TW201927340A - Cellulose powder - Google Patents

Abstract

The present invention provides a cellulose powder or the like, the cellulose powder comprising cellulose particles having an average particle diameter of 45 mm or less, wherein particles remaining on a sieve with an opening size of 20 mm and passing through a sieve with an opening size of 45 mm are contained more than 40% by mass with respect to the total amount of the powder.

Description

Cellulose powder

The present invention relates to a cellulose powder which helps prevent segregation of active ingredients used in the fields of medicine, health food, etc., has excellent balance between hardness and disintegrability, and is useful as an additive for tablets.
This case claims priority based on Japanese Patent Application No. 2017-249590 filed in Japan on December 26, 2017, and the contents are incorporated herein by reference.

Conventionally, in the fields of medicine, health food, food, and industry, the production of a composition in which an active ingredient and other additives are mixed is widely performed. In particular, since the active ingredients used in the fields of medicine and health food are mostly those with low formability, excipients are usually used as other additives when preparing compositions such as tablets, granules, and fine granules. Among them, crystalline cellulose is widely used as an excipient for tablets because it has both high moldability and rapid disintegration.

In the case of manufacturing lozenges, uniformity of the content of the active ingredient is required. In the case where the content of the active ingredient is 20% by mass or less, in order to accurately exhibit the medicinal effect, it is more strongly required to make the content of the active ingredient in the tablet uniform. In order to obtain tablets with a uniform content of active ingredients, the industry mainly uses a wet tableting method or a wet tableting method. The wet tableting method is as follows: mixing the active ingredient and other additives, and then granulating the binder and water together to make granules, adding a lubricant, etc. to mix and pelleting, thereby making Lozenge. The final method after the wet tableting is a method in which crystalline cellulose, a disintegrant, and the like are added to the granules and mixed, and then a lubricant and the like are added and mixed, and tableting is performed to prepare a tablet. In the wet tableting method, it is preferable that the particles containing the active ingredient and other additives such as crystalline cellulose or disintegrants are not separated or segregated during the steps passed until the tablets are made. .

On the other hand, as a method for manufacturing a tablet, a direct tableting method is commonly used, that is, an active ingredient is mixed with other additives, and then a lubricant is added and mixed, and tableting is performed to prepare a tablet. However, the direct ingot method has no step of processing the active ingredient into granules, and is directly affected by the physical properties of the active ingredient. Therefore, compared with the wet ingot method and the wet after ingot method, it is often difficult to ensure uniform content. . Therefore, in order to reduce the influence of the physical properties of the active ingredient, an operation of pulverizing the active ingredient and controlling the particle size to be small is performed. However, if the particle size of the active ingredient is controlled to be small, the fluidity is deteriorated due to a reduction in weight or an increase in surface adhesion. As a result, the filling of the punching die becomes insufficient during tableting, and variations in the weight of the tablet are likely to occur, but it is difficult to ensure uniformity of the content of the active ingredient.

In this way, in order to ensure uniform content of the active ingredient in the direct tableting method, it is important to simultaneously stabilize the physical properties of the active ingredient and the fluidity to the extent that it can be tableted. To ensure fluidity, additives with good fluidity are usually added. However, among the additives with good fluidity, the larger the average particle size is. When the difference between the average particle diameter of the active ingredient and the particle diameter of the additive increases, separation segregation tends to occur. The following methods have been disclosed as methods for solving the segregation.

Patent Document 1 describes that cellulose powder having a specific particle structure by controlling average particle diameter, repose angle, bulk density, tapped bulk density, specific surface area, and internal friction angle is unlikely to cause segregation of active ingredients and other additives. In the example of Patent Document 1, the effect of preventing segregation was verified using acetaminophen.

Patent Document 2 describes that powder cellulose, which appropriately controls the acid concentration by using an acid hydrolysis method, and improves powder flowability while maintaining strength, is used in fields such as pharmaceuticals. It also describes that the strength (average particle size) of the cellulose powder is opposite to the powder flowability.

Patent Document 3 has the following description: In the previous powder mixing method, because of the drug with high cohesiveness, when the concentration of the drug is low, the mixing speed of the drug and the additive is slow, and it is difficult to improve the uniformity of the content of the drug. The tendency. It is described in the document that before mixing drugs and additives, after mixing the drugs and flow modifiers in advance, the mixed powder and other additives are further mixed, thereby speeding up the mixing speed of the drugs and improving the uniformity of the content of the drugs.

Patent Document 4 describes a cellulose powder prepared during tableting, having an average particle size of more than 30 μm and less than 250 μm, and an apparent specific volume or a pore volume within a particle within a specific range. It is described in this document that the cellulose powder is excellent in compression moldability, and when granulating Chinese herbal medicine and adhesive ingredients, the particle size of the cellulose powder is kept uniform because the adhesive ingredients are kept uniform. The distribution is steep, so the particle size distribution of the particles can also be steepened, which can not only shorten the disintegration time, but also form stable disintegration over time.
[Prior technical literature]
[Patent Literature]

[Patent Document 1] Japanese Patent No. 5439366
[Patent Document 2] Japanese Patent Laid-Open No. 2013-189572
[Patent Document 3] Japanese Patent No. 4925526
[Patent Document 4] Japanese Patent No. 6104905

[Problems to be solved by the invention]

As described above, in the prior art, various studies have been conducted to prevent segregation of drugs, but there are cases in which the effects are not sufficiently exerted on specific types of drugs, or the manufacturing steps are complicated due to the need for special steps. . In addition, at the time of mixing the powder, even if the content uniformity is sufficient, there is a problem that the drug segregation occurs in the tabletting step, and the unevenness of the content in the obtained tablet is increased.

According to the research conducted by the present inventors, it is known that cellulose powder has a large correlation with the chargeability (electrostatic characteristics) of the drug and the segregation of the drug. If the balance between the charging properties of the cellulose powder and the drug is poor, segregation is liable to occur, and the types of drugs that can be used as cellulose segregation preventing agents in the past are limited. Therefore, there is still a need for cellulose powder that can prevent segregation in lozenges containing a wide range of active ingredients.
[Technical means to solve the problem]

In order to solve the above-mentioned problems, the inventors and others conducted diligent research, and found that by blending a cellulose powder having a specific particle size distribution, segregation can be suppressed in an active ingredient that is particularly difficult to prevent segregation, and hardness and hardness can be obtained. The tablet is excellent in disintegrability and balance, and completed the present invention. That is, the present invention is as follows.

[1] A cellulose powder in which the average particle size of the cellulose powder is 45 μm or less, and the ratio of particles remaining on the 20 μm mesh sieve passing through a 45 μm mesh sieve exceeds the total powder 40% by mass.
[2] The cellulose powder according to [1], which contains particles remaining on a sieve with a mesh size of 32 μm and passed through a sieve with a mesh size of 45 μm, and the aspect ratio of the particles is in the range of 1.2 to 2.3. .
[3] The cellulose powder as described in [1] or [2], wherein the ratio of particles remaining on the sieve with a mesh of 32 μm passing through a sieve with a mesh size of 45 μm exceeds 6% by mass relative to the total powder .
[4] The cellulose powder according to any one of [1] to [3], whose repose angle is in a range of 45 to 58 °.
[5] A formed body comprising the cellulose powder according to any one of [1] to [4].
[6] A method for producing a lozenge, which comprises tabletizing a composition comprising the cellulose powder and the active ingredient according to any one of [1] to [4].
[Effect of the invention]

The cellulose powder of this embodiment is extremely excellent in preventing segregation and segregation of active ingredients in compositions containing active ingredients in the fields of medicine, health food, food, and industry. Therefore, in the production of a composition containing an active ingredient, by using the cellulose powder of this embodiment as a segregation preventing agent, it is possible to improve the uniformity of the content of the active ingredient that is not easily dispersed uniformly, and then in the transportation step after mixing, In the input step, the filling step, etc., it is difficult to cause segregation of the active ingredient and other additives even when subjected to gravity or vibration. Furthermore, by using the cellulose powder, it is possible to provide a tablet having a compression-moldability which is significantly improved in a composition containing an active ingredient and is also excellent in disintegrability of the composition.

Hereinafter, the form (hereinafter, abbreviated as "this embodiment") for implementing this invention is demonstrated in detail. The present invention is not limited to the following embodiments, and can be implemented with various changes within the scope of the gist thereof.

<Cellulose powder>
The cellulose powder is generally called crystalline cellulose, powdered cellulose, or the like, and is suitably used as a pharmaceutical additive or a food additive. The cellulose powder is preferably crystalline cellulose. The so-called crystalline cellulose is at least suitable for the confirmation test of the microcrystalline cellulose described in the 8th edition of the Food Additives Draft, and it is more suitable for the confirmation of the crystalline cellulose described in the 17th revision of the Japanese Pharmacopoeia. Experimenter.

The cellulose powder of this embodiment is preferably a type I crystal. As the crystal form of cellulose, type I, type II, type III, type IV, etc. are known. Since type I has the same crystalline structure as natural cellulose such as ramie, cotton wool, and wood pulp, it is not necessary to use only natural resources. Special treatment is superior in terms of cost / environmental impact.

The average particle diameter of the cellulose powder in this embodiment is 45 μm or less. When the average particle diameter is 45 μm or less, it is easy to uniformly mix with an active ingredient such as a drug. It is preferably 40 μm or less. It is more preferably 30 μm or less. The lower limit is not particularly limited. In view of operability, it is preferably about 5 μm even if it is small.

The cellulose powder of the present embodiment is one in which the ratio of the particles remaining on the sieve with a mesh size of 20 μm to the total powder amount exceeds 40% by mass through a sieve with a mesh size of 45 μm. When the ratio of particles having a size within this range exceeds 40% by mass, cellulose powder enters between active ingredients such as drugs, and segregation is unlikely to occur. The ratio of the particles of the cellulose powder passing through a sieve with a mesh size of 45 μm and remaining on a sieve with a size of 20 μm to the total powder is preferably 50% by mass or more, particularly preferably 60% by mass or more. The higher the ratio of the particles, the better, but 100% by mass or less, 95% by mass or less, or 90% by mass is a realistic range.

In the cellulose powder of this embodiment, it is preferred that the ratio of the particles remaining on the sieve with a mesh size of 32 μm to the total powder through a sieve with a mesh size of 45 μm exceeds 6 mass%. If the ratio of the particles in this range to the total amount of powder exceeds 6% by mass, the cellulose powder will more easily enter between active ingredients such as pharmaceuticals, and it will be less likely to cause segregation. The ratio of the particles of the cellulose powder passing through a sieve with a mesh size of 45 μm and remaining on a sieve with a mesh size of 32 μm to the total powder is preferably 10% by mass or more, more preferably 15% by mass or more, Especially preferably, it is 20 mass% or more. The higher the ratio of the particles, the better, but 100% by mass or less, 90% by mass or less, or 80% by mass is a realistic range.

