Cellulose powder and molded body

Abstract

To provide a cellulose powder which exhibits less variability in mass and has excellent hardness and friability while maintaining good disintegratability, and from which a smaller molded body can be obtained without changing the amount of active ingredients such as drugs, and a molded body using the cellulose powder.SOLUTION: The present invention provides: a cellulose powder in which the ratio Y (Cv / D50) of the water absorption rate Cv to the average particle diameter D50 is 0.12 g2 / (s μm) or more and the loose bulk density X is 0.135 g / cm3 or less; a cellulose powder in which the relationship between the ratio Y (Cv / D50) of the water absorption rate Cv to the average particle diameter D50 and the loose bulk density X satisfies formula (1-1) [Y≥1.5×X-0.06]; and a molded body including one or more active ingredients and any of the cellulose powders.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a cellulose powder and a molded product. This application claims priority based on Japanese Patent Application No. 2023-058328, filed on March 31, 2023, the contents of which are incorporated herein by reference. [Background technology]

[0002] Conventionally, in the fields of medicine, food, and other chemical industries, etc., cellulose powders such as crystalline cellulose and powdered cellulose have been widely used as excipients to prepare compacts containing active ingredients. These cellulose powders are particularly required to have good moldability, and further, to be able to easily take the compacts by reducing the size of the compacts without changing the amount of the active ingredient such as a drug.

[0003] For example, Patent Document 1 discloses an absorbent article having an excellent permeation rate, and water-absorbent resin particles and an absorbent body that provide the absorbent article. Specifically, the absorbent article includes an absorbent body that contains water-absorbent resin particles, and the water-absorbent resin particles have a packed bulk density of 0.500 g / cm. 3 or more, and the change in packed bulk density after absorbing moisture for 1 hour at a temperature of 30°C and a relative humidity of 80% is 0.020 g / cm 3 The above is disclosed.

[0004] Patent Document 2 discloses a cellulose powder that has excellent compression moldability, uniformly maintains sticky components during granulation, has a sharp granule size distribution, shortens the disintegration time of a compact, and can impart stable disintegrability over time. Specifically, it discloses that the cellulose powder has a particle size distribution sharpness of 1.5 to 2.9 and a total organic carbon content derived from residual impurities of more than 0.07 and 0.25% or less. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Publication No. 2020-121298 [Patent Document 2] Patent No. 6273052 Summary of the Invention [Problem to be solved by the invention]

[0006] However, Patent Document 1 discloses resin particles having structural units derived from at least one selected from the group consisting of (meth)acrylic acid and salts thereof as a material that exhibits an excellent penetration rate for liquids whose main component is water and can retain the liquid, but does not consider cellulose powder.

[0007] Furthermore, Patent Document 2 only discloses compacts obtained by wet tableting, and does not consider direct tableting, nor does it consider miniaturization of compacts.

[0008] The present invention has been made in consideration of the above circumstances, and provides a cellulose powder that has little variation in mass, excellent disintegrability, excellent hardness and friability, and allows for the production of smaller molded bodies without changing the amount of an active ingredient such as a drug, and a molded body using the cellulose powder. [Means for solving the problem]

[0009] That is, the present invention includes the following aspects. [1] Average particle diameter D 50 The ratio of water absorption rate Cv to 50 ) is 0.12g 2 / (s·μm) or more, Loose bulk density X is 0.135 g / cm 3 The following is cellulose powder. [2] Average particle diameter D 50 The ratio of water absorption rate Cv to 50 The relationship between the loose bulk density X and the cellulose sieve mass (μm) satisfies the following formula (1-1): Y≧1.5×X-0.06...Formula (1-1) [3] Average particle diameter D 50 The ratio of water absorption rate Cv to 50 ) is 0.12g 2 / (s·μm) or more, Loose bulk density X is 0.135 g / cm 3 The cellulose powder according to [2] above, which is as follows: [4] Average particle diameter D 50 The ratio of cohesive strength F to D 50 The cellulose powder according to any one of [1] to [3] above, wherein the particle size is 0.01 N% / μm or more. [5] The cellulose powder according to any one of [1] to [4] above, having a powder dynamic friction angle of 30° or more. [6] The cellulose powder according to any one of [1] to [5] above, wherein the primary particle ratio is 20% or more. [7] The cellulose powder according to any one of [1] to [6] above, wherein the L / D ratio of the primary particles is 2.0 or more. [8] The cellulose powder according to any one of [1] to [7] above, which has a compressibility of 40% or more. [9] The cellulose powder according to any one of [1] to [8] above, having an average degree of polymerization of 100 or more and 450 or less.

[10] Average particle diameter D 50 The cellulose powder according to any one of [1] to [9] above, wherein the particle size is 15 μm or more and 300 μm or less.

[11] Water absorption rate Cv is 2.0g 2 / s or more 12.0g 2 The cellulose powder according to any one of [1] to

[10] above, wherein the viscosity is 1 / s or less.

[12] The cellulose powder according to any one of [1] to

[11] above, wherein the cohesive strength F is 30 N% or more and 100 N% or less.

[13] one or more active ingredients; The cellulose powder according to any one of [1] to

[12] above, A molded body comprising:

[14] The molded article according to

[13] , wherein the active ingredient is a pharmaceutical active ingredient.

[15] The molded article according to

[13] , wherein the active ingredient is a food active ingredient.

[16] The molded product according to any one of

[13] to

[15] above, which is a tablet. [Effects of the Invention]

[0010] According to the cellulose powder of the above-mentioned embodiment, it is possible to provide a cellulose powder that has excellent hardness and friability while maintaining small mass variation and good disintegrability, and that can be used to obtain smaller molded bodies without changing the amount of active ingredient such as a drug. DETAILED DESCRIPTION OF THE INVENTION

[0011] <Cellulose powder> The cellulose powder according to one embodiment of the present invention (hereinafter referred to as "this embodiment") has an average particle diameter D 50 The ratio of water absorption rate Cv to 50 ) is 0.12g 2 / (s·μm) or more, and the loose bulk density X is 0.135 g / cm 3 or less," or "average particle diameter D 50 The ratio of water absorption rate Cv to 50 The relationship between the loose bulk density X and the loose bulk density Y is Y≧1.5×X-0.06.

[0012] The cellulose powder of this embodiment has the above-mentioned configuration, which allows for small mass variation, excellent disintegrability, excellent hardness and abrasion resistance, and the production of smaller molded bodies without changing the amount of active ingredients such as drugs.

[0013] The cellulose powder referred to 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 these, crystalline cellulose is preferred as the cellulose powder. Known examples of crystalline cellulose include microcrystalline cellulose described in the 9th edition of the Japanese Pharmacopoeia of Food Additives, crystalline cellulose described in the Japanese Pharmacopoeia (18th revision), and crystalline cellulose described in the United States Pharmacopoeia, European Pharmacopoeia, etc.

[0014] [Average degree of polymerization] The average degree of polymerization of the cellulose powder of this embodiment is from 100 to 450, preferably from 150 to 450, more preferably from 200 to 450, even more preferably from 200 to 350, even more preferably from 200 to 310, and particularly preferably from 200 to 300. When the average degree of polymerization of the cellulose powder is within the above range, a molded product with good moldability can be obtained.

[0015] The average degree of polymerization of the cellulose powder is measured by the following method. Approximately 1.3 g of cellulose powder (approximately 0.25 g for powdered cellulose) was accurately weighed as a sample and placed in a 125 mL Erlenmeyer flask. 25 mL of water and 25 mL of 1 mol / L copper ethylenediamine TS were then accurately added. Nitrogen was immediately purged into the flask, and the flask was sealed and shaken to dissolve. An accurate drop of this solution was measured and subjected to a test at 25 ± 0.1°C using a capillary viscometer with an approximate viscometer constant (K) of 0.03 according to Viscosity Measurement Method 1 (2.53) to determine the kinematic viscosity (ν). Separately, 25 mL of water and 25 mL of 1 mol / L copper ethylenediamine TS were accurately weighed, and the resulting mixture was tested in the same manner using a capillary viscometer with an approximate viscometer constant (K) of 0.01 to determine the kinematic viscosity (ν). The relative viscosity (ηrel) of the cellulose powder was calculated using the following equation:

[0016] ηrel = ν / ν0

[0017] From the relative viscosity ηrel, the product [η]C of the intrinsic viscosity [η] (mL / g) and the concentration C (g / 100 mL) is calculated from the relative viscosity ηrel using Tables 1 and 2, and the average degree of polymerization P is calculated using the following formula: In the formula below, MT is the weighed amount (g) of cellulose powder converted to a dry matter.

[0018] P = 95[η]C / MT

[0019] [Table 1]

[0020] [Table 2]

[0021] Specifically, the average degree of polymerization of the cellulose powder can be measured using the method described in the examples below.

[0022] [Average particle diameter D 50 ] The average particle diameter D of the cellulose powder of this embodiment 50 The average particle diameter D of the cellulose powder is preferably 15 μm or more and 300 μm or less, more preferably 20 μm or more and 200 μm or less, even more preferably 25 μm or more and 150 μm or less, even more preferably 25 μm or more and 100 μm or less, and particularly preferably 25 μm or more and 70 μm or less. 50 On the other hand, when the average particle diameter D of the cellulose powder is equal to or larger than the above lower limit, the flowability tends to be improved. 50 When the value is equal to or less than the upper limit, the active ingredient such as a drug tends to be easily mixed uniformly.

[0023] The average particle diameter of the cellulose powder is D 50 is the particle size at 50% cumulative volume measured using a laser diffraction / scattering particle size distribution analyzer (LA-950 V2 (product name), manufactured by Horiba, Ltd.). Specifically, it can be measured using the method described in the Examples below.

