Cellulose powder and molded body

Abstract

The present invention provides a cellulose powder having a loose bulk density of less than 0.160 g / cm3, an average particle diameter of 90 to 250 μm, and a flowability speed index of 1.40 or less. Also provided is a molded body comprising at least one active component and the cellulose powder.

Description

Cellulose powder and compacts

[0001] The present invention relates to a cellulose powder and a molded product.

[0002] In the fields of medicine, food, and other chemical industries, it has been common to prepare compacts containing active ingredients by using cellulose powders such as crystalline cellulose and powdered cellulose as excipients. These cellulose particles are required to have good moldability, flowability, and disintegrability.

[0003] Tablets are widely used oral solid preparations because they are easy to take and handle and have relatively low production costs, but it is difficult for the cellulose powder used as an excipient to achieve both compactibility and disintegrability. Generally, when a cellulose powder with good compactibility is used, tablets with sufficiently high hardness and resistance to cracking or chipping are obtained, but such tablets tend to have insufficient disintegrability when taken. There is a demand for a cellulose powder that can achieve both high levels of compactibility and disintegrability.

[0004] For example, Patent Document 1 discloses that by controlling the particle structure of cellulose aggregates, developing a secondary aggregation structure, increasing the intraparticle pore volume of the cellulose aggregates, and controlling the powder properties of the cellulose aggregates within a specific range, porous cellulose aggregates with excellent moldability, fluidity, and disintegrability can be obtained, and that by using the porous cellulose aggregates as an excipient, molded products can be obtained that have no mass variation, excellent active ingredient content uniformity, sufficient hardness, no tableting problems, low friability, and excellent disintegrability. Patent Document 2 also discloses that by adjusting the powder properties of cellulose powder, such as the average degree of polymerization, average particle size, apparent specific volume, and retention rate of polyethylene glycol with a molecular weight of 400, within specific ranges, compression moldability and retention of liquid components can be improved, and that by using the resulting cellulose powder as an excipient, molded products with appropriate hardness, no liquid component seepage, and no tableting problems can be obtained. Furthermore, Patent Document 3 discloses that by adjusting the average degree of polymerization, weight-average particle diameter, and apparent specific volume to fall within specific ranges, powdered cellulose can be obtained that has good moldability when molded into a tablet or other molded article.

[0005] Patent No. 5240822 Patent No. 4737754 JP 2023-39557 A

[0006] Although the cellulose powders described in Patent Documents 1 to 3 have been developed as excipients with excellent moldability and disintegrability, further improvements are required.

[0007] In addition, powder flowability is also important for tablet production to ensure uniform weight and drug content, and the powder mixtures used to produce tablets are mixed using a wide variety of processes, so it is desirable for cellulose powders used as excipients to have good flowability in a variety of environments.

[0008] The present invention has been made in view of the above circumstances, and provides a cellulose powder that can be used to obtain tablets that have high fluidity and both high hardness and excellent disintegrability, and a molded product using the cellulose powder.

[0009] That is, the present invention includes the following aspects: [1] A loose bulk density of 0.160 g / cm ３ [1] The cellulose powder of [1] above, having an average particle size of 90 μm or more and 250 μm or less, and a fluidity rate index of 1.40 or less. [2] The cellulose powder of [1] above, having a particle size distribution sharpness of 0.50 or more and 2.50 or less. [3] The cellulose powder of [1] or [2] above, having a basic fluidity energy of 400 mJ or more and less than 850 mJ. [4] The cellulose powder of [1] above, having a tap density of 0.150 g / cm or more. ３ 0.300g / cm or more ３ [5] The cellulose powder of any one of [1] to [3] above, having a compressibility of 20% or more and less than 50%. [6] The cellulose powder of any one of [1] to [5] above, having a content of particles having a particle width of 2 μm or more of 50% or more. [7] The cellulose powder of any one of [1] to [5] above, having a loose bulk density of 0.090 g / cm ３

[10] The cellulose powder according to any one of [1] to [6], wherein the cellulose powder has a flow rate index of 1.00 or more.

[11] The cellulose powder according to any one of [1] to [6], wherein the flow rate index is 1.00 or more.

[12] A molded product comprising one or more active ingredients and the cellulose powder according to any one of [1] to [7].

[13] The molded product according to

[10] , wherein the active ingredient is a pharmaceutical active ingredient or a food active ingredient.

[0010] According to the present invention, a cellulose powder can be provided that can give a molded product having high fluidity and both high moldability and excellent disintegrability. Furthermore, by using the cellulose powder, a molded product having excellent moldability and disintegrability, particularly a tablet having high hardness and excellent disintegrability, can be provided.

[0011] <Cellulose powder> The cellulose powder according to one embodiment of the present invention (hereinafter referred to as "this embodiment") has a loose bulk density of 0.160 g / cm ３The cellulose powder of this embodiment has a loose bulk density of less than 100 μm, an average particle size of 90 μm or more and 250 μm or less, and a flow rate index (FRI) of 1.40 or less. The cellulose powder of this embodiment has a low loose bulk density, a large particle size, and a small FRI (change in flow rate with change in flow rate), and therefore has high flowability. In addition, by incorporating it as a raw material, tablets having both high hardness and excellent disintegrability can be obtained. For this reason, the cellulose powder of this embodiment is suitable as a raw material for molded products produced from powder as a raw material, and particularly as a raw material for tablets.

[0012] The cellulose powder in this specification is generally referred to as crystalline cellulose, powdered cellulose, etc., and is suitable for use as a pharmaceutical additive or food additive. Among them, crystalline cellulose is preferred as the cellulose powder. Known examples of crystalline cellulose include microcrystalline cellulose described in the 9th edition of the Official Specification of Food Additives, crystalline cellulose described in the Japanese Pharmacopoeia (18th edition), and crystalline cellulose described in the United States Pharmacopoeia, European Pharmacopoeia, etc.

[0013] [Average particle size] In the present invention and this specification, the average particle size of the cellulose powder refers to the average particle size measured with a laser diffraction / scattering particle size distribution analyzer (LA-950 V2 (trade name), manufactured by Horiba, Ltd.). Specifically, it can be measured using the method described in the examples below.

[0014] The average particle size of the cellulose powder of this embodiment may be in the range of 90 μm or more and 250 μm or less. The average particle size of the cellulose powder of this embodiment is preferably 100 μm or more, more preferably 110 μm or more, even more preferably 120 μm or more, and most preferably 130 μm or more. The average particle size of the cellulose powder of this embodiment is preferably 200 μm or less, more preferably 180 μm or less, and even more preferably 170 μm or less. Since the cellulose powder of this embodiment has an average particle size equal to or greater than the lower limit, the angle of repose is 45° or less and the flowability is good. Since the cellulose powder of this embodiment has an average particle size equal to or less than the upper limit, tablets with sufficient hardness can be produced when used as a raw material for tablets.

[0015] [Particle size distribution sharpness] The particle size distribution is a histogram with the particle size on the horizontal axis and the frequency on the vertical axis. In the present invention and this specification, the particle size distribution of the cellulose powder is measured using a laser diffraction / scattering particle size distribution analyzer (LA-950 V2 (trade name), manufactured by Horiba, Ltd.). In the present invention and this specification, the "particle size distribution sharpness" of the cellulose powder is a value expressed by the following formula. In the following formula, D １０ , D ５０ , and D ９０ are the particle diameters at 10% cumulative volume, 50% cumulative volume, and 90% cumulative volume, respectively.

[0016] [Particle size distribution sharpness] = (D ９０ -D １０ ) / D ５０

[0017] The particle size distribution sharpness of the cellulose powder of this embodiment is not particularly limited, but from the viewpoint of high fluidity and enabling the production of tablets with sufficient hardness when used as a tablet raw material, it is preferably 2.50 or less, more preferably 2.00 or less, even more preferably 1.50 or less, and most preferably 1.00 or less. The lower limit of the particle size distribution sharpness of the cellulose powder of this embodiment is not particularly limited, and is, for example, preferably 0.50 or more, more preferably 0.60 or more, and even more preferably 0.70 or more.

[0018] [Loose bulk density] The loose bulk density refers to the value obtained by dividing the mass of a powder lightly packed into a certain volume by the volume. In the present invention and this specification, the loose bulk density of a cellulose powder is measured by the following method. A Scott volumeter (Model ASTM B-329-85, manufactured by Tsutsui Scientific Instruments Co., Ltd.) is used to pack the cellulose powder into a 25 mL cylindrical metal container. The cellulose powder in the 25 mL cylindrical metal container is leveled off, and the mass (g) of the cellulose powder in the container is divided by 25 mL to obtain the loose bulk density (g / cm ３ Specifically, it can be measured using the method described in the Examples below.

[0019] The loose bulk density of the cellulose powder of this embodiment is 0.160 g / cm ３ The loose bulk density of the cellulose powder of this embodiment is less than 0.140 g / cm ３ Preferably, 0.130 g / cm or less ３ The loose bulk density of the cellulose powder of this embodiment is more preferably 0.090 g / cm ３ More than 0.100 g / cm ３ The above is more preferable. The cellulose powder of this embodiment has a loose bulk density within the above range, which means that it has high moldability, and when used as a raw material for tablets, it can produce tablets that have both high hardness and excellent disintegrability. In particular, when the loose bulk density is equal to or less than the above upper limit, it has high moldability, and when used as a raw material for tablets, it can produce tablets that have sufficient hardness.

