JP5249568B2 - Molding powder, compression molding composition using the same, and method for producing molding powder - Google Patents

Description

  The present invention provides a molding powder useful in the chemical industry field, particularly in the pharmaceutical and food fields, which suppresses oozing of a liquid active ingredient particularly during compression molding and has good storage stability after compression molding, and The present invention relates to a compression-molding composition using the above and a method for producing molding powder.

Many molding powders and compositions containing liquid active ingredients are known.
For example, Patent Document 1 describes a tablet obtained by compressing a low melting point oily substance after adsorbing 30% by mass or more of calcium silicate with respect to the low melting point oily substance. In Example 1, there is a description of a granulated product adsorbed with 47.6% by mass of tocopherol acetate, 47.6% by mass of fluorite R, and 4.8% by mass of methylcellulose. Tablet in which 100 parts of granules, 90 parts of spray-dried lactose and 10 parts of talc are mixed (tocopherol acetate / florite R / methylcellulose / spray-dried lactose / talc = 23.8 / 23.8 / 2.4 / 45/5) Describes that there is no occurrence of crushing to the turntable, crushing to the punch, or capping tableting.

  Patent Document 2 discloses water obtained by spray-drying a mixture comprising vitamin E, low-substituted hydroxypropylcellulose or crystalline cellulose / carboxymethylcellulose sodium, a pluronic-type or tween-type surfactant and silicic anhydride. A dispersible vitamin E-containing powder is described. In Experimental Example 2, spray-dried granules that can be interpreted as a composition of vitamin E / aerosil (light anhydrous silicic acid) / tween 20 = 41.6 / 55.6 / 2.8 are described.

  Furthermore, Patent Document 3 discloses a solid preparation of an oily liquid substance comprising a step of adding an emulsifier and water to an oily liquid substance to form an oil-in-water emulsion, and a step of adsorbing the emulsifier to an adsorbent granular material. The manufacturing method of is described. In Example 2, a mixed dry product of tocopherol acetate / gum arabic powder / colloidal anhydrous silicic acid / sodium carboxymethylcellulose = 32.8 / 32.8 / 32.8 / 1.6 is described. .

  In Patent Document 4, a physiologically active substance that is sparingly soluble in water and a nonionic surfactant and / or an anionic surfactant are mixed and then supported on a water-swellable polymer compound and then granulated. A method for producing a solid formulation is described. In this patent document, a water-swellable polymer compound is used to support a physiologically active ingredient.

  Furthermore, Patent Document 5 is suitable for a direct compression tableting method by spray drying in which a spray body of a substance to be spray-dried is brought into contact with a powder spray body of an ultrafine absorbent during drying in a spray drying chamber. There is a description of a method for producing free-flowing, high-density agglomerated powder.

  Patent Document 6 discloses that an aqueous emulsion containing vitamin E active compound and hydrolyzed gelatin is spray-dried to obtain 40 to about 60% by mass of the vitamin active compound and about 60 to 60 hydrolyzed gelatin. A method for producing vitamin E powder containing about 40% by weight is described.

  Further, Patent Document 7 describes a method for solidifying an oily substance in which an oily substance is emulsified using a surfactant and water, and the oily substance emulsion and adsorbent are mixed and then dried. In addition, the examples include soybean oil unsaponifiable matter / light anhydrous silicic acid / emulsifier (polyoxyl stearate, sodium lauryl sulfate) /others=59.2/35.5/3.5/1.8 soybean oil. Unsaponifiable solids are described.

  Patent Document 8 describes a method for producing an oily drug-containing composition in which an oily drug is emulsified in water with a water-soluble polymer substance or a surfactant and then adsorbed to a powder to be solidified.

  Furthermore, Patent Document 9 discloses that an oily substance such as clofibrate, geraniol, and gefurnate is emulsified using an aqueous solution containing a water-soluble polymer substance such as gelatin and methylcellulose, and the oily substance emulsion and the water-soluble polymer are emulsified. A method for solidifying an oily substance is described, in which a larger amount of starch, Avicel, or other excipient than the substance is mixed, granulated by a wet granulation method other than spray drying, and then dried.

  Patent Document 10 describes a method for producing an oily substance-containing granular material in which an oily substance is emulsified in a water-soluble polymer aqueous solution, and the resulting emulsion is sprayed on an additive to perform adsorption and granulation. Has been.

  Further, Patent Document 11 describes a fluid powder containing at least one selected from the group consisting of a fat-soluble drug, gelatin and casein, and an adsorbent.

  Patent Document 12 sprays a mixture of vitamin E nicotinate, low-substituted hydroxypropylcellulose or crystalline cellulose / sodium carboxymethylcellulose, pluronic-type or tween-type surfactant, silicic anhydride, and medium-chain fatty acid triglyceride. A water-dispersible vitamin E nicotinate-containing powder obtained by drying is described. Further, Comparative Example 1 describes spray-dried granules of vitamin E nicotinate / aerosil (light anhydrous silicic acid) / pluronic F28 / L-HPC = 31.3 / 31.3 / 6.1 / 31.3. ing.

Japanese Patent No. 2626975 Japanese Patent No. 2506812 JP 52-66615 A JP 2001-335469 A Japanese Patent Publication No.54-18331 Japanese Patent Publication No.49-46900 JP 58-213073 A JP 2001-316248 A Japanese Patent Publication No.55-30411 JP-A-8-157362 JP 2000-44462 A Japanese Patent No. 2643246

  In recent years, it has been desired to realize a molding powder in which a larger amount of a liquid active ingredient is blended to improve its performance. However, according to the knowledge of the present inventors, when the blending amount of the liquid active ingredient is increased, the liquid active ingredient oozes out when the molding powder is tableted to produce a molded product. Lamination breakage tends to occur, and it is difficult to maintain the required tablet hardness, and the tablet hardness decreases during long-term storage, resulting in deterioration of storage stability. Turned out to cause problems.

  For example, adsorbed granules of tocopherol acetate (tocopherol acetate / florite / methylcellulose = 47.6 / 47.6 / 4.8) described in Example 1 of Patent Document 1 and 30% by mass of spray-dried lactose Even when a cylindrical molded body having a diameter of 0.8 cm is produced by compression molding the mixture of 10 at a compression pressure of 10 kN, the liquid active ingredient is often oozed out, lamination breakage occurs, and the tablet hardness during storage is reduced. It was big.

  Further, even when a mixture of 70% by mass of spray-dried granules and 30% by mass of spray-dried lactose described in Example 2 of Patent Document 2 is compression-molded at a compression pressure of 10 kN, a cylindrical molded body having a diameter of 0.8 cm is produced. The liquid active ingredient oozes out, the lamination breaks, and the tablet hardness during storage is greatly reduced. Furthermore, in this patent document 2, although the spray-drying method is essential, since spray-drying has high equipment cost, there also existed a fault of causing the fall of productivity and economical efficiency.

  Furthermore, even if a mixture of 70% by mass of the dry blended product described in Example 2 of Patent Document 3 and 30% by mass of spray-dried lactose is compression molded at a compression pressure of 10 kN, a cylindrical molded body having a diameter of 0.8 cm is produced. The liquid active ingredient oozes out so much that lamination destruction cannot be suppressed. In Example 2 of Patent Document 3, a tablet containing 20% by mass of tocopherol acetate obtained by tableting a blended dried product with granular lactose and magnesium stearate is described. Tocopherol acetate at the time of tableting is described. Since there was much ooze out, tablet hardness was greatly reduced during storage.

  In Example 2 of Patent Document 4, a tablet containing 18.1% by mass of tocopherol acetate and vitamin A as liquid active ingredients is described. However, crosslinked polyvinylpyrrolidone, carmellose calcium, hydroxypropyl starch, low Substitution degree hydroxypropyl cellulose, corn starch, crystalline cellulose, partially pregelatinized starch, carmellose, croscarmellose or a salt thereof has an α-tocopherol supporting capacity of less than 190%, and is used for molding as described in Example 2 of Patent Document 4 Even when a mixture of 70% by weight of powder and 30% by weight of spray-dried lactose is compression-molded at a compression pressure of 10 kN to produce a cylindrical molded body with a diameter of 0.8 cm, liquid active ingredient oozes out and lamination destruction is suppressed. I couldn't. In addition, the obtained tablets had a large amount of liquid active ingredient oozing, and the initial tablet hardness was about 2.4 kg, which was not practical. Furthermore, the tablet of Patent Document 4 is difficult in the first place to contain a large amount of the liquid active ingredient.

  Furthermore, in Example 1 of Patent Document 5, a chewable tablet containing 29.7% by mass of tocopherol acetate is described, but 30% of silicic acid or silicate having an α-tocopherol carrying capacity of 190% or more is described. Even if a mixture of 70% by mass of the molding powder described in Example 1 and 30% by mass of spray-dried lactose is compression-molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, There was much oozing out of the liquid active ingredient, and lamination destruction could not be suppressed. In addition, the tablets obtained had a large decrease in tablet hardness during long-term storage. Further, in Patent Document 5, the spray drying method is essential, but since the spray drying has a high equipment cost, there is also a disadvantage that the productivity and the economic efficiency are lowered.

  Moreover, in patent document 6, the gelatin content which is an emulsifier exceeds 10%, the liquid active ingredient in a tablet is less than 10%, and the mixture of the powder 70 mass% and spray-dried lactose described in an Example is 30 mass%. Even when a cylindrical molded body having a diameter of 0.8 cm was produced by compression molding at a compression pressure of 10 kN, the liquid active ingredient oozed out frequently, resulting in lamination failure, and a significant decrease in tablet hardness during storage.