[0024] [Water absorption rate Cv] In the cellulose powder of this embodiment, the water absorption rate Cv is 2.0 g 2 / s or more 12.0g 2 / s or less is preferable, and 3.0g 2 / s or more 10.0g 2 / s or less is more preferable, and 4.5g 2 / s or more 10.0g 2 / s or less is more preferable. When the water absorption rate Cv is within the above range, high compression moldability can be achieved.

[0025] The water absorption rate Cv of the cellulose powder is measured by the following method. First, approximately 5.0 g of cellulose powder that had passed through a 500 μm mesh sieve was filled into a Teflon (registered trademark) container and tapped 300 times with a stroke length of 18 mm and a weight of 198 g. The tapped cellulose powder was then immersed in 300 mL of pure water at a rate of 0.5 mm / s until it was saturated. The square of the penetration rate (g) of the pure water until it was saturated during the measurement time was measured. 2 The square of the penetration rate (g) until the saturated state is measured using a commercially available water absorption rate measuring device (Penet Analyzer PNT-N type (trade name), manufactured by Hosokawa Micron Corporation). 2 The graph of the water absorption rate (g) versus the measurement time was linearized using the least squares method, and the slope of the linearized graph was used to calculate the water absorption rate (g 2 / s). Specifically, it can be measured using the method described in the Examples below.

[0026] [Average particle diameter D 50 Ratio of water absorption rate Cv to water absorption rate Cv / D 50 ] Cv / D 50 is the water absorption rate Cv(g 2 / s) to the average particle diameter D 50 It can be calculated by dividing by the square root of the square root of the In the cellulose powder of this embodiment, the average particle diameter D 50 (μm) vs. water absorption rate Cv (g 2 / s) ratio Cv / D 50 is 0.12g 2 / (s·μm) or more is preferable, and 0.13g 2 / (s·μm) or more is preferable, and 0.14g 2 / (s·μm) or more is more preferable, and 0.153g 2 / (s·μm) or more is even more preferable, and 0.154g 2 / (s·μm) or more is particularly preferable.50 When the Cv / D is equal to or greater than the lower limit, the hydrogen bonds between the cellulose particles in the cellulose powder can be strengthened and the plastic deformability can be increased. This allows the cellulose powder of this embodiment to exhibit high compression moldability. 50 By controlling the value to be equal to or greater than the lower limit, good moldability can be ensured regardless of the particle shape. On the other hand, Cv / D 50 The upper limit is not particularly limited, but is, for example, 0.50 g. 2 / (s·μm), 0.30g 2 / (s·μm), 0.25g 2 / (s·μm), 0.24g 2 / (s·μm).

[0027] [Loose bulk density] In the cellulose powder of this embodiment, the loose bulk density is 0.135 g / cm 3 Preferably, it is 0.130 g / cm or less. 3 The following is more preferable: When the loose bulk density is equal to or less than the above upper limit, sufficient mechanical strength can be imparted to a molded article. On the other hand, the lower limit of the loose bulk density is not particularly limited, but is, for example, 0.03 g / cm 3 and 0.05 g / cm 3 0.07g / cm 3 0.08g / cm 3 It can be said that:

[0028] The loose bulk density of the cellulose powder is measured by the following method. Using a Scott volumeter (Model ASTM B-329-85, manufactured by Tsutsui Scientific Instruments Co., Ltd.), 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 ) is calculated. Specifically, it can be measured using the method described in the Examples below.

[0029] In the cellulose powder of this embodiment, the average particle diameter D 50 The ratio of water absorption rate Cv to 50 )(g 2 / (s·μm)) and loose bulk density X (g / cm 3 The relationship between Cv / D preferably satisfies the following formula (1-1), and more preferably satisfies the following formula (1-2): 50 When the loose bulk density is within the range that satisfies the above relational expression, the hydrogen bonds between the cellulose particles in the cellulose powder can be strengthened and the plastic deformability can be increased. This allows the cellulose powder of this embodiment to exhibit high compression moldability. That is, the cellulose powder of this embodiment has a high compressibility. 50 By controlling the loose bulk density (X) and the loose bulk density (X) within a range that satisfies the above relational expression, good compactibility can be ensured regardless of the particle shape.

[0030] Y≧1.5×X-0.06...Formula (1-1) Y≧2.8×X-0.2...Formula (1-2)

[0031] The cellulose powder of this embodiment has better moldability and can be molded into tablets with good hardness and disintegration properties. 50 The relationship between the loose bulk density X and the sintered body preferably satisfies the above formula (1-1) or (1-2) and satisfies X≦0.135, preferably satisfies the above formula (1-1) or (1-2) and satisfies 0.12≦Y, and more preferably satisfies the above formula (1-1) or (1-2) and satisfies both X≦0.135 and 0.12≦Y.

[0032] In the cellulose powder of this embodiment, the average particle diameter D 50 The ratio of water absorption rate Cv to 50The relationship between the loose bulk density X and the cellulose powder of the present embodiment preferably satisfies the following formula (2-1), more preferably the following formula (2-2), and even more preferably the following formula (2-3). 50 The relationship between the loose bulk density X and the sintered body preferably satisfies any one of the following formulae (2-1) to (2-3) and satisfies X≦0.135, preferably any one of the following formulae (2-1) to (2-3) and satisfies 0.12≦Y, and more preferably any one of the following formulae (2-1) to (2-3) and satisfies both X≦0.135 and 0.12≦Y.

[0033] Y≦-2.0×X+0.53...Equation (2-1) Y≦-2.0×X+0.50...Equation (2-2) Y≦-2.0×X+0.47...Equation (2-3)

[0034] In the cellulose powder of this embodiment, the average particle diameter D 50 The ratio of water absorption rate Cv to 50 The relationship between the loose bulk density X and the cellulose powder of the present embodiment preferably satisfies the following formula (3-1), more preferably the following formula (3-2), and even more preferably the following formula (3-3). 50 The relationship between the loose bulk density X and the sintered body preferably satisfies any one of the following formulae (3-1) to (3-3) and satisfies X≦0.135, preferably any one of the following formulae (3-1) to (3-3) and satisfies 0.12≦Y, and more preferably any one of the following formulae (3-1) to (3-3) and satisfies both X≦0.135 and 0.12≦Y.

[0035] Y≧-0.72×X+0.15 · · · Formula (3-1) Y≧-2.0×X+0.28...Equation (3-2) Y≧-4.4×X+0.50...Formula (3-3)

[0036] In the cellulose powder of this embodiment, the average particle diameter D 50 The ratio of water absorption rate Cv to 50 The relationship between the loose bulk density X and the cellulose powder of the present embodiment preferably satisfies the following formula (4-1), more preferably the following formula (4-2), even more preferably the following formula (4-3), and even more preferably the following formula (4-4). 50 The relationship between the loose bulk density X and the sintered body preferably satisfies any one of the following formulae (4-1) to (4-4) and satisfies X≦0.135, preferably any one of the following formulae (4-1) to (4-4) and satisfies 0.12≦Y, and more preferably any one of the following formulae (4-1) to (4-4) and satisfies both X≦0.135 and 0.12≦Y.

[0037] Y≦X+0.25...Equation (4-1) Y≦X+0.21...Equation (4-2) Y≦X+0.18...Equation (4-3) Y≦X+0.16...Equation (4-4)

[0038] In the cellulose powder of this embodiment, the average particle diameter D 50 The ratio of water absorption rate Cv to 50 The relationship between the average particle diameter D and the loose bulk density X preferably satisfies two or more relational expressions selected from the group consisting of the above formulas (1-1) to (1-2), the above formulas (2-1) to (2-3), the above formulas (3-1) to (3-3), and the above formulas (4-1) to (4-4). 50 The ratio of water absorption rate Cv to 50The relationship between the loose bulk density X and the loose bulk density X preferably satisfies two or more relational expressions selected from the group consisting of the formulas (1-1) to (1-2), the formulas (2-1) to (2-3), the formulas (3-1) to (3-3), and the formulas (4-1) to (4-4), and satisfies X≦0.135; the relationship between the loose bulk density X and the loose bulk density X preferably satisfies two or more relational expressions selected from the group consisting of the formulas (1-1) to (1-2), the formulas (2-1) to (2-3), the formulas (3-1) to (3-3), and the formula (4-1) to (4-4), and satisfies X≦0.135. It is also preferable that two or more relational expressions selected from the group consisting of the formulas (1-1) to (1-2), the formulas (2-1) to (2-3), the formulas (3-1) to (3-3), and the formulas (4-1) to (4-4) are satisfied, and 0.12≦Y is satisfied; it is more preferable that two or more relational expressions selected from the group consisting of the formulas (1-1) to (1-2), the formulas (2-1) to (2-3), the formulas (3-1) to (3-3), and the formulas (4-1) to (4-4) are satisfied, and both X≦0.135 and 0.12≦Y are satisfied.

[0039] The cellulose powder of this embodiment has better moldability and can be molded into tablets with good hardness and disintegration properties. 50The relationship between the loose bulk density X and any of the formulae (1-1) to (1-2) preferably satisfies X≦0.135 and 0.12≦Y; more preferably satisfies any of the formulae (1-1) to (1-2), X≦0.135, 0.12≦Y, and any of the formulae (2-1) to (2-3); and more preferably satisfies any of the formulae (1-1) to (1-2), X≦0.135, 0.12≦Y, any of the formulae (2-1) to (2-3), and any of the formulae (3-1) to (3-3). It is more preferable that the formula (1-1) or (1-2), X≦0.135, 0.12≦Y, any one of the formulas (2-1) or (2-3), and any one of the formulas (4-1) or (4-4) are satisfied; and it is even more preferable that the formula (1-1) or (1-2), X≦0.135, 0.12≦Y, any one of the formulas (2-1) or (2-3), any one of the formulas (3-1) or (3-3), and any one of the formulas (4-1) or (4-4) are satisfied. Among these, it is preferable that the formula (1-1), X≦0.135, 0.12≦Y, and the formula (2-3) are satisfied; it is more preferable that the formula (1-1), X≦0.135, 0.12≦Y, the formula (2-3), and the formula (3-2) are satisfied; it is even more preferable that the formula (1-1), X≦0.135, 0.12≦Y, the formula (2-3), and the formula (3-3) are satisfied, or it is even more preferable that the formula (1-1), X≦0.135, 0.12≦Y, the formula (2-3), and the formula (4-4) are satisfied; and it is even more preferable that the formula (1-1), X≦0.135, 0.12≦Y, the formula (2-3), the formula (3-3), and the formula (4-4) are satisfied.