[0020] [Fluidity Rate Index (FRI) and Basic Fluidity Energy (BFE)] The basic fluidity energy (BFE) is a type of index of the dynamic fluidity of a powder, and is a stable value of the total amount of energy required to move the powder from a stationary state downward while rotating the blade. The fluidity rate index (FRI) is a type of index of the dynamic fluidity of a powder, and is a coefficient that indicates the change in the energy value required to fluidize the powder layer when the blade speed is changed.

[0021] In the present invention and the present specification, the BFE and FRI of cellulose powder are measured by the following method. A powder rheometer (model FT4, manufactured by Freeman Technology) is used to fill a cylindrical container (50 mm x 160 mL) with cellulose powder. The "total energy amount" is calculated from the "rotational torque" and "vertical load" obtained by the spiral rotation of a blade (48.0 mm) in the cylindrical container. Continuous measurements are performed, and the most stable data is taken as the BFE. After determining the BFE, the blade rotation speed is gradually reduced to determine the total energy amount for each step. The ratio of the total energy amount at the minimum rotation speed to the total energy amount at the maximum rotation speed is taken as the FRI. The closer the FRI of a powder is to 1, the more stable the powder is against changes in flow rate. Specifically, measurements can be performed using the method described in the Examples below.

[0022] The FRI of the cellulose powder of this embodiment may be 1.40 or less. Since the cellulose powder of this embodiment has an FRI of 1.40 or less, the angle of repose is 45° or less, which not only provides good fluidity, but also enables the production of tablets with good disintegration properties when used as a tablet raw material. The FRI of the cellulose powder of this embodiment is preferably 1.30 or less, and more preferably 1.20 or less. The lower limit of the FRI of the cellulose powder of this embodiment is not particularly limited, and is, for example, preferably 1.00 or more, and more preferably 1.05 or more. Since the cellulose powder of this embodiment has an FRI within the above range, it has good stability against changes in flow rate, and the fluidity is less likely to change even when the stirring speed is changed during the stirring process in the production of a molded body, i.e., it can maintain good fluidity in various production processes.

[0023] The BFE of the cellulose powder of this embodiment is not particularly limited. The BFE of the cellulose powder of this embodiment is preferably less than 850 mJ, more preferably 830 mJ or less, from the viewpoint that the energy required for stirring in the stirring process during the production of a compact can be reduced and the physical properties of the produced compact, such as the hardness and uniformity of the active ingredient content, can be more stabilized. The lower limit of the BFE of the cellulose powder of this embodiment is not particularly limited, and is preferably 400 mJ or more, more preferably 500 mJ or more, and most preferably 550 mJ or more.

[0024] [Tap Density] Tap density refers to the bulk density when a container containing powder is mechanically tapped. In the present invention and this specification, the tap density of a cellulose powder is measured by the following method. Using a powder property measuring instrument (Powder Tester PT-R, manufactured by Hosokawa Micron Corporation), the cellulose powder is tapped onto a 100 cm ３ The container was tapped 180 times while additional cellulose powder was added at each tapping, and the mass (g) of the cellulose powder in the container was then calculated based on the container volume (100 cm ３ ) to obtain the tap density (g / cm ３ Specifically, it can be measured using the method described in the Examples below.

[0025] The tap density of the cellulose powder of this embodiment is not particularly limited. The tap density of the cellulose powder of this embodiment is 0.300 g / cm ３ Preferably less than 0.250 g / cm ３ More preferably, 0.230 g / cm or less ３ More preferably, 0.200 g / cm ３ The lower limit of the tap density of the cellulose powder of the present embodiment is not particularly limited, and is, for example, 0.150 g / cm ３ More preferably, the density is 0.160 g / cm 3 or more.

[0026] [Compressibility] Compressibility is an index that indicates the fluidity of a powder, calculated from the loose bulk density and tap density. The compressibility (%) can be calculated using the average value of the tap density (P) (g / cm3) and the average value of the loose bulk density (A) (g / cm3) according to the following formula: [Compressibility] = (P - A) / P Specifically, it can be measured using the method described in the examples below.

[0027] The degree of compression of the cellulose powder of this embodiment is not particularly limited. The degree of compression of the cellulose powder of this embodiment is preferably less than 50%, more preferably less than 45%, and even more preferably less than 40%. The lower limit of the degree of compression of the cellulose powder of this embodiment is not particularly limited, and is, for example, preferably 20% or more, more preferably 25% or more, and even more preferably 30% or more.

[0028] [Particle Width] Particle width is a value representing the length of the minor axis of a particle. With a particle stably stationary on a horizontal surface, light is applied from above in the vertical direction, and a projected image of the particle on the horizontal surface is taken. The projected image is sandwiched between two parallel lines tangent to the projected image. The smallest distance between the parallel lines is taken as the particle width. Specifically, it can be measured using the method described in the Examples below.

[0029] The content of particles having a particle width of 2 μm or more in the cellulose powder of this embodiment is not particularly limited. The content of particles having a particle width of 2 μm or more in the cellulose powder of this embodiment is preferably 50% or more, more preferably 80% or more, and even more preferably 90% or more. The upper limit of the content of particles having a particle width of 2 μm or more in the cellulose powder of this embodiment is not particularly limited, and is preferably 100% or less.

[0030] The cellulose powder of this embodiment is particularly suitable for use in tablets having a loose bulk density of 0.090 g / cm3, as it has better fluidity and can be molded into tablets having good hardness and disintegration properties. ３ 0.160g / cm or more ３ It is preferable that the average particle size is 90 μm or more and 250 μm or less, and the FRI is 1.00 or more and 1.40 or less; and the loose bulk density is 0.090 g / cm ３0.140g / cm or more ３ More preferably, the average particle size is 100 μm or more and 180 μm or less, and the FRI is 1.00 or more and 1.30 or less; and the loose bulk density is 0.100 g / cm ３ 0.120g / cm or more ３ It is more preferable that the average particle size is 130 μm or more and 170 μm or less, and that the FRI is 1.00 or more and 1.20 or less.

[0031] The cellulose powder of this embodiment is particularly suitable for use in tablets having a loose bulk density of 0.090 g / cm3, as it has better fluidity and can be molded into tablets having good hardness and disintegration properties. ３ 0.160g / cm or more ３ It is preferable that the average particle size is 90 μm or more and 250 μm or less, the FRI is 1.00 or more and 1.40 or less, and the particle size distribution sharpness is 0.50 or more and 2.50 or less; and the loose bulk density is 0.090 g / cm ３ 0.140g / cm or more ３ more preferably, the average particle size is 100 μm or more and 180 μm or less, the FRI is 1.00 or more and 1.30 or less, and the particle size distribution sharpness is 0.50 or more and 2.00 or less; and the loose bulk density is 0.100 g / cm ３ 0.120g / cm or more ３ It is more preferable that the average particle size is 130 μm or more and 170 μm or less, the FRI is 1.00 or more and 1.20 or less, and the particle size distribution sharpness is 0.70 or more and 1.00 or less.

[0032] For tablets with good flowability, hardness and disintegration properties, a loose bulk density of 0.090 g / cm ３ 0.160g / cm or more ３ A cellulose powder having an average particle size of 90 μm or more and 250 μm or less and a particle size distribution sharpness of 0.50 or more and 2.50 or less is also preferred; a loose bulk density of 0.090 g / cm ３ 0.140g / cm or more ３More preferred is a cellulose powder having an average particle size of 100 μm or more and 180 μm or less, and a particle size distribution sharpness of 0.50 or more and 1.30 or less; a loose bulk density of 0.100 g / cm ３ 0.120g / cm or more ３ More preferred is a cellulose powder having an average particle size of 130 μm or more and 170 μm or less, and a particle size distribution sharpness of 0.70 or more and 1.20 or less.

[0033] [Method for Producing Cellulose Powder] The method for producing the cellulose powder of this embodiment is described below. The cellulose powder of this embodiment is mainly characterized by a low loose bulk density and a large average particle size. Such a cellulose powder can be produced, for example, by drying a relatively low-concentration cellulose dispersion. The cellulose dispersion can be produced by dispersing a pulverized product of a natural cellulosic material in an appropriate medium.

[0034] The natural cellulosic material used as the raw material may be plant-based or animal-based. Examples of natural cellulosic materials include cellulose-containing fibrous materials derived from natural sources, such as wood, bamboo, wheat straw, rice straw, cotton, ramie, bagasse, kenaf, beet, sea squirt, and bacterial cellulose. The natural cellulosic material has a cellulose type I crystal structure. One of the above natural cellulosic materials may be used as the raw material, or a mixture of two or more of them may be used.

[0035] Here, the natural cellulosic material may be obtained by hydrolyzing a raw material such as pulp, or may not be hydrolyzed. In particular, when hydrolysis is performed, it may be acid hydrolysis, alkaline oxidative decomposition, hydrothermal decomposition, or steam explosion. Of these hydrolysis methods, any one method may be used alone, or two or more methods may be used in combination.

[0036] Furthermore, the raw material pulp is preferably used in the form of refined pulp. There are no particular limitations on the method of refining the pulp, and either mechanical pulp or chemical pulp may be used, and the method of cooking the chemical pulp may be either the SP method or the KP method. Wood-derived pulp is preferred from the viewpoints of high α-cellulose purity, easy availability, and stable supply.