  Furthermore, even if a mixture of 70% by mass of the powder described in Patent Document 7 and 30% by mass of spray-dried lactose is compression-molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, the liquid active ingredient bleeds. There was a lot of dispensing, destruction of the lamination occurred, and the tablet hardness was greatly reduced during storage.

  Further, in Patent Document 8, the adsorbent having an α-tocopherol supporting ability of 190% or more is less than 30%, and the oily drug-containing composition described in Example 3 is 70% by mass and the spray-dried lactose is 30% by mass. Even when a cylindrical molded body having a diameter of 0.8 cm is produced by compression molding the mixture of 10 at a compression pressure of 10 kN, the liquid active ingredient is often oozed out, lamination breakage occurs, and the tablet hardness during storage is reduced. It was big. Furthermore, in the oily drug-containing composition of Patent Document 8, it is difficult to blend a large amount of liquid active ingredient, and in addition, oozing out of the liquid active ingredient occurs during tableting, and hardness during storage. There is no recognition of issues regarding storage stability, such as decline.

  On the other hand, in the solidification method of the oily substance of Patent Document 9, an adsorption carrier having an α-tocopherol adsorption capacity of 190% or more is not used, and it is difficult to blend a large amount of liquid active ingredient. In the first place, there is no recognition of problems regarding storage stability, such as bleeding of liquid active ingredients during tableting and a decrease in hardness during storage. Even when a mixture of 70% by mass of the powder described in Patent Document 9 and 30% by mass of spray-dried lactose is compression-molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, the liquid active ingredient bleeds. There are many discharges, lamination destruction occurs, and the tablet hardness is greatly reduced during storage.

  Moreover, in patent document 10, it is difficult to mix | blend a liquid active ingredient in a large quantity so that the compounding quantity of the liquid active ingredient in an Example may be all 5 mass%.

  On the other hand, Patent Document 11 requires a further improvement technique in terms of increasing the content of a fat-soluble drug as much as possible in the case of making a tablet, and exuding the fat-soluble drug or irritating the tableting machine. Although there is a description that the liquid active ingredient oozes out during tableting, there is no recognition of problems regarding storage stability such as hardness reduction during storage. Even when a mixture of 70% by mass of the powder described in Patent Document 11 and 30% by mass of spray-dried lactose is compression-molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, the liquid active ingredient bleeds. There was a lot of dispensing, destruction of the lamination occurred, and the tablet hardness was greatly reduced during storage.

  In addition, the spray-dried granule described in Patent Document 12 has an adsorption carrier content of less than 30% by mass, and a mixture of 70% by mass of this spray-dried granule and 30% by mass of spray-dried lactose is compression-molded at a compression pressure of 10 kN. Even when a cylindrical molded body having a diameter of 0.8 cm is produced, the liquid active ingredient is often oozed out, resulting in destruction of the lamination, and a significant decrease in tablet hardness during storage. Furthermore, although the spray drying method is indispensable in this patent document 12, since the spray drying has a high equipment cost, there is also a drawback that the productivity and the economy are lowered.

  As described above, in the past, a molding powder having an increased amount of the liquid active ingredient has not been realized yet with practically sufficient performance. In addition, there is a need for establishment of a simpler production method that does not require a spray drying method, can carry a liquid active ingredient at a high concentration, and can suppress oozing out of the liquid active ingredient during compression molding.

  The present invention has been made in view of such circumstances, and can contain 10% by mass or more of a liquid active ingredient, and can suppress lamination breakage by suppressing oozing of the liquid active ingredient during compression molding or the like. Yes, molding powder, compression molding composition using the same, and production of molding powder capable of suppressing the decrease in hardness of the molded body over a long period of time and improving the storage stability of the molded body after compression molding It aims to provide a method.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have used a specific adsorption carrier together with the liquid active ingredient and an emulsifier when carrying a large amount of liquid active ingredient on the adsorption carrier. Surprisingly, when the bulk density is adjusted to 0.2 to 0.7 g / cm ^{3 by} , for example, applying slurging to the slug after supporting the liquid active ingredient, mechanical stress is applied to the slug. It is possible to remarkably suppress the exudation of the liquid active ingredient in the product, and to prevent lamination destruction. Presumably because the exudation of the liquid active ingredient is small during compression molding, the resulting molded product does not cause a decrease in hardness and is stable in storage. The inventors have found that it is possible to increase the value of the present invention, and have reached the present invention.

That is, the present invention is as follows.
(1) 10 to 70% by mass of a liquid active ingredient, 29 to 89% by mass of an adsorption carrier having an α-tocopherol carrying capacity of 190% or more, and 1 to 20% by mass of an emulsifier, and a bulk density of 0.2 to 0. Molding powder, 7 g / cm ³ .
(2) The molding powder as set forth in (1) above, wherein when a compact having a diameter of 0.8 cm is produced by compression molding at a compression pressure of 12 kN, the compact does not cause lamination fracture.
(3) When a mixture containing 70% by mass of molding powder and 30% by mass of spray-dried lactose is compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, the cylindrical molded body is laminated. The molding powder as set forth in (1) or (2) above, wherein
(4) A slug is formed from a granulated product containing 10 to 70% by mass of a liquid active ingredient, 29 to 89% by mass of an adsorbent carrier having an α-tocopherol carrying capacity of 190% or more, and 1 to 20% by mass of an emulsifier, Molding powder having a bulk density of 0.2 to 0.7 g / cm ³ obtained by applying mechanical stress to slug.
(5) including a powder for molding containing the liquid active ingredient according to any one of (1) to (4) above and crystalline cellulose, containing 10 to 60% by mass of the liquid active ingredient, and the crystalline cellulose A compression molding composition containing 5 to 90% by mass.
(6) A step of obtaining a granulated product comprising 10 to 70% by mass of a liquid active ingredient, 29 to 89% by mass of an adsorbent carrier having an α-tocopherol carrying capacity of 190% or more, and 1 to 20% by mass of an emulsifier. A method for producing a molding powder having a bulk density of 0.2 to 0.7 g / cm ³ , comprising a step of forming slug from the granulated product and a step of applying mechanical stress to the slug.

  According to the present invention, since the liquid active ingredient is sufficiently taken into the adsorption carrier, mechanical stress applied from the outside (for example, impact caused by a turntable rotating at high speed, impact caused by a die or a punch during compression molding, etc.) ) To prevent the liquid active ingredient from oozing out, the lamination destruction of the resulting molded article is suppressed, and as a result, the hardness reduction of the obtained molded article is suppressed and storage stability can be enhanced. Adherence of liquid active ingredients to turntables, mortars, punches, etc., and tableting troubles during compression such as sticking, capping and lamination can be suppressed. In addition, since the liquid active ingredient tends to ooze out more as the content of the liquid active ingredient increases, according to the present invention, a molding powder having a high storage stability and containing a large amount of liquid active ingredient is realized. can do. Furthermore, according to the present invention, there is an advantage that the liquid active ingredient is not easily transferred to the protective film of the compression molded body, and the storage stability can be enhanced.

  Embodiments of the present invention will be described below. In addition, this invention is not limited only to this embodiment, Unless it deviates from the summary, it can implement with a various form.

The molding powder of the present embodiment includes 10 to 70% by mass of a liquid active ingredient, 29 to 89% by mass of an adsorbent carrier having an α-tocopherol supporting ability of 190% or more, and 1 to 20% by mass of an emulsifier, and has a bulk density. 0.2 to 0.7 g / cm ³ .

  In the present specification, the liquid active ingredient means a liquid at room temperature (20 ± 15 ° C.), and is not particularly limited. For example, pharmaceutical medicinal ingredients, agricultural chemical ingredients, fertilizer ingredients, feed ingredients, Examples include food ingredients, cosmetic ingredients, pigments, fragrances, metals, ceramics, catalysts, and surfactants. Specific examples of the liquid active ingredient include, for example, d-α-tocopherol, dl-α-tocopherol, d-α-tocopherol acetate, dl-α-tocopherol acetate, dl-α-nicotinic acid tocopherol, and succinic acid-d. -Α-tocopherol, succinic acid-dl-α-tocopherol, tocopherol esters such as tocopherol palmitate, tocopherol succinate, retinol, retinol acetate, retinol palmitate, vitamin A oil, vitamin A ester such as vitamin A palmitate, DHA (Docosahexaenoic acid), EPA (eicosapentaenoic acid), higher unsaturated fatty acids such as liver oil, soybean oil, castor oil, clofibrate, geraniol, gefarnate, linoleic acid, linolenic acid, eugenol, squalane, phytonagio , Menatetrenone, phenipentol, menfenegol, creosote, teprenone, indomethacin farnesyl, praunotol, dimethylpolysiloxane, kanokoso soft extract, toki soft extract, senkyu soft extract and other herbal medicine extracts, lecithin, yolk lecithin, safflower oil, eucalyptus And oil-soluble flavorings such as vegetable oils such as oil, henopositive oil, orange oil, lemon oil, peppermint oil, and other edible fragrance oils. Vitamins include various homologues and derivatives, but are not particularly limited as long as they are liquid at room temperature. These may be used alone or in combination of two or more.

  In the present specification, an adsorption carrier (hereinafter also simply referred to as “adsorption carrier”) having an α-tocopherol carrying capacity of 190% or more refers to the amount of α-tocopherol carried (adsorption) in the measurement method described in the Examples described later. Amount) means 1.9 g or more per gram. Specific examples of this adsorption carrier include, for example, light anhydrous silicic acid, hydrous silicon dioxide, anhydrous calcium hydrogen phosphate, aluminum silicate, magnesium silicate, calcium silicate, synthetic aluminum silicate such as magnesium metasilicate aluminate, Examples thereof include porous substances such as magnesium carbonate, calcium carbonate, magnesium oxide, calcium phosphate, aluminum hydroxide, calcium citrate, synthetic resin, kaolin, and bentonite, and cellulose powder described in WO 2004/106416. Calcium silicate such as fluorite (trade name, manufactured by Tokuyama) is preferred. These may be used alone or in combination of two or more.