[0040] The cellulose powder of this embodiment has better moldability and can be molded into tablets with good hardness and disintegration properties. 50The relationship between the loose bulk density X and any of the formulae (1-1) to (1-2) preferably satisfies X≦0.135 and 0.12≦Y; more preferably satisfies any of the formulae (1-1) to (1-2), X≦0.135, 0.12≦Y, and any of the formulae (3-1) to (3-3); and more preferably satisfies any of the formulae (1-1) to (1-2), X≦0.135, 0.12≦Y, any of the formulae (3-1) to (3-3), and any of the formulae (4-1) to (4-4). It is more preferable that the formula (1-1) or (1-2), X≦0.135, 0.12≦Y, any one of the formulas (3-1) or (3-3), and any one of the formulas (2-1) or (2-3) are satisfied; and it is even more preferable that the formula (1-1) or (1-2), X≦0.135, 0.12≦Y, any one of the formulas (2-1) or (2-3), any one of the formulas (3-1) or (3-3), and any one of the formulas (4-1) or (4-4) are satisfied. Among these, it is preferable to satisfy the formula (1-1), X≦0.135, 0.12≦Y, and the formula (3-2); it is more preferable to satisfy the formula (1-1), X≦0.135, 0.12≦Y, and the formula (3-3); it is even more preferable to satisfy the formula (1-1), X≦0.135, 0.12≦Y, the formula (3-3), and the formula (2-3); and it is even more preferable to satisfy the formula (1-1), X≦0.135, 0.12≦Y, the formula (3-3), the formula (2-3), and the formula (4-4).

[0041] The cellulose powder of this embodiment has better moldability and can be molded into tablets with good hardness and disintegration properties. 50The relationship between the loose bulk density X and any of the formulae (1-1) to (1-2) preferably satisfies X≦0.135 and 0.12≦Y; more preferably satisfies any of the formulae (1-1) to (1-2), X≦0.135, 0.12≦Y, and any of the formulae (4-1) to (4-4); and more preferably satisfies any of the formulae (1-1) to (1-2), X≦0.135, 0.12≦Y, any of the formulae (4-1) to (4-4), and any of the formulae (2-1) to (2-3). It is more preferable that the formula (1-1) or (1-2), X≦0.135, 0.12≦Y, any one of the formulas (4-1) or (4-4), and any one of the formulas (3-1) or (3-3) are satisfied; and it is even more preferable that the formula (1-1) or (1-2), X≦0.135, 0.12≦Y, any one of the formulas (4-1) or (4-4), any one of the formulas (2-1) or (2-3), and any one of the formulas (3-1) or (3-3) are satisfied. Among these, it is preferable that the formula (1-1), X≦0.135, 0.12≦Y, and the formula (4-4) are satisfied; it is preferable that the formula (1-1), X≦0.135, 0.12≦Y, the formula (4-4), and the formula (2-3) are satisfied, or it is preferable that the formula (1-1), X≦0.135, 0.12≦Y, the formula (4-4), and the formula (3-2) or (3-3) are satisfied. It is more preferable to satisfy the above; it is even more preferable to satisfy the above formula (1-1), X≦0.135, 0.12≦Y, the above formula (4-4), the above formula (2-3), and the above formula (3-2) or (3-3); it is particularly preferable to satisfy the above formula (1-1), X≦0.135, 0.12≦Y, the above formula (4-4), the above formula (2-3), and the above formula (3-3).

[0042] Y(Cv / D 50The relationship between the loose bulk density X and the loose bulk density X preferably satisfies any one of the formulas (1-1) to (1-2) and any one of the formulas (2-1) to (2-3); more preferably satisfies any one of the formulas (1-1) to (1-2), any one of the formulas (2-1) to (2-3), and any one of the formulas (3-1) to (3-3), or any one of the formulas (1-1) to (1-2), any one of the formulas (2-1) to (2-3), and any one of the formulas (4-1) to (4-4); and even more preferably satisfies any one of the formulas (1-1) to (1-2), any one of the formulas (2-1) to (2-3), any one of the formulas (3-1) to (3-3), and any one of the formulas (4-1) to (4-4). Among these, it is preferable to satisfy the formula (1-1) and the formula (2-3); it is more preferable to satisfy the formula (1-1), the formula (2-3), and the formula (3-2); it is even more preferable to satisfy the formula (1-1), the formula (2-3), and the formula (3-3), or it is even more preferable to satisfy the formula (1-1), the formula (2-3), and the formula (4-4); and it is even more preferable to satisfy the formula (1-1), the formula (2-3), the formula (3-3), and the formula (4-4).

[0043] Y(Cv / D 50The relationship between the loose bulk density X and the loose bulk density X preferably satisfies any one of the formulas (1-1) to (1-2) and any one of the formulas (3-1) to (3-3); more preferably satisfies any one of the formulas (1-1) to (1-2), any one of the formulas (3-1) to (3-3), and any one of the formulas (2-1) to (2-3), or any one of the formulas (1-1) to (1-2), any one of the formulas (3-1) to (3-3), and any one of the formulas (4-1) to (4-4); and even more preferably satisfies any one of the formulas (1-1) to (1-2), any one of the formulas (2-1) to (2-3), any one of the formulas (3-1) to (3-3), and any one of the formulas (4-1) to (4-4). Among these, it is preferable to satisfy both the formula (1-1) and the formula (3-2); it is more preferable to satisfy both the formula (1-1) and the formula (3-3); it is even more preferable to satisfy both the formula (1-1), the formula (3-3), and the formula (2-3), or it is even more preferable to satisfy both the formula (1-1), the formula (3-3), and the formula (4-4); and it is even more preferable to satisfy both the formula (1-1), the formula (2-3), the formula (3-3), and the formula (4-4).

[0044] Y(Cv / D 50 The relationship between the loose bulk density X and the slack bulk density X preferably satisfies any one of the formulas (1-1) to (1-2) and any one of the formulas (4-1) to (4-4); more preferably satisfies both the formulas (1-1) and (4-1); even more preferably satisfies both the formulas (1-1) and (4-2); still more preferably satisfies both the formulas (1-1) and (4-3); and particularly preferably satisfies both the formulas (1-1) and (4-4).

[0045] [Cohesive force F] In the cellulose powder of this embodiment, the cohesive strength F is preferably 30N% or more and 100N% or less, more preferably 45N% or more and 90N% or less, even more preferably 50N% or more and 80N% or less, and even more preferably 55N% or more and 80N% or less. When the cohesive strength F is within the above range, the cohesive strength of the cellulose powder is increased, and a molded body with low abrasion can be obtained in the molded body manufacturing process.

[0046] The cohesive strength F of the cellulose powder is measured by the following method. First, cellulose powder is filled into a shear cell (φ15 mm, upper and lower cell lengths: 34 mm, 5 mm) and the top surface of the powder bed is flattened. Then, using a powder bed shear force measuring device (NS-S300 (product name), manufactured by Nano Seeds Co., Ltd.), a shear test is performed at a shear rate of 50 μm / s with a target indentation load of 20 N as the indentation control condition. When the target load is reached, indentation is stopped, and lateral sliding is initiated, after which the static and dynamic friction coefficients are measured. For analysis, the elapsed measurement time (s) is plotted on the horizontal axis and the load (N) applied to the shear plane on the vertical axis. The maximum and minimum values ​​of the shear plane load are determined, and the cohesion force, defined by the following formula, is calculated.

[0047] [Cohesive force F (N%)] = ([Maximum shear plane load (N)] - [Minimum shear plane load (N)]) / [Maximum shear plane load (N)] x 100

[0048] Specifically, the cohesive force F of the cellulose powder can be measured using the method described in the examples below.

[0049] [Average particle diameter D 50 Ratio of cohesive force F to D 50 ] In the cellulose powder of this embodiment, the average particle diameter D 50 Ratio of cohesive force F to D 50is preferably 0.01 N% / μm or more, more preferably 0.8 N% / μm or more, even more preferably 0.9 N% / μm or more, even more preferably 1.3 N% / μm or more, particularly preferably 1.4 N% / μm or more, and most preferably 1.6 N% / μm or more. 50 When F / D is equal to or greater than the lower limit, the cohesive force of the cellulose powder is increased, and a compact with low abrasion can be obtained in the compact manufacturing process. 50 can be made equal to or greater than the above lower limit by controlling the shape of the cellulose particles in the cellulose powder. On the other hand, F / D 50 The upper limit is not particularly limited, but may be 3.0N% / μm, 2.5N% / μm, 2.4N% / μm, 2.3N% / μm, or 2.2N% / μm.

[0050] [Powder dynamic friction angle] In the cellulose powder of this embodiment, the powder kinetic friction angle is preferably 30° or more, more preferably 40° or more, even more preferably 43° or more, even more preferably 49° or more, particularly preferably 50° or more, and most preferably 51° or more. When the powder kinetic friction angle is equal to or greater than the above lower limit, friction between the cellulose powder particles increases, and a molded body with low abrasion can be obtained in the molded body manufacturing process. On the other hand, the upper limit of the powder kinetic friction angle is not particularly limited, but can be set to 70°, 65°, 60°, or 57°.