[0037] Water is preferred as the medium used when dispersing the solid content containing the natural cellulosic material in an appropriate medium. Furthermore, the medium may be any medium other than water, as long as it is industrially used. For example, a mixture of water and an organic solvent may be used. Examples of such organic solvents include alcohols such as methanol, ethanol, isopropyl alcohol, butyl alcohol, 2-methylbutyl alcohol, and benzyl alcohol; hydrocarbons such as pentane, hexane, heptane, and cyclohexane; and ketones such as acetone and ethyl methyl ketone. In particular, organic solvents used in pharmaceuticals are preferred, including those classified as solvents in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.). Water and organic solvents may be used alone or in combination of two or more. The material may be dispersed in one medium, and then the medium may be removed and the material may be dispersed in a different medium.

[0038] The natural cellulosic material is subjected to a known treatment, such as mechanical treatment such as pulverization or grinding, chemical treatment such as hydrolysis, or a suitable combination of both. If necessary, a separation treatment such as centrifugation using a cyclone or centrifuge, or classification using a sieve, can also be combined. These treatments can yield a dispersion having a sufficiently small cellulose solid content. The average particle size of the cellulose in the cellulose dispersion is not particularly limited, but is preferably 300 μm or less, more preferably 5 μm to 300 μm, even more preferably 5 μm to 200 μm, and even more preferably 10 μm to 200 μm.

[0039] Examples of the pulverization method include screen pulverization methods such as a screen mill and a hammer mill; blade rotary shear screen pulverization methods such as a flash mill; airflow pulverization methods such as a jet mill; ball pulverization methods such as a ball mill and a vibration ball mill; and blade stirring pulverization methods.

[0040] Examples of the grinding method include grinding methods using stirring blades such as unidirectional rotation, multi-axis rotation, reciprocating inversion, up-down movement, rotation + up-down movement, and pipeline type blades of a portable mixer, a three-dimensional mixer, or a side mixer; jet-type stirring and grinding methods such as a line mixer; grinding methods using a high-shear homogenizer, a high-pressure homogenizer, or an ultrasonic homogenizer; and shaft rotation extrusion grinding methods such as a kneader.

[0041] In producing the cellulose powder of this embodiment, it is preferable to use a cellulose dispersion having a relatively low solid content concentration, it is more preferable to use a cellulose dispersion having a solid content concentration of 10% by mass or less, and it is even more preferable to use a cellulose dispersion having a solid content concentration of 1.0% by mass or more and 10% by mass or less.

[0042] The cellulose concentration in a cellulose dispersion is measured by the following method: 5 g of the cellulose dispersion is placed on an aluminum sheet attached to an infrared moisture meter (Kett Electric Laboratory, Model FD-240), and the dispersion is heated and dried by infrared irradiation. The cellulose concentration in the cellulose dispersion is calculated by the following formula using the moisture value (%) obtained from the mass change due to evaporation of water.

[0043] [Cellulose concentration in cellulose dispersion (%)] = 100 - [moisture value (%)]

[0044] The cellulose powder of this embodiment is then obtained by drying the resulting cellulose dispersion. The drying method is not particularly limited, and examples include freeze drying, spray drying, drum drying, shelf drying, flash drying, and vacuum drying. These drying methods may be used alone, or two or more may be used in combination. Examples of spray methods used in spray drying include disk-type, pressurized nozzle, pressurized two-fluid nozzle, and pressurized four-fluid nozzle. These spray methods may be used alone, or two or more may be used in combination. Among these, spray drying or flash drying is preferred as the drying method, since it is easy to prepare a cellulose powder having a low loose bulk density and a large average particle size, and spray drying is more preferred, with disk-type spray drying being particularly preferred.

[0045] When the cellulose dispersion is dried by disk spray drying, it is preferable to set the disk rotation peripheral speed low, for example, 105 m / s or less. By spray drying a low-concentration cellulose dispersion under conditions where the disk rotation speed is kept low, large cellulose particles with low bulk can be obtained.

[0046] During the spray drying, a small amount of a water-soluble polymer or a surfactant may be added to the dispersion in order to reduce the surface tension of the dispersion, and a foaming agent or gas may be added to the dispersion in order to accelerate the evaporation rate of the medium.

[0047] Examples of water-soluble polymers include those listed in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, gum arabic, and starch paste. These water-soluble polymers may be used alone or in combination of two or more.

[0048] Examples of surfactants include those classified as surfactants in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as phospholipids, glycerin fatty acid esters, polyethylene glycol fatty acid esters, sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene polyoxypropylene glycol, polyoxyethylene sorbitan monolaurate, polysorbate, sorbitan monooleate, glyceride monostearate, monooxyethylene sorbitan monopalmitate, monooxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, sorbitan monopalmitate, and sodium lauryl sulfate. These surfactants may be used alone or in combination of two or more.

[0049] Examples of foaming agents include those listed in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as tartaric acid, sodium bicarbonate, potato starch, anhydrous citric acid, medicated soap, sodium lauryl sulfate, lauric acid diethanolamide, and lauromacrogol. These foaming agents may be used alone or in combination of two or more.

[0050] In addition to pharmaceutical additives, other examples include bicarbonates such as sodium bicarbonate and ammonium bicarbonate that generate gas upon thermal decomposition; and carbonates such as sodium carbonate and ammonium carbonate that generate gas upon reaction with an acid. However, when using the carbonates, they must be used together with an acid. Examples of acids include organic acids such as citric acid, acetic acid, ascorbic acid, and adipic acid; protonic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, and nitric acid; and Lewis acids such as boron fluoride. Of these, acids used in pharmaceuticals or foods are preferred, but other acids also have similar effects.

[0051] Alternatively, instead of a foaming agent, a gas such as nitrogen, carbon dioxide, liquefied petroleum gas, or dimethyl ether may be impregnated into the dispersion.

[0052] The water-soluble polymer, surfactant, and gas-generating substance such as a foaming agent may be added before drying, and there is no particular limitation on the timing of their addition.

[0053] In the production of the cellulose powder of this embodiment, it is preferable to remove particles with small particle diameters from the obtained cellulose powder in advance. By removing small particles, the FRI can be kept small, and the sharpness of the particle size distribution can also be kept small. The method for removing small particles is not particularly limited, and for example, sieving using a sieve with a certain mesh size can be preferably used. For example, the sieve used in the sieving process preferably has a mesh size of 50 μm or more, more preferably a mesh size of 65 μm to 120 μm, and even more preferably a mesh size of 75 μm to 105 μm.

[0054] <Uses> The cellulose powder of this embodiment has excellent flowability, and when incorporated into solid preparations, particularly tablets, it is possible to produce tablets that are excellent in both compactibility and disintegrability. Therefore, the cellulose powder of this embodiment is extremely useful as a raw material for compacts, particularly as an additive for tablets.

[0055] <Molded Body> The molded body of the present embodiment contains one or more active ingredients and the cellulose powder of the present embodiment.

[0056] Examples of the molded article of this embodiment, when used in pharmaceuticals, include tablets, powders, fine granules, granules, extracts, pills, etc. Among these, tablets are preferred. Furthermore, the molded article of this embodiment can be used not only in pharmaceuticals but also in foods such as confectionery, health foods, texture improvers, and dietary fiber enrichment agents; solid foundations, bath additives, veterinary drugs, diagnostic agents, pesticides, fertilizers, ceramic catalysts, etc.

[0057] In the molded body of this embodiment, there are no particular restrictions on the contents of the active ingredient and cellulose powder, but in typical use ranges, the content of the active ingredient is from 0.001% by mass to 99% by mass, and the content of the cellulose powder of this embodiment is from 1% by mass to 99% by mass, relative to the total mass of the molded body. By ensuring that the content of the active ingredient is equal to or greater than the lower limit, an amount effective for treatment can be ensured, while by ensuring that the content is equal to or less than the upper limit, the content of the cellulose powder of this embodiment can be equal to or greater than the lower limit, resulting in a molded body that exhibits practical hardness and disintegratability.

[0058] The molded body of this embodiment may contain, in addition to the active ingredient and cellulose powder, excipients, disintegrants, binders, flow agents, lubricants, flavoring agents, fragrances, colorants, and sweeteners, as necessary.

[0059] [Active ingredient] The active ingredient includes a pharmaceutical active ingredient, an agricultural chemical ingredient, a fertilizer ingredient, a feed ingredient, a food ingredient, a cosmetic ingredient, a dye, a fragrance, a metal, a ceramic, a catalyst, and a surfactant. The active ingredient may be in any form, such as a solid (powder, crystal, etc.), an oil, a liquid, or a semi-solid. The active ingredient may be coated for the purpose of controlling dissolution, reducing bitterness, etc. The active ingredient may be used alone or in combination. The active ingredient may be used by dissolving, suspending, or emulsifying in a medium. Among these, a pharmaceutical active ingredient or a food active ingredient is preferred as the active ingredient.

[0060] Examples of pharmaceutically active ingredients include orally administered drugs such as antipyretic analgesics and anti-inflammatory drugs, hypnotics and sedatives, anti-drowsiness drugs, antivertigo drugs, pediatric analgesics, stomachics, antacids, digestive drugs, cardiac stimulants, antiarrhythmic drugs, antihypertensive drugs, vasodilators, diuretics, antiulcer drugs, intestinal regulators, drugs for treating osteoporosis, antitussives and expectorants, antiasthmatic drugs, antibacterial agents, agents for improving frequent urination, tonics, vitamins, etc. These pharmaceutically active ingredients may be used alone or in combination of two or more.