  In this specification, an emulsifier means what can emulsify said liquid active ingredient in water. Specific examples of this emulsifier are not particularly limited. For example, gum arabic, tragacanth gum, karaya gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, low substitution degree Hydroxypropylcellulose, pregelatinized starch, starch phosphate, sodium alginate, polyoxyl stearate, pluronic type such as Pluronic F-68, tween type such as Tween 20, 80, sodium lauryl sulfate, polyoxyethylene hydrogenated castor oil, polyoxy Ethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene poly Carboxymethyl propylene glycol, polyoxyethylene sorbitan monolaurate, polysorbate, sucrose fatty acid esters, sorbitan fatty acid esters, sorbitan mono-oleate, surfactants such as lecithin. These may be used alone or in combination of two or more.

  It is essential that the molding powder of this embodiment contains 10 to 70% by mass of the liquid active ingredient with respect to the total mass of the molding powder. As the content of the liquid active ingredient increases, the problem of oozing out of the liquid active ingredient tends to become more prominent. If the content of the liquid active ingredient is less than 10% by mass, there may be no problem due to the oozing of the liquid active ingredient from the adsorption carrier. On the other hand, when the content of the liquid active ingredient exceeds 70% by mass, the amount of the liquid active ingredient that exudes during compression increases, and it becomes difficult to obtain a storage-stable molded product. The preferable range of the content of the liquid active ingredient amount is 20 to 70% by mass, and more preferably 30 to 60% by mass.

  Moreover, it is essential that the molding powder of this embodiment contains 29 to 89% by mass of an adsorption carrier having an α-tocopherol supporting ability of 190% or more with respect to the total mass of the molding powder. When the content ratio of the adsorbent carrier is less than 30% by mass, the absolute amount of the adsorbent carrier on which the liquid active ingredient is to be supported is insufficient, and the liquid active ingredient may ooze out due to external mechanical stress. On the other hand, when the content ratio of the adsorbent carrier exceeds 90% by mass, the content of the liquid active ingredient in the compression molded product is reduced, and the effective amount required for treatment or the like cannot be blended. In some cases, the resulting molded product becomes large, which makes it difficult for children and the elderly to swallow. From these viewpoints, the preferable range of the content of the adsorption carrier is 30 to 60% by mass.

  Furthermore, the molding powder of the present embodiment needs to contain an amount of an emulsifier sufficient to cause emulsification (dispersion) of the liquid active ingredient in water, and more specifically, the total mass of the molding powder. On the other hand, it is essential to contain 1 to 20% by mass of the above emulsifier. When the content of the emulsifier is less than 1% by mass, the liquid active ingredient is not sufficiently emulsified, and the incorporation into the adsorption carrier becomes insufficient, and the pH 1.2 or 6.8 artificial gastric juice, artificial intestinal juice or Since it becomes difficult to elute the liquid active ingredient in the actual gastrointestinal fluid, it is difficult to obtain the expected medicinal effects. On the other hand, if the content of the emulsifier exceeds 20%, the emulsifier may cause problems such as obstructing the gastrointestinal mucosa, and the effective amount required for treatment due to the decrease in the content of the liquid active ingredient May cause problems such as inability to mix. From these viewpoints, the preferable range of the content of the adsorption carrier is 1 to 10% by mass.

It is essential that the molding powder of the present embodiment has a bulk density of 0.2 to 0.7 g / cm ³ . When the bulk density of the molding powder is less than 0.2 g / cm ³ , the liquid active ingredient is not sufficiently adsorbed on the adsorption carrier, and the liquid active ingredient tends to ooze out during the subsequent compression process. Storage stability tends to decrease due to the occurrence of tableting troubles such as capping, lamination, and the like, or the tablet hardness decreases with time due to the exuded liquid active ingredient.

Here, the molding powder of this embodiment has a bulk density increased so that a 0.8 cm diameter molded product obtained by compression molding the powder at a compression pressure of 12 kN does not cause lamination failure. And / or the bulk density of a 0.8 cm diameter cylindrical molded body obtained by compression molding a mixture of 70% by mass of powder and 30% by mass of spray-dried lactose at a compression pressure of 10 kN so as not to cause lamination failure. It is desired to be enhanced. From this point of view, it is preferable to increase the bulk density of the molding powder as much as possible. By increasing the bulk density in this way, not only the bleeding of the liquid active ingredient is suppressed, but also the fluidity is improved. Specifically, the bulk density of the molding powder varies depending on the blending ratio of the liquid active ingredient and the adsorption carrier having α-tocopherol carrying ability of 190% or more, and also depending on the method of applying the mechanical stress. Preferably it is 0.25-0.7 g / cm < ³ >, More preferably, it is 0.3-0.7 g / cm < ³ >.

  The molded product referred to here may be a 12R tablet having a curvature radius of 1.2 cm or a cylindrical molded product. In addition, the term “laminar fracture” as used herein means a phenomenon in which a side surface portion of a tablet after compression molding is cracked and layered division (separation / peeling) occurs in a direction perpendicular to the side surface portion of the molded body. The lamination fracture can be confirmed by visual observation, and even when visual discrimination is difficult, a method of sandwiching the side surface portion of the molded body from both sides (for example, measuring with a Schleingel hardness meter). It can be clearly confirmed by determining whether or not there is a layered division (separation / peeling) in a direction perpendicular to the side surface of the molded body when the load is applied in the method.

  The average particle size of the molding powder is not particularly limited, but the average particle size when measured with a low-tap sieving machine is preferably in the range of 100 to 500 μm, more preferably 150 to 500 μm. . When the average particle size of the molding powder is less than 100 μm, the fluidity at the time of compression molding or the like becomes poor, and the mass of the resulting molded body tends to fluctuate. On the other hand, when the average particle size of the molding powder exceeds 500 μm, the mixing property with other inclusions tends to deteriorate, and the content of the liquid active ingredient in the obtained molded product tends to fluctuate.

  The molding powder of the present embodiment is used for pharmaceuticals, confectionery, health foods, food texture improvers, dietary fiber reinforcing agents and other foods, solid foundations, bath preparations, animal drugs, diagnostic agents, agricultural chemicals, fertilizers, ceramics catalysts, etc. be able to. When used for pharmaceuticals, for example, in the known dosage forms such as tablets, powders, fine granules, granules, extracts and pills, the molding powder of this embodiment can be suitably used.

  The powder for molding of this embodiment can be particularly suitably used in tablet molding. When the molding powder of this embodiment is used, a tablet having a practical hardness and friability can be obtained by a simple method such as a direct tableting method without going through complicated steps. In the manufacture of tablets, if necessary, dry granule compression method, wet granule compression method, later powder method, multi-core tablet with pre-compressed tablet as inner core and multiple pre-compressed compacts are compressed again It is possible to adopt a known method such as a method for producing a multilayer tablet, and the obtained tablet may be coated.

  When coating the obtained tablets or the like, the coating agent is not particularly limited, and known ones can be used. Specific examples of the coating agent include, for example, ethyl acrylate / methyl methacrylate copolymer dispersion, acetyl glycerin fatty acid ester, aminoalkyl methacrylate copolymer, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersion, octyl decyl triglyceride, olive oil, kaolin, Cocoa butter, Kaso, castor wax, caramel, carnauba wax, carboxyvinyl polymer, carboxymethylethylcellulose, sodium carboxymethyl starch, carmellose calcium, carmellose sodium, hydrous silicon dioxide, dry aluminum hydroxide gel, dry milky white rack, dry methacryl Acid copolymer, ginger powder, fish scale powder, gold foil, silver foil, triethyl citrate, glycerin, glycerin fatty acid ester, Magnesium silicate, light anhydrous silicic acid, light anhydrous silicic acid-containing hydroxypropylcellulose, light liquid paraffin, whale wax, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, synthetic wax, high glucose starch syrup, hard wax, succinated gelatin, wheat flour , Wheat starch, rice starch, cellulose acetate, vinyl acetate resin, cellulose acetate phthalate, white beeswax, titanium oxide, magnesium oxide, dimethylaminoethyl methacrylate / methyl methacrylate copolymer, dimethylpolysiloxane, dimethylpolysiloxane / silicon dioxide mixture , Silicon oxide mixture, baked gypsum, sucrose fatty acid ester, zinc oxide powder, aluminum hydroxide gel, hydrogenated rosin glycerin ester, stearyl alcohol, stearic acid, stearic acid Minium, calcium stearate, polyoxyl stearate, magnesium stearate, purified gelatin, purified shellac, purified white sugar, zein, sorbitan sesquioleate, cetanol, gypsum, gelatin, shellac, sorbitan fatty acid ester, D-sorbitol, D-sorbitol solution, Tricalcium phosphate, talc, calcium carbonate, magnesium carbonate, simple syrup, medium gold foil, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, terpene resin, starch (soluble), corn syrup, corn oil, triacetin, calcium lactate, white shellac , White sugar, honey, hard fat, paraffin, pearl powder, potato starch, hydroxypropylcellulose, hydroxypropylcellulose, hydroxypro Pyrucellulose acetate succinate, hydroxypropylcellulose / titanium oxide / polyethylene glycol mixture, hydroxypropylmethylcellulose phthalate, piperonyl butoxide, castor oil, diethyl phthalate, dibutyl phthalate, britphthalyl butyl glycolate, glucose, partially pregelatinized starch, fumarate Acid / stearic acid / polyvinyl acetal diethylaminoacetate / hydroxypropyl cellulose mixture, pullulan, propylene glycolose, powdered sugar, bentonite, povidone, polyoxyethylene hydrogenated castor oil, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxy Ethylene (160) polyoxypropylene (30) glycol, polyoxyethylene sorbitan monostea , Polyvinyl acetal diethylaminoacetate, polyvinyl alcohol (partially saponified product), polyethylene glycol, terminal hydroxyl group-substituted methylpolysiloxane silicone resin copolymer, D-mannitol, chickenpox, beeswax, myristyl alcohol, anhydrous silicic acid hydrate, anhydrous Phthalic acid, anhydrous calcium hydrogen phosphate, methacrylic acid copolymer, magnesium metasilicate aluminate, methylcellulose, 2-methyl-5-vinylpyridine methyl acrylate / methacrylic acid copolymer, moscow, glyceryl monostearate, sorbitan monostearate, monolauryl Acid sorbitan, montanic acid ester wax, medicinal charcoal, lauromacrogol, calcium sulfate, liquid coumarone resin, liquid paraffin, dl-malic acid, monohydrogen phosphate Cium, calcium hydrogen phosphate, sodium hydrogen phosphate, calcium dihydrogen phosphate, rosin, etc. are mentioned, and those described in the “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) are preferably used. Can do. These may be used alone or in combination of two or more.