[0051] The powder kinetic friction angle of the cellulose powder is measured by the following method. First, cellulose powder was filled into a shear cell (φ15 mm, upper and lower cell lengths: 34 mm, 5 mm) and the top surface of the powder bed was flattened. Then, a shear test was performed using a powder bed shear force measuring device (NS-S300 (product name), manufactured by Nano Seeds Co., Ltd.) with indentation target loads of 20 N, 30 N, and 40 N at a shear rate of 50 μm / s. When the target load was reached, indentation was stopped, and lateral sliding was initiated, after which the static and kinetic friction coefficients were measured. Analysis was performed by first plotting the elapsed time (s) of measurement on the horizontal axis and shear force (N) on the vertical axis to determine the maximum shear force and the indentation load value at that time. The results were plotted on a graph with shear stress on the vertical axis and normal stress on the horizontal axis, and the angle of the line connecting these points with the origin relative to the x-axis was calculated as the powder kinetic friction angle.

[0052] [Compression Ratio] In the cellulose powder of this embodiment, the compressibility is preferably 40% or more, more preferably 45% or more, even more preferably 50% or more, even more preferably 53% or more, and particularly preferably 55% or more. When the compressibility is equal to or greater than the above-mentioned lower limit, a cellulose powder that is easily compressed can be obtained, and high compression moldability can be achieved. On the other hand, the upper limit of the compression rate is not particularly limited, but can be set to 70%, 65%, or 62%.

[0053] The compressibility of the cellulose powder is measured by the following method. First, the packed bulk density was measured using a powder property evaluation device (Powder Tester, manufactured by Hosokawa Micron Corporation). A sieve with a mesh size of 710 μm and a metal funnel with an inner diameter of 0.8 cm were used, and the vibration was set to 2.0 (power supply: AC 100 V, 60 Hz). The loose bulk density was measured using the method described above, and the compressibility, defined by the following formula, was calculated.

[0054] [Compression ratio (%)] = ([hardened bulk density (g / cm 3 )]-[Loose bulk density (g / cm 3)]) / [hardened bulk density (g / cm 3 )] × 100

[0055] [Particle structure] The cellulose powder of this embodiment preferably has a high proportion of particles with a primary particle structure. The structure formed by aggregation of these primary particles is called a secondary aggregate structure. Whether a particle is a primary particle or has a secondary aggregate structure can be determined by photographing the particle at 5x magnification using a dry image analyzer (Malvern Morphorogi G3S). The resulting image can be used to confirm whether the particle is a primary particle or has a secondary aggregate structure with clearly defined boundaries between primary particles. This cellulose powder of this embodiment focuses on the shape of the primary cellulose particles and demonstrates for the first time that high moldability and wear prevention effects can be achieved by controlling the proportion of particles with a primary particle structure within a specific range. The primary particle structure is closely related to the moldability of the compact. The more primary particles there are, the higher the plastic deformability during compression and the more easily the particles become entangled, resulting in high moldability and wear prevention effects.

[0056] The proportion of particles having a primary particle structure to the total number of particles in the cellulose powder (primary particle ratio) can be measured by the method described below. Using a dry image analyzer (Malvern Morphorogi G3S), 10,000 particles are photographed and analyzed to determine the particle diameter and aspect ratio of each particle. From the results, images of particles with an equivalent diameter of 30 μm to 90 μm and an aspect ratio of less than the average aspect ratio of the 10,000 particles + 0.1 are selected. The particle shape of each sampled particle image is visually confirmed, and individual particles are determined to be primary particles, while aggregates of particles are determined to be secondary particles. The proportion of particle images determined to be primary particles among the sampled particle images is calculated as the primary particle rate. Note that particle shape in particle images can also be confirmed using image processing software. As a simple method, the brightness dispersion value of each sampled particle image is selected from the range of 1 to 26 as primary particles, and the brightness dispersion value of each sampled particle image is selected from the range of 26 to 100 as secondary particles, and the primary particle ratio (%) can be calculated by dividing the number of primary particles by the total number of particles × 100. In this example, the method using the image processing software described above was adopted.

[0057] In the present invention and this specification, a cellulose powder in which 20% or more of the total number of particles have a primary particle structure, i.e., a cellulose powder with a primary particle ratio of 20% or more, is referred to as a "cellulose powder with a high proportion of particles having a primary particle structure." Note that, in the cellulose powder of this embodiment, particles having a primary particle structure preferably account for 25% or more of the total number of particles, more preferably 26% or more, even more preferably 30% or more, and even more preferably 31% or more. Meanwhile, the upper limit of the primary particle ratio is not particularly limited, but can be set to 50% or 45%.

[0058] The cellulose powder of this embodiment has a high proportion of particles with a primary particle structure, and the particles are easily entangled, which results in high moldability. Due to this property, by using the cellulose powder of this embodiment, the amount of cellulose powder added to prepare a molded product can be reduced, and smaller molded products can be obtained without changing the amount of active ingredient such as a drug.

[0059] Furthermore, since a powder having a primary particle structure can be molded with a low compression force during molding, the proportion of particles having a primary particle structure in the powder is closely related not only to moldability and friability, but also to the disintegration property of the molded body and the elution property of the active ingredient. When the compression force during molding is low, the gaps between the primary particles are maintained in the molded body. In other words, by using the cellulose powder of this embodiment, which has a high proportion of particles having a primary particle structure, a molded body containing many gaps between the cellulose primary particles can be obtained.

[0060] In a molded product containing many gaps between the primary cellulose particles, water penetrates quickly into the gaps between the primary particles in water, accelerating particle disintegration. Furthermore, when an active ingredient is held in the gaps between the primary cellulose particles, contact between the active ingredient and water is promoted, and the elution of the active ingredient is also promoted. In other words, by producing a molded product using the cellulose powder of this embodiment, the disintegration properties of the molded product and the elution properties of the active ingredient can be improved.

[0061] Furthermore, the primary cellulose particles have high compressibility and are effective in preventing abrasion, and are also easily disintegrated in water. Therefore, by using the cellulose powder of this embodiment, a molded product having an excellent balance between moldability and disintegrability can be obtained.

[0062] In addition, the gaps between the primary cellulose particles in the molded body also contribute to the retention of liquid components. Therefore, by producing a molded body using the cellulose powder of this embodiment, it is possible to particularly prevent the liquid components from seeping out.

[0063] Furthermore, the gaps between the primary cellulose particles in the compact also contribute to improving the mixing rate with other components such as the active ingredient. Therefore, by producing a compact using the cellulose powder of this embodiment, mixing uniformity can be improved and concentration variation can be significantly reduced.

[0064] Furthermore, the cellulose powder of this embodiment has a high proportion of particles with a primary particle structure, which results in a low loose bulk density and light weight, and therefore high dynamic fluidity. Therefore, by using the cellulose powder of this embodiment, it is possible to reduce the variation in mass of molded bodies.

[0065] [L / D of primary particles] The cellulose powder of this embodiment preferably has a ratio L / D of the major axis (L) to the minor axis (D) of the primary particles of 2.0 or more, more preferably 2.5 or more, even more preferably 3.0 or more, even more preferably 3.5 or more, and particularly preferably 3.8 or more. When the L / D of the primary particles is equal to or greater than the above lower limit, entanglement of the elongated particles can be promoted when the cellulose powder is compression molded, and high compression moldability can be achieved. On the other hand, the upper limit of the L / D of the primary particles of the cellulose powder of this embodiment is not particularly limited, but can be set to 6.0 or 5.0.

[0066] The L / D of the primary particles of the cellulose powder is measured by the following method. Using a dry image analyzer (Malvern Morphorogi G3S), particle images of primary particles are extracted in the same manner as described above. The long diameter (L) / short diameter (D) ratio is calculated from the long diameter (L) and short diameter (D) obtained from each extracted particle image, and the average value of all the extracted primary particle images is calculated as the L / D ratio of the primary particles of the cellulose powder.

[0067] [Method of manufacturing cellulose powder] The method for producing the cellulose powder of this embodiment will be described below. In the production of the cellulose powder of this embodiment, for example, first, a dispersion containing a natural cellulosic material is obtained, in which the primary cellulose particles have an average particle size of 10 μm or more but less than 300 μm, an average width of 2 μm or more but 30 μm or less, and an average thickness of 0.5 μm or more but 5 μm or less (hereinafter also referred to as "cellulose dispersion"). By giving the primary cellulose particles in the cellulose dispersion this shape, entanglement between the primary particles of the cellulose powder can be promoted when the dried cellulose powder is compression-molded.

[0068] Conventionally, the more primary particles there are in a cellulose dispersion, the more likely the particles are to become entangled during the drying process, resulting in secondary agglomeration of the cellulose powder particles and making it difficult to maintain the primary particle structure. In contrast, the cellulose powder of the present embodiment focuses on the primary cellulose particle structure and controls it within a specific range, demonstrating for the first time that it is possible to promote high plastic deformability of the primary cellulose particles and entanglement of the primary particles when the cellulose powder is compression molded. By promoting high plastic deformability and entanglement of the primary cellulose particles, it becomes easier to impart moldability to a molded body than before, and it has become possible for the first time to obtain a smaller molded body without changing the amount of an active ingredient such as a drug.

[0069] In light of the above issues, in the production of the cellulose powder of this embodiment, it is preferable to prepare a cellulose dispersion having a cellulose concentration of 0.5% by mass or more and 40% by mass or less, since the more primary particles there are in the cellulose dispersion, the more likely it is that a secondary aggregate structure will form.

[0070] The resulting cellulose dispersion is then dried to obtain the cellulose powder of this embodiment.

[0071] Natural cellulosic materials 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. Natural cellulosic materials have a cellulose type I crystal structure. As a raw material, one of the above natural cellulosic materials may be used, or a mixture of two or more may be used.

[0072] It is also preferable to use it in the form of purified pulp. There are no particular limitations on the method for purifying the pulp, and any pulp such as dissolving pulp, kraft pulp, or NBKP pulp may be used. Wood-derived pulp is preferred from the viewpoints of high α-cellulose purity, easy availability, and stable supply.