[0061] Specific examples of the medicament active ingredient include aspirin, aluminum aspirin, acetaminophen, ethenzamide, sazapirin, salicylamide, lactylphenetidine, isothibenzyl hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, difeterol hydrochloride, triprolidine hydrochloride, tripelennamine hydrochloride, thonzylamine hydrochloride, fenethazine hydrochloride, methdilazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline teoclate, na Mebhydroline padisylate, promethazine methylene disalicylate, carbinoxamine maleate, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, difeterol phosphate, alloclamide hydrochloride, cloperastine hydrochloride, pentoxyverine citrate (carbetapentane citrate), tipepidine citrate, dibunate sodium, dextromethorphan hydrobromide, dextromethorphan phenolphthalic acid, tipepidine hibenzate, cloperastine fendizoate, codeine phosphate, dihydrocodeine phosphate, nosca hydrochloride pine, noscapine, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, potassium guaiacolsulfonate, guaifenesin, sodium benzoate, caffeine, anhydrous caffeine, vitamin B1 and its derivatives and their salts, vitamin B2 and its derivatives and their salts, vitamin C and its derivatives and their salts, hesperidin and its derivatives and their salts, vitamin B6 and its derivatives and their salts, nicotinamide, calcium pantothenate, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel (as dried aluminum hydroxide gel), dried aluminum hydroxide gel, mixed dried gel of aluminum hydroxide and magnesium carbonate, co-precipitation product of aluminum hydroxide and sodium bicarbonate, co-precipitation product of aluminum hydroxide, calcium carbonate and magnesium carbonate, co-precipitation product of magnesium hydroxide and aluminum potassium sulfate, magnesium carbonate, magnesium aluminometasilicate,Ranitidine hydrochloride, cimetidine, famotidine, naproxen, diclofenac sodium, piroxicam, azulene, indomethacin, ketoprofen, ibuprofen, difenidol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, promethazine hydrochloride, meclizine hydrochloride, dimenhydrinate, diphenhydramine tannate, fenethazine tannate, diphenylpyraline teoclate, diphenhydramine fumarate, promethazine Chilendisalicylate, spocolamine hydrobromide, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, atropine methyl bromide, anisotropine methyl bromide, spocolamine methyl bromide, 1-hyoscyamine methyl bromide, benactidium methyl bromide, belladonna extract, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, papaverine hydrochloride, aminobenzoic acid, cesium oxalate, piperidylacetylaminobenzoate Ethyl phosphate, aminophylline, diprophylline, theophylline, sodium bicarbonate, fursultiamine, isosorbide dinitrate, ephedrine, cephalexin, ampicillin, sulfixazole, sucralfate, allylisopropylacetylurea, bromvalerylurea, etc., ephedra, nandina, chervil, onion, licorice, bellflower, scutellaria, scutellaria, senega, fritillaria, fennel, Phellodendron bark, coptis, zedoary, chamomile, Examples of pharmaceutically active ingredients include cinnamon bark, gentian, bezoar, animal gall (including yutan), shanghai root, ginger, sophora rhizome, clove, tangerine peel, Atractylodes orbiculatus, earth dragon, ginseng, carrot, valerian, moutan pea, Japanese pepper, and extracts thereof, as well as insulin, vasopressin, interferon, urokinase, serratiopeptidase, somatostatin, and other pharmaceutically active ingredients listed in the Japanese Pharmacopoeia, USP, NF, and EP. These pharmaceutically active ingredients may be used alone or in combination of two or more.

[0062] The term "poorly water-soluble active ingredient" as used herein refers to, for example, a pharmaceutical active ingredient that, according to the 18th Edition of the Japanese Pharmacopoeia, requires 30 mL or more of water to dissolve 1 g of solute. If the active ingredient is poorly soluble in water, it can be effectively incorporated into the molded article of the present embodiment, regardless of the degree of sublimation or surface polarity.

[0063] Examples of poorly water-soluble solid active ingredients include antipyretics and analgesics such as acetaminophen, ibuprofen, benzoic acid, ethenzamide, caffeine, camphor, quinine, calcium gluconate, dimethylcaprol, sulfamine, theophylline, theopromine, riboflavin, mephenesin, phenobarbital, aminophylline, thioacetazone, quercetin, rutin, salicylic acid, theophylline sodium salt, pyrapital, quinine hydrochloride, irgapyrin, digitoxin, griseofulvin, and phenacetin, nervous system drugs, sedatives and hypnotics, muscle relaxants, blood pressure sclerosing agents, and antihistamines; acetylspiramycin, ampicillin, erythromycin, xatamycin, chloramphenicol, trimethicone, thiamin ... Examples of the active ingredient include antibiotics such as cetyloleandomycin, nystatin, colistin sulfate, etc.; steroid hormones such as methyltestosterone, methylandrosterone diol, progesterone, estradiol benzoate, ethinylestradiol, deoxycorticosterone acetate, cortisone acetate, hydrocortisone, hydrocortisone acetate, prednisolone, etc.; non-steroidal egg yolk hormones such as dienstrol, hexastrol, diethylstilbesterol, diethylstilbesterol dibromothionate, chlorotrianisene, etc.; and other active pharmaceutical ingredients listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia, the USP, the NF, and the EP, such as fat-soluble vitamins. These active ingredients may be used alone or in combination of two or more.

[0064] Examples of poorly water-soluble liquid active ingredients include teprenone, indomethacin farnesyl, menatetrenone, and phytonadione; vitamins such as vitamin A oil, phenipentol, vitamin D, and vitamin E; higher unsaturated fatty acids such as DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), and cod liver oil; coenzymes Q; and oil-soluble flavorings such as orange oil, lemon oil, and peppermint oil, all of which are listed in the Japanese Pharmacopoeia, USP, NF, and EP. Vitamin E comes in a variety of homologs and derivatives, and is not particularly limited as long as it is liquid at room temperature. Specific examples of such homologs and derivatives of vitamin E include dl-α-tocopherol, dl-α-tocopherol acetate, d-α-tocopherol, and d-α-tocopherol acetate. These active ingredients may be used alone, or two or more may be used in combination.

[0065] Examples of water-insoluble semi-solid active ingredients include Chinese herbal medicines or herbal extracts such as earth dragon, licorice, cinnamon bark, peony root, moutan pea, valerian, Japanese pepper, ginger, tangerine peel, ephedra, nandina fruit, scutellaria, onion root, platycodon, rhododendron, rhododendron bark, rhododendron japonica, garlic, seneca, fritillary, fennel, Phellodendron bark, coptis, zedoary, chamomile, gentian, bezoar, animal gall, rhododendron, ginger, soju, clove, chinese herb, atractylodes rhizome, chikusetsuninjin, ginseng, kakkonto, keishito, kososan, shikokeishito, shosaikoto, shoseiryuto, bakumondoto, hangehoubokuto, and maoto, oyster meat extract, propolis, and propolis extract. These active ingredients may be used alone or in combination of two or more.

[0066] The sublimable active ingredient is not particularly limited as long as it has sublimability. The sublimable active ingredient may be solid, liquid, or semi-solid at room temperature. Examples of the sublimable active ingredient include sublimable pharmaceutical active ingredients listed in the Japanese Pharmacopoeia, the USP, the NF, and the EP, such as benzoic acid, ethenzamide, caffeine, camphor, salicylic acid, phenacetin, and ibuprofen. These active ingredients may be used alone or in combination of two or more.

[0067] [Other Components] Examples of excipients include starch acrylate, L-aspartic acid, aminoethylsulfonic acid, aminoacetic acid, candy (powder), gum arabic, powdered gum arabic, alginic acid, sodium alginate, pregelatinized starch, pumice granules, inositol, ethyl cellulose, ethylene vinyl acetate copolymer, sodium chloride, olive oil, kaolin, cacao butter, casein, fructose, pumice granules, carmellose, carmellose sodium, hydrated silicon dioxide, dry yeast, dried aluminum hydroxide gel, dried sodium sulfate, dried magnesium sulfate, agar, and the like. Powder, xylitol, citric acid, sodium citrate, disodium citrate, glycerin, calcium glycerophosphate, sodium gluconate, L-glutamine, clay, clay 3, clay granules, croscarmellose sodium, crospovidone, magnesium aluminosilicate, calcium silicate, silicic acid-treated crystalline cellulose, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, cinnamon powder, crystalline cellulose, crystalline cellulose / carmellose sodium, crystalline cellulose (granules), Genmai Koji, synthetic aluminum silicate, synthetic hydrotalsa Thread, sesame oil, wheat flour, wheat starch, wheat germ flour, rice, rice starch, potassium acetate, calcium acetate, cellulose acetate phthalate, safflower oil, white beeswax, zinc oxide, titanium oxide, magnesium oxide, β-cyclodextrin, dihydroxyaluminum aminoacetate, 2,6-di-butyl-4-methylphenol, dimethylpolysiloxane, tartaric acid, potassium hydrogen tartrate, calcined gypsum, sucrose fatty acid ester, magnesium alumina hydroxide, aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate coprecipitate, hydroxyl magnesium stearate, squalane, stearyl alcohol, stearic acid, calcium stearate, polyoxyl stearate, magnesium stearate, hardened soybean oil, refined gelatin, refined shellac, refined white sugar, refined white sugar spherical granules, cetostearyl alcohol, polyethylene glycol 1000 monocetyl ether, gelatin, sorbitan fatty acid ester, D-sorbitol, tricalcium phosphate, soybean oil, soybean unsaponifiables, soybean lecithin, skim milk powder, talc, ammonium carbonate, calcium carbonate, magnesium carbonate, neutral anhydrous sodium sulfate,Low-substituted hydroxypropyl cellulose, dextran, dextrin, natural aluminum silicate, corn starch, tragacanth powder, silicon dioxide, calcium lactate, lactose, lactose granules, Perfiller 101, white shellac, white petrolatum, hakudo, white sugar, white sugar and starch spherical granules, naked barley leaf extract powder, naked malt leaf green juice dried powder, honey, paraffin, potato starch, semi-digested starch, human serum albumin, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose phthalate, phytic acid, glucose, glucose hydrate, partially pregelatinized starch, pullulan, propylene glycol, powdered reduced maltose syrup, powdered cellulose, pectin, bentonite, sodium polyacrylate, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene (105) polyoxypropylene (5) glycol, poly Examples of excipients include oxyethylene (160) polyoxypropylene (30) glycol, polysodium styrene sulfonate, polysorbate 80, polyvinyl acetal diethylaminoacetate, polyvinylpyrrolidone, polyethylene glycol, maltitol, maltose, D-mannitol, starch syrup, isopropyl myristate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate granules, magnesium aluminometasilicate, methylcellulose, cottonseed flour, cottonseed oil, Japan wax, aluminum monostearate, glycerin monostearate, sorbitan monostearate, medicinal charcoal, peanut oil, aluminum sulfate, calcium sulfate, granular corn starch, liquid paraffin, dl-malic acid, calcium hydrogen phosphate, calcium hydrogen phosphate, calcium hydrogen phosphate granules, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, and sodium dihydrogen phosphate, which are classified as excipients in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.). These excipients may be used alone or in combination of two or more.