  The molding powder of the present embodiment contains an excipient, a disintegrant, a binder, a fluidizing agent, a lubricant, a corrigent, a fragrance, a coloring agent, a sweetener, and the like as necessary. Also good.

  Examples of excipients include starch acrylate, L-aspartic acid, aminoethylsulfonic acid, aminoacetic acid, candy (powder), gum arabic, gum arabic powder, alginic acid, sodium alginate, pregelatinized starch, pumice granules, inositol , Ethyl cellulose, ethylene vinyl acetate copolymer, sodium chloride, olive oil, kaolin, cacao butter, casein, fructose, pumice grains, carmellose, carmellose sodium, hydrous silicon dioxide, dry yeast, dry aluminum hydroxide gel, dry sodium sulfate, dry sulfuric acid Magnesium, agar, agar powder, xylitol, citric acid, sodium citrate, disodium citrate, glycerin, calcium glycerophosphate, sodium gluconate, L-glutamine, clay, clay 3, clay granules Croscarmellose sodium, crospovidone, magnesium aluminate silicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, cinnamon powder, crystalline cellulose, crystalline cellulose / carmellose sodium, crystalline cellulose (grain), Pearl millet, synthetic aluminum silicate, synthetic hydrotalcite, sesame oil, wheat flour, wheat starch, wheat germ powder, riceko, rice starch, potassium acetate, calcium acetate, cellulose acetate phthalate, safflower oil, white beeswax, zinc oxide, Titanium oxide, magnesium oxide, β-cyclodextrin, dihydroxyaluminum aminoacetate, 2,6-dibutyl-4-methylphenol, dimethylpolysiloxane, tartaric acid, potassium hydrogen tartrate, baked gypsum, shochu Sugar fatty acid ester, magnesium hydroxide alumina, aluminum hydroxide gel, aluminum hydroxide / sodium hydrogen carbonate coprecipitate, magnesium hydroxide, scrawan, stearyl alcohol, stearic acid, calcium stearate, polyoxyl stearate, magnesium stearate, soybean hardened Oil, purified gelatin, purified shellac, purified white sugar, purified white sugar spherical granules, cetostearyl alcohol, polyethylene glycol 1000 monocetyl ether, gelatin, sorbitan fatty acid ester, D-sorbitol, tricalcium phosphate, soybean oil, soybean unsaponifiable matter, soybean Lecithin, skim milk powder, talc, ammonium carbonate, calcium carbonate, magnesium carbonate, neutral anhydrous sodium sulfate, low substituted hydroxypropylcellulose, dextran Dextrin, natural aluminum silicate, corn starch, tragacanth powder, silicon dioxide, calcium lactate, lactose, lactose granulated product, perfiller 101, white shellac, white petrolatum, crushed, white sugar, white sugar / starch spherical granule, powdered green leaf extract powder , Naked malt green juice dry powder, honey, paraffin, potato starch, semi-digested starch, human serum albumin, hydroxypropyl starch, hydroxypropylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose phthalate, phytic acid, Glucose, glucose hydrate, partially pregelatinized starch, pullulan, propylene glycol, powdered reduced maltose starch syrup, powdered cellulose, pectin, bentonite , Sodium polyacrylate, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polystyrene sulfonic acid Sodium, polysorbate 80, polyvinyl acetal diethylaminoacetate, polyvinyl pyrrolidone, polyethylene glycol, maltitol, maltose, D-mannitol, water candy, isopropyl myristate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate granule, aluminum metasilicate Magnesium acid, methylcellulose, cottonseed powder, cottonseed oil, mole, aluminum monostearate, glyceryl monostearate, monosteary Sorbitan phosphate, medicinal charcoal, peanut oil, aluminum sulfate, calcium sulfate, granular corn starch, liquid paraffin, dl-malic acid, calcium phosphate-hydrogen hydrogen, calcium hydrogen phosphate, calcium hydrogen phosphate granulated product, phosphoric acid Sodium hydrogen, potassium dihydrogen phosphate, calcium dihydrogen phosphate, sodium dihydrogen phosphate, etc. are listed as excipients in the “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) Can be suitably used. These may be used alone or in combination of two or more. In particular, from the viewpoint of imparting high hardness and friability to the molded body, the excipient is preferably crystalline cellulose, and has high moldability and α-tocopherol supporting ability, and sticking, capping when the amount of liquid active ingredient is increased, From the viewpoint of improving tableting troubles such as lamination, cellulose powder described in WO 2004/106416 is more preferable.

  Disintegrants include, for example, croscarmellose sodium, carmellose, carmellose calcium, carmellose sodium, celluloses such as low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, hydroxypropyl starch, rice starch, wheat starch, corn starch , Starches such as potato starch and partially pregelatinized starch, synthetic polymers such as crospovidone and crospovidone copolymer, etc., and listed as a disintegrant in the “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) Can be used suitably. These may be used alone or in combination of two or more.

  Examples of the binder include sugars such as sucrose, glucose, lactose, and fructose, sugar alcohols such as mannitol, xylitol, maltitol, erythritol, sorbitol, gelatin, pullulan, carrageenan, locust bean gum, agar, glucomannan, xanthan gum Water-soluble polysaccharides such as tamarind gum, pectin, sodium alginate, gum arabic, etc., celluloses such as crystalline cellulose, powdered cellulose, hydroxypropylcellulose, methylcellulose, starches such as pregelatinized starch, starch paste, polyvinylpyrrolidone, carboxyvinyl Polymers, synthetic polymers such as polyvinyl alcohol, inorganic compounds such as calcium hydrogen phosphate, calcium carbonate, synthetic hydrotalcite, magnesium aluminate silicate, etc. , It can be suitably used those described as binders in "Pharmaceutical Excipients Dictionary" (Yakujinipposha Corporation published). These may be used alone or in combination of two or more.

  Examples of the fluidizing agent include silicon compounds such as hydrous silicon dioxide and light anhydrous silicic acid, and are described as fluidizing agents in “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.). A thing can be used suitably. These may be used alone or in combination of two or more.

  Examples of lubricants include magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid ester, talc, etc., and are described as lubricants in the “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.). What is done can be used suitably. These may be used alone or in combination of two or more.

  Examples of the corrigent include glutamic acid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaric acid, malic acid, ascorbic acid, sodium chloride, 1-menthol and the like. What is described as a taste-masking agent in the company (issued by Co., Ltd.) can be suitably used. These may be used alone or in combination of two or more.

  Examples of the fragrances include oranges, vanilla, strawberry, yogurt, menthol, fennel oil, cinnamon oil, spruce oil, mint oil, green tea powder, etc., and “Pharmaceutical Additives Encyclopedia” (Pharmaceutical Daily Report ( What is described as a flavoring agent or a fragrance | flavor in the (issue) issue) can be used conveniently. These may be used alone or in combination of two or more.

  Examples of the colorant include food colors such as food red No. 3, food yellow No. 5, and food blue No. 1, copper chlorofin sodium, titanium oxide, riboflavin, etc. What is described as a colorant in (issued by Co., Ltd.) can be suitably used. These may be used alone or in combination of two or more.

  Examples of the sweetener include aspartame, saccharin, dipotassium gilicylicylate, stevia, maltose, maltitol, chickenpox, and amacha powder. What is described as can be used suitably. These may be used alone or in combination of two or more.

  The molding powder described above comprises a liquid active ingredient, an adsorption carrier having an α-tocopherol carrying capacity of 190% or more, and an emulsifier, a homomixer, a stirrer granulator, a tumbling granulator, a crush granulator, an extrusion granulator. It can obtain by mixing and granulating using well-known granulators, such as a granulator, a fluid bed granulator, a rolling fluid bed granulator, a heating granulator, a spray dryer.

Here, when the liquid active ingredient in the blending ratio of the present embodiment, the adsorption carrier having an α-tocopherol carrying capacity of 190% or more and the emulsifier are simply mixed by a known method, the bulk density of the obtained mixed powder is tend to be less than 0.2 g / cm ^3, it is the difficult tendency that rather adjusted to 0.2 g / cm ³ or more. Therefore, in such a case, it is necessary to adjust the bulk density of the mixed powder (granulated product) having a bulk density of less than 0.2 g / cm ³ within the range of 0.2 to 0.7 g / cm ^3. .