The repose angle of the cellulose powder in this embodiment is preferably 45 to 58 °. If the repose angle is 58 ° or less, the fluidity of the cellulose powder itself is good, and segregation is unlikely to occur, which is preferable. The repose angle is an indicator of fluidity commonly used in the field of powders. The lower the repose angle, the better the fluidity. In order to mix evenly with the active ingredients, the lower the repose angle of the cellulose powder, the better. However, if the fluidity of the cellulose powder itself becomes too good, there is also segregation caused by the desorption of the active ingredients carried on the cellulose powder during mixing, or only the cellulose powder flows into the forming mold, and it is difficult to maintain the content. Uniformity. Therefore, from the viewpoint of achieving a balance between fluidity and segregation prevention, the repose angle of the cellulose powder of this embodiment is preferably 45 to 58 ° or more, more preferably 47 to 55 °, and even more preferably 49 to 53 °. .

In the cellulose powder of this embodiment, the aspect ratio of the particles remaining on the sieve with a mesh of 32 μm and passing through a sieve with a mesh of 45 μm is preferably 1.2 to 2.3. If the aspect ratio of the particles is within this range, the miscibility with the active ingredient is also good, the cross-linking of the slender particles with each other is also moderate, and the balance between moldability and disintegration is excellent. In addition, when the cellulose powder and the active ingredient are mixed, the active ingredient carried on the cellulose powder is difficult to desorb, and the segregation prevention tends to be excellent. In the cellulose powder of this embodiment, the aspect ratio of particles passing through a 45 μm mesh sieve and remaining on a 32 μm mesh is preferably 1.2 to 2.1, more preferably 1.2 to 1.9, and even more preferably 1.2 to 1.8. .

The degree of compression of the cellulose powder in this embodiment is preferably 32 to 45%. When the degree of compression is within the above range, the fluidity of the cellulose powder itself is good, and it is preferable from the viewpoint of preventing segregation. The compression degree of the cellulose powder in this embodiment is preferably 32 to 43%, and particularly preferably 36 to 42%. In addition, the so-called compression degree is an index indicating the fluidity of the powder, and is used as a value for predicting the failure of air transportation of the powder or discharge from the hopper.

The sharpness of the cellulose powder in this embodiment is preferably 1.5 to 2.1. When the sharpness is within the above range, the prevention of segregation is more excellent. The sharpness of the cellulose powder in this embodiment is particularly preferably 1.5 to 1.7. In addition, the so-called sharpness is an index indicating fluidity, and is a value obtained by digitizing the particle size distribution width of a powder. The closer the powder's sharpness is to 1, the more the powder has a steep particle size distribution and the higher the fluidity. Therefore, from the viewpoint of achieving a balance between fluidity and prevention of segregation, the sharpness of the cellulose powder of this embodiment is preferably within the above range.

The pore volume of the cellulose powder in this embodiment is preferably 1.0 mL / g or more. When the pore volume is 1.0 mL / g or more, the moldability is more excellent. The pore volume of the cellulose powder in this embodiment is preferably 1.3 mL / g or more, and particularly preferably 1.5 mL / g or more. Even if the pore volume becomes high, segregation, hardness, and disintegration are not affected. Therefore, the upper limit range is not particularly limited, but the realistic range is 2.7 mL / g or less. The pore volume is an index indicating a porous body on the surface of the cellulose powder. If the pore volume is 1.0 mL / g or more, the active ingredients such as drugs are stuck on the surface of the cellulose powder, so it is not easy to desorb when flowing, and the plastic deformation of the cellulose powder plays a role in the compression of the tablet, Therefore, the hardness becomes higher. In addition, during the disintegration of the lozenge, water is also guided from the contact portions between the cellulose powders. Therefore, by using a cellulose powder having a pore volume within the above range, a tablet can be obtained which exhibits high hardness but disintegrates quickly, and has achieved balance.

In addition, the physical property value of the said cellulose powder is the value measured by the method as described in the following Example.

<Method for producing cellulose powder>
Hereinafter, the manufacturing method of the cellulose powder of this embodiment is described.
The cellulose powder of this embodiment can be obtained by, for example, including the steps of dispersing a hydrolyzed natural cellulose-based substance in an appropriate medium to obtain a cellulose dispersion; and drying the dispersion. The concentration of the solid content of the cellulose dispersion is not particularly limited, and may be, for example, 1 to 10% by mass. In this case, from the hydrolysis reaction solution obtained by the hydrolysis treatment, a solid component containing the cellulose-based substance subjected to the hydrolysis treatment can be isolated and dispersed in an appropriate medium to prepare a dispersion liquid. And this dispersion was dried. When a cellulose dispersion is formed in the same hydrolysis solution in its original state, the dispersion may be directly dried.

The so-called natural cellulose-based substance may be of a plant or animal nature. For example, it is a fiber derived from natural materials containing cellulose such as wood, bamboo, cotton, ramie, ascidian, bagasse, kenaf, and bacterial cellulose. The substance is preferably a cellulose I-type crystal structure. As the raw material, one of the above-mentioned natural cellulose-based substances may be used, or two or more of them may be mixed. In addition, it is preferably used in the form of refined pulp. The method for refining the pulp is not particularly limited, and any pulp such as dissolving pulp, kraft pulp, NBKP (Northern Bleached Kraft Pulp) pulp can be used.

In the above-mentioned production method, as a medium used in a case where a solid component containing a natural cellulose-based substance is dispersed in an appropriate medium, water is preferred, and there is no particular limitation as long as it is an industrial user, For example, organic solvents can be used. Examples of the organic solvent include alcohols such as methanol, ethanol, isopropanol, butanol, 2-methylbutanol, and benzyl alcohol; hydrocarbons such as pentane, hexane, heptane, and cyclohexane; acetone, Ketones such as ethyl methyl ketone. Organic solvents are particularly preferred for use in pharmaceuticals. Examples of such organic solvents include those classified as solvents in the "Pharmaceutical Additives Code" (issued by Pharmaceutical Affairs Daily Co., Ltd.). Water and organic solvents may be used alone, or two or more of them may be used in combination, or one medium may be temporarily dispersed, and then the medium may be removed and dispersed in different mediums.

The average particle diameter of the cellulose particles (cellulose dispersed particles) in the dispersion is preferably 21 to 50 μm, more preferably 21 to 40 μm, and even more preferably 21 to 30 μm. If the average particle diameter of the cellulose dispersed particles is within the above range, it is easy to control the average particle diameter of the cellulose particles obtained after drying to 45 μm or less, and the ratio of particles having a range of 45-20 μm easily exceeds 40. Mass% tendency. From the viewpoint of controlling the aspect ratio of the 45-32 μm particles to a better range, it is also desirable to control the average particle diameter of the cellulose-dispersed particles to fall within the above range.

The average particle diameter of the cellulose dispersed particles can be controlled to a desired range by adjusting the degree of polymerization of the raw material cellulose caused by hydrolysis and the stirring force in the hydrolysis and / or dispersion step of cellulose. Generally, if the acid concentration and reaction temperature of the hydrolysis solution are increased, the degree of cellulose polymerization decreases and the average particle size of cellulose in the dispersion tends to decrease. Moreover, even if the stirring force of the solution is enhanced, the cellulose dispersed particles tend to The average particle size also tends to decrease.

The concentration of the acid when hydrolyzing the natural cellulose-based substance is preferably 0.1 to 1.0% by mass. When the acid concentration is in the above range, it is easy to control the average particle diameter of the cellulose dispersed particles to less than 45 μm. Moreover, in the cellulose powder obtained after drying cellulose-dispersed particles, the repose angle and the aspect ratio of the particles in the range of 45-32 μm tend to be easily controlled within a specific range.

For example, under pressure, 0.1 to 1.0% by mass of hydrochloric acid and 110 to 140 ° C are used to rotate the mixer while hydrolyzing pulp fibers having an average width of 2 to 30 μm and an average thickness of 0.5 to 5 μm. The degree of hydrolysis can be controlled by adjusting the motor power (P: unit W) and the stirring capacity (L: unit L) of the mixer. For example, by adjusting the P / V represented by the following formula to a range of 0.2 to 6.0 (W / L), the average particle size of the finally obtained cellulose particles can be controlled to 45 μm or less, and 45-20 μm The ratio of particles in the range is controlled to exceed 40% by mass.

P / V (W / L) = [Actual power of motor of mixer (W)] / [Stirring capacity (L)]

When manufacturing the cellulose powder of this embodiment, P / V is preferably in the range of 0.2 to 6.0 (W / L), more preferably 0.2 to 4.0 (W / L), and still more preferably 0.2 to 3.0 (W / L). When P / V is 0.2 (W / L) or more, the natural cellulose-based substance is decomposed moderately, and the average particle diameter of the cellulose dispersed particles is likely to be 50 μm or less. Therefore, there is an average particle diameter of the cellulose powder after drying. Also, the ratio of particles in the range of 45 μm or less and 45-20 μm tends to exceed 40% by mass. If P / V is 6.0 (W / L) or less, decomposition of natural cellulose-based substances will not be excessive, and the average particle diameter of cellulose dispersed particles will be 21 μm or more, making it easy to control the aspect ratio or repose angle of the dried product. It is a specific range or a predetermined range, and the cellulose powder thus obtained tends to exhibit the effect of preventing segregation and segregation easily.

There is no particular limitation on the drying method when the cellulose dispersion is dried to obtain a cellulose powder. For example, any one of freeze-drying, spray-drying, drum-drying, cabinet-drying, air-drying, and vacuum-drying can be used, and one kind can be used alone or two or more kinds can be used in combination. The spray method for spray drying may be any of spray methods such as a disc type, a pressurized nozzle, a pressurized two-fluid nozzle, and a pressurized four-fluid nozzle, and may be used alone or in combination of two or more. In the above-mentioned spray drying, in order to reduce the surface tension of the dispersion liquid, a small amount of a water-soluble polymer and a surfactant can be added. In order to promote the gasification rate of the medium, a foaming agent or a gas can be added to the dispersion liquid.

For example, in the case of disc-type spray drying, in order to control the average particle diameter and pore volume of the cellulose powder obtained after drying, it is preferable to control the speed of the disc-type rotating disc and the method for spray drying. The solid content concentration of the cellulose dispersion. The solid component concentration of the cellulose dispersion during spray drying is preferably in the range of 1 to 7 mass%. Even if the solid component concentration is less than 1% by mass, there is a possibility that the required physical properties can be achieved, but the productivity is poor and it is not a practical condition. When the solid component concentration is 7 mass% or less, coarse secondary agglomerates are less likely to occur, and the average particle diameter of the obtained cellulose powder is likely to be 45 μm or less, and the pore volume is also likely to be 1.0 mL / g or more. . When drying the cellulose dispersion having a solid content concentration of 1 to 7 mass%, the peripheral speed of the spray-dried disc is preferably 130 to 220 m / sec. By selecting appropriate convergence according to the solid component concentration, it is easy to control the average particle diameter to 45 μm or less, and it is easy to control the particle size distribution to an appropriate range. The tablets obtained by blending the cellulose powder obtained in this way tend to have high hardness and excellent disintegration time.