[0068] Examples of disintegrants include those classified as disintegrants in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as celluloses such as croscarmellose sodium, carmellose, carmellose calcium, carmellose sodium, and low-substituted hydroxypropyl cellulose; starches such as carboxymethyl starch sodium, hydroxypropyl starch, rice starch, wheat starch, corn starch, potato starch, and partially pregelatinized starch; and synthetic polymers such as crospovidone and crospovidone copolymer. These disintegrants may be used alone or in combination of two or more.

[0069] Examples of binders include sugars such as sucrose, glucose, lactose, and fructose; sugar alcohols such as mannitol, xylitol, maltitol, erythritol, and sorbitol; water-soluble polysaccharides such as gelatin, pullulan, carrageenan, locust bean gum, agar, glucomannan, xanthan gum, tamarind gum, pectin, sodium alginate, and gum arabic; celluloses such as crystalline cellulose, powdered cellulose, hydroxypropyl cellulose, and methylcellulose; starches such as pregelatinized starch and starch paste; synthetic polymers such as polyvinylpyrrolidone, carboxyvinyl polymer, and polyvinyl alcohol; and inorganic compounds such as calcium hydrogen phosphate, calcium carbonate, synthetic hydrotalcite, and magnesium aluminosilicate, all of which are classified as binders in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.). These binders may be used alone or in combination of two or more.

[0070] Examples of the fluidizing agent include silicon compounds such as hydrous silicon dioxide and light anhydrous silicic acid, which are classified as fluidizing agents in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.) These fluidizing agents may be used alone or in combination of two or more.

[0071] Examples of lubricants include those classified as lubricants in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid esters, talc, etc. These lubricants may be used alone or in combination of two or more.

[0072] Examples of flavoring agents include those classified as flavoring agents in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as glutamic acid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaric acid, malic acid, ascorbic acid, sodium chloride, 1-menthol, etc. These flavoring agents may be used alone or in combination of two or more.

[0073] Examples of flavoring agents include those classified as flavoring agents and fragrances in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as oils such as orange, vanilla, strawberry, yogurt, menthol, fennel oil, cinnamon oil, spruce oil, and peppermint oil, and green tea powder. These flavoring agents and fragrances may be used alone or in combination of two or more.

[0074] Examples of coloring agents include food dyes such as Food Red No. 3, Food Yellow No. 5, and Food Blue No. 1; and those classified as coloring agents in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as copper chlorophine sodium, titanium oxide, and riboflavin. These coloring agents may be used alone or in combination of two or more.

[0075] Examples of sweeteners include those classified as sweeteners in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as aspartame, saccharin, dipotassium glycyrrhizinate, stevia, maltose, maltitol, starch syrup, and powdered amacha tea. These sweeteners may be used alone or in combination of two or more.

[0076] [Method for producing molded body] The molded body of this embodiment can be obtained by mixing and stirring one or more active ingredients and cellulose powder, and processing the resulting composition by known methods such as granulation, sizing, and tableting. When the composition containing the active ingredient and cellulose powder is in powder or granular form, it may be used as a solid formulation in powder or granular form as is, or the powder or granular composition may be further coated with a coating agent and used as a solid formulation. The coated or uncoated powder or granular composition may be filled into capsules for use, or may be compressed and used as a tablet-type solid formulation. Furthermore, capsules or tablets may be coated for use.

[0077] A method for producing a tablet containing one or more active ingredients and the cellulose powder of this embodiment as the main components will be described below. Note that this is just one example of a method for producing the molded product of this embodiment, and the effects of the molded product of this embodiment are not limited to the following method.

[0078] The term "tablet" as used herein refers to a compact obtained by compression molding containing the cellulose powder of this embodiment, one or more active ingredients, and, if necessary, other additives. Examples of such additives include excipients, disintegrants, binders, flow agents, lubricants, flavoring agents, flavorings, colorants, sweeteners, and solubilizers. These additives may be used alone or in combination of two or more.

[0079] When the molded product of this embodiment is a tablet, examples of the manufacturing method of the tablet include: i) a mixture of an active ingredient and cellulose powder, or a mixture of one or more active ingredients and cellulose powder, and optionally other additives, is compressed and molded by a conventional method (direct tableting); ii) an active ingredient and cellulose powder, and optionally other additives, are mixed, granulated to form granules, and then compressed and molded by a conventional method (wet or dry granulation compression method); iii) an active ingredient and cellulose powder, and optionally other additives are mixed, granulated to form granules, and then cellulose powder and optionally other additives are mixed, and then compressed and molded by a conventional method (wet or dry granulation post-powder compression method), etc. Other methods that can be used include a method for manufacturing a polynuclear tablet using a pre-compressed tablet as the core, and a method for manufacturing a multilayer tablet in which multiple pre-compressed molded products are stacked and compressed again.

[0080] In the manufacturing process, there is no particular limitation on the order of addition of each component. In direct compression, for example, the active ingredient, the cellulose powder of this embodiment, and other additives as needed may be mixed together and compression-molded. The active ingredient and additives such as a fluidizer or lubricant may be pre-mixed, and the cellulose powder of this embodiment and other additives as needed may be mixed with this, followed by compression molding. A lubricant may be added to the powder mixture for compression molding obtained by these methods, and further mixed, followed by compression molding.

[0081] The method for adding each component is not particularly limited as long as it is a commonly used method. For example, the components may be added continuously using a small suction transport device, a pneumatic transport device, a bucket conveyor, a pressure-feed transport device, a vacuum conveyor, a vibrating metering feeder, a spray, a funnel, or the like, or may be added all at once.

[0082] The mixing method is not particularly limited as long as it is a commonly used method, and examples thereof include methods using a container rotation type mixer such as a V-type, W-type, double cone type, or container tuck type mixer; a stirring type mixer such as a high-speed stirring type, universal stirring type, ribbon type, Pug type, or Nauta type mixer; a high-speed fluid type mixer, a drum type mixer, or a fluidized bed type mixer; and a method using a container shaking type mixer such as a shaker.

[0083] When the active ingredient is in the form of a solution, suspension, or emulsion, it can be sprayed onto cellulose powder or other additives. This can reduce the variation in the active ingredient content in the final product. Examples of spraying methods include spraying the active ingredient solution or dispersion using a pressure nozzle, two-fluid nozzle, four-fluid nozzle, rotating disk, ultrasonic nozzle, etc.; or dripping the active ingredient solution or dispersion from a tubular nozzle. When adding the active ingredient solution or dispersion, layering or coating may be performed to layer the active ingredient on the surface of cellulose particles in the cellulose powder, or the active ingredient may be supported inside the cellulose powder particles. Alternatively, a mixture of cellulose powder particles or porous cellulose and other additives may be granulated into a matrix using the active ingredient solution or dispersion as a binding liquid. Layering or coating may be performed using either a wet method or a dry method.

[0084] In particular, when an active ingredient that is poorly soluble in water is used, examples of methods include: i-1) a method in which the active ingredient is pulverized or used as is, and then mixed with the cellulose powder of this embodiment and other ingredients as needed, followed by compression molding; and i-2) a method in which the active ingredient is dissolved or dispersed in one or more media selected from the group consisting of water, organic solvents, and solubilizing agents, and then adsorbed onto the cellulose powder of this embodiment or other additives as needed, mixed with the cellulose powder of this embodiment or other additives as needed, and the medium is distilled off as needed, followed by compression molding. Examples of solubilizing agents include water-soluble polymers and surfactants.

[0085] The method for dissolving or dispersing the active ingredient in a medium is not particularly limited as long as it is a commonly used dissolution or dispersion method, and examples include stirring and mixing methods using stirring blades such as unidirectional rotation, multi-axis rotation, reciprocating inversion, up-down movement, rotation + up-down movement, and pipeline type blades of a portable mixer, three-dimensional mixer, side mixer, etc.; jet-type stirring and mixing methods such as a line mixer; gas-blowing stirring and mixing methods; mixing methods using a high-shear homogenizer, high-pressure homogenizer, ultrasonic homogenizer, etc.; and container-shaking mixing methods using a shaker.