The method for controlling the bulk density of the molding powder in the range of 0.2 to 0.7 g / cm ³ is not particularly limited, and a known method can be appropriately employed. A slug is formed from the mixed powder (granulated product) obtained as described above, and mechanical stress is applied to the slug to adjust to a molding powder having a bulk density of 0.2 to 0.7 g / cm ^3. The method is mentioned as simple and efficient. According to this method, a molding powder having a bulk density of 0.2 to 0.7 g / cm ³ can be easily obtained without using spray drying.

  The method of applying mechanical stress to the mixed powder (granulated product) is not particularly limited. For example, a roller type such as a briquetting roller type press such as a roller compactor or a smooth roller type press. Once the sheet is formed by a dry granulation method using a press or the like, the sheet is crushed, and once the slug is formed using a compression molding machine capable of compacting powder such as a tableting machine, the slug is Mixed powder using devices such as crushing method, homomixer, stirring granulator, rolling granulator, crushing granulator, extrusion granulator, fluid bed granulator, rolling fluid bed granulator And a method of adjusting the bulk density by adding a stirring shear by one or a combination of two or more of these apparatuses after adjusting the above. Among these, from the viewpoint of easy operation and productivity, a method of crushing the slug after forming the slug once using a device capable of compacting powder such as a tableting machine is preferable. Examples of the compression molding machine that can be used in the above include a static pressure press, a single punch tableting machine, and a rotary tableting machine.

When a mechanical stress is applied to the mixed powder (granulated product) as described above to adjust the bulk density of the molding powder to a range of 0.2 to 0.7 g / cm ³ , the liquid active ingredient is transferred to the adsorption carrier. Not only will it be adsorbed uniformly, but the liquid active ingredient will be dispersed to a smaller size and pushed into the pores of the adsorbent carrier, possibly when the liquid active ingredient interacts strongly with the adsorbent carrier during compression. By forming an environment in which the exudation from the adsorption carrier is suppressed, a special effect that the exudation of the liquid active ingredient is remarkably suppressed in the subsequent compression process is exhibited. In addition, in the technique of applying mechanical stress to the mixed powder (granulated product) to adjust the bulk density of the powder for molding, the bulk density and mechanical stress of the mixed powder (granulated product) to be used are applied. The upper limit of the bulk density of the resulting molding powder is determined by the mechanical application ability of the apparatus used for the purpose, and even when the most mechanical application is given, it is at most about 0.7 g / cm ^3. .

  When producing the molding powder, it is preferable to mix the liquid active ingredient and the emulsifier in advance and sufficiently emulsify the liquid active ingredient. Thus, by sufficiently emulsifying the liquid active ingredient in advance, the adsorptivity to the adsorption carrier is improved and uniform dispersion is achieved, and the liquid active ingredient is prevented from being deactivated by contact with air.

  The emulsification method of the liquid active ingredient is not particularly limited. For example, a one-way rotation type such as a portable mixer, a three-dimensional mixer, a side mixer, a multi-axis rotation type, a reciprocating reversal type, a vertical movement type, a rotation and a vertical movement Mixing method using a stirring blade such as a pipe type, a jet type stirring mixing method such as a line mixer, a gas blowing type stirring mixing method, a mixing method using a high shear homogenizer, a high pressure homogenizer, an ultrasonic homogenizer, etc. A known method such as a container-shaking mixing method using a shaker can be appropriately employed.

  The method of supplying the emulsified liquid active ingredient to the particle surface of the adsorption carrier is not particularly limited, and can be performed according to a known method. For example, a small suction transport device, a pneumatic transport device, a bucket conveyor, a pressure feed What is necessary is just to supply continuously to an adsorption | suction support | carrier using a type | formula transport apparatus, a vacuum conveyor, a vibration-type fixed feeder, a spray, a funnel, etc .. In addition, the method of spraying the emulsified liquid active ingredient and supplying it to the particle surface of the adsorption carrier is a preferable embodiment because the variation in the concentration of the liquid active ingredient in the final product is reduced. Examples of the spraying method of the emulsified liquid active ingredient include a spraying method using a pressure nozzle, a two-fluid nozzle, a four-fluid nozzle, a rotating disk, an ultrasonic nozzle and the like, and a dropping method from a tubular nozzle. Furthermore, a method of performing layering or coating in which a liquid active component is laminated on the particle surface of the adsorption carrier is also a preferable aspect.

  As a solvent that can be used in the production of the molding powder, water and / or an organic solvent that are generally used in pharmaceutical applications can be suitably used. Specific examples of the solvent include, for example, water, methanol, ethanol, isopropyl alcohol, butyl alcohol, 2-methylbutyl alcohol, benzyl alcohol and other alcohols, pentane, hexane, heptane, cyclohexane and other hydrocarbons, acetone, ethyl Examples include ketones such as methyl ketone, and those described as solvents in the “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) can be suitably used. These may be used alone or in combination of two or more. Moreover, after using 1 type, or 2 or more types of solvents, the solvent may be removed, and also 1 type, or 2 or more types of other solvents may be used. In addition, it is preferable to use water as a solvent from the viewpoints of influence on the environment and human body, equipment cost, and the like.

  A compression-molded product (compression-molded composition) can be obtained by compression-molding the above-described molding powder alone or in combination with other components. The compression-molded product thus obtained preferably contains 10 to 60% by mass of the liquid active ingredient and 5 to 90% by mass of crystalline cellulose. If the crystalline cellulose content is less than 5% by mass, the moldability and disintegration may not be sufficiently imparted. On the other hand, if the crystalline cellulose content exceeds 90% by mass, the liquid active ingredient is contained. The amount can be insufficient.

  EXAMPLES Next, although an Example and a comparative example demonstrate this invention further in detail, this invention is not limited to these. In addition, unless otherwise indicated, parts and% of an Example etc. are the mass display.

First, methods for measuring various physical properties in Examples and Comparative Examples are described below.
(1) α-Tocopherol carrying capacity (%)
Α-tocopherol is dropped into 2 g of the adsorption carrier and mixed with a spatula to form a kneaded product. At this time, the exudation of α-tocopherol on the surface of the kneaded product is judged visually, and the time when α-tocopherol slightly exudes on the surface of the kneaded material is taken as the end point, and the dripping amount of α-tocopherol at the end point Is a (g) and is calculated based on the following formula (1).
α-tocopherol carrying capacity (%) = a / 2 × 100 Formula (1)

(2) Bulk density (g / cm ³ )
After using a 100 cm ³ graduated cylinder and roughly filling a powder sample with a quantitative feeder or the like over 2 to 3 minutes and leveling the upper surface of the powder layer horizontally using a soft brush like a brush The volume (V) is read out and taken as the value divided by the mass of the powder sample. The mass of the powder is appropriately set so that the volume (V) is 70 to 100 cm ³ .

(3) Compression of molding powder 0.2 g of molding powder is put into a mortar of a compression moldability measuring apparatus (trade name: Tabflex, manufactured by Okada Seiko Co., Ltd.), and a punch having a diameter of 0.8 cm (curvature radius 1.2 cm) To obtain a molded body having a diameter of 0.8 cm by compressing to a striking pressure of 12 kN (compression speed: 20 mm / s). Thereafter, the molded body is taken out, and the presence or absence of cracks (lamination destruction) on the side of the tablet is observed.

(4) Compression of mixture of molding powder and spray-dried lactose First, 70% by mass of molding powder and 30% by mass of spray-dried lactose (trade name: Supertub, manufactured by Lactose New Zealand) are mixed in a polyethylene bag for 3 minutes. Next, 0.2 g of the obtained mixed powder is weighed and put into a mortar of a compression moldability measuring apparatus (trade name: Tabflex, manufactured by Okada Seiko Co., Ltd.) with a punch having a diameter of 0.8 cm to a punching pressure of 10 kN. A cylindrical shaped body having a diameter of 0.8 cm is produced by compressing until it becomes. Thereafter, the cylindrical molded body is taken out, and the presence or absence of cracks (lamination destruction) on the side of the tablet is observed.

(5) Tablet mass variation (%)
After measuring the mass of 20 tablets obtained by rotary tableting and calculating the average mass and the standard deviation of the mass, the coefficient of variation (%) defined by the following formula (2) is calculated, and the mass Dispersion was evaluated. The smaller the variation coefficient, the smaller the variation.
Coefficient of variation (%) = (standard deviation / average mass) * 100 Expression (2)

(6) Tablet hardness (N)
Using a Schleingel hardness tester (trade name: 6D type, manufactured by Freund Sangyo Co., Ltd.), a load is applied in the diameter direction of the cylindrical molded body or tablet to break the tablet, and the load at that time is measured. The tablet hardness (N) is an average value of 10 samples.

(7) Tableting failure rate (%)
Randomly select 100 tablets obtained by a rotary tableting machine, visually observe them, and count the number of cracks (lamination), chipping (chipping, sticking), peeling (capping) on the side of the tablet, The total number of these is shown as a value (percentage) divided by the number of tablets observed.

[Example 1]
360 g of calcium silicate (trade name: FLORITE R, manufactured by Tokuyama) is put into a vertical granulator VG-10 (manufactured by POWREC), 360 g of d-α-tocopherol and polyoxyethylene sorbitan monooleate (trade name: Tween 80) , Manufactured by Kishida Chemical Co., Ltd.) and a dispersion emulsified at 10,000 rpm for 15 minutes with a homomixer, mixed for 6 minutes under conditions of blade 200 rpm and chopper 2100 rpm, and granulated, and then in an oven at 60 ° C. for 16 hours. Dried. Next, the obtained dried product was sized using a 710 μm sieve. The bulk density of the dried product after sizing was 0.185 g / cm ³ .