By controlling the stirring conditions when preparing the cellulose dispersion liquid, a cellulose dispersion liquid containing cellulose dispersed particles having an average particle size of a specific size can be obtained, and further, the cellulose dispersion liquid can be adjusted by drying the cellulose dispersion liquid. The solid component concentration or drying conditions can control the average particle diameter, degree of compression, repose angle, pore volume, and particle size distribution (sharpness) of the obtained cellulose powder. For example, in the case where the cellulose dispersion is dried by disc spray drying, the stirring power at the time of preparing the cellulose dispersion is set to a specific range, and the cellulose dispersion at the time of spray drying is The conditions for the concentration of the solid component and the number of revolutions of the disc spray drying are set in a specific range, and a cellulose powder having an average particle diameter and a particle size distribution in a specific range can be obtained. The compression degree, repose angle, sharpness, and pore volume can also be adjusted by controlling the stirring conditions.

＜ Lozenges ＞
By blending the cellulose powder according to this embodiment to a composition containing an active ingredient for tableting, a tablet can be obtained which suppresses segregation of the active ingredient and has excellent balance between hardness and disintegrability. Hereinafter, a composition for tableting and containing one or more active ingredients and the cellulose powder of this embodiment is referred to as a "composition of this embodiment".

The blending ratio of the cellulose powder of this embodiment to the composition of this embodiment is preferably about 0.1 to 50% by mass, more preferably 0.1 to 20% by mass, and even more preferably 0.1 to 10% by mass.

＜ Active ingredient ＞
In the present invention and the specification of the present case, the term "active ingredient" refers to those added to a powder, a molded product, a processed product, or the like in order to exert a target function or effect in pharmaceuticals, health foods, foods, industrial fields, and the like. For example, the active ingredient in the pharmaceutical field is a medicinal active ingredient.

The following are examples of those which are suitable as the active ingredient contained in the composition of this embodiment.
As a medicinal ingredient, an effective ingredient of a medicinal product administered orally is preferred. Examples of medicines for oral administration include antipyretic analgesics and anti-inflammatory drugs, hypnotic sedatives, drowsiness suppressants, anti-dizziness drugs, children's analgesics, stomachic drugs, antacids, digestive drugs, cardiotonics, and arrhythmia drugs , Antihypertensive drugs, vasodilators, diuretics, anti-ulcer drugs, intestinal regulators, osteoporosis drugs, antitussive and expectorants, anti-asthma drugs, antibacterial agents, frequent urination improvers, nourishing and strengthening agents, vitamins, etc. . The medicinal ingredients can be used alone or in combination of two or more.

Specifically, for example, aspirin, aspirin aluminum, acetaminophen, o-ethoxybenzamide, salicylic acid, salicylic acid, salicylamine, lactam ethoxyaniline, nitroisopropyl hydrochloride, and diphenyllaline , Diphenhydramine hydrochloride, diphenterol hydrochloride, triprolidine hydrochloride, triprenamin hydrochloride, senacetin hydrochloride, fenethyl hydrochloride, medicin hydrochloride, diphenhydramine salicylate, diphenyl disulfon Carbishamine tartrate, Alima tartrate, diphenhydramine tanninate, diphenylarin theophylline, mechelin, promintadine methylene disalicylate, carbitamin maleate, dl- Chlorpheniramine maleate, chlorpheniramine d-maleate, diphenterol phosphate, aloramine hydrochloride, clopistine hydrochloride, pentovirin citrate (vitretinine citrate), Tepididine citrate, Sodium Dibuterol, Dextromethorphan Hydrobromide, Dextromethorphan phthaloline, Tepidine Phenylphenate, Cloperastine Fendizoate, Codeine Phosphate , Codeine dihydrogen phosphate, narcotine hydrochloride, narcotine hydrochloride, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, guaiacol Potassium acid, guaiacol glyceryl ether, sodium benzoate caffeine, caffeine, anhydrous caffeine, vitamin B1 and its derivatives, and salts thereof, vitamin B2 and its derivatives, and salts thereof, and vitamin C And its derivatives and such salts, hesperidin and its derivatives and these salts, vitamin B6 and its derivatives and these salts, nicotinamide, calcium pantothenate, aminoacetic acid, Magnesium silicate, synthetic aluminum silicate, synthetic aluminum magnesium carbonate, magnesium oxide, dihydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel (as dry aluminum hydroxide gel), dry aluminum hydroxide Gel, aluminum hydroxide-magnesium carbonate mixed dry gel, co-precipitation product of aluminum hydroxide-sodium bicarbonate, co-precipitation product of aluminum hydroxide-calcium carbonate-magnesium carbonate, co-precipitation of magnesium hydroxide-potassium aluminum sulfate Products, magnesium carbonate, magnesium aluminum silicate, ranitidine hydrochloride, cimetidine, famotidine, naproxen, diclofenac sodium, piroxicam, osmium, indomethacin, ketoprofen, cloth Ibuprofen, Difenidol hydrochloride, Dibenylline hydrochloride, Diphenhydramine hydrochloride, Prominta hydrochloride Benzylamine hydrochloride, Diphenhydramine tanninate, Diphenhydramine tanninate, Diphenylline tanninate, Diphenylline theophylline chlorate, Diphenhydramine fumarate, Puminyl methylene disalicylate Scopolamine hydrobromide, oxybenzamine hydrochloride, dicyclovirin hydrochloride, methioxanthine hydrochloride, atropine methyl bromide, methylbromotropine, methylbromoscopolamine, methyl bromide-1-butanine, formazan Brombratinate, Belladonna Extract, Isopropylamine, Diphenylpiperidylmethyldioxolane iodide, Papaverine hydrochloride, Aminobenzoic acid, Cesium oxalate, Piperidylacetamidine Ethyl benzoate, amine theophylline, dihydroxyprophylline, theophylline, sodium bicarbonate, furan Thiamine, isosorbide nitrate, ephedrine, cephalexin, ampicillin, sulfisoxazole, sucralfate , Allyl isopropyl acetourea, bromisopreneurea, etc., ephedra, pelargonium, yellow arsenic, polygala, licorice, platycodon, plantain, plantain, beautiful polygala, caladium, fennel, cork, coptis , Curcuma, Chamomile, Cinnamon, Gentian, Bezoar, Animal Gall (including bear bile), Adenophora, Ginger, Atractylodes, Clove, Chenpi, Atractylodes, Earth , Bamboo ginseng, ginseng, valerian, peony peel, Japanese pepper, and extracts thereof, insulin, vasopressin, interferon, urokinase, seraminase, somatostatin and other "Japanese Pharmacopoeia", "Japan "Pharmacopharmaceutical Standards (External Base)", "United States Pharmacopoeia (USP)", "National Medicines Collection (NF)", "European Pharmacopoeia (EP)", etc. One kind selected from the above may be used alone, or two or more kinds may be used in combination.

The active ingredient for health foods is not particularly limited as long as it is an ingredient formulated for the purpose of improving health, and examples thereof include green juice powder, aglycones, Brazilian mushrooms, Brazilian Ashwagandha, astaxanthin, and western Indian cherry, amino acids (valine, leucine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, histamine, cystine, tyramine Acid, arginine, alanine, aspartic acid, seaweed powder, glutamine, glutamic acid, glycine, proline, serine, etc.), alginic acid, ginkgo leaf extract, sardine peptide, Turmeric, uronic acid, Echinacea, Acanthopanax senticosus, oligosaccharide, oleic acid, riboprotein, catfish peptide, catechin, potassium, calcium, carotenoids, garcinia cambogia, L-carnitine , Chitosan, conjugated linoleic acid, aloe vera, Gymnema sylvestre extract, citric acid, orthosiphon aristatus, glycerides, glycerin, glucagon, curcumin, glucose Amine, L-glutamine, green algae, bilberry extract, cat's claw, germanium, enzyme, Korean ginseng extract , Coenzyme Q10, Collagen, Collagen peptide, Coleus forskohlii, Chondroitin, Psyllium husk powder, Hawthorn extract, Saponin, Lipid, L-cystine, Perilla extract, Vine Yellow fruit, fatty acids, phytosterols, seed extracts, spirulina, squalene, white willow, ceramide, selenium, St. John's wort extract, soy isoflavones, soy saponins, soy peptides, soy lecithin, single Sugar, protein, Vitex agnus-castus extract, iron, copper, docosahexaenoic acid, tocotrienol, nattokinase, natto culture extract, sodium nicotinate, nicotinic acid , Disaccharide, lactic acid bacteria, garlic, saw palmetto, germinated rice, coriander extract, herbal extract, valerian extract, pantothenic acid, hyaluronic acid, biotin, chromium picolinate, vitamin A, A2, vitamin B1, B2 , B6, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K, Hydroxytyrosol, Bifidobacterium, Saccharomyces cerevisiae, Fructooligosaccharides, Flavonoids, Pseudoleaf Tree Extract, Actaea racemosa, Blueberry, plum tree extract, ex Anthocyanins, protein, propolis, pineapple protein, probiotics, phospholipids, choline, phospholipids, serine, β-carotene, peptides, safflower extract, Maitake extract, maca extract, magnesium, Milk thistle, manganese, mitochondria, minerals, mucopolysaccharides, melatonin, Phellinus Linteus, yellow vanilla extract, molybdenum, vegetable powder, folic acid, lactose, lycopene, linseed oil Acid, lipoic acid, phosphorus, lutein, lecithin, rosemary acid, royal jelly, DHA (Docosahexaenoic Acid, docosahexaenoic acid), EPA (Eicosapentaenoic Acid, eicosapentaenoic acid) and the like.

The active ingredient may be water-soluble or hardly soluble. The so-called "insoluble" means that in the 17th revision of the Japanese Pharmacopoeia, the amount of water required to dissolve 1 g of the solute needs to be 30 mL or more. Examples of the active ingredient which is hardly soluble in water include acetaminophen, ibuprofen, benzoic acid, o-ethoxybenzamide, caffeine, camphor, quinine, calcium gluconate, dimercaptopropanol, sulfonamide, Theophylline, theobromine, riboflavin, mephenoxine, phenobarbital, amine theophylline, thiothiourea, quercetin, rutin, salicylic acid, theophylline sodium salt, pitbitru, hydrochloride Ning, igbilin, digitalis toxin, griseofulvin, phenacetin and other antipyretic and analgesics, neurological medicine, sedative hypnotics, muscle relaxants, blood pressure sclerosing agents, antihistamines, etc. Antibiotics such as spiramycin, ampicillin, erythromycin, guitomycin, chloramphenicol, triethylamycin, nystatin, colistin sulfate, etc .; methyltestosterone, methylandrodiol, pregnancy Steroid hormones such as ketones, estradiol benzoate, ethinyl estradiol, deoxycorticosterone acetate, cortisone acetate, hydrocortisone, hydrocortisone acetate, prednisolone; diestradiol , Non-steroidal eggs such as diethylstilbestrol, diethylstilbestrol, diethylstilbestrol dipropionate and chlorestradiol Hormonal agents; fat-soluble vitamins like other "Japanese Pharmacopoeia", "outlier group", "USP", "NF", "EP" as described in the pharmaceutical and medicinal substances. One kind selected from the above may be used alone, or two or more kinds may be used in combination. If it is poorly soluble in water, the effect of the present invention can be obtained by blending it as the active ingredient in the composition of this embodiment regardless of the degree of sublimation and surface polarity.