[0073] Among these, wood pulp is preferably wood pulp having a level-off degree of polymerization of 130 to 250, a whiteness of 90% to 99%, an S10 of 5% to 20%, and an S18 of 1% to 10%, as measured by the copper ethylenediamine solution method. When the level-off degree of polymerization is equal to or greater than the lower limit, moldability is more readily achieved. On the other hand, when the degree of polymerization is equal to or less than the upper limit, the average width and average thickness of the cellulose primary particles can be more easily controlled within specific ranges. When the whiteness is equal to or greater than the lower limit, the appearance of the cellulose powder can be improved. A higher whiteness is preferable, but the highest whiteness is usually around 99%. When S10 and S18 are within the above ranges, moldability and yield are improved. Here, the natural cellulosic material may be prepared by hydrolyzing raw materials such as pulp, or may not be hydrolyzed. In particular, when hydrolysis is performed, it may be by acid hydrolysis, alkaline oxidative decomposition, hot water decomposition, or steam explosion. Among these hydrolysis methods, any one of them may be used alone, or two or more of them may be used in combination.

[0074] In the above-mentioned production method, the medium used when dispersing the solid content containing the natural cellulosic material in an appropriate medium is preferably water. 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. After dispersing in one medium, the medium may be removed and the resulting material may be dispersed in a different medium.

[0075] In the method for producing a cellulose powder of this embodiment, a natural cellulosic material is subjected to a known treatment, such as mechanical treatment such as pulverization or grinding, chemical treatment such as hydrolysis, or an appropriate combination of both. This treatment produces a cellulose dispersion in which the primary cellulose particles have an average particle size of 10 μm or more but less than 300 μm, an average width of 2 μm or more but 30 μm or less, an average thickness of 0.5 μm or more but 5 μm or less, and a solids content of 0.5% by mass or more but 40% by mass or less. The cellulose dispersion is then dried.

[0076] In this specification, primary cellulose particles refer to particles having a size ranging from 1 μm to 500 μm that are newly formed when the fibers that make up a natural cellulosic material are split, or when the natural cellulosic material is subjected to mechanical treatment such as pulverization or grinding, or when the natural cellulosic material is subjected to chemical treatment such as hydrolysis.

[0077] Methods for reducing the average particle size of primary cellulose particles to less than 300 μm include, for example, mechanical treatments such as pulverization and grinding; known fractionation treatments such as cyclones, centrifugal separation, and sieving; and methods that appropriately combine both. The average particle size of primary cellulose particles can be reduced to less than 300 μm by appropriately adjusting conditions known to generally affect the treatment, such as the treatment volume, shear force (affected by the rotation speed, blade shape, blade dimensions, etc.), centrifugal force, and sieve mesh size. Furthermore, when chemical treatments such as acid hydrolysis are performed, the average particle size of primary cellulose particles can be reduced to less than 300 μm by appropriately changing conditions such as the acid concentration and temperature, or, in addition, by appropriately changing conditions known to affect the mechanical treatments and fractionation treatments.

[0078] In general, increasing the acid or alkali concentration or reaction temperature of the hydrolysis solution reduces the degree of cellulose polymerization and tends to reduce the average particle size of cellulose particles in the dispersion. Increasing the stirring force of the solution also tends to reduce the average particle size of cellulose particles in the dispersion. Therefore, by adjusting the degree of polymerization of the raw cellulose and the stirring force during the hydrolysis or dispersion process of the natural cellulosic material, the degree of polymerization and average particle size of the cellulose particles can be controlled within a desired range. The stirring force depends on the width, height, volume, type of blade, blade diameter, and stirring speed of the stirring layer. Therefore, it is difficult to specify a specific range, but the product of the blade diameter (m) and the stirring speed (rpm) is preferably 5 to 2000, more preferably 10 to 1000, and even more preferably 10 to 700.

[0079] In the method for producing a cellulose powder according to the present embodiment, it is preferable that the hydrolysis of the raw cellulose is carried out in a relatively short time by setting the acid or alkali concentration at a relatively low level and the reaction temperature at a relatively high level. By drying the cellulose dispersion prepared under such reaction conditions, the (Cv / D 50 ) is 0.12g 2 / (s·μm) or more, and the loose bulk density is 0.135 g / cm 3 It is easy to obtain a cellulose powder having a concentration of 0.05% by mass or more and 0.3% by mass or less, preferably 0.1% by mass or more and 0.3% by mass or less, and more preferably 0.1% by mass or more and 0.2% by mass or less, of hydrochloric acid. For example, hydrolysis can be carried out at 85°C or more and 150°C or less, preferably 100°C or more and 135°C or less, and more preferably 105°C or more and 130°C or less, in a hydrolysis solution of 0.05% by mass or more and 0.3% by mass or less, and more preferably 0.1 ...2% by mass or less. The reaction time for the hydrolysis reaction is appropriately set depending on the amount of raw cellulose, the amount of reaction solution, the strength of the stirring force of the solution, and the like. For example, it is preferably 10 minutes to 3 hours, more preferably 30 minutes to 3 hours, and even more preferably 1 hour to 2 hours.

[0080] The method for achieving an average width of 2 μm to 30 μm and an average thickness of 0.5 μm to 5 μm is not particularly limited, as long as it involves tearing the primary cellulose particles primarily in the longitudinal direction. Specific examples of such methods include subjecting wood pulp to a high-pressure homogenizer treatment, followed by mechanical treatment such as grinding, fractionation, or a suitable combination of both, as needed. When performing high-pressure homogenizer treatment, the pressure may be adjusted appropriately within a range of approximately 10 MPa to 200 MPa, depending on the treatment volume. Alternatively, for example, pulp having an average width of 2 μm to 30 μm and an average thickness of 0.5 μm to 5 μm may be selected and used.

[0081] The cellulose dispersion is preferably 0.5% by mass or more and 40% by mass or less. By obtaining a cellulose dispersion that satisfies this condition, the particles of the cellulose powder can be maintained in their primary particle structure. This increases plastic deformability during compression and promotes entanglement of the primary particles.

[0082] The cellulose concentration in the cellulose dispersion is measured by the following method. Five grams of the cellulose dispersion was placed on an aluminum sheet attached to an infrared moisture meter (Kett Electric Laboratory, Model FD-240) and dried by heating using infrared radiation. The moisture content (%) obtained from the mass change due to evaporation of water was used to calculate the cellulose concentration in the cellulose dispersion using the following formula:

[0083] [Cellulose concentration in cellulose dispersion (%)] = 100 - [moisture value (%)]

[0084] By preparing a cellulose dispersion in which the primary cellulose particles have an average particle size of 10 μm or more but less than 300 μm, an average width of 2 μm or more but 30 μm or less, and an average thickness of 0.5 μm or more but 5 μm or less, preferably a cellulose dispersion in which the cellulose concentration in the cellulose dispersion is 0.5% by mass or more but 40% by mass or less, the primary particle structure is easily maintained when the cellulose dispersion is dried. Furthermore, because primary cellulose particles having a specific average particle size, average width, and average thickness are easily bent, when the cellulose powder is compression-molded, high plastic deformability of the primary cellulose particles and entanglement between the primary particles are promoted, resulting in a molded product that exhibits high moldability and the effects of preventing abrasion.

[0085] When the average particle size of the primary cellulose particles is less than the above upper limit, the primary cellulose particles are more easily bent when the shape of the primary cellulose particles is within a specific range, thereby increasing the plastic deformability during compression molding and further promoting entanglement of the primary particles. On the other hand, when the average particle size of the primary cellulose particles is equal to or greater than the above lower limit, the particles are prevented from becoming fine particles, the gaps between the primary cellulose particles in the molded product can be more effectively maintained, and a molded product with better disintegrability and dissolution properties can be obtained.

[0086] When the average width of the primary cellulose particles is less than the above upper limit, the primary cellulose particles are more easily bent, which increases the plastic deformability during compression molding and further promotes entanglement of the primary particles. On the other hand, when the average width of the primary cellulose particles is equal to or greater than the above lower limit, the gaps between the primary cellulose particles in the molded product can be more effectively maintained, and a molded product with better disintegration properties and dissolution properties can be obtained.

[0087] When the average thickness of the primary cellulose particles is less than the above upper limit, the primary cellulose particles are more easily bent, the plastic deformability during compression molding is higher, and the entanglement of the primary particles can be further promoted. The lower limit of the average thickness of the primary cellulose particles is preferably as low as possible because the entanglement of the particles is more easily caused, and is usually about 0.5 μm.

[0088] When the average width of the primary cellulose particles is equal to or greater than the above-mentioned lower limit and the average thickness is equal to or greater than the above-mentioned lower limit, the particles are prevented from becoming fine particles, the gaps between the primary cellulose particles in the molded body can be more effectively maintained, and the disintegration property and dissolution property are more excellent.

[0089] The method for producing a cellulose dispersion in the present specification is not particularly limited, and examples thereof include: i) a method in which primary cellulose particles obtained by treating one or more natural cellulosic substances are used to prepare a cellulose dispersion; ii) a method in which the cellulose dispersion obtained in i) above is divided, subjected to separate treatments, and then mixed to prepare a cellulose dispersion; iii) a method in which the cellulose dispersion obtained in i) or ii) above is fractionated, subjected to separate treatments, and then mixed to prepare a cellulose dispersion; and iv) a method in which two or more types of separately prepared primary cellulose particles are mixed to prepare a cellulose dispersion. Among these, i) is preferred from an economical viewpoint. The treatment method used here may be a wet method or a dry method, and materials obtained by a wet method may be mixed before drying, materials obtained by a dry method may be mixed before drying, or materials obtained by a wet method or a dry method may be combined.