Using the rotary tableting machine (trade name: LIBLA2, manufactured by Kikusui Seisakusho, φ8 mm, 12-barrel, using an open feed shoe, punching pressure of 2 kN), the dried product after the sizing obtained as described above is used as a slug. Thereafter, the slug was crushed using a comil (trade name: QC-197S, manufactured by Paul Wreck, screen 1.143 cm, screw speed 2400 rpm), whereby the molding powder of Example 1 was produced. The molding powder obtained in Example 1 had a bulk density of 0.48 g / cm ³ , an angle of repose of 38.5 °, and an average particle size of 180 μm.

  Next, the molding powder of Example 1 was compression-molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm. No lamination failure was observed.

  Next, a mixture containing 70% by mass of the molding powder of Example 1 and 30% by mass of spray-dried lactose was compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm. Was not.

Although the bulk density of the dried product after the sizing was 0.185 g / cm ³ , the bulk density of the molding powder of Example 1 was reduced to 0 by once producing a slug and applying mechanical stress thereto. It was confirmed that it could be adjusted to .48 g / cm ³ . And perhaps d-α-tocopherol, which is a liquid active ingredient, is sufficiently adsorbed to Florite R, which is an adsorbing carrier, so that exudation during tableting is suppressed and occurrence of lamination destruction is suppressed. it is conceivable that.

[Example 2]
360 g of calcium silicate (trade name: FLORITE R, manufactured by Tokuyama) is put into a fluidized bed granulator (trade name: multiplex MP-01 type, manufactured by POWREC), and 360 g of d-α-tocopherol and polyoxyethylene are added thereto. A dispersion obtained by emulsifying 40 g of sorbitan monooleate (trade name: Tween 80, manufactured by Kishida Chemical Co., Ltd.) with a homomixer at 10,000 rpm for 15 minutes was spray-dried and granulated, followed by drying in a 60 ° C. oven for 16 hours. Next, the obtained dried product was sized using a 710 μm sieve. The bulk density of the dried product after the sizing was 0.180 g / cm ³ .

Using the rotary tableting machine (trade name: LIBLA2, manufactured by Kikusui Seisakusho, φ8 mm, 12-barrel, using an open feed shoe, punching pressure of 2 kN), the dried product after the sizing obtained as described above is used as a slug. Thereafter, the slug was crushed using a comil (trade name: QC-197S, manufactured by Paul Wreck, screen 1.143 cm, screw speed 2400 rpm), whereby the molding powder of Example 2 was produced. The molding powder obtained in Example 2 had a bulk density of 0.50 g / cm ³ , an angle of repose of 37.5 °, and an average particle size of 177 μm.

  Next, when the molding powder of Example 2 was compression molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm, lamination failure was not observed.

  Subsequently, a mixture containing 70% by mass of the molding powder of Example 2 and 30% by mass of spray-dried lactose was compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm. Was not.

[Example 3]
After sufficiently mixing 60 parts by mass of the molding powder prepared in Example 1, 37 parts by mass of crystalline cellulose (trade name: Theolas KG-1000, manufactured by Asahi Kasei Chemicals), and 3 parts by mass of magnesium aluminate metasilicate, To the mixed powder, 0.8 parts by weight of light anhydrous silicic acid and 1.5 parts by weight of magnesium stearate were added and further mixed to obtain d-α-tocopherol / florite R / tween 80 / crystalline cellulose / aluminum metasilicate. Magnesium (external split) / light anhydrous silicic acid / magnesium stearate (external split) = 27.8 / 27.8 / 3.1 / 36.2 / 2.9 / 0.8 / 1.5 Was made.

  The obtained mixture was compression molded at a compression pressure of 10 kN using a rotary type tableting machine (trade name: LIBLA2, manufactured by Kikusui Seisakusho) to produce a molded body (200 mg tablet) having a diameter of 0.8 cm.

  The tablet hardness at a tableting pressure of 10 kN was measured, and the presence or absence of tableting failure was observed. Furthermore, the obtained tablet was stored in a 40 ° C. 75% RH glass container for 1 month, and the tablet hardness after storage was measured. The results are shown in Table 1.

[Example 4]
40 parts by weight of the molding powder prepared in Example 1, 32.8 parts by weight of crystalline cellulose (trade name: Theolas KG-1000, manufactured by Asahi Kasei Chemicals) and spray-dried lactose (trade name: Supertub, manufactured by Asahi Kasei Chemicals) After sufficiently mixing 18.8 parts by mass and 3 parts by mass of croscarmellose sodium (trade name: Kikkolate ND-2HS, manufactured by Asahi Kasei Chemicals), 3 parts by mass of magnesium aluminate tableting powder is added to the mixed powder. Parts, 0.53 parts by weight of light anhydrous silicic acid, 2 parts by weight of magnesium stearate and further mixed, and d-α-tocopherol / Florite R / Tween 80 / crystalline cellulose / spray-dried lactose / croscarmellose sodium / Magnesium aluminate metasilicate / Light anhydrous silicic acid / Magnesium stearate = 18/1 A mixture having the composition of 8 / 1.9 / 36.2 / 27.8 / 2.8 / 2.8 / 0.5 / 1.9 was prepared.

  The obtained mixture was compression-molded at a compression pressure of 12 kN using a rotary tableting machine (trade name: LIBLA2, manufactured by Kikusui Seisakusho) to produce a molded body (200 mg tablet) having a diameter of 0.8 cm.

  The tablet hardness at a tableting pressure of 12 kN was measured, and the presence or absence of tableting failure was observed. Furthermore, the obtained tablet was stored in a 40 ° C. 75% RH glass container for 1 month, and the tablet hardness after storage was measured. The results are shown in Table 2.

[Example 5]
30 parts by mass of the molding powder prepared in Example 1, 67 parts by mass of crystalline cellulose (trade name: Theolas PH-102, manufactured by Asahi Kasei Chemicals), and croscarmellose sodium (trade name: Kikkolate ND-2HS, manufactured by Asahi Kasei Chemicals) ) After 3 parts by mass were sufficiently mixed, 3 parts by mass of the magnesium aluminate metasilicate tableting powder and 2 parts by mass of magnesium stearate were added to the mixed powder and further mixed to obtain d-α-tocopherol / flow. Light R / Tween 80 / crystalline cellulose / croscarmellose sodium / magnesium aluminate metasilicate / magnesium stearate = 13.5 / 13.5 / 1.5 / 63.8 / 2.9 / 2.8 / 1. A mixture of 9 compositions was made.

  The obtained mixture was compression molded at a compression pressure of 10 kN using a rotary type tableting machine (trade name: LIBLA2, manufactured by Kikusui Seisakusho) to produce a molded body (200 mg tablet) having a diameter of 0.8 cm.

  The tablet hardness at a tableting pressure of 10 kN was measured, and the presence or absence of tableting failure was observed. Furthermore, the obtained tablet was stored in a 40 ° C. 75% RH glass container for 1 month, and the tablet hardness after storage was measured. The results are shown in Table 3.

[Comparative Example 1] (corresponding to Example 1 of Patent Document 1)
360 g of calcium silicate (trade name: Fluorite R, manufactured by Tokuyama) is added to Henschel mixer FM-25 [manufactured by Mitsui Miike Seisakusho], 360 g of dl-α-tocopherol acetate is added to this, and Fluorite R is added. The dl-α-tocopherol acetate was adsorbed. Thereafter, 36 g of methylcellulose was added, granulated, dried and sized according to a conventional method, and the composition of dl-α-tocopherol acetate / florite R / methylcellulose = 47.6 / 47.6 / 4.8 was established. Adsorbed granules of dl-α-tocopherol acetate were obtained. The bulk density of the obtained adsorption granule of Comparative Example 1 was 0.190 g / cm ³ .

  Next, when the adsorbed granules of Comparative Example 1 were compression molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm, lamination fracture was observed.

  Next, a mixture containing 70% by mass of the adsorbed granules of Comparative Example 1 and 30% by mass of spray-dried lactose was compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, as shown in FIG. Lamination destruction was observed.

In the (cylindrical) molded body of Comparative Example 1, bleeding at the time of tableting was large, and the occurrence of lamination destruction was not suppressed. This is because the bulk density of the adsorbed granules of Comparative Example 1 is less than 0.2 g / cm ³ , and no mechanical stress is applied to the adsorbed granules of Comparative Example 1, so that the liquid active ingredient dl- It is presumed that α-tocopherol was not sufficiently adsorbed on Florite R, which is an adsorption carrier.

  Further, 100 parts by mass of the adsorbed granules of Comparative Example 1, 90 parts by mass of sprayed lactose, and 10 parts by mass of talc were mixed to produce a tableting powder of Comparative Example 1. The tableting powder of Comparative Example 1 was compression-molded at a compression pressure of 10 kN using a rotary tableting machine (trade name: LIBLA2, manufactured by Kikusui Seisakusho), and a molded article having a diameter of 0.8 cm (200 mg tablet). Was made.

When the tablet hardness at a tableting pressure of 10 kN was measured, the initial tablet hardness was 43N. Moreover, when the obtained tablet was preserve | saved for one month in a 40 degreeC75% RH glass container and the tablet hardness after a preservation | save was measured, the tablet hardness after a preservation | save was reduced with 30N. It should be noted that no tableting failure (skinning to the turntable, tableting to the punch, capping) was observed.
Practically, tablet hardness of 0.6-0.8cm in diameter is desirable to be 50N or more (Yasuhiko Nakamura, Yasuo Izutsu, powder compression molding technology (powder engineering society, formulation and particle design subcommittee edition 1998 daily publication) Kogyo Shimbun, p. 135), the molded article of Comparative Example 1 was practically insufficient in tablet hardness.