[0086] The medium used in the above-mentioned manufacturing method is not particularly limited as long as it is one used in pharmaceuticals, and for example, water or an organic solvent can be used. Examples of organic solvents include those classified as solvents in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as alcohols such as methanol, ethanol, isopropyl alcohol, butyl alcohol, 2-methylbutyl alcohol, and benzyl alcohol; hydrocarbons such as pentane, hexane, heptane, and cyclohexane; and ketones such as acetone and ethyl methyl ketone. These media may be used alone, or two or more may be used in combination. After dispersion in one medium, the medium may be removed and the resulting mixture may be dispersed in a different medium.

[0087] Examples of water-soluble polymers usable as solubilizers include those listed in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, ethyl cellulose, gum arabic, and starch paste. These water-soluble polymers may be used alone or in combination of two or more.

[0088] Examples of fats and oils as solubilizers include those described in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as stearic acid monoglyceride, stearic acid triglyceride, sucrose stearate, paraffins such as liquid paraffin, carnauba wax, hydrogenated oils such as hydrogenated castor oil, castor oil, stearic acid, stearyl alcohol, polyethylene glycol, etc. These fats and oils may be used alone or in combination of two or more.

[0089] Examples of surfactants that can be used as solubilizers include those classified as surfactants in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as phospholipids, glycerin fatty acid esters, polyethylene glycol fatty acid esters, sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene polyoxypropylene glycol, polyoxyethylene sorbitan monolaurate, polysorbate, sorbitan monooleate, glyceride monostearate, monooxyethylene sorbitan monopalmitate, monooxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, sorbitan monopalmitate, sodium lauryl sulfate, etc. These surfactants may be used alone or in combination of two or more.

[0090] Examples of granulation methods used in the manufacturing process include dry granulation, wet granulation, heat granulation, spray granulation, and microencapsulation. Specifically, effective wet granulation methods include fluidized bed granulation, agitation granulation, extrusion granulation, crushing granulation, and tumbling granulation. In the fluidized bed granulation method, a binder liquid is sprayed onto fluidized powder in a fluidized bed granulator to form granules. In the agitation granulation method, a binder liquid is added while rotating the agitator blades in a mixing vessel, thereby simultaneously mixing, kneading, and granulating the powder in a sealed structure. In the extrusion granulation method, a wet mass kneaded by adding a binder liquid is forcibly extruded through an appropriate size screen using a screw or basket method, for example, to form granules. In the crushing granulation method, a wet mass kneaded by adding a binder liquid is sheared or crushed by the rotating blades of a granulator, and then granulated by being ejected through an outer screen by the centrifugal force. In the rolling granulation method, the material is rolled by the centrifugal force of a rotating rotor, and at this time, a binding liquid is sprayed from a spray gun, causing the material to grow into spherical granules with uniform particle size in a snowball-like manner.

[0091] Granulated materials can be dried using, for example, hot air heating methods (shelf drying, vacuum drying, fluidized bed drying), conduction heat transfer methods (pan type, tray box type, drum type), freeze drying, etc. In the hot air heating method, hot air is brought into direct contact with the material, and evaporated water is removed at the same time. In the conduction heat transfer method, the material is indirectly heated through a heat transfer wall. In freeze drying, the material is frozen at a temperature between -10°C and -40°C, and then freeze-dried under high vacuum (1.3 x 10 －５ MPa or more 2.6 x 10 －４ By heating at a pressure of 1000 kJ / cm2 or less, water is sublimated and removed.

[0092] The method for compression molding the composition containing the active ingredient and the cellulose powder of this embodiment is not particularly limited as long as it is a commonly used method, and examples thereof include a method of compression molding into a desired shape using a mortar and pestle, a method of compression molding into a sheet in advance and then cutting into the desired shape, etc. Examples of compression molding machines include roller presses such as hydrostatic presses, briquetting roller presses, and smooth roller presses, single punch tablet presses, rotary tablet presses, etc.

[0093] The crystalline form of the active ingredient before compression molding may be the same as or different from the state before formulation. In particular, from the viewpoint of stability, it is preferable that the crystalline form of the active ingredient before compression molding is the same as the state before formulation.

[0094] A powdered or granular composition containing an active ingredient and the cellulose powder of this embodiment may be coated before compression molding. A coating may also be applied to the tablet obtained after compression molding. Examples of coating agents used for these include ethyl acrylate-methyl methacrylate copolymer dispersions, acetylglycerin fatty acid esters, aminoalkyl methacrylate copolymers, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersions, octyldecyl triglyceride, olive oil, kaolin, cacao butter, kagoso, castor wax, caramel, carnauba wax, carboxyvinyl polymers, carboxymethyl ethyl cellulose, carboxymethyl starch sodium, carmellose calcium, carmellose sodium, hydrated silicon dioxide, dried aluminum hydroxide gel, dried milky white lac, dried methacrylic acid copolymers, winter plum powder, fish scale powder, gold leaf, silver leaf, triethyl citrate, glycerin, glycerin fatty acid esters, magnesium silicate, light anhydrous silicic acid, light anhydrous silicic acid-containing hydroxypropyl cellulose, light liquid paraffin, spermaceti, crystalline cellulose, hardened oil, synthetic aluminum silicate, synthetic wax, high glucose starch syrup, hard wax, succinated gelatin, wheat flour, wheat starch Ingredients: cellulose acetate, vinyl acetate resin, cellulose acetate phthalate, white beeswax, titanium oxide, magnesium oxide, dimethylaminoethyl methacrylate-methyl methacrylate copolymer, dimethylpolysiloxane, dimethylpolysiloxane-silicon dioxide mixture, silicon oxide mixture, calcined gypsum, sucrose fatty acid ester, zinc powder, aluminum hydroxide gel, hydrogenated rosin glycerin ester, stearyl alcohol, stearic acid, aluminum stearate, stearic acid Calcium, polyoxyl stearate, magnesium stearate, refined gelatin, refined shellac, refined white sugar, zein, sorbitan sesquioleate, cetanol, gypsum, gelatin, shellac, sorbitan fatty acid ester, D-sorbitol, D-sorbitol liquid, tricalcium phosphate, talc, calcium carbonate, magnesium carbonate, simple syrup, medium gold leaf, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, terpene resin, starch (soluble), corn syrup, corn oil,Triacetin, calcium lactate, white shellac, white sugar, honey, hard fat, paraffin, pearl powder, potato starch, hydroxypropyl cellulose, hydroxypropyl cellulose, hydroxypropyl cellulose acetate succinate, hydroxypropyl cellulose-titanium oxide-polyethylene glycol mixture, hydroxypropyl methylcellulose phthalate, piperonyl butoxide, castor oil, diethyl phthalate, dibutyl phthalate, butyl phthalyl glycolate, glucose, partially pregelatinized starch, fumaric acid-stearic acid-polyvinyl acetal diethylaminoacetate-hydroxypropyl cellulose mixture, pullulan, propylene glycol, powdered sugar, bentonite, povidone, polyoxyethylene hydrogenated castor oil, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene sorbitan mononitrate Examples of coating agents include those listed in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as monostearate, polyvinyl acetal diethylaminoacetate, polyvinyl alcohol (partially saponified), polyethylene glycol, hydroxyl-terminated methylpolysiloxane silicone resin copolymer, D-mannitol, starch syrup, beeswax, myristyl alcohol, anhydrous silicic acid hydrate, phthalic anhydride, anhydrous calcium hydrogen phosphate, methacrylic acid copolymer, magnesium aluminometasilicate, methylcellulose, 2-methyl-5-vinylpyridine methylacrylate-methacrylic acid copolymer, Japan wax, glycerin monostearate, sorbitan monostearate, sorbitan monolaurate, montan acid ester wax, medicinal charcoal, lauromacrogol, calcium sulfate, liquid coumarone resin, liquid paraffin, dl-malic acid, calcium hydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, calcium dihydrogen phosphate, and rosin. These coating agents may be used alone or in combination of two or more.

[0095] [Physical properties of tablets] When the molded product of this embodiment is a tablet, its hardness is preferably 50N or more, more preferably 55N or more, and even more preferably 60N or more. On the other hand, the higher the tablet hardness, the more preferable it is, and the upper limit is not particularly limited, but is usually about 150N. The tablet hardness may be 150N or less, or may be 80N or less. The tablet hardness can be measured, for example, using the method described in the Examples below.

[0096] When the molded article of this embodiment is a tablet, its disintegration time is preferably within 1800 seconds, more preferably within 1500 seconds, and even more preferably within 1200 seconds. On the other hand, the shorter the disintegration time, the better, and the lower limit is not particularly limited, but is usually about 10 seconds. The disintegration time may be 10 seconds or more, or may be 60 seconds or more. The disintegration time can be measured, for example, using the method described in the Examples below.

[0097] When the molded product of this embodiment is a tablet, its friability is preferably 1.0% by mass or less, more preferably 0.5% by mass or less, even more preferably 0.4% by mass or less, and particularly preferably 0.3% by mass or less. On the other hand, the lower the friability, the more preferable it is, and the lower limit is not particularly limited, but is usually about 0.01% by mass or less. The friability may be 0.01% by mass or more. The friability can be measured, for example, using the method described in the Examples below.

[0098] When the molded product of this embodiment is a tablet, the tablet mass variation is preferably 1.0% by mass or less, more preferably 0.7% by mass or less, even more preferably 0.6% by mass or less, and particularly preferably 0.5% by mass or less. On the other hand, the smaller the tablet mass variation, the more preferable, and the lower limit is not particularly limited, but is usually about 0.01% by mass. The tablet mass variation may be 0.01% by mass or more. The tablet mass variation can be measured, for example, using the method described in the Examples below.

