La particule selon l'invention a une résistance mécanique élevée, une aptitude à absorber l'eau élevée et une sphéricité élevée, est insoluble dans l'eau, et a une bonne aptitude au moulage. Le méthaluminosilicate de magnésium non cristallin est pulvérisé et lyophilisé, pour obtenir un aluminosilicate de magnésium non cristallin sphérique ayant une résistance mécanique de particule et une sphéricité améliorées tout en conservant de bonnes propriétés d'aluminosilicate de magnésium non cristallin pouvant être utilisé à titre d'excipient (aptitude à absorber l'huile, aptitude à absorber l'eau, aire spécifique élevée, et propriétés antiacides).
PCT/JP2009/002972 2008-06-27 2009-06-26 Aluminosilicate de magnésium non cristallin sphérique WO2009157214A1 (fr)

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JP2011184328A (ja) * 2010-03-05 2011-09-22 Fuji Silysia Chemical Ltd 医薬品又は食品用の粉体圧縮成形物、及びその製造方法
JP2012025711A (ja) * 2010-07-27 2012-02-09 Ohara Yakuhin Kogyo Kk 生理活性物質含有粒子の製造方法
WO2012091040A1 (fr) * 2010-12-27 2012-07-05 富田製薬株式会社 Particule nucléaire de type à désagrégation pour formulation pharmaceutique
JP2013056791A (ja) * 2011-09-07 2013-03-28 Fuji Kagaku Kk 非晶質ケイ酸アルミニウムナトリウム及びその製造方法
JP2013241451A (ja) * 2013-08-05 2013-12-05 Ohara Yakuhin Kogyo Kk 生理活性物質含有粒子の製造方法
JP2015048352A (ja) * 2014-01-08 2015-03-16 旭化成ケミカルズ株式会社 セルロース系核粒子及びその製造方法
WO2017204142A1 (fr) * 2016-05-23 2017-11-30 沢井製薬株式会社 Comprimé orodispersible comprenant un olmésartan médoxomil
JPWO2018087870A1 (ja) * 2016-11-10 2019-09-26 日本たばこ産業株式会社 球状の粉末凝集体及びその製造方法
JPWO2020071539A1 (ja) * 2018-10-05 2021-09-02 富士化学工業株式会社 多孔性シリカ粒子組成物
CN114149011A (zh) * 2020-09-08 2022-03-08 浙江丰虹新材料股份有限公司 一种药用辅料硅酸铝镁及其合成方法

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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011184328A (ja) * 2010-03-05 2011-09-22 Fuji Silysia Chemical Ltd 医薬品又は食品用の粉体圧縮成形物、及びその製造方法
JP2012025711A (ja) * 2010-07-27 2012-02-09 Ohara Yakuhin Kogyo Kk 生理活性物質含有粒子の製造方法
JP5578534B2 (ja) * 2010-12-27 2014-08-27 富田製薬株式会社 製剤用崩壊型核粒子
WO2012091040A1 (fr) * 2010-12-27 2012-07-05 富田製薬株式会社 Particule nucléaire de type à désagrégation pour formulation pharmaceutique
JP2014169318A (ja) * 2010-12-27 2014-09-18 Tomita Pharmaceutical Co Ltd 製剤用崩壊型核粒子
JP2013056791A (ja) * 2011-09-07 2013-03-28 Fuji Kagaku Kk 非晶質ケイ酸アルミニウムナトリウム及びその製造方法
JP2013241451A (ja) * 2013-08-05 2013-12-05 Ohara Yakuhin Kogyo Kk 生理活性物質含有粒子の製造方法
JP2015048352A (ja) * 2014-01-08 2015-03-16 旭化成ケミカルズ株式会社 セルロース系核粒子及びその製造方法
WO2017204142A1 (fr) * 2016-05-23 2017-11-30 沢井製薬株式会社 Comprimé orodispersible comprenant un olmésartan médoxomil
JPWO2018087870A1 (ja) * 2016-11-10 2019-09-26 日本たばこ産業株式会社 球状の粉末凝集体及びその製造方法
JPWO2020071539A1 (ja) * 2018-10-05 2021-09-02 富士化学工業株式会社 多孔性シリカ粒子組成物
JP7124107B2 (ja) 2018-10-05 2022-08-23 富士化学工業株式会社 多孔性シリカ粒子組成物
JP7471675B2 (ja) 2018-10-05 2024-04-22 富士化学工業株式会社 多孔性シリカ粒子組成物
CN114149011A (zh) * 2020-09-08 2022-03-08 浙江丰虹新材料股份有限公司 一种药用辅料硅酸铝镁及其合成方法

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