[0090] The method for applying the cellulose dispersion liquid is not particularly limited as long as it is a known method, and examples thereof include mechanical treatments such as pulverization or grinding, centrifugal separation using a cyclone or a centrifuge, and separation treatments such as classification using a sieve, etc. These treatment methods may be used alone or in combination of two or more.

[0091] 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.

[0092] 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, three-dimensional mixer, and side mixer; jet-type stirring and grinding methods such as a line mixer; grinding methods using a high-shear homogenizer, high-pressure homogenizer, ultrasonic homogenizer, and the like; and shaft rotation extrusion grinding methods such as a kneader.

[0093] The cellulose dispersion particles obtained by the above procedure preferably have a concentration in the dispersion before drying of 0.5% by mass to 40% by mass, more preferably 1.0% by mass to 30% by mass, even more preferably 2.0% by mass to 10% by mass, particularly preferably 3.0% by mass to 9.0% by mass, even more particularly preferably 3.5% by mass to 8.0% by mass, and most preferably 4.0% by mass to 7.0% by mass. When the concentration of cellulose dispersion particles in the dispersion is equal to or greater than the lower limit, the average particle size of the obtained cellulose particles becomes larger and the flowability becomes more excellent. On the other hand, when the concentration of cellulose dispersion particles in the dispersion is equal to or less than the upper limit, the apparent specific volume of the cellulose particles becomes larger and the compression moldability becomes more excellent.

[0094] The drying method is not particularly limited, and examples thereof 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 from an economical viewpoint.

[0095] When carrying out the above-mentioned 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.

[0096] 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.

[0097] 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.

[0098] 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.

[0099] 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 above 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.

[0100] 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.

[0101] 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.

[0102] <Application> When the cellulose powder of this embodiment is incorporated into a solid preparation containing an active ingredient, it exhibits excellent hardness and friability while maintaining small mass variation and good disintegrability, and also enables the solid preparation to be miniaturized without changing the amount of the active ingredient, making it particularly useful as an excipient for solid preparations aimed at miniaturization.

[0103] When the cellulose powder of this embodiment is incorporated into a solid preparation containing a poorly water-soluble active ingredient, it exhibits small mass variation, good disintegrability, and excellent tableting properties, making it particularly useful as an excipient for solid preparations containing a poorly water-soluble active ingredient.

[0104] Furthermore, when the cellulose powder of this embodiment is incorporated into a solid preparation containing a liquid or semi-solid active ingredient, it maintains good disintegrability while preventing the liquid or semi-solid active ingredient from seeping out, making it particularly useful as an excipient for solid preparations containing a liquid or semi-solid active ingredient.

[0105] In addition, the cellulose powder of this embodiment contains a trace amount of the active ingredient, and in particular, the average particle diameter D 50 When an active ingredient having a small particle size and high adhesive and cohesive properties is mixed with an ingredient other than the active ingredient, or when the active ingredient is incorporated into a solid preparation using the mixture, the mixing speed of the active ingredient and the concentration variation can be reduced, resulting in good tableting properties. 50 It is particularly useful as an excipient for a mixture of an active ingredient having small particle size and high adhesive and cohesive properties with ingredients other than the active ingredient, or for a solid preparation using the mixture.

[0106] Furthermore, when the cellulose powder of the present embodiment is incorporated into a solid preparation containing a sublimable active ingredient, it can prevent recrystallization due to sublimation of the sublimable active ingredient, thereby preventing a decrease in commercial value. Therefore, it is particularly useful as an excipient for solid preparations containing a sublimable active ingredient.

[0107] <Molded body> The molded body of this embodiment contains one or more active ingredients and the cellulose powder of this embodiment.

[0108] When the molded product of this embodiment is a tablet, by including the cellulose powder of this embodiment, it is possible to obtain smaller tablets that have excellent hardness and friability while reducing mass variation and maintaining good disintegrability, and without changing the amount of active ingredient such as a drug.

[0109] 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 0.001% by mass to 99% by mass, and the content of the cellulose powder of this embodiment is 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 above-mentioned lower limit, an amount effective for treatment can be ensured, while by ensuring that the content is equal to or less than the above-mentioned upper limit, the content of the cellulose powder of this embodiment can be equal to or greater than the above-mentioned lower limit, resulting in a molded body that exhibits practical hardness, friability, and disintegration. Furthermore, the active ingredient and cellulose powder are processed by known methods such as mixing, stirring, granulating, sizing, and tableting to obtain the molded article of this embodiment. Furthermore, 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 needed.

[0110] When used as a pharmaceutical product, the molded article of this embodiment may be in the form of a tablet, powder, fine granules, granules, extract, pill, etc. Among these, a tablet is preferred. Furthermore, the molded article of the present embodiment can be used not only for pharmaceuticals but also for foods such as confectioneries, health foods, texture improvers, and dietary fiber enrichment agents; solid foundations, bath additives, veterinary drugs, diagnostic agents, pesticides, fertilizers, and ceramic catalysts.

[0111] [Active ingredient] Active ingredients include pharmaceutical active ingredients, pesticide ingredients, fertilizer ingredients, feed ingredients, food ingredients, cosmetic ingredients, pigments, fragrances, metals, ceramics, catalysts, and surfactants. Active ingredients may be in any form, such as solid (powder, crystalline, etc.), oil, liquid, or semi-solid. They may also be coated for purposes such as controlling release or reducing bitterness. Active ingredients may be used alone or in combination. They may be used by dissolving, suspending, or emulsifying them in a medium. Among these, the active ingredient is preferably a pharmaceutical active ingredient or a food active ingredient.

[0112] 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, osteoporosis drugs, 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.

[0113] 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, napadi Mebhydroline silate, 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, noscapine hydrochloride, Scapine, 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 potassium aluminum 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 methylenediamine Cilicate, 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, ethyl piperidylacetylaminobenzoate Medicinal herbs, such as thiamine dinitrate, aminophylline, diprophylline, theophylline, sodium bicarbonate, fursultiamine dinitrate, isosorbide dinitrate, ephedrine, cephalexin, ampicillin, sulfixazole, sucralfate, allylisopropylacetylurea, bromvalerylurea, etc., ephedra, nandina fruit, scutellaria bark, onion root, licorice, bellflower, scutellaria, scutellaria, senega, fritillaria, fennel, Phellodendron bark, coptis, zedoary, chamomile, kaempferia Examples of pharmaceutically active ingredients include barley, 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.

[0114] In the present specification, a poorly water-soluble active ingredient refers to, for example, a pharmaceutical active ingredient, which, 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 incorporated into the molded article of the present embodiment as an active ingredient to provide an effect, regardless of the degree of sublimation or surface polarity.

[0115] Examples of water-insoluble 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 active pharmaceutical ingredients include antibiotics such as cetyloleandomycin, nystatin, and colistin sulfate; steroid hormones such as methyltestosterone, methylandrosterone diol, progesterone, estradiol benzoate, ethinylestradiol, deoxycorticosterone acetate, cortisone acetate, hydrocortisone, hydrocortisone acetate, and prednisolone; nonsteroidal yolk hormones such as dienstrol, hexastrol, diethylstilbesterol, diethylstilbesterol dibromohydratate, and chlorotrianisene; and other fat-soluble vitamins, as listed in the Japanese Pharmacopoeia, USP, NF, and EP. These active ingredients may be used alone or in combination.

[0116] 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; coenzyme Q; and oil-soluble flavorings such as orange oil, lemon oil, and peppermint oil. Various homologs and derivatives of vitamin E are available, but they are not particularly limited as long as they are 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 in combination.

[0117] 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 rhododendron, garlic, seneca, fritillary, fennel, Phellodendron bark, coptis, zedoary, chamomile, gentian, bezoar, animal gall, rhododendron, ginger, soju, clove, chinese herb, atractylodes rhododendron, 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.

[0118] The sublimable active ingredient is not particularly limited as long as it has sublimability. The sublimable active ingredient may be in a solid, liquid, or semi-solid state at room temperature. Examples of sublimable active ingredients include sublimable pharmaceutical active ingredients listed in the Japanese Pharmacopoeia, USP, NF, and 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.

[0119] [Other ingredients] 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, powdered agar, and cinnamon. Ciritol, 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, 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 hydrotalcite, 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, magnesium hydroxide, 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, tribasic calcium 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 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, polyoxyethylene (160) poly Examples of excipients include those classified as excipients in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as propylene (30) glycol, sodium polystyrene 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. These excipients may be used alone or in combination of two or more.

[0120] 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.

[0121] 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.

[0122] 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.

[0123] 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.

[0124] 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, and 1-menthol. These flavoring agents may be used alone or in combination of two or more.

[0125] 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.

[0126] 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.

[0127] Examples of sweeteners include aspartame, saccharin, dipotassium glycyrrhizinate, stevia, maltose, maltitol, starch syrup, and powdered amacha tea, which are classified as sweeteners in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.). These sweeteners may be used alone or in combination of two or more.

[0128] [Method of manufacturing molded body] A method for producing a tablet containing one or more active ingredients and the cellulose powder of this embodiment as the main ingredients is 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. For example, the cellulose powder of the present embodiment may be mixed with the active ingredient and then compressed and molded. In this process, other additives may be added as needed in addition to the active ingredient. Examples of other additives include one or more selected from the group consisting of excipients, disintegrants, binders, flow agents, lubricants, flavoring agents, flavorings, colorants, sweeteners, and solubilizers.

[0129] There are no particular restrictions on the order in which the components are added, and examples include: i-1) a method in which the active ingredient, the cellulose powder of this embodiment, and other additives, if necessary, are mixed together and compression-molded; and ii-1) a method in which the active ingredient and additives such as a fluidizer or lubricant are premixed, the cellulose powder of this embodiment, and other additives, if necessary, are mixed, and then compression-molded. A lubricant may be added to the powder mixture for compression molding obtained by method i-1) or ii-1), and the mixture may be further mixed and then compression-molded.