[0099] When the molded product of this embodiment is a tablet, its active ingredient content variation is preferably 1.5% by mass or less, more preferably 1.0% by mass or less, even more preferably 0.7% by mass or less, even more preferably 0.6% by mass or less, and particularly preferably 0.5% by mass or less. On the other hand, the smaller the active ingredient content variation, the more preferable, and the lower limit is not particularly limited, but is usually about 0.01% by mass. The active ingredient content variation may be 0.01% by mass or more. The active ingredient content variation can be measured, for example, using the method described in the Examples below.

[0100] When the molded product of this embodiment is a tablet, it is preferable that the tablet mass variation is 1.0% by mass or less, the active ingredient content variation is 1.5% by mass or less, the tablet hardness is 55 N or more, the disintegration time is 1800 seconds or less, and the friability is 0.5% by mass.

[0101] The present invention will be described based on examples. However, the embodiments of the present invention are not limited to the descriptions of these examples. The methods for measuring and evaluating each physical property in the examples and comparative examples are as follows.

[0102] <Methods for Measuring Physical Properties> [Physical Property 1] (Average Particle Diameter of Cellulose Powder) The average particle diameter of cellulose powder was determined using a laser diffraction / scattering particle size distribution analyzer (LA-950 V2 (trade name), manufactured by Horiba, Ltd.). Approximately 1.0 g of cellulose powder was placed on a powder sample shooter, and the sample was dispersed under conditions of a feeder strength of 160 and a compressed air pressure of 0.03 MPa. Scattered light measurement was performed within a laser light (red) transmittance range of 95% to 98%, and the particle size distribution was determined. The average diameter measured based on the obtained particle size distribution was taken as the average particle diameter. The average value of two measurements was shown.

[0103] [Property 2] (Particle size distribution sharpness) The particle size (D) of 10% by volume measured based on the particle size distribution obtained in [Property 1] above １０ ), 50% particle diameter by volume (D ５０ ), 90% particle diameter by volume (D ９０Using the average value of the two measurements, the particle size distribution sharpness was calculated according to the following formula:

[0104] [Particle size distribution sharpness] = (D ９０ -D １０ ) / D ５０

[0105] [Physical Property 3] (Loose Bulk Density of Cellulose Powder) The loose bulk density of the cellulose powder was measured by the following method. Using a Scott volumeter (Model ASTM B-329-85, manufactured by Tsutsui Scientific Instruments Co., Ltd.), the cellulose powder was filled into a 25 mL cylindrical metal container. The cellulose powder in the 25 mL cylindrical metal container was leveled off, and the mass (g) of the cellulose powder in the container was divided by 25 mL to obtain the loose bulk density (g / cm ３ ) was calculated and shown as the average value of two measurements.

[0106] [Physical Property 4] (Tap Density of Cellulose Powder) The tap density of the cellulose powder was measured by the following method. Using a commercially available powder property measuring instrument (Powder Tester TR type, manufactured by Hosokawa Micron Corporation), the cellulose powder was ３ The cellulose powder was filled into a container and tapped 180 times. The mass of the cellulose powder filled into the container was divided by the volume of the container to obtain the tap density (g / cm). ３ )

[0107] [Physical Property 5] (FRI and BFE of Cellulose Powder) The FRI and BFE of the cellulose powder were measured by the following method.

[0108] <Measurement details> Measurement device: Powder rheometer FT4 (manufactured by Freeman Technology) Measurement software: Powder Rheometer Measurement container: Split vessel (50 mm x 160 mL) Blade: 48.0 mm (diameter)

[0109] Measurement program: 50mm_1C_Split_Rep+VFR (11 consecutive measurements. Blade rotation speed: 100mm / s for the 1st to 8th measurements, 70mm / s for the 9th measurement, 40mm / s for the 10th measurement, and 10mm / s for the 11th measurement) Analysis program: Freeman Technology Data Analysis

[0110] <Procedure> First, the powder to be measured was sieved using a sieve (product name: THE IIDA TESTING SIEVE, mesh size: 250 μm, wire: 160 μm, plain weave (P)). 160 mL or more of the sieved powder was placed in a specified measurement container and set in the measurement device. Measurement was performed according to the measurement program provided as standard with the measurement device. The measurement data was read from the analysis program, and the automatically calculated FRI and BFE values ​​were used as the FRI and BFE of the powder. BFE is usually the value obtained from the seventh measurement value, which is usually the most stable data. FRI is usually the value obtained from the eighth measurement value (blade rotation speed 100 mm / s) and the eleventh measurement value (blade rotation speed 10 mm / s).

[0111] [Physical Property 6] (Compressibility) Tap density (P) (g / cm ３ ) and loose bulk density (A) (g / cm ３ ) was used to calculate the degree of compression (%) according to the following formula.

[0112] [Compression ratio] = (P - A) / P

[0113] [Physical Property 7] (Proportion of Particles with a Particle Width of 2 μm or More) Particle width was measured by the following method. First, a sample was prepared by sprinkling a thin layer of the powder to be measured on carbon tape so that the particles did not overlap. This sample was observed using an electron microscope SEM image, with the observation magnification adjusted so that approximately 20 to 100 particles could be observed in the field of view, depending on the size of the constituent particles. A particle was sandwiched between two parallel lines tangent to the particle, and the smallest distance between the parallel lines was measured as the particle width. Twenty particles were randomly selected per image, and the particle width was measured. This procedure was repeated five times, and the particle width of a total of 100 particles was measured. Of these, the proportion of particles with a particle width of 2 μm or more was calculated.

[0114] Example 1 Cellulose powder was produced and used as an excipient to produce tablets, and the physical properties of the tablets were evaluated.

[0115] <Production of Cellulose Powder> 3 kg of commercially available shredded pulp and 35 L of aqueous hydrochloric acid were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed for 75 minutes while stirring at a stirring speed of 290 rpm. The mixture was then neutralized with aqueous ammonia to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche funnel to obtain a filtration residue with a solids concentration of 35 to 45% by mass. The mixture was then placed in a 20 L stainless steel tank, pure water was added, and the mixture was stirred at a stirring speed of 75 rpm using a mixer (HANWA AGITATOR, Hanwa Chemical Engineering Co., Ltd., Model KP-4003, stirring blade diameter approximately 17 cm) to obtain a cellulose dispersion with a solids concentration listed in Table 1. The average particle size of the cellulose particles in each cellulose dispersion was measured, and the size was as listed in Table 1. These cellulose dispersions were spray-dried to obtain cellulose powders. Spray drying was performed at an inlet temperature of 180°C to 270°C, an outlet temperature of 70°C to 120°C, and an atomizer disk rotation peripheral speed (m / s) as shown in Table 1. The obtained cellulose powder was first sieved using a sieve with 250 μm openings, and the powder that passed through the sieve was collected to remove foreign matter and coarse particles. The cellulose powder from which coarse particles and other particles had been removed was then sieved using a sieve with openings of the sizes shown in Table 1, and the powder remaining on the sieve was collected to obtain cellulose powders A to D, O, and P. Cellulose powders E to H were spray-dried and used as they were without sieving after removing coarse particles and other particles.

[0116]

[0117] Cellulose powder L was prepared by the method described in Example 1 of Patent Document 3. Similarly, cellulose powder M was prepared by the method described in Example 2 of Patent Document 3.

[0118] Cellulose powder N was obtained by mixing cellulose powder A and cellulose powder I in a ratio of A:I = 90% by mass:10% by mass. Cellulose powder Q was obtained by mixing cellulose powder P and cellulose powder I in a ratio of P:I = 80% by mass:20% by mass.

[0119]

[0120]

[0121]

[0122] The physical properties of each cellulose powder obtained were measured. The results are shown in Tables 2, 3, and 4. Cellulose powders A to C, G, I, K, and N to Q had angles of repose of 45° or less and good fluidity. Furthermore, cellulose powders A to D and N to Q, which were produced under conditions where the cellulose dispersion concentration was relatively low (10% by mass or less) and the disk rotation peripheral speed during spray drying was relatively slow (105 m / s or less), had low loose bulk densities and relatively small FRIs. Of cellulose powders A to D and N to Q, cellulose powders A to C, O, and P, which were sieved using a sieve with large mesh sizes (75 μm or more), had larger average particle diameters, smaller particle size distribution sharpness, and smaller FRIs than cellulose powder D, which was sieved using a sieve with small mesh sizes (32 μm). On the other hand, the powdered celluloses E, J, L and M, which had an FRI of more than 1.40, also had a large angle of repose of more than 45° and had low fluidity.

[0123] Tablet Production 1 (500 mg, 7 kN impact force) Acetaminophen (manufactured by Shin-Nihon Pharmaceutical Co., Ltd.) and each cellulose powder were placed in a plastic bag and mixed by shaking for 3 minutes to obtain a final formulation powder. The final formulation powder had a mass ratio of acetaminophen / each cellulose powder = 7 / 3.

[0124] The final formulated powder was then compressed into tablets using a large benchtop load tester (Model 1325VCW, manufactured by AIKOH ENGINEERING) to obtain tablets weighing approximately 500 mg. The formulated powder was fed using an open feeder and compressed into tablets using a flat tablet mortar and pestle with a diameter of 11.3 mm at a compression force of 7 kN.

[0125] <Tablet Production 2 (500 mg, hardness 85-120 kN)> Acetaminophen (manufactured by Shin-Nihon Pharmaceutical Co., Ltd.) and each cellulose powder were placed in a plastic bag and mixed by shaking for 3 minutes to obtain a final formulated powder. The final formulated powder had a mass ratio of acetaminophen / each cellulose powder = 7 / 3.