The active ingredient may be oily or liquid insoluble in water. As the water-insoluble, oily or liquid active ingredient in the active ingredient, for example, teprenone, indomethacin, esters of tetramenaquinone, phytonadione, vitamin A oil, and phenylpentane Alcohols, vitamin D, vitamin E and other vitamins, DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), liver oil and other higher unsaturated fatty acids, coenzyme Q, orange oil, lemon oil, Oil-soluble flavorings such as peppermint oil and other medicinal ingredients such as those described in "Japanese Pharmacopoeia", "External Base", "USP", "NF", and "EP". Various homologues and derivatives exist in vitamin E, and they are not particularly limited as long as they are liquid at normal temperature. Examples include dl-α-tocopherol, dl-α-tocopheryl acetate, d-α-tocopherol, and d-α-tocopheryl acetate. One kind selected from the above may be used alone, or two or more kinds may be used in combination.

The active ingredient may be a semi-solid active ingredient which is poorly soluble in water. Examples of semi-solid shapes that are insoluble in water in the active ingredient include: Dilong, Licorice, Cinnamon, Paeonia lactiflora, Peony skin, Valerian, Japanese pepper, Ginger, Chenpi, Ephedra, Pelargonium, Yellow Arsenic, Polygala, Platycodon , Plantain, Plantain, Amaryllid, Polygala, Fritillaria, Fennel, Cork, Pistacia, Curcuma, Chamomile, Gentian, Bezoar, Animal Gall, Ginseng, Ginger, Atractylodes, Clove, Chenpi, Atractylodes, Bamboo Ginseng Chinese herbal medicine or natural medicine extracts such as ginseng, pueraria tang, Guizhi Tang, Xiangsu San, Zihu Guizhi Tang, Xiaozihu Tang, Xiaoqinglong Soup, Maimendong Soup, Pinellia Officinalis Soup, Ephedra Soup, etc .; oyster meat extract Substances, propolis and propolis extracts, coenzyme Q and so on. One kind selected from the above may be used alone, or two or more kinds may be used in combination.

The active ingredient may be sublimable. Examples of sublimable active ingredients include "Japanese Pharmacopoeia" and "Exobase" such as benzoic acid, o-ethoxybenzamide, caffeine, camphor, salicylic acid, phenacetin, and ibuprofen. , "USP", "NF", "EP" as sublimable medicinal ingredients, etc. One kind selected from the above may be used alone, or two or more kinds may be used in combination. In addition, the so-called sublimable active ingredient described in the present invention is not particularly limited as long as it has a sublimable property, and may be solid, liquid, semi-solid, or semi-solid at normal temperature. For either state.

These active ingredients can be formulated into the composition of the present embodiment together with the cellulose powder of the present embodiment in a finely pulverized state. For example, the active ingredient used in the present invention may be finely pulverized with an average particle diameter of 1 to 40 μm in order to improve the dispersibility of the active ingredient, or to improve the mixing uniformity of a small amount of active ingredient with medicinal effects. The smaller the average particle diameter of the active ingredient, the greater the effects such as the prevention of segregation of the cellulose powder in this embodiment. The average particle diameter of the active ingredient is more preferably 1 to 20 μm, and still more preferably 1 to 10 μm.

Both of these active ingredients and the cellulose powder of this embodiment have charging characteristics. The charge of the cellulose powder in this embodiment is +1 to 10 nC / g. The active ingredient exists either in a case where it is mixed with an ingredient such as an excipient and changes or decreases due to frictional charging, or there is a case where the active ingredient is kept still. By mixing with the cellulose powder of this embodiment, the negatively charged active ingredient interacts with and adsorbs the cellulose powder, so segregation is not likely to occur. On the other hand, the positively charged active ingredients do not interact with the cellulose powder, and they exist separately. Therefore, when flowing, the excipient with the higher flow flows first, and the active ingredient with the lower flowability flows later, so segregation is likely to occur.

The charge of the active ingredient can be measured using a Faraday meter (manufactured by Kasuga Electric Corporation). For example, about 10 g of the active ingredient can be added to a glass container, and the charged amount can be measured after being mixed by hand and shaken up and down 120 times. Among the above active ingredients, examples of the charged amount after shaking are 0 to +5 nC / g include, for example, chloropheniramine 1-maleate, chlorpheniramine d-maleate, aminophylline, O-ethoxybenzamide and so on. Aspirin is used if the charged amount after shaking is -5 to 0 nC / g. Examples of a charged amount after shaking are -5 to -20 nC / g, such as acetaminophen and ibuprofen. The cellulose powder of this embodiment has a segregation prevention effect widely in various active ingredients from the lower charged to the higher.

The composition of this embodiment may further contain other additives in addition to the above-mentioned active ingredients. Examples of other additives include excipients, disintegrating agents, binding agents, plasticizers, lubricants, and flavoring agents.

Examples of the excipient include acrylic acid starch, L-aspartic acid, aminoethylsulfonic acid, aminoacetic acid, sugar (powder), gum arabic, gum arabic, alginic acid, sodium alginate, α- Starch, pumice, inositol, ethyl cellulose, ethylene vinyl acetate copolymer, sodium chloride, olive oil, kaolin, cocoa butter, casein, fructose, pumice, carboxymethyl cellulose, carboxylate Sodium methylcellulose, hydrous silica, dried yeast, dried aluminum hydroxide gel, dried sodium sulfate, dried magnesium sulfate, agar, agar powder, xylitol, citric acid, sodium citrate, disodium citrate, Glycerin, calcium glycerophosphate, sodium gluconate, L-glutamine, clay, clay 3, clay particles, croscarmellose sodium, crospovidone, magnesium aluminosilicate, calcium silicate, silicic acid Magnesium, light silicic anhydride, light liquid paraffin, cinnamon powder, crystalline cellulose, crystalline cellulose-sodium carboxymethyl cellulose, crystalline cellulose (grain), Xuanmiqu, synthetic aluminum silicate, synthetic aluminum magnesium carbonate, Sesame oil, wheat flour, wheat starch, wheat germ flour, rice flour, rice starch , Potassium acetate, calcium acetate, silicic acid crystalline cellulose, cellulose acetate phthalate, safflower oil, white beeswax, zinc oxide, titanium oxide, magnesium oxide, β-cyclodextrin, dihydroxyaluminum aminoacetate , 2,6-dibutyl-4-methylphenol, dimethyl polysiloxane, tartaric acid, potassium hydrogen tartrate, calcined gypsum, sucrose fatty acid ester, magnesium aluminum hydroxide, aluminum hydroxide gel, hydroxide Aluminum-sodium bicarbonate coprecipitate, magnesium hydroxide, squalane, stearyl alcohol, stearic acid, calcium stearate, polyoxystearate, magnesium stearate, soybean hydrogenated oil, refined gelatin, Refined shellac, refined white sugar, refined white sugar spherical particles, cetylstearyl alcohol, polyethylene glycol 1000 monocetyl ether, gelatin, sorbitan fatty acid ester, D-sorbitol, tricalcium phosphate, large Soy oil, soybean unsaponifiables, soybean lecithin, skimmed milk, talc, ammonium carbonate, calcium carbonate, magnesium carbonate, neutral anhydrous sodium sulfate, low-substituted hydroxypropyl cellulose, dextran, dextrin, natural aluminum silicate , Corn starch, tragacanth, silica, calcium lactate, lactose, lactose granules, perfille r101, white shellac, white vaseline, white clay, white sugar, white sugar-starch spherical particles, rye green leaf extract powder, rye malt green juice dry powder, honey, paraffin, potato starch, semi-digestive starch, human serum Albumin, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose phthalate, phytic acid , Glucose, glucose hydrate, partially alpha-starch, amylopectin, propylene glycol, powder reduced maltose sugar, powdered cellulose, pectin, bentonite, sodium polyacrylate, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil , Polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, sodium polystyrene sulfonate, polysorbate 80, polyvinyl acetal Diethylaminoacetate, polyvinylpyrrolidone, polyethylene glycol, maltitol, maltose, D-mannitol, caramel, isopropyl myristate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate Granulated matter, aluminum magnesium silicate, methyl cellulose, cottonseed meal Cottonseed oil, wood wax, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, medicinal carbon, peanut oil, aluminum sulfate, calcium sulfate, granular corn starch, liquid paraffin, dl -Malic acid, calcium phosphate-hydrogen phosphate, calcium hydrogen phosphate, calcium hydrogen phosphate granules, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, and sodium dihydrogen phosphate are equivalent to "Pharmaceutical Additives" Issued by a company limited by shares) as an excipient. These can be used alone or in combination of two or more.

Examples of the disintegrant include celluloses such as croscarmellose sodium, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose; carboxyl groups Starches such as sodium methyl starch, hydroxypropyl starch, rice starch, wheat starch, corn starch, potato starch, and partially α- starch; synthetic polymers such as crospovidone and crospovidone copolymers are equal to " "Pharmaceutical Supplements" (published by Pharmaceutical Affairs Daily Co., Ltd.) as a disintegrant. One kind selected from the above may be used alone, or two or more kinds may be used in combination. Examples of the binding agent include sugars such as white sugar, glucose, lactose, and fructose; sugar alcohols such as mannitol, xylitol, maltitol, erythritol, and sorbitol; gelatin, amylopectin, carrageenan, Locust bean gum, agar, polyglucomannose, Sanxian gum, tamarind gum, pectin, sodium alginate, acacia and other water-soluble polysaccharides; crystalline cellulose, powdered cellulose, hydroxypropyl cellulose, methyl Cellulose and other cellulose; starches such as α-chemical starch and starch paste; synthetic polymers such as polyvinylpyrrolidone, carboxyvinyl polymer, and polyvinyl alcohol; calcium hydrogen phosphate, calcium carbonate, and synthetic aluminum magnesium carbonate Inorganic compounds such as aluminum magnesium silicate are classified as binders in the "Pharmaceutical Additives Code" (issued by Pharmaceutical Affairs Daily Co., Ltd.). One kind selected from the above may be used alone, or two or more kinds may be used in combination.

Examples of the plasticizer include those classified as plasticizers in the "Pharmaceutical Additives Code" (issued by Pharmaceutical Affairs Daily Co., Ltd.) as silicon compounds such as hydrous silicon dioxide and light silicic anhydride. One kind selected from the above may be used alone, or two or more kinds may be used in combination.
Examples of the lubricant include those classified as lubricants in magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid ester, and talc equal to the "Pharmaceutical Additives Code" (published by Pharmaceutical Affairs Daily). One kind selected from the above may be used alone, or two or more kinds may be used in combination.
Examples of the flavoring agent include glutamic acid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaric acid, malic acid, ascorbic acid, sodium chloride, and 1-menthol equal to "Pharmaceutical Supplements" (medicine) Classified as a flavoring agent in the Japan Daily News Co., Ltd.). One kind selected from the above may be used alone, or two or more kinds may be used in combination.