[0130] In particular, when an active ingredient that is poorly soluble in water is used, the following production methods can be employed. Examples of production methods include i-2) a method in which the active ingredient is pulverized or used as is, mixed with the cellulose powder of this embodiment and other ingredients as needed, and compression-molded; and ii-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 media is removed as needed, followed by compression-molding.

[0131] Among these, in terms of moldability and fluidity, i-2) is particularly preferred, in which the active ingredient is pre-mixed with additives such as a fluidizing agent, and then mixed with the cellulose powder of this embodiment and other ingredients as necessary, followed by compression molding.

[0132] 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.

[0133] When using an active ingredient that is poorly soluble in water, it is particularly effective to use a water-soluble polymer or a surfactant as a solubilizing agent and disperse it in a medium. The other additives referred to here are additives other than the cellulose powder of this embodiment, and examples include excipients, disintegrants, binders, fluidizing agents, lubricants, flavoring agents, flavorings, colorants, sweeteners, solubilizing agents, and the like. These additives may be used alone or in combination of two or more.

[0134] In particular, method ii-2) involves a step of dissolving or dispersing a poorly water-soluble or insoluble active ingredient, which also has the effect of improving the dissolution of the active ingredient. In particular, when a liquid dispersion such as polyethylene glycol is used in combination as a dispersion of a pharmaceutical active ingredient, even if the active ingredient is originally a crystalline powder, the resulting dispersion will be liquid or semi-solid. Therefore, unless the active ingredient has excellent compression moldability and flowability, such as the cellulose powder of this embodiment, the active ingredient cannot be tableted. Furthermore, when polyethylene glycol or the like is used as a dispersion of a pharmaceutical active ingredient, it is said that when the active ingredient is absorbed into the body, it takes on a polyethylene glycol-coated structure in the blood. Therefore, the effect of prolonging the efficacy of active ingredients that are easily metabolized in the liver is also expected.

[0135] 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.

[0136] When the active ingredient is in the form of a solution, suspension, or emulsion, it is preferable to spray it onto cellulose powder or other additives. This can further reduce the variation in active ingredient concentration in the final product. Examples of spraying methods include spraying the active ingredient solution or dispersion using a Tao Teva nozzle, 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 or dry method.

[0137] The mixing method is not particularly limited as long as it is a commonly used method, and examples thereof include methods using container rotation mixers such as V-type, W-type, double cone-type, and container tuck-type mixers; stirring mixers such as high-speed stirring, universal stirring, ribbon-type, pug-type, and Nauta-type mixers; high-speed fluid mixers, drum-type mixers, and fluidized bed mixers; and methods using container shaking mixers such as shakers.

[0138] The method for compression molding the composition 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 a desired shape, etc. Examples of compression molding machines include roller presses such as static pressure presses, briquetting roller presses, and smooth roller presses, single punch tablet presses, rotary tablet presses, etc.

[0139] The method for dissolving or dispersing the active ingredient in the 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-injection 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.

[0140] The medium used in the above-mentioned manufacturing method is not particularly limited as long as it is one used in pharmaceuticals, but for example, water or an organic solvent can be used. Examples of 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, which are classified as solvents in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.). These media may be used alone or in combination of two or more. After dispersing in one medium, the medium may be removed and the resulting mixture may be dispersed in a different medium.

[0141] 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.

[0142] Examples of fats and oils as solubilizing agents 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.

[0143] Examples of surfactants 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, and sodium lauryl sulfate. These surfactants may be used alone or in combination of two or more.

[0144] 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. Tablet compositions incorporating the cellulose powder of this embodiment are particularly suitable for achieving practical hardness using a simple method such as direct tableting without complex steps. Tablet manufacturing methods may include, as needed, dry granule compression, wet granule compression, post-compression, a method for manufacturing a multi-core tablet using a pre-compressed tablet as the core, and a method for manufacturing a multi-layer tablet in which multiple pre-compressed compacts are stacked and compressed again.

[0145] The cellulose powder of this embodiment has excellent physical properties required for an excipient in terms of compression moldability, flowability, and disintegrability. Therefore, it is particularly effective for tablets containing a variety of drugs or large amounts of drugs that are difficult to achieve tablet hardness and prone to tableting problems such as cracks, chips, internal peeling, and cracks on the tablet surface, such as tablets containing powdered extracts of over-the-counter drugs and traditional Chinese medicines; small tablets; irregularly shaped tablets that are not round, such as those with narrowed edges that make it difficult to apply even compression pressure; and tablets containing drugs such as enzymes and proteins that are easily inactivated by compression pressure or friction with excipients, or tablets containing coated granules. Furthermore, because the cellulose powder of this embodiment has excellent compression moldability, it can produce tablets that exhibit practical friability at relatively low compression pressures. Therefore, since voids (water channels) can be maintained within the tablet, it is also effective for orally disintegrating tablets that disintegrate quickly in the oral cavity.

[0146] Furthermore, in the case of multi-layer tablets or dry-coated tablets in which several components are compressed in one or more steps, in addition to imparting hardness and suppressing general tableting problems, the cellulose powder of this embodiment also has the effect of suppressing peeling and cracking between layers. Since the cellulose powder of this embodiment has a high proportion of primary particles, the particles themselves have excellent divisibility, and when used for scored tablets, etc., the tablets can be easily divided uniformly. Furthermore, the cellulose powder of this embodiment has a developed porous structure, and the cellulose particles themselves have excellent retention properties for particulate drugs, suspension drugs, and solution-like components. Therefore, tablets using it also have excellent retention properties for particulate drugs, suspension drugs, and solution-like components. Therefore, the cellulose powder of this embodiment is also effective for preventing and reinforcing the layering layer, coating layer, or sugar-coating layer in layered or coated tablets that use suspension or solution-like components in the tablet, and in sugar-coated tablets that have components such as sugar and calcium carbonate layered in a suspended state on the tablet surface.

[0147] Next, methods for using compositions containing one or more active ingredients and cellulose powder will be described. The solid, liquid, or semi-solid compositions containing active ingredients and cellulose powder obtained by the methods described above may be used as solid formulations in powder or granular form, or the powder or granular composition may be further coated with a coating agent and used as a coated powder or granular solid formulation. The powder or granular composition obtained here, with or without coating, 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.

[0148] Examples of coating agents for coating include ethyl acrylate-methyl methacrylate copolymer dispersion, acetylglycerin fatty acid ester, aminoalkyl methacrylate copolymer, gum arabic, ethyl cellulose, ethyl cellulose aqueous dispersion, octyldecyl triglyceride, olive oil, kaolin, cacao butter, kagoso, castor wax, caramel, carnauba wax, carboxyvinyl polymer, carboxymethylethyl cellulose, sodium carboxymethyl starch, carmellose calcium, carmellose, Sodium citrate, hydrous silicon dioxide, dried aluminum hydroxide gel, dried milky white lac, dried methacrylic acid copolymer, winter plum powder, fish scale powder, gold leaf, silver leaf, triethyl citrate, glycerin, glycerin fatty acid ester, magnesium silicate, light anhydrous silicic acid, light anhydrous silicic acid-containing hydroxypropyl cellulose, light liquid paraffin, spermaceti, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, synthetic wax, high glucose starch syrup, hard wax, succinated gelatin, wheat flour, wheat starch, rice starch, cellulose acetate, vinyl acetate resin, cellulose acetate phthalate Rose, 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, calcium stearate, polyoxyl stearate, magnesium stearate, refined gelatin, refined shellac, refined white sugar, gelatin Ingredients: 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 phthalate 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 monostearate, polyvinyl acetal diethylaminoacetate, polyvinyl Examples of coating agents include those listed in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as 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.

[0149] The cellulose powder of this embodiment has a well-developed porous structure, and the particles themselves have excellent drug retention. Therefore, the particles with the drug loaded in the pores may be used as fine granules as they are, or may be granulated and used as granules, or these may be compressed and molded. These fine granules, granules, or tablets may be further coated.

[0150] The method for loading a drug into the pores of cellulose powder is not particularly limited as long as it is a known method, but examples include: i) mixing with a particulate drug and loading into the pores; ii) mixing with a powdered drug under high shear and forcibly loading into the pores; iii) mixing with a drug that has been made into a solution or dispersion, loading into the pores, and then drying as necessary; iv) mixing with a sublimable drug and heating or reducing pressure to sublimate and adsorb into the pores; v) mixing with a drug before or during heating, melting the mixture, and loading into the pores, etc. These methods may be used alone or in combination of two or more.

[0151] The cellulose powder of this embodiment has a developed pore structure and moderate water and oil retention. Therefore, in addition to being used as an excipient, it can also be used as core particles for layering or coating. In this case, it has the effect of suppressing aggregation between particles during the layering or coating process. Layering or coating may be performed by either a dry method or a wet method.

[0152] Furthermore, when the active ingredient is in the form of a solution, suspension, or emulsion, a method can be employed in which cellulose powder or a mixture of cellulose powder and other additives is used as a carrier, and the carrier is immersed in the active ingredient solution, suspension, or emulsion to retain the active ingredient, such as by dipping. Although it depends on the type of active ingredient, concentration, and other conditions, such a liquid immersion method as dipping can practically maintain the uniformity of the active ingredient and is superior to the above-mentioned spraying method in that the process is simpler. Furthermore, when the active ingredient is in the form of a solution, suspension, or emulsion, a method may be used in which cellulose powder or a mixture of cellulose powder and other additives is used as a carrier and immersed in the active ingredient solution, suspension, or emulsion, and then the resulting dispersion is spray-dried to form a complex.

[0153] The cellulose powder before and after the addition of the active ingredient solution or active ingredient dispersion, or the mixture of cellulose powder and other additives, may be in a state in which each unit particle is individually dispersed, or may be in the form of an agglomerated granule.