[0126] The final formulated powder was then compressed into tablets using a large benchtop load tester (Model 1325VCW, manufactured by AIKOH ENGINEERING) to obtain tablets with a mass of approximately 500 mg. The formulated powder was fed and compressed into tablets using a flat tablet mortar and pestle with a diameter of 11.3 mm, adjusting the compression pressure so that the hardness of the resulting tablets would be within the range of 85 to 120 kN.

[0127] Tablet Production 3 (180 mg, hardness 70-80 kN) Acetaminophen (manufactured by Shin-Nihon Pharmaceutical Co., Ltd.) and silicon dioxide (Aerosil 200, manufactured by Nippon Aerosil Co., Ltd.) were placed in a plastic bag and mixed by shaking for 3 minutes. Next, granulated lactose (manufactured by DFE Pharma Co., Ltd., SuperTab 11SD (trade name)) and each cellulose powder were placed in a plastic bag and mixed by shaking for 1 minute. The mixed powder was then sieved through a sieve with 710 μm openings. The sieved mixed powder was then placed in a plastic bag and mixed by shaking for 3 minutes. Next, magnesium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) was added and mixed for an additional 30 seconds to obtain the final formulated powder. The final composition of the final formulated powder was acetaminophen / silicon dioxide / granulated lactose / each cellulose powder / magnesium stearate = 35 / 0.3 / 53.7 / 10 / 1 by mass.

[0128] Next, the final formulated powder was compressed into tablets using a rotary tablet press (manufactured by Kikusui Seisakusho Co., Ltd., 12-barrel) to obtain tablets weighing approximately 180 mg. The formulated powder was supplied by an open feeder, and compressed using a 12R mortar and pestle with a diameter of 8 mm, while varying the compression pressure in 2 kN increments within the range of 6 to 14 kN, and adjusting the compression pressure so that the hardness of the resulting tablets was within the range of 70 to 80 kN.

[0129] <Evaluation of physical properties> The physical properties of each tablet produced were evaluated. The evaluation results are shown in Tables 5 to 7. In Table 7, "-" indicates that the measurement was not performed.

[0130] [Evaluation 1] (Tablet hardness (N)) A load was applied to the tablets obtained by the large benchtop load tester in the diameter direction of the tablet using a Schleuninger hardness tester (Model 6D (trade name) manufactured by Freund Corporation) until the tablet was broken, and the load (N) at that time was measured. The average value for 10 tablets was expressed. Tablets with a load (N) of 50 N or more were evaluated as having good hardness.

[0131] [Evaluation 2] (Disintegration time (minutes)) A disintegration test was conducted in accordance with the general test method, tablet disintegration test method, of the 18th edition of the Japanese Pharmacopoeia. The disintegration time of the tablets was determined in pure water at 37°C using a disintegration tester (NT-40HS model (trade name), manufactured by Toyama Sangyo Co., Ltd., without a disk). The disintegration time was expressed as the average value of three tablets. Tablets with a disintegration time of 30 minutes (1800 seconds) or less were evaluated as having excellent disintegrability.

[0132] [Evaluation 3] (Friability (%)) The weight (Wa) (g) of 37 tablets was measured, and they were placed in a tablet friability tester (PT-F30 ERA, manufactured by PHARMA TEST) and rotated at 25 rpm for 4 minutes. After that, fine powder adhering to the tablets was removed, and the weight (Wb) (g) was measured again, and the friability was calculated using the following formula.

[0133] [Friability (%)] = 100 × (Wa - Wb) / Wa

[0134] [Evaluation 4] (Occurrence of Capping) The surfaces of 30 tablets were observed to check whether capping (a phenomenon in which the upper or lower surface of the tablet peels off in a hat-like shape) had occurred. Tablets in which no capping was observed were evaluated as "Good moldability" and tablets in which capping had occurred were evaluated as "Poor moldability."

[0135] [Evaluation 5] (Tablet mass variation (mass %)) The masses of 10 tablets obtained by rotary tableting were measured, and the average mass and standard deviation (g) of the mass were calculated. The mass variation was evaluated from the coefficient of variation (mass %) defined by the following formula: The smaller the coefficient of variation, the smaller the variation can be evaluated, and tablets with a mass CV of 1.0 mass % or less were evaluated as having good variation.

[0136] [Mass CV (mass%)] = [standard deviation (g)] / [average mass (g)] x 100

[0137] [Evaluation 6] (Variation in Active Ingredient Content (% by mass)) First, a calibration curve for acetaminophen was prepared. The absorption spectrum of acetaminophen was measured using an absorption spectrometer, and a calibration curve was prepared based on the wavelength of the peak (wavelength of acetaminophen: 244 nm). The acetaminophen content of each of the 10 tablets was measured, and the average acetaminophen content (average active ingredient content) and standard deviation relative to the tablet mass were calculated. The acetaminophen content of each tablet was determined by first placing the tablet in a 100 mL volumetric flask, measuring up to 100 mL with Japanese Pharmacopoeia Dissolution Test Fluid 1 (pH 1.2), filtering the resulting aqueous solution through a resin filter to remove insoluble matter, and then quantifying the amount of acetaminophen in the filtrate using an absorbance method. Next, the variation in the active ingredient content was evaluated using the coefficient of variation (% by mass; hereinafter, the coefficient of variation is also referred to as "active ingredient content CV") defined by the following formula: The smaller the coefficient of variation, the smaller the variation can be evaluated, and those with an active ingredient content CV of 1.5 mass % or less were evaluated as having good variation.

[0138] [Active ingredient content CV (mass%)] = [Standard deviation (g)] / [Average active ingredient content (g)] × 100

[0139]

[0140]

[0141]

[0142] As shown in Table 5, when tablets A-1 to Q-1 produced at a constant tableting pressure were compared, the hardness of the tablets produced using cellulose powders A to F, J, and L to Q, which had relatively low loose bulk densities, was higher than that of the tablets produced using cellulose powders G, H, I, and K, which had relatively high loose bulk densities, and they had sufficient hardness.

[0143] As shown in Table 6, when comparing tablets A-2 to Q-2 manufactured to have a hardness in the range of 85 to 120 kN, the disintegration time of the tablets manufactured using cellulose powders E, L, and M with high FRI was 30 minutes or more, whereas the disintegration time of the tablets manufactured using cellulose powders A to D and F to Q with relatively low FRI was short and the disintegration properties were good. In particular, the loose bulk density was 0.160 g / cm ３ Tablets A-2 to C-2 and N-2 to Q-2, which were produced using cellulose powders A to C and N to Q, each having an average particle size of 90 μm or more and 250 μm or less, and an FRI of 1.40 or less, all had a disintegration time of 20 minutes or less and a hardness of 85 kN or more, and were excellent in both disintegrability and hardness. When cellulose powder K, which had a very high loose bulk density, was used, tablets with a loose bulk density of 85 to 120 kN could not be produced.

[0144] As shown in Table 7, when tablets A-3, E-3 to K-3 manufactured so as to have a hardness in the range of 70 to 80 kN are compared, the loose bulk density is 0.250 g / cm ３ When cellulose powders G to I and K having a hardness of 0.250 g / cm or more were used, tablets with the desired hardness could not be produced. ３ When cellulose powder J having an FRI of more than 1.50 was used, tablets with the desired hardness could not be produced. ３ When cellulose powders A, E and F, each having a densitometric value of 0.160 g / cm or less and an FRI of 1.50 or less, were used, tablets with the desired hardness could be produced. ３ Tablets produced using cellulose powder A, which had an FRI of 1.40 or more and an average particle size of 90 μm or more and 250 μm or less, and an FRI of 1.40 or less, had good disintegrability and little variation in the active ingredient content. Tablets produced using cellulose powder E, which had an FRI of 1.40 or more and an average particle size of less than 90 μm, had poor disintegrability. In addition, the loose bulk density was 0.160 g / cm ３ In addition, the tablets obtained using cellulose powder F having an average particle size of less than 90 μm had a large variation in the active ingredient content.

[0145] According to the cellulose powder of the present embodiment, it is possible to provide a cellulose powder that has high fluidity and can give tablets that have both high hardness and excellent disintegrability, and a molded product using the cellulose powder.

Claims

1. Loose bulk density is 0.160 g / cm ３ a mean particle size of 90 μm or more and 250 μm or less; and a fluidity rate index of 1.40 or less.

2. The cellulose powder according to claim 1, having a particle size distribution sharpness of 0.50 or more and 2.50 or less.

3. The cellulose powder according to claim 1, having a basic fluidity energy of 400 mJ or more and less than 850 mJ.

4. Tap density is 0.150 g / cm ３ 0.300g / cm or more ３ The cellulose powder of claim 1, wherein the cellulose powder has a molecular weight of less than 10 ....

5. The cellulose powder according to claim 1, having a compressibility of 20% or more and less than 50%.

6. The cellulose powder according to claim 1, in which the content of particles having a particle width of 2 μm or more is 50% or more.

7. Loose bulk density is 0.090 g / cm ３ The cellulose powder according to claim 1, having a fluidity rate index of 1.00 or more.

8. A molded body comprising one or more active ingredients and the cellulose powder according to any one of claims 1 to 7.

9. The molded product according to claim 8, which is a tablet.

10. The molded article according to claim 9, wherein the active ingredient is a pharmaceutical active ingredient or a food active ingredient.

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