Examples of the flavor include oils such as orange, vanilla, strawberry, yogurt, menthol, fennel oil, cinnamon oil, bitter orange oil, and peppermint oil, and green tea powder is equivalent to "Pharmaceutical Supplements" (issued by Pharmaceutical Affairs Daily) ) Are classified as fragrances and fragrances. One kind selected from the above may be used alone, or two or more kinds may be used in combination.
Examples of the colorant include food colorants such as Edible Red No. 3, Edible Yellow No. 5, and Edible Blue No. 1, sodium sodium chlorophyll, titanium oxide, and riboflavin. ) Are classified as colorants. One kind selected from the above may be used alone, or two or more kinds may be used in combination.
Examples of sweeteners include aspartame, saccharin, dipotassium glycyrrhetinate, stevia, maltose, maltitol, caramel, and powdered tea, which are classified as "Pharmaceutical Supplements" (published by Pharmaceutical Affairs Daily) Sweetener. One kind selected from the above may be used alone, or two or more kinds may be used in combination.

＜ Method for manufacturing lozenges ＞
Hereinafter, a method for manufacturing a tablet (a method for manufacturing a tablet according to this embodiment) by tableting a composition containing one or more active ingredients and the cellulose powder according to this embodiment is described, but this is an example. The effects of this embodiment are not limited to the following methods.

As a method for manufacturing a lozenge, a method in which the active ingredient and the cellulose powder of this embodiment are mixed and then compression-molded can be adopted. In this case, in addition to the active ingredient, other additives may be blended as necessary. Examples of the other additives include those selected from the above-mentioned components such as excipients, disintegrating agents, binders, plasticizers, lubricants, flavoring agents, flavors, colorants, sweeteners, and dissolution aids. 1 or more.

The order of adding the ingredients is not particularly limited, and may be i) a method of mixing the active ingredient, the cellulose powder of this embodiment, and other additives as needed, and performing compression molding; ii) the active ingredient and plasticizing Additives such as agents and / or lubricants are pre-processed and mixed, and after the cellulose powder of this embodiment is mixed with other additives as needed, compression molding is performed. Due to the simplicity of operation, i) is preferred. A lubricant may be added to the compression molding mixture obtained in i) and ii), and after further mixing, compression molding may be performed. The method for adding each component is not particularly limited as long as it is a conventional method, and a small suction conveying device, an air conveying device, a bucket conveyer, a pressure conveying conveying device, a vacuum conveying device, a vibration type dosing device, Sprayers, funnels, etc. are added continuously, or they can be put in at once. The spraying method may be a method of spraying an active ingredient solution / dispersion liquid using a pressure nozzle, a two-fluid nozzle, a four-fluid nozzle, a rotating disk, an ultrasonic nozzle, or the like; a method of dripping an active ingredient solution / dispersion liquid from a tubular nozzle Either of them.

The mixing method is not particularly limited as long as it is a conventional method, and a container-type rotary mixer such as a V-shaped, W-shaped, double-cone, and tank-type mixer can be used; or a high-speed stirring type, a universal stirring type, a belt type, Stirring type mixers such as kneading type and conical spiral type mixers, high-speed flow type mixers, drum type mixers, and flow layer type mixers. Alternatively, a container-oscillating mixer such as an oscillator may be used.

The compression molding method of the composition is not particularly limited as long as it is a conventional method, and may be a method of compression molding using a die and a punch into a desired shape, and cutting into a desired shape after compression molding into a sheet shape in advance Method. As the compression molding machine, for example, a roll press such as a static press, a block roll press, a smooth roll press, a single punch tableting machine, or a rotary tableting machine can be used.

The method for dissolving or dispersing the active ingredient in the medium is not particularly limited as long as it is a conventional method of dissolving or dispersing, and it may be a unidirectional rotary, multi-axis, such as a portable mixer, a three-dimensional mixer, and a side mixer. Rotary type, reciprocating type, vertical type, rotary type + vertical type, pipeline type, etc. Stirring mixing method using stirring blades, jet flow type mixing method such as line stirrer, gas blowing type mixing method, use The mixing method of a high-shear homogenizer, a high-pressure homogenizer, and an ultrasonic homogenizer can also be a container-oscillation mixing method using an oscillator.

The solvent used in the production method is not particularly limited as long as it is a user of a pharmaceutical product, and for example, water and / or an organic solvent can be used. Examples include: alcohols such as methanol, ethanol, isopropanol, butanol, 2-methylbutanol, benzyl alcohol; hydrocarbons such as pentane, hexane, heptane, cyclohexane; acetone, ethyl methyl ketone Equal ketones are equal to those classified as solvents in "Pharmaceutical Additives" (published by Pharmaceutical Affairs Daily). It can be used singly or in combination of two or more. After one kind of medium is temporarily dispersed, the medium can be removed and dispersed in different mediums.

When dissolving an active ingredient in a medium, as a dissolution aid, a water-soluble polymer, a fat, a surfactant, and the like can be used. Water-soluble polymers, oils, and surfactants used as dissolution aids can be appropriately used as described in "Pharmaceutical Additives" (published by Pharmaceutical Affairs Daily). These can be used alone or in combination of two or more.

The so-called formed body described in the present invention is in the form of granules, fine particles, slag, lozenges, etc., and contains the cellulose powder of this embodiment, one or more active ingredients, and other additives as needed. Examples of the method for forming a tablet include a direct tableting method: a method in which an active ingredient is mixed with the cellulose powder of the present embodiment, or one or more active ingredients are mixed, the cellulose powder in the present embodiment, And other additives as needed directly compression molding. In addition, a manufacturing method such as a multi-core ingot in which a compression-molded tablet is used as a core, and a multilayer ingot in which a plurality of compacts that have been compressed in advance are stacked and compressed again may be used. In terms of productivity and ease of step management, the direct ingot method is preferred.

The compression-molded tablet (molded article) may be further coated. Examples of the coating agent used in this case include the coating agents described in the "Pharmaceutical Additives Code" (issued by Pharmaceutical Affairs Daily). These can be used alone or in combination of two or more.

As a granulation method when granulation is performed in a manufacturing step, there are dry granulation, wet granulation, heating granulation, spray granulation, and microencapsulation. Regarding the wet granulation method, specifically, the flow layer granulation method, the agitation granulation method, the extrusion granulation method, the pulverization granulation method, and the rotary granulation method are more effective. In a fluidized bed granulation device, granulation is performed by spraying a binding liquid onto the fluidized powder. In the stirring granulation method, while adding a binding liquid, the stirring blade is rotated in a mixing tank, thereby simultaneously performing powder mixing, kneading, and granulating in a closed structure. In the extrusion granulation method, by using a spiral type or a basket type, a wet block kneaded by adding a binding liquid is forcibly extruded from a screen of an appropriate size, thereby granulating. In the pulverization and granulation method, the rotating blade of the granulator is used to cut and pulverize the wet mass kneaded by adding a binding liquid, and then discharge it from the outer sieve by using the centrifugal force, thereby granulating. In the rotary granulation method, the centrifugal force of the rotating rotor is used to rotate. At this time, the binding liquid sprayed from the spray gun is used to gradually grow spherical particles with a uniform particle size in a snowball manner, thereby granulating.

The granulated material can be dried by any method, such as hot air heating (cabinet drying, vacuum drying, and fluidized layer drying), conduction heat transfer (pan type, shelf type, drum type), or freeze drying. a way. In the hot air heating type, the additive is directly contacted with the hot air, and the evaporated water is removed at the same time. In the conductive heat transfer type, the additive is indirectly heated by the heat transfer wall. In freeze-drying, the additives were frozen in advance at -10 to 40 ° C, followed by heating under high vacuum (1.3 × 10 ^-5 to 2.6 × 10 ^-4 MPa), whereby the water was sublimated and removed.

The method for adding one or more active ingredients, the cellulose powder, other additives, or granules of this embodiment is not particularly limited as long as it is a conventional method, and a small suction conveying device, an air conveying device, and a bucket conveyance can be used. Machines, pressure-feeding conveyors, vacuum conveyors, vibratory dosing machines, sprayers, funnels, etc. are added continuously, and can also be put in at one time. It is preferable that the content of the active ingredient in the composition and the molded body of the present embodiment, CV (Coefficient of variation, variation), by adding 0.1 to 50 parts by mass of the cellulose powder of the present embodiment and containing 0.1 to 20% by weight of the active ingredient. Coefficient) is 5% or less, preferably 2% or less, and particularly preferably 1.5% or less. The content CV of the active ingredient is expressed by the following formula by using the average value and standard deviation of the content of the active ingredient in the composition or the formed body. In addition, the content of the active ingredients in the tablets and powders is as follows, and a calibration curve of each active ingredient can be prepared and obtained by a quantitative method using an absorbance method, but it can also be based on the situation of each active ingredient. Choose the appropriate quantitative method. For example, when the active ingredient is poorly soluble, a quantitative method using gas chromatography is appropriate, and when a plurality of active ingredients are included, a quantitative method using liquid chromatography is appropriate. For the method of quantifying the active ingredient, please refer to the description of the 17th revised general test method of the Japanese Pharmacopoeia.

[Content CV (%)] = [Standard deviation of content of active ingredient] / [Average value of content of active ingredient] × 100
[Example]

The present embodiment will be described in detail below with reference to examples and comparative examples. The embodiments of the present invention are not limited to these, and the measurement methods of various physical properties are based on the description of the following examples.

(1) Average particle diameter of cellulose dispersed particles (μm)
The sample dispersed in water was measured with a refractive index of 1.20 using a laser diffraction particle size distribution meter (LA-950 V2 (trade name): manufactured by HORIBA, Ltd.) without ultrasonic treatment. The 50% cumulative volume of particles obtained by the measurement is defined as the average particle diameter (μm) of the cellulose dispersed particles.

(2) Water content of cellulose powder The water content of cellulose powder was measured using a moisture meter (FD-240: manufactured by Kett Scientific Research Institute). About 3.0 g of powder was used for measurement, and the measurement conditions of this moisture meter were set to 105 ° C (automatic measurement mode, monitoring time: 60 seconds).

(3) average particle size of cellulose powder (μm)
Use a jet sieve (A200 LS: manufactured by ALPINE) to suck 5.0 g of the powder for 5 minutes (-2.0 Pa or more), and divide the weight of the powder remaining on each sieve by the original powder weight. Calculate the ratio of particles. The sieve used is a stainless steel (manufactured by ALPINE) specified in the JIS standard, and the mesh size is selected from 45 μm (outer shape 200f), 32 μm (outer shape 200f), and 20 μm (outer shape 70f).