[Comparative Example 2] (Experimental Example 2 of Patent Document 2, FIG. 1, equivalent to the experiment of Aerosil 100%)
First, light anhydrous silicic acid (trade name: Aerosil, manufactured by Nippon Aerosil Co., Ltd.) is dispersed in purified water, a 10% aqueous solution of Tween 20 is added to the dispersion, and vitamin E is further added. The mixture was prepared by emulsifying at 6000 rpm for minutes. Next, this mixed solution is spray-dried (inlet temperature: 220 ° C., outlet temperature: 120-130 ° C., atomizer rotation speed: 16500 rpm), and vitamin E / Aerosil / Tween 20 = 41.6 / 55.6 / 2. A spray-dried powder of composition 8 was obtained. The bulk density of the spray-dried powder of Comparative Example 2 obtained was 0.15 g / cm ³ .

  Next, when the spray-dried powder of Comparative Example 2 was compression molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm, lamination failure was observed.

  Subsequently, a mixture containing 70% by mass of the spray-dried powder of Comparative Example 2 and 30% by mass of the spray-dried lactose was compression-molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm. It was done.

In the (cylindrical) molded body of Comparative Example 2, bleeding at the time of tableting was large, and the occurrence of lamination destruction was not suppressed. This is because the bulk density of the spray-dried powder of Comparative Example 2 is less than 0.2 g / cm ³ and no mechanical stress is imparted to the spray-dried powder of Comparative Example 2, so that the vitamin that is a liquid active ingredient This is presumably because E was not sufficiently adsorbed on the aerosil which is the adsorption carrier.

[Comparative Example 3] (corresponding to Example 2 of Patent Document 3)
First, 100 g of dl-α-tocopherol acetate was added with 100 g ³ of gum arabic powder as an emulsifier and 100 cm ³ of purified water, kneaded and kneaded with 5 g of sodium carboxymethylcellulose, and then colloidal anhydrous silica. An acid (trade name: Aerosil, manufactured by Nippon Aerosil Co., Ltd.) 100 g was added and mixed until homogeneous to prepare a mixed solution. Next, this mixed liquid was dried and coarsely pulverized, whereby dl-α-tocopherol acetate / gum arabic powder / sodium carboxymethylcellulose / colloidal silicic acid = 32.8 / 32.8 / 1.6 / 32. A dry powder having a composition of 8 was obtained. The bulk density of the obtained dry powder of Comparative Example 3 was 0.23 cm ³ / g.

  Next, when the dry powder of Comparative Example 3 was compression molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm, lamination fracture was observed.

  Next, when a mixture containing 70% by mass of the dry powder of Comparative Example 3 and 30% by mass of spray-dried lactose was compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, lamination fracture was observed. It was.

In the (cylindrical) molded body of Comparative Example 3, the bleeding at the time of tableting was large, and the occurrence of lamination destruction was not suppressed. The bulk density of the dry powder of Comparative Example 3 was relatively large at 0.23 cm ³ / g, but the blending amount of gum arabic powder as an emulsifier was as large as 32.8% by mass. Since no stress was applied, it is presumed that dl-α-tocopherol acetate, which is a liquid active ingredient, was not sufficiently adsorbed on colloidal silicic acid anhydride, which was an adsorption carrier.

  Further, the dry powder of Comparative Example 3, 145 g of granular lactose and 5 g of magnesium stearate were mixed to produce a tableting powder of Comparative Example 3. The tableting powder of Comparative Example 3 was compression-molded using a rotary type tableting machine (trade name: LIBLA2, manufactured by Kikusui Seisakusho) and dl-α-tocopherol acetate / gum arabic powder / sodium carboxymethylcellulose / colloid. Molded silicic acid / granular lactose / magnesium stearate = 22.0 / 22.0 / 1.1 / 22.0 / 31.9 / 1.0 molded product with a diameter of 0.8 cm (250 mg tablets: 1 tablet contains 55 mg of dl-α-tocopherol acetate).

  When the tablet hardness of the obtained molded product of Comparative Example 3 (250 mg tablet) was measured, the initial tablet hardness was 40N. Moreover, when the molded body of Comparative Example 3 (250 mg tablet) was stored in a 40 ° C. 75% RH glass container for 1 month and the tablet hardness after storage was measured, it was reduced to 30 N. From the above, the molded article of Comparative Example 3 was practically insufficient in tablet hardness.

[Comparative Example 4] (corresponding to Example 2 of Patent Document 4)
First, 755 g of crosslinked polyvinylpyrrolidone, 450 g of crystalline cellulose, and 154 g of carmellose were introduced into a V-type mixer (trade name: V-5 type, manufactured by Tokuju Seisakusho) and then mixed for 15 minutes to prepare a mixed powder. . On the other hand, 20 g of tocopherol acetate, 20 g of vitamin A oil, and 45 g of polyoxyethylene hydrogenated castor oil (water content 0.11% by mass, HLB 12.5) were rotated 300 times using a grinder (R-8: Nippon Rikagaku Co., Ltd.). The dispersion was adjusted by gently dispersing every minute. This dispersion was added to a V-type mixer charged with 100 g of the mixed powder and mixed for 15 minutes, then 20 g of l-menthol passed through a 75 μm sieve was further added and mixed for 15 minutes, and 16 g of magnesium stearate was added. Furthermore, the powder for tableting of the comparative example 4 was obtained by adding and mixing for 5 minutes.

  Next, the tableting powder of Comparative Example 4 was compression-molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm, and lamination destruction was observed.

  Subsequently, a mixture containing 70% by mass of the tableting powder of Comparative Example 4 and 30% by mass of spray-dried lactose was compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm. Observed.

  Further, the tableting powder of Comparative Example 4 was used and compression-molded at a compression pressure of 10 kN using a rotary tableting machine (trade name: LIBLA2, manufactured by Kikusui Seisakusho). Tocopherol acetate and vitamin A oil / polyoxy Molding of 0.7 cm in diameter with a composition of ethylene hydrogenated castor oil / mixture of PVP / MCC / carmellose / l-menthol / magnesium stearate = 18.1 / 20.4 / 45.2 / 9.0 / 7.3 A body (tablet with an average mass of 148 mg) was prepared.

  When the tablet hardness of the obtained molded product of Comparative Example 4 (tablet having an average mass of 148 mg) was measured, the initial tablet hardness was as low as 24N, and the liquid active ingredient oozes out during tableting, which is practically sufficient. High hardness could not be imparted.

  In the (cylindrical) molded body of Comparative Example 4, the bleeding at the time of tableting was large, and the occurrence of lamination destruction was not suppressed. Moreover, the molded product of Comparative Example 4 could not sufficiently increase the initial tablet hardness. The powder for tableting of Comparative Example 4 does not use an adsorption carrier having an α-tocopherol supporting ability of 190% or more, and the blending amount of polyoxyethylene hydrogenated castor oil as an emulsifier is 23.1% by mass. In many cases, since no mechanical stress is applied after mixing, it is presumed that the liquid active component was not sufficiently adsorbed on the adsorption carrier.

[Comparative Example 5] (corresponding to Example 1 of Patent Document 5)
First, 10 g of sodium benzoate and 20 g of sorbic acid were dissolved in 5470 g of distilled water by heating to 65-70 ° C., and 4500 g of hydrolyzed gelatin was gradually added with stirring to prepare a slurry. The slurry was stirred for 2 hours while maintaining the temperature at 70-80 ° C., and allowed to stand overnight at a temperature of 70 ° C., after which bubbles were removed. To this slurry, 6000 g of dl-α-tocopherol acetate heated to 40-50 ° C. was gradually added and sufficiently emulsified to prepare an emulsion.

The obtained emulsion was spray-dried in the presence of silicic acid corresponding to 3% by mass of solid content with respect to the dry powder, tocopherol acetate / gelatin / sodium benzoate / sorbic acid / silicic acid (external) Percent) = 57.0 / 42.7 / 0.1 / 0.2 / 3, and a tableting powder was obtained. The bulk density of the obtained tableting powder of Comparative Example 5 was 0.45 g / cm ³ .

  Next, the tableting powder of Comparative Example 5 was compression molded at a compression pressure of 12 kN to produce a cylindrical molded body having a diameter of 0.8 cm, and lamination fracture was observed.

  Subsequently, a mixture containing 70% by mass of the tableting powder of Comparative Example 5 and 30% by mass of spray-dried lactose was compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm. Observed

  Furthermore, a chewable tablet (molded body) having a diameter of 1.2 cm was prepared using 400 parts by mass of the tableting powder of Comparative Example 5, 22 parts by mass of cocoa, 35 parts by mass of silicic acid, and 311.5 parts by mass of sugar. Produced.

  When the tablet hardness of the obtained molded product (chewable tablet) of Comparative Example 5 was measured, the initial tablet hardness was 240N. Moreover, when the molded body of Comparative Example 5 (chewable tablet) was stored in a 40 ° C. 75% RH glass bottle for 1 month and the tablet hardness after storage was measured, it was reduced to 125 N. Capping occurred during the production of the molded body (chewable tablet) of Comparative Example 5.

  In the (cylindrical) molded body of Comparative Example 5, the bleeding at the time of tableting was large, and the occurrence of lamination destruction was not suppressed. In addition, the molded product of Comparative Example 5 significantly decreased in tablet hardness after storage. In the tableting powder of Comparative Example 5, the amount of adsorbing carrier having α-tocopherol carrying ability of 190% or more is as small as 3% by mass, and the amount of gelatin as an emulsifier is as large as 42.7% by mass, It is presumed that the liquid active ingredient was not sufficiently adsorbed on the adsorption carrier because no mechanical stress was applied after mixing.