The ratio of particles remaining on the sieve with a mesh size of 45 μm is calculated by the following method: about 5.0 g of powder is sucked for 5 minutes (-2.0 Pa or more), and the powder remaining on the sieve with a mesh size of 45 μm The weight of the body divided by the weight of the powder used in the measurement. The ratio of particles passing through a sieve with a mesh size of 45 μm and remaining on a sieve with a mesh size of 32 μm (hereinafter referred to as “particles with a mesh size of 45-32 μm”) was calculated by the following method: The powder with a mesh of 45 μm passed through a 32 μm mesh, and the weight of the powder remaining on the sieve was divided by the weight of the powder used in the measurement. The ratio of particles passing through a sieve with a mesh size of 32 μm and remaining on a sieve with a mesh size of 20 μm (hereinafter referred to as “particles with a mesh size of 32-20 μm”) is similarly calculated by the following method: The powder that passed the sieve with a mesh size of 32 μm was passed through a sieve with a mesh size of 20 μm. The weight of the powder remaining on the sieve was divided by the weight of the powder used before the measurement. The ratio of particles with a mesh size of 45-20 μm is the total of particles with a mesh size of 45-32 μm and particles with a mesh size of 32-20 μm. Determine the size of the cumulative mass of 50% based on the ratio (mass%) of the weight of the powder remaining on each sieve to the weight of the powder used in the measurement, and set it as the average particle size of the powder (μm ).

(4) Sharpness of cellulose powder According to the ratio (mass%) of the weight of the powder remaining on each sieve measured in (3), the cumulative mass of 10% particle diameter (D10) and the cumulative mass of 50% The particle diameter (D50) and the cumulative mass 90% particle diameter (D90) were calculated by the following formula.

[Sharpness of particle size distribution] = [(D50 / D10) + (D90 / D50)] / 2

(5) The measurement of the repose angle of the cellulose powder is a powder whose moisture content is adjusted to 3.5 to 4.5% by mass. When the range of the moisture content of the powder is lower than the lower limit, the powder is adjusted to absorb moisture by using a constant temperature and humidity machine. When the upper limit is exceeded, a hot air oven is used to uniformly supply hot air at 60 ° C. to the powder to adjust the moisture content within the range. The rest angle of cellulose powder is determined by using a Sugihara-type repose angle measuring device (slot scale: depth 10 × width 50 × height 140 mm, width 50 mm). The metering device is used at 50 cc / min. The dynamic self-flow property when the cellulose powder was dropped into the slit at a speed was determined. The angle between the bottom of the device and the layer forming the cellulose powder is the angle of repose. The measurement was performed 5 times, and the average value was calculated.

(6) Aspect ratio of cellulose powder The "particles with a mesh size of 45 to 32 µm" obtained in (3) were measured. Particles with a mesh size of 45-32 μm were placed on a glass plate, and the particles were dispersed so as not to overlap each other, and photographed at a magnification of 500 times using a microscope (VHS-1000: manufactured by Keyence). The image processing analysis system software (Image HyperII: manufactured by DigiMo) was used to analyze the captured images in the following order to determine the aspect ratio of the particles. At least 50 particles were measured and the average value was determined.

Sequence 1 Binarization process The image captured by the microscope is taken into the analysis software in monochrome, and the scale of the image is set by the 2-point distance method. Next, select "Otsu method" in the binarization process and set the threshold. Since the optimal threshold is different for each image, the threshold is selected in such a manner as to be consistent with the shape of the original particle while observing and comparing with the original image.

Sequence 2 Binarize manually to observe and compare with the captured original image, delete particles that overlap with each other, particles that overflow from the screen, particles that are unclear and blurred, and other particles that cannot obtain appropriate measurement results, and Excluded from the measurement object.

Step 3 Fill in "Fill" mode, select "8" for "Near", and execute "Fill". Next, use the "two-value image manual correction" again to compare with the original image, and check whether the correction can be performed normally. If the correction cannot be performed normally, perform manual correction again.

Sequence 4 Set the number of deleted pixels to "100" for image measurement, and select "8" for "Nearby", and then perform "Image measurement". The measurement results of "long diameter" and "short diameter" are displayed on a personal computer for each measurement particle. The value obtained by dividing the "long diameter" by the "short diameter" is set to the aspect ratio.

(7) The measurement of the degree of compression of the cellulose powder is a powder whose moisture content is adjusted to 3.5 to 4.5% by mass. The moisture content of the powder was adjusted in the same manner as in the above (5).
A powder physical property measuring machine (PT-R: manufactured by Hosokawa Micron) was used to measure "loose apparent specific gravity" and "compact apparent specific gravity", and the degree of compression was measured according to the following formula. The mesh size of the sieve used is 710 μm, and the funnel uses a metal (antistatic spray coating) inner diameter of 0.8 cm. VIBRATION was performed at 2.0 (60 Hz).

[Compression (%)] = ([Tensional Apparent Specific Gravity]-[Loose Apparent Specific Gravity]) / [Tensional Apparent Specific Gravity] × 100

(8) Pore volume of cellulose powder The pore volume of cellulose powder was measured using a pore distribution measuring device (AutoPore 9520 type: manufactured by Micromeritics (Shimadzu Corporation)) using a mercury intrusion method. The measurement is to divide about 0.12 g of cellulose powder into a standard unit for 5 cc powder (stem volume 4 cc) at an initial pressure of 20 kPa (about 3 psia and a pore diameter equivalent to about 60 μm). get on. Mercury parameters were set to a mercury contact angle of 130.0 degrees and a mercury surface tension of 485.0 dynes / cm. As a result, the pore volume was measured over the entire range.

(9) Compressibility of cellulose powder alone Compressing and molding only cellulose powder using a compressor to produce a tablet. For tableting, a cellulose powder whose moisture content is adjusted to 3.5 to 4.5% by mass is used. The moisture content of the cellulose powder was adjusted in the same manner as in the above (5). Lozenges of system use is provided with a diameter of 1.13 cm (bottom area of 1 cm ²⁾ of the flat-faced punches (Kikusui Seisakusho, material used SUK2,3) and a die (Kikusui Seisakusho, the material uses SUK2,3) of the tabletting machine (1325VCW: manufactured by Aikoh Engineering). Specifically, 500 mg of powder was put into a die, and compressed at 1 kN and 3 kN using a tableting machine, and held under the stress for 10 seconds, thereby preparing a tablet.

(10) Hardness measurement of tablets The hardness of tablets made only of cellulose powder. Specifically, the hardness of the tablet prepared in (9) was measured with a hardness tester (Tablet Tester 8M: manufactured by DR. Schleuniger) after 20 to 48 hours after the tableting. The tablet prepared in (9) is added to Lamizip so as not to be hygroscopic until the hardness is measured, sealed, and stored at room temperature. The average value of each 5 ingots was set as the hardness of the tablets.

(11) Disintegration test of tablets According to the 17th revision of the Japanese Pharmacopoeia, the general test method "disintegration test method" (test liquid: conditions for the presence of water and discs), investigation of the disintegration of tablets using only cellulose powder Solution. The disintegration tester (NT-40HS (trade name): manufactured by Toyama Industries) was used for the tablet prepared in (9), and the disintegration time (seconds) in pure water at 37 ° C was determined. The average value of 6 tablets of the sample was taken as the disintegration time of the tablet.

(12) Weight of tablet CV
The weight of 10 tablets obtained by rotating the tablets was measured, the standard deviation of the average weight and the weight was taken, and the weight unevenness was evaluated according to the coefficient of variation (%) defined by (standard deviation / average weight) × 100. The smaller the coefficient of variation, the smaller the unevenness.

(13) Active ingredient content CV
First, a calibration curve of the active ingredient is prepared. In the examples and comparative examples of this case, the absorption spectrum of the active ingredient is measured using an absorbance meter, and a calibration curve is prepared based on the wavelength of the peak (example: d-chloropheniramine maleate: 264 nm, aspirin: 276 nm, acetaminophen wavelength: 244 nm).

(In the case of powder) 500 mg of powder was sampled and added to a 100 mL volumetric flask, and the volume was adjusted to 100 mL with pure water. After removing the insoluble component by filtering the obtained aqueous solution with a resin filter, the content of the active component in the filtrate relative to the weight of the sampled powder was quantified by the absorbance method. The powder was measured at 9 points in total, and the average value and standard deviation of the active ingredient content were determined.

(In the case of lozenges) After exactly weighing one lozenge, the same operation as the powder sample was performed to quantify the content of the active ingredient contained in the one lozenge. In the case of lozenges, the average value and standard deviation of the active ingredient content were calculated for a total of ten.

The coefficient of variation (also referred to as the content CV) as a measure of uniformity was obtained by the following formula. The lower the coefficient of variation, the better the content uniformity.
[Content CV (%)] = ([standard deviation] / [average value]) × 100

(14) Abrasion measurement of the weight (Wa) of 30 tablets, put them in a tablet abrasion tester (PTFR-A: manufactured by PHARMA TEST), rotate it at 25 rpm for 4 minutes, remove the adhesion The weight (Wb) of the fine powder of the tablet was measured again, and the degree of wear was calculated according to the following formula.

[Abrasion degree] = 100 × (Wa－Wb) / Wa

[Example 1]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped and placed in 30 L of 0.2% by mass aqueous hydrochloric acid solution, and carried out using a low-speed mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 140 ° C for 120 minutes with stirring to obtain an acid-insoluble residue. P / V was 0.3 w / L, and the average particle diameter of the cellulose-dispersed particles was 44 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) A cellulose dispersion (pH 7.5, IC54 μS / cm) with a solid content concentration of 7% by mass was prepared.
This cellulose dispersion was spray-dried (circle speed 135 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder A (drying loss 3.7% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder A are shown in Table 2.

[Example 2]
2.0 kg of commercially available KP pulp (polymerization degree 840, equilibrium polymerization degree 145) was chopped, put into 30 L of 0.3% by mass aqueous hydrochloric acid solution, and carried out using a low-speed mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 135 ° C for 100 minutes with stirring to obtain an acid-insoluble residue. P / V was 3.0 w / L, and the average particle diameter of the cellulose dispersed particles was 39 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.1, IC45 μS / cm) with a solid content concentration of 6% by mass was prepared.
This cellulose dispersion was spray-dried (circle disk speed 140 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder B (drying loss 3.9% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder B are shown in Table 2.

[Example 3]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped, put into 30 L of a 1.00 mass% hydrochloric acid aqueous solution, and carried out using a low-speed mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 130 ° C for 60 minutes with stirring to obtain an acid-insoluble residue. P / V was 1.0 w / L, and the average particle diameter of the cellulose dispersed particles was 32 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.5, IC40 μS / cm) with a solid content concentration of 4% by mass was prepared.
This cellulose dispersion was spray-dried (circle speed 170 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder C (drying loss 3.5% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder C are shown in Table 2.

[Example 4]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped and placed in 30 L of 0.65% by mass aqueous hydrochloric acid solution, and carried out using a low-speed mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 130 ° C for 60 minutes with stirring to obtain an acid-insoluble residue. P / V was 1.0 w / L, and the average particle diameter of the cellulose dispersed particles was 44 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.8, IC35 μS / cm) with a solid content concentration of 5% by mass was prepared.
This cellulose dispersion was spray-dried (circle speed 170 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder D (drying loss) 4.0% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder D are shown in Table 2.