[Comparative Example 6] (corresponding to Example of Patent Document 7)
First, a mixture of 500 g of soybean oil unsaponifiable matter, 20 g of polyoxyl stearate and 10 g of sodium lauryl sulfate was heated to 80 ° C. and emulsified by adding a mixed solution of 400 g of purified water, 11 g of citric acid and 4 g of ascorbic acid, The emulsion was prepared. The obtained emulsion was kneaded and adsorbed with 300 g of light anhydrous silicic acid, and then the adsorbed product was dried to obtain soybean oil saponified product / polyoxyl stearate / sodium lauryl sulfate / citric acid / ascorbic acid. / Light anhydrous silicic acid = 59.2 / 2.3 / 1.2 / 1.3 / 0.5 / 35.5 A dry powder of soybean oil unsaponifiable matter was obtained. The bulk density of the obtained dry powder of Comparative Example 6 was 0.190 g / cm ³ .

  Next, when the dry powder of Comparative Example 6 was compression-molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm, lamination fracture was observed.

  Next, when a mixture containing 70% by mass of the dry powder of Comparative Example 6 and 30% by mass of spray-dried lactose was compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, lamination fracture was observed. It was.

In the (cylindrical) molded body of Comparative Example 6, the bleeding at the time of tableting was large, and the occurrence of lamination destruction was not suppressed. The tableting powder of Comparative Example 6 has a dry powder bulk density of 0.190 g / cm ³ and no mechanical stress applied after mixing, so that the liquid active ingredient is sufficiently adsorbed on the adsorption carrier. It is presumed that it was due to a lack of it.

[Comparative Example 7] (corresponding to Example 3 of Patent Document 8)
First, 7.0 kg of light anhydrous silicic acid (trade name: Aergel 200), 7.35 kg of low-substituted hydroxymethyl cellulose, 11.55 kg of corn starch and 70.35 kg of lactose were mixed with a 600 l stirring granulator (trade name: VG-600). The mixed powder was prepared by stirring and mixing. On the other hand, 7.0 kg of d-α-tocopherol acetate was mixed with 30 L of purified water in which 2.1 kg of hydroxypropylcellulose was dissolved, and emulsified with a high-speed stirrer to prepare a tocopherol emulsion. Then, while stirring the above-mentioned mixed powder, the tocopherol emulsion is added and granulated, followed by drying in a dryer at 50 ° C. for 2 hours, whereby d-α-tocopherol acetate / light anhydrous silicic acid / low substitution degree. Vitamin E-containing composition (dry powder) having a composition of hydroxymethylcellulose / corn starch / lactose / hydroxypropylcellulose = 22.2 / 22.1 / 23.3 / 3.7 / 22.2 / 6.6 was obtained. .

  Next, when the vitamin E composition of Comparative Example 7 was compression molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm, lamination failure was observed.

  Subsequently, a mixture containing 70% by mass of the vitamin E composition of Comparative Example 7 and 30% by mass of spray-dried lactose was compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm. Observed.

  In the (cylindrical) molded body of Comparative Example 7, the bleeding at the time of tableting was large, and the occurrence of lamination destruction was not suppressed. In the dry powder of Comparative Example 7, the adsorbent having an α-tocopherol supporting ability of 190% or more is as low as 22.1% by mass, and no mechanical stress is applied after mixing. This is presumably due to insufficient adsorption on the adsorption carrier.

[Comparative Example 8] (corresponding to Comparative Example 1 of Patent Document 12)
First, in a solution of 900 g ^{3 of} purified water containing 2 g of Pluronic F-68, 10 g of colloidal silica and 10 g of L-HPC, a solution obtained by dissolving 10 g of molten vitamin E nicotinate in 150 ml of ethanol is stirred with a homomixer. To produce an emulsion. Then, the produced emulsion is used as a feed liquid, spray dried (inlet temperature: 125 ° C., outlet temperature: 84 ° C., atomizer rotation speed: 16500 rpm), vitamin E nicotinate / pluronic F-68 / colloidal silica / L-HPC = A spray-dried product having a composition of 31.25 / 6.25 / 31.25 / 31.25 was obtained. The bulk density of the obtained spray-dried product of Comparative Example 8 was 0.195 g / cm ³ .

  Next, the spray-dried product of Comparative Example 8 was compression-molded at a compression pressure of 12 kN to produce a molded body having a diameter of 0.8 cm, and lamination destruction was observed.

  Next, a mixture containing 70% by mass of the spray-dried product of Comparative Example 8 and 30% by mass of spray-dried lactose was compression-molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm. It was done.

In the (cylindrical) molded body of Comparative Example 8, the bleeding at the time of tableting was large, and the occurrence of lamination destruction was not suppressed. In the spray-dried product of Comparative Example 8, the dry powder has a bulk density of 0.195 g / cm ³ and no mechanical stress is applied after mixing, so that the liquid active component is not sufficiently adsorbed on the adsorption carrier. It is presumed that

From the above, it contains 10 to 70% by mass of liquid active ingredient, 29 to 89% by mass of an adsorbent carrier having an α-tocopherol carrying capacity of 190% or more, and 1 to 20% by mass of an emulsifier, and has a bulk density of 0.2 to 0.2%. By using the molding powders of Examples 1 to 5 of 0.7 g / cm ³ , the liquid active ingredient exudation during compression molding can be suppressed, and lamination destruction can be prevented. It was confirmed that a decrease in hardness of the body over time was suppressed, and the storage stability of the molded body after compression molding was improved.

  According to the present invention, it is possible to remarkably suppress the oozing of the liquid active ingredient during compression molding and the like, it is possible to prevent lamination destruction, and it is possible to improve the storage stability without causing a decrease in the hardness of the obtained molded body, The amount of the liquid active ingredient can be increased, and further, the productivity and economy can be improved, so that it can be widely and effectively used in various applications in the chemical industry field. It can be suitably used in the field.

It is an external appearance schematic diagram which shows the lamination destruction (crack of the tablet side surface) in the cylindrical molded object of the comparative example 1.

Claims (4)

Tocopherol ester, retinol, retinol acetate, retinol palmitate, vitamin A oil, vitamin A ester, higher unsaturated fatty acids, soybean oil, castor oil, clofibrate, geraniol, gefarnate, linoleic acid, linolenic acid, eugenol, squalane, phytonadione , Menatetrenone, phenipentol, memphegol, creosote, teprenone, indomethacin farnesyl, praunotol, dimethylpolysiloxane, herbal soft extract, lecithin, york lecithin, oil-soluble flavoring and edible fragrance oil more liquid active ingredients 10 to 70% by weight and light anhydrous silicic acid, hydrated silicon dioxide, anhydrous calcium hydrogen phosphate, aluminum silicate, magnesium silicate, calcium silicate, synthetic silicate Aluminum, magnesium carbonate, calcium carbonate, magnesium oxide, calcium phosphate, aluminum hydroxide, calcium citrate, synthetic resins, kaolin, bentonite and one or more α- tocopherol supporting ability 190% or more selected from the group consisting of cellulose powder the adsorption carrier 29-89 wt% and an emulsifier 1 to 20 mass% to form a slug from including granules is obtained by applying a mechanical stress to the slug, the bulk density is from 0.2 to 0. 7 g / cm ³ of a molding powder, characterized in that when a molded body having a diameter of 0.8 cm is produced by compression molding at a compression pressure of 12 kN, the molded body does not cause lamination destruction.
Powder for molding. When a mixture containing 70% by mass of powder for molding and 30% by mass of spray-dried lactose is compression molded at a compression pressure of 10 kN to produce a cylindrical molded body having a diameter of 0.8 cm, the cylindrical molded body does not cause lamination. It is characterized by
The molding powder according to claim 1 . A powder for molding containing the liquid active ingredient according to claim 1 or claim 2 and crystalline cellulose,
Containing 10-60 mass% of the liquid active ingredient,
Containing 5 to 90% by mass of the crystalline cellulose,
Compression molding composition. Tocopherol ester, retinol, retinol acetate, retinol palmitate, vitamin A oil, vitamin A ester, higher unsaturated fatty acids, soybean oil, castor oil, clofibrate, geraniol, gefarnate, linoleic acid, linolenic acid, eugenol, squalane, phytonadione , Menatetrenone, phenipentol, memphegol, creosote, teprenone, indomethacin farnesyl, praunotol, dimethylpolysiloxane, herbal soft extract, lecithin, york lecithin, oil-soluble flavoring and edible fragrance oil more liquid active ingredients 10 to 70 wt%, light anhydrous silicic acid, hydrated silicon dioxide, anhydrous calcium hydrogen phosphate, aluminum silicate, magnesium silicate, calcium silicate, synthetic silicate Aluminum, magnesium carbonate, calcium carbonate, magnesium oxide, calcium phosphate, aluminum hydroxide, calcium citrate, synthetic resins, kaolin, bentonite and one or more α- tocopherol supporting ability 190% or more selected from the group consisting of cellulose powder A step of obtaining a granulated product comprising 29 to 89% by mass of an adsorption carrier and 1 to 20% by mass of an emulsifier,
Forming a slug from the obtained granulated product,
Applying mechanical stress to the slug;
When the molded body having a diameter of 0.8 cm is produced by compression molding at a compression pressure of 12 kN and a bulk density of 0.2 to 0.7 g / cm ³ , the molded body does not cause lamination destruction. A method for producing a molding powder characterized by the above .