[Example 5]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped and placed in 30 L of 0.65% by mass aqueous hydrochloric acid solution, and carried out using a low-speed mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 130 ° C for 60 minutes with stirring to obtain an acid-insoluble residue. P / V was 1.0 w / L, and the average particle diameter of the cellulose dispersed particles was 44 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) A cellulose dispersion (pH 7.4, IC43 μS / cm) with a solid content concentration of 5% by mass was prepared.
This cellulose dispersion was spray-dried (circumferential disk speed 180 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder E (drying loss 3.9% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder E are shown in Table 2.

[Example 6]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped and placed in 30 L of 0.65% by mass aqueous hydrochloric acid solution, and carried out using a low-speed mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 130 ° C for 60 minutes with stirring to obtain an acid-insoluble residue. P / V was 1.0 w / L, and the average particle diameter of the cellulose dispersed particles was 43 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.3, IC53 μS / cm) with a solid content concentration of 4.5% by mass was prepared.
This cellulose dispersion was spray-dried (circumferential disk speed 180 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder F (drying loss 3.8% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder F are shown in Table 2.

[Example 7]
2.0 kg of commercially available KP pulp (polymerization degree 840, equilibrium polymerization degree 145) was chopped, put into 30 L of 0.85% by mass aqueous hydrochloric acid solution, and carried out using a low-speed type mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 110 ° C for 160 minutes with stirring to obtain an acid-insoluble residue. P / V was 6.0 w / L, and the average particle diameter of the cellulose dispersed particles was 28 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.3, IC44 μS / cm) with a solid content concentration of 2% by mass was prepared.
This cellulose dispersion was spray-dried (circle disk speed 140 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder G (drying loss 3.9% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder G are shown in Table 2.

[Example 8]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped, put into 30 L of 0.60 mass% hydrochloric acid aqueous solution, and carried out using a low-speed type mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 130 ° C for 40 minutes with stirring to obtain an acid-insoluble residue. P / V was 7 w / L, and the average particle diameter of the cellulose dispersed particles was 45 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) A cellulose dispersion (pH 7.1, IC48 μS / cm) with a solid content concentration of 6% by mass was prepared.
This cellulose dispersion was spray-dried (160 m / sec disc peripheral speed, 6 L / h liquid supply speed, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder H (drying loss 4.2% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder H are shown in Table 2.

[Comparative Example 1]
A commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) of 2.0 kg was chopped, put into 30 L of a 10% by mass aqueous hydrochloric acid solution, and carried out using a low-speed type mixer (30 L GL reactor: manufactured by Ikebukuro Enamel Industries). Hydrolysis was performed at 105 ° C for 30 minutes with stirring to obtain an acid-insoluble residue. P / V was 7.0 w / L, and the average particle diameter of the cellulose dispersed particles was 18 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.6, IC56 μS / cm) with a solid content concentration of 10% by mass was prepared.
This cellulose dispersion was spray-dried (circle speed 151 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder I (drying loss 3.8% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder I are shown in Table 2.

[Comparative Example 2]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped and placed in 30 L of 1.5% by mass aqueous hydrochloric acid solution, and carried out using a low-speed mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 135 ° C for 90 minutes with stirring to obtain an acid-insoluble residue. P / V was 7.0 w / L, and the average particle diameter of the cellulose dispersed particles was 4 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.3, IC52 μS / cm) with a solid content concentration of 10% by mass was prepared.
This cellulose dispersion was spray-dried (circle speed 151 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder J (drying loss 3.8% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder J are shown in Table 2.

[Comparative Example 3]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped, put into 30 L of 0.8% by mass aqueous hydrochloric acid solution, and carried out using a low-speed mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 130 ° C for 50 minutes with stirring to obtain an acid-insoluble residue. P / V was 7.0 w / L, and the average particle diameter of the cellulose dispersed particles was 14 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.3, IC50 μS / cm) with a solid content concentration of 8% by mass was prepared.
This cellulose dispersion was spray-dried (circle speed 151 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder K (drying loss 3.8% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder K are shown in Table 2.

[Comparative Example 4]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped, put into 30 L of 0.39% by mass aqueous hydrochloric acid solution, and carried out using a low-speed type mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 128 ° C for 145 minutes with stirring to obtain an acid-insoluble residue. P / V was 0.2 w / L, and the average particle diameter of the cellulose-dispersed particles was 85 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.3, IC43 μS / cm) with a solid content concentration of 18% by mass was prepared.
This cellulose dispersion was spray-dried (peripheral disc speed 110 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder L (drying loss 3.8% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder L are shown in Table 2.

[Comparative Example 5]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped, put into 30 L of a 0.1% by mass aqueous hydrochloric acid solution, and carried out using a low-speed type mixer (30 L GL reactor: manufactured by Ikebukuro Enamel) Hydrolysis was performed at 135 ° C for 120 minutes with stirring to obtain an acid-insoluble residue. P / V was 0.2 w / L, and the average particle diameter of the cellulose dispersed particles was 110 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) , A cellulose dispersion (pH 7.4, IC50 μS / cm) with a solid content concentration of 20% by mass was prepared.
This cellulose dispersion was spray-dried (peripheral disc speed 110 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder M (drying loss) 3.8% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder M are shown in Table 2.

[Comparative Example 6]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped and put into 30 L of 0.49% by mass aqueous hydrochloric acid solution, and a 30 L GL reaction was performed using a low-speed type mixer (manufactured by Ikebukuro Enamel Industrial Co., Ltd. Under the conditions of stirring, hydrolysis was performed at 121 ° C. for 60 minutes to obtain an acid-insoluble residue. P / V was 0.2 w / L, and the average particle diameter of the cellulose dispersed particles was 65 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) A cellulose dispersion (pH 7.2, IC46 μS / cm) with a solid content concentration of 17% by mass was prepared.
This cellulose dispersion was spray-dried (circle disk speed 120 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder N (drying loss 4.0% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder N are shown in Table 2.

[Comparative Example 7]
2.0 kg of commercially available KP pulp (degree of polymerization 840, equilibrium degree of polymerization 145) was chopped and placed in 30 L of a 0.7% by mass aqueous hydrochloric acid solution, and a 30 L GL reaction was performed using a low-speed mixer (manufactured by Ikebukuro Enamel Industrial Co., Ltd.) Under the conditions of stirring, hydrolysis was performed at 150 ° C. for 30 minutes to obtain an acid-insoluble residue. P / V was 0.2 w / L, and the average particle diameter of the cellulose-dispersed particles was 53 μm.
The obtained acid-insoluble residue was filtered using a Buchner funnel, and the filtered residue was washed 4 times with 70 L of pure water, and neutralized with ammonia water. Add the neutralized residue to a 90 L plastic bucket and add pure water. Stir using a Sany motor (BLh1200 type, 8M / M, blade diameter about 10 cm: manufactured by HEIDON) (stirring speed 500 rpm) A cellulose dispersion (pH 7.3, IC51 μS / cm) with a solid content concentration of 10% by mass was prepared.
This cellulose dispersion was spray-dried (circle speed 115 m / sec, liquid supply speed 6 L / h, inlet temperature 180-220 ° C, outlet temperature 50-70 ° C) to obtain cellulose powder O (drying loss 3.8% by mass). The conditions at the time of manufacture are shown in Table 1, and the physical properties of cellulose powder O are shown in Table 2.

[Table 1]

[Table 2]

In Table 2, “45-20 μm” indicates the ratio (%) of the weight of particles with a mesh size of 45-20 μm to the total weight of the powder used in the measurement, and “45-32 μm” indicates a mesh size of 45- The ratio (%) of the weight of the particles of 32 μm to the total weight of the powder used in the measurement.

[Examples 9 to 16]
The cellulose powders A to H were individually compression-molded to prepare a lozenge. The hardness and disintegration test results of the obtained tablets are shown in Table 3 (the hardness is an average of 5 tablets, and the disintegration test is an average of 6 tablets).

[Comparative Examples 8 to 14]
The cellulose powders I to O were individually compression-molded to prepare a lozenge. The hardness and disintegration test results of the obtained tablets are shown in Table 3 (the hardness is an average of 5 tablets, and the disintegration test is an average of 6 tablets).

[table 3]

As shown in Table 3, the tablets of Examples 9 to 16 prepared from cellulose powders A to H were observed to have higher hardness than the tablets of Comparative Examples 8 to 14 prepared from cellulose powders I to O. And the disintegration time tends to be shortened.

[Examples 17 to 24]
10 parts by mass of each of cellulose powder A to H, 0.1 parts by mass of chloropheniramine d-maleate (average particle diameter 12 μm, charged (after 120 oscillations): 0.5 nC / g: manufactured by King Kong Chemical Co., Ltd.), and lactose ( Pharmatose 100M (trade name): manufactured by DFE pharma) 89.9 parts by mass was added to a 5 L scale V-type mixer (manufactured by Teshou Co., Ltd.) and mixed for 120 minutes, and then 1.0% by mass of magnesium stearate (additional ratio) ) And mixed, and further mixed with a V-type mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder at 9 points was sampled at 9 points, and the content of chlorpheniramine maleate was measured with an absorbance meter, and it was confirmed that it was 2% or less (essentially 1.5 ～ 1.9%).

Using a large rotary tableting machine (LIBRA2: Kikusui Manufacturing Co., Ltd.), a punch with a diameter of 8 mmf was used for the prepared mixed powder (SUK2, 3: Kikusui Manufacturing Co., Ltd.). The tablet weight was 200 mg, and the pressure was 1200 kgf. The ingot was beaten at 30 rpm for 10 minutes. About 300 ingots were sampled 10 minutes after the start of ingotting. The sampled tablets were evaluated for weight CV, hardness, disintegration test, abrasion, and content CV of chlorpheniramine d-maleate. The results are shown in Table 4.

[Comparative Examples 15 to 21]
10 parts by mass of each of cellulose powders I to O, 0.1 parts by mass of chlorpheniramine d-maleate (average particle size 12 μm, charged 0.5 nC / g), and granulated lactose (Pharmatose 100M (trade name): DFE 89.9 parts by mass was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate (additional ratio) was added and mixed. Mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder at 9 points was sampled at 9 points, and the content of chlorpheniramine maleate was measured with an absorbance meter, and it was confirmed that it was 2% or less (essentially 1.5 ～ 1.9%).
Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 4.

[Table 4]

[Examples 25 to 32] 20 parts by mass of each of cellulose powders A to H, 0.1 parts by mass of chloropheniramine d-maleate (average particle diameter 12 μm, charged 0.3 nC / g), and lactose (Pharmatose 100M ( (Product name): DFE) 79.9 parts by mass was added to a 5 L scale V-type mixer (manufactured by Teshou Kogyo Co., Ltd.) and mixed for 120 minutes, and then 1.0% (additional ratio) of magnesium stearate was added and mixed. The mixture was further mixed with a V-type mixer for 3 minutes. From the upper part, the middle part and the lower part of the V-type mixer, the mixed powder at 9 points was sampled at 9 points, and the content of chlorpheniramine maleate was measured with an absorbance meter, and it was confirmed to be less than 2% ( The content of CV is 1.3 to 1.9%. Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 5.

[Comparative Examples 22 to 28] 20 parts by mass of each of cellulose powders I to O and 0.1 parts by mass of chlorpheniramine d-maleate (average particle diameter 12 μm, charged (after 120 oscillations) 0.5 nC / g) 7, lactose (Pharmatose 100M (trade name): made by DFE) 79.9 parts by mass was added to a 5 L scale V-type mixer (manufactured by Deshou Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate was added (plus Ratio) and mixed, and further mixed with a V-type mixer for 3 minutes. From the upper part, the middle part and the lower part of the V-type mixer, the mixed powder at 9 points was sampled at 9 points, and the content of chlorpheniramine maleate was measured with an absorbance meter, and it was confirmed to be less than 2% ( The content of CV is 1.3 to 1.9%. Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 5.

[table 5]

As shown in Tables 4 and 5, in the case of using any one of the cellulose powders, the hardness of the 20% by mass tablet was higher than that of the 10% by mass tablet, and the disintegration time was prolonged. In addition, the tablets of Examples 17 to 24 made of cellulose powders A to H have smaller CV content, higher hardness, and abrasion than the tablets of Comparative Examples 15 to 21 made of cellulose powders I to O. The degree is small and the disintegration time is short (Table 4). Similarly, the tablets of Examples 25 to 32 prepared from cellulose powders A to H have a smaller CV content and higher hardness than the tablets of Comparative Examples 22 to 28 prepared from cellulose powders I to O. The degree of wear is small and the disintegration time is short (Table 5).

[Examples 33 to 40] 10 parts by mass of each of cellulose powders A to H, aspirin (average particle size 14 μm, charged (after 120 oscillations) -7.8 nC / g: manufactured by Mitsui Fine Chemicals), 12 parts by mass, lactose (Pharmatose 100M (trade name): manufactured by DFE pharma) 78 parts by mass was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate was added (additional ratio ) And mixed, and further mixed with a V-type mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powders at 9 points each were counted at 9 points, and the aspirin content was measured by the absorbance meter, and the deviation was confirmed to be less than 2% (essentially 1.3 to 1.9%). . Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 6.

[Comparative Examples 29 to 35] 10 parts by mass of each of cellulose powders I to O, aspirin (average particle size 14 μm, charged (after 120 oscillations) -7.8 nC / g: manufactured by Mitsui Fine Chemicals), 12 parts by mass, lactose (Pharmatose 100M (trade name): manufactured by DFE pharma) 78 parts by mass was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate was added (additional ratio ) And mixed, and further mixed with a V-type mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powders at 9 points each were counted at 9 points, and the aspirin content was measured by the absorbance meter, and the deviation was confirmed to be less than 2% (essentially 1.3 to 1.9%). . Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 6.

[TABLE 6]

As shown in Table 6, the tablets of Examples 33 to 40 prepared from cellulose powders A to H and the comparative examples 29 to 35 prepared from cellulose powders I to O were taken as tablets using aspirin as an active ingredient. Compared with tablets, it also has a lower CV content, higher hardness, less wear, and shorter disintegration time.

[Examples 41 to 48]
10 parts by mass of each of cellulose powders A to H, 10 parts by mass of acetaminophen (average particle size: 17 μm, charged (after 120 oscillations)-16.8 nC / g: manufactured by Shin-Nihon Pharmaceutical), and lactose (Pharmatose 100M (trade name)) : Made by DFE pharma) 80 parts by mass was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate (additional ratio) was added and mixed, and further utilized V mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder at 9 points each was counted at 9 points, and the content of acetaminophen was measured by an absorbance meter. .
Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 7.

[Comparative Examples 36 to 42]
10 parts by mass of each of cellulose powders I to O, 10 parts by mass of acetaminophen (average particle size 17 μm, charged (after 120 oscillations)-16.8 nC / g: manufactured by Shin Nippon Pharmaceutical), and lactose (Pharmatose 100M (trade name)) : Made by DFE pharma) 80 parts by mass was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate (additional ratio) was added and mixed, and further utilized V mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder at 9 points each was counted at 9 points, and the content of acetaminophen was measured by an absorbance meter. .
Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 7.

[TABLE 7]

As shown in Table 7, even in the case of acetaminophen as an active ingredient, the tablets of Examples 41 to 48 produced using cellulose powders A to H and the comparative examples 36 to 42 produced using cellulose powders I to O Compared with tablets, it also has a lower CV content, higher hardness, less wear, and shorter disintegration time.

[Example 49] 5 parts by mass of cellulose powder D, 5 parts by mass of o-ethoxybenzamide (average particle diameter 15 μm, charged (after 120 oscillations) + 3.9 nC / g: manufactured by Yamamoto Chemical Industry Co., Ltd.), 85 parts by mass of lactose (Pharmatose 100M (trade name): manufactured by DFE pharma) was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate was added (plus Ratio) and mixed, and further mixed with a V-type mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder at 9 points was sampled at 9 points, and the content of o-ethoxybenzamide was measured by an absorbance meter, and a deviation of 2% or less was confirmed. Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 8.

[Comparative Example 43] Except that cellulose powder D was not added, and lactose was 95 parts by mass, a lozenge was produced and evaluated under the same conditions as in Example 49. The results are shown in Table 8.

[TABLE 8]

[Example 50] 10 parts by mass of cellulose powder D, ascorbic acid (average particle size 10 μm, charged (after 120 oscillations)-0.5 nC / g: manufactured by northeast pharmaceutical group) 0.3 parts by mass, lactose (Pharmatose 100M (commercial product Name): DFE Pharma) 89.7 parts by mass was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, 1.0% by mass of magnesium stearate (additional ratio) was added and mixed, The mixture was further mixed with a V-type mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder at 9 points each was counted at 9 points, and the ascorbic acid content was measured by an absorbance meter, and the deviation was confirmed to be less than 2% (essentially 1.3 to 1.9%). . Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 9. [Comparative Example 44] Except that cellulose powder D was not added, and lactose was 99.7 parts by mass, a tablet was produced under the same conditions as in Example 50 and evaluated. The results are shown in Table 9.

[TABLE 9]

[Example 51] 0.3 parts by mass of cellulose powder D10, sodium salicylate (average particle size 6 μm, charged (after 120 oscillations)-1.4 nC / g: manufactured by API Corporation), lactose (Pharmatose 100M (Brand name): DFE Pharma) 89.7 parts by mass was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate (additional ratio) was added. Mix and further mix with a V-type mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder was sampled at 9 points from each 3 points, and the content of sodium salicylate was measured with an absorbance meter, and it was confirmed that it was 2% or less (essentially 1.3 to 1.9%). ). Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 10.

[Comparative Example 45] Except that cellulose powder D was not added, and lactose was 99.7 parts by mass, a tablet was produced under the same conditions as in Example 51 and evaluated. The results are shown in Table 10.

[TABLE 10]

[Example 52] 5 parts by mass of cellulose powder D10, ibuprofen (average particle size 15 μm, charged (after 120 oscillations)-12.0 nC / g: manufactured by Yonezawa Hamari Pharmaceutical Industry Co., Ltd.), lactose ( Pharmatose 100M (trade name): manufactured by DFE pharma) 85 parts by mass was added to a 5 L scale V-type mixer (manufactured by Tokusho Works) and mixed for 120 minutes, and 1.0% by mass of magnesium stearate (addition ratio) The mixture was mixed and further mixed with a V-type mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder was sampled at 9 points from each 3 points, and the content of ibuprofen was measured by an absorbance meter, and it was confirmed that it was 2% or less (essentially 1.3 to 1.9%). The deviation. Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 11. [Comparative Example 46] Except that cellulose powder D was not added, and lactose was adjusted to 95 parts by mass, a lozenge was produced and evaluated under the same conditions as in Example 52. The results are shown in Table 11.

[TABLE 11]

[Example 53]
20 parts by mass of cellulose powder D, 60 parts by mass of cellulose powder PH-102 (manufactured by Asahi Kasei Co., Ltd.), Levothyroxine (average particle size 10 μm, charged (after 120 oscillations)-1.1 nC / g : 0.1 parts by mass of manufactured by Chengdu Firster Pharmaceutical Co., 17.9 parts by mass of D-mannitol (manufactured by PEARLITOL 200SD ROQUETTE), 2 parts by mass of croscarmellose sodium (manufactured by Kiccolate ND-2HS Asahi Kasei Co., Ltd.) A 5 L scale V-type mixer (manufactured by Tokusho Works) was mixed for 120 minutes, 1.0% by mass of magnesium stearate (additional ratio) was added and mixed, and further mixed with a V-type mixer for 3 minutes. From the upper part, middle part, and lower part of the V-type mixer, the mixed powder at 9 points was sampled at 3 points, and the content of levothyroxine was measured with an absorbance meter. The deviation.
Ingot making was performed under the same conditions as in Examples 17 to 24, and evaluation was performed. The results are shown in Table 12.

[Comparative Example 47]
Except that cellulose powder D was not added, and PH-102 was 80 parts by mass, a tablet was produced under the same conditions as in Example 53 and evaluated. The results are shown in Table 12.

[TABLE 12] As shown in Tables 8 to 12, in the tablets containing o-ethoxybenzamide, ascorbic acid, sodium salicylate, ibuprofen, and levothyroxine as active ingredients, the tablets containing cellulose powder D and each Compared with comparable tablets, the comparative example also has a lower CV content, higher hardness, less wear, and shorter disintegration time.
[Industrial availability]

The cellulose powder of this embodiment is excellent in the prevention of segregation of active ingredients, and the balance between hardness and disintegrability, and thus can be suitably used in the fields of pharmaceutical preparations and health foods containing pharmaceuticals and drugs.

Claims (6)

A cellulose powder in which the average particle size of the cellulose powder is 45 μm or less, and the ratio of particles remaining on the 20 μm mesh sieve passing through a 45 μm mesh sieve exceeds 40% by mass of the total powder . For example, the cellulose powder of claim 1 includes particles remaining on a sieve with a mesh size of 32 μm and passed through a sieve with a mesh size of 45 μm, and the aspect ratio of the particles is in the range of 1.2 to 2.3. For example, the cellulose powder of claim 1 or 2, wherein the ratio of the particles remaining on the sieve with a mesh of 32 μm through a sieve with a mesh of 45 μm is more than 6 mass% with respect to the total powder. For the cellulose powder according to any one of claims 1 to 3, the repose angle is in a range of 45 to 58 °. A formed body comprising the cellulose powder according to any one of claims 1 to 4. A method for manufacturing a lozenge, which lozenges a composition comprising a cellulose powder according to any one of claims 1 to 4 and an active ingredient.