[0154] 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.

[0155] 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), and freeze drying. In hot air heating methods, hot air is directly brought into contact with the material, simultaneously removing evaporated water. In conduction heat transfer methods, the material is indirectly heated through a heat transfer wall. In freeze drying, the material is frozen at temperatures between -10°C and -40°C, and then heated under a high vacuum (1.3 x 10-5 MPa to 2.6 x 10-4 MPa) to sublimate and remove water.

[0156] Based on the above, examples of methods for manufacturing tablets include: i) a mixture of an active ingredient and cellulose powder, or a mixture of one or more active ingredients and cellulose powder and, if necessary, other additives, is compressed and molded by a conventional method (direct tableting); ii) an active ingredient and cellulose powder and, if necessary, other additives are mixed, and then the mixture is granulated to form granules, which are then compressed and molded by a conventional method (wet or dry granulation compression method); iii) an active ingredient and cellulose powder and, if necessary, other additives are mixed, granulated to form granules, which are then mixed with cellulose powder and, if necessary, other additives, and then compressed and molded by a conventional method (wet or dry granulation post-powder compression method).

[0157] The method of adding one or more active ingredients, cellulose powder, other additives, or granules is not particularly limited as long as it is a commonly used method, and for example, they 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, etc., or they may be added all at once. In addition to being used as tablets after compression molding as described above, the composition containing the active ingredient and cellulose powder is excellent in retaining solid or liquid ingredients, and therefore may be used as granules or powders, particularly for the purpose of improving flowability, blocking resistance, and aggregation resistance. Methods for producing granules or powders include, for example, dry granulation, wet granulation, heat granulation, spray drying, and microencapsulation.

[0158] [Physical properties of tablets] The molded article of this embodiment is a mixture of (1) 603.2 parts by mass of ascorbic acid (manufactured by Watanabe Chemical Co., Ltd., used after sieving through a sieve with 2 mm mesh; the average particle size D50 of the obtained ascorbic acid is 320 μm), 603.2 parts by mass of spray-dried lactose (manufactured by DFE Pharma Co., Ltd., SuperTab 108.8 parts by mass of cellulose powder of the present embodiment (product number 11SD (product name)) and 80 parts by mass of the cellulose powder of the present embodiment were placed in a plastic bag and mixed by shaking for 3 minutes. Next, 8 parts by mass of calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) was added, and the mixture was further mixed for 30 seconds to obtain a formulated powder (the final composition was ascorbic acid / spray-dried lactose / cellulose powder / calcium stearate in mass ratios of 75.4 / 13.6 / 10 / 1). The obtained formulated powder was supplied using an open feeder and compressed into tablets using a rotary tablet press (manufactured by Kikusui Seisakusho Co., Ltd., 12-tablet) with a mortar and pestle having a diameter of 9 mm and R at a turntable rotation speed of 54 rpm. When the obtained tablets had a mass of approximately 370 mg, (2) ascorbic acid (manufactured by Watanabe Chemical Co., Ltd., used after sieving through a sieve with 2 mm openings).The resulting ascorbic acid had an average particle size D50 of 320 μm (544.4 parts by mass), spray-dried lactose (SuperTab (3) 167.6 parts by mass of cellulose powder of the present embodiment, 11SD (product name) and 80 parts by mass of the cellulose powder of the present embodiment are placed in a plastic bag and mixed by shaking for 3 minutes, and then 8 parts by mass of calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) are added and mixed for an additional 30 seconds to obtain a formulated powder (the final composition is ascorbic acid / spray-dried lactose / cellulose powder / calcium stearate=68 / 21 / 10 / 1 by mass ratio), and the obtained formulated powder is fed by an open feeder and compressed into tablets using a rotary tablet press (manufactured by Kikusui Seisakusho Co., Ltd., 12-tablet) with a mortar and pestle of 9 mm diameter and R at a turntable rotation speed of 54 rpm to obtain tablets with a mass of approximately 410 mg; or 245 parts by mass of cellulose powder of the present embodiment (ascorbic acid / spray-dried lactose / cellulose powder / calcium stearate (trade name)), 50 parts by mass of the cellulose powder of the present embodiment, and 5 parts by mass of light anhydrous silicic acid (manufactured by Nippon Aerosil Co., Ltd., AEROSIL 200 (trade name)) were placed in a plastic bag and mixed by shaking for 3 minutes. Five parts by mass of magnesium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) were then added and mixed for an additional 30 seconds to obtain a formulated powder (final composition by mass ratio: ascorbic acid / spray-dried lactose / cellulose powder / calcium stearate = 40 / 49 / 10 / 1 / 1). The formulated powder obtained was compressed into tablets using a single-punch tablet press (manufactured by Ichikawa Seiki Co., Ltd.) with a mortar and pestle having a diameter of 8 mm and R at a rate of 30 tablets per minute. When the obtained tablets had a mass of approximately 470 mg, the tablet mass variation was 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. Tablet weight variation can be measured, for example, using the method described in the Examples below.

[0159] Furthermore, when the molded product of this embodiment is a tablet produced under the same conditions as above, its hardness is preferably 40 N or more, more preferably 45 N or more, even more preferably 50 N or more, and particularly preferably 55 N or more. On the other hand, the greater the tablet hardness, the better, and although the upper limit is not particularly limited, it is usually about 150 N. The tablet hardness can be measured, for example, by the method described in the Examples below.

[0160] Furthermore, when the molded product of this embodiment is a tablet produced under the same conditions as above, 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 can be measured, for example, by the method described in the Examples below.

[0161] Furthermore, when the molded product of this embodiment is a tablet produced under the same conditions as above, 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 better, and the lower limit is not particularly limited, but is usually about 0.01% by mass. The friability can be measured, for example, by the method described in the Examples below.

[0162] That is, when the molded body of this embodiment is a tablet manufactured under the same conditions as above, it is preferable that the tablet has a tablet mass variation of 1.0% by mass or less, a tablet hardness of 40 N or more, a disintegration time of 1800 seconds or less, and a friability of less than 0.5% by mass. [Example]

[0163] The present invention will be described based on examples, but the embodiments of the present invention are not limited to the descriptions of these examples. The methods for measuring and evaluating the various physical properties in the examples and comparative examples are as follows.

[0164] <Methods for measuring physical properties> [Physical Properties 1] (average particle size of cellulose powder) Average particle size of cellulose powder D 50 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 with a laser light (red) transmittance in the range of 95% to 98%. The particle size at 50% of the cumulative volume measured was taken as the average particle size D 50 The values ​​are shown as the average of two measurements.

[0165] [Physical Properties 2] (Average degree of polymerization of cellulose powder) Approximately 1.3 g of cellulose powder (approximately 0.25 g for powdered cellulose) was accurately weighed and placed in a 125 mL Erlenmeyer flask. 25 mL of water and 25 mL of 1 mol / L copper ethylenediamine TS were added. Nitrogen was immediately purged into the flask, and the flask was sealed and shaken to dissolve. An accurately weighed drop of this solution was tested at 25 ± 0.1°C using a capillary viscometer with an approximate viscometer constant (K) of 0.03 according to Viscosity Measurement Method 1 (2.53), to determine the kinematic viscosity (ν). Separately, 25 mL of water and 25 mL of 1 mol / L copper ethylenediamine TS were accurately weighed, and the resulting mixture was tested in the same manner using a capillary viscometer with an approximate viscometer constant (K) of 0.01 to determine the kinematic viscosity (ν). The relative viscosity (ηrel) of the cellulose powder was calculated using the following equation:

[0166] ηrel = ν / ν0

[0167] From the relative viscosity ηrel, the product [η]C of the intrinsic viscosity [η] (mL / g) and the concentration C (g / 100 mL) was determined, and the average degree of polymerization P was calculated using the following formula: In the formula below, MT is the weighed amount (g) of the cellulose powder converted into a dry matter.

[0168] P = 95[η]C / MT

[0169] [Physical Properties 3] (Water absorption rate of cellulose powder) The water absorption rate was determined using a commercially available water absorption rate measuring device (Penet Analyzer PNT-N (trade name), manufactured by Hosokawa Micron Corporation). Specifically, approximately 5.0 g of cellulose powder that had passed through a 500 μm mesh sieve was filled into a Teflon (registered trademark) container, and tapping was performed under the following conditions: 300 tappings, stroke length: 18 mm, and weight: 198 g. After tapping, the powder was thoroughly immersed in 300 mL of pure water at a speed of 0.5 mm / s until it became saturated, and the square of the penetration rate of pure water (g 2 The square of the permeation rate (g) until the saturation state was measured using the above-mentioned measuring device. 2 The graph of the water absorption rate (g) versus the measurement time was linearized using the least squares method, and the slope of the linearized graph was used to calculate the water absorption rate (g 2 / s) and the average value of five measurements was shown.

[0170] [Physical Properties 4] (Cohesion of cellulose powder F) The cohesion force of cellulose powder was calculated using a powder bed shear force measuring device (NS-S300 (trade name), manufactured by Nano Seeds Co., Ltd.). Specifically, cellulose powder was filled into a shear cell (φ15 mm, upper and lower cell lengths: 34 mm, 5 mm), and the top surface of the powder bed was flattened. A shear test was then performed at a shear rate of 50 μm / s, with a target indentation load of 20 N as the indentation control condition. When the target load was reached, indentation was stopped, and lateral sliding was initiated. The static and kinetic friction coefficients were then measured. For analysis, the elapsed measurement time (s) was plotted on the horizontal axis and the load (N) applied to the shear surface on the vertical axis. The maximum and minimum values ​​of the shear surface load were determined, and the cohesion force, defined by the following formula, was calculated. The average value of two measurements was shown.

[0171] [Cohesion strength F (N%)] = ([Maximum shear plane load (N)] - [Minimum shear plane load (N)]) / [Maximum shear plane load (N)] × 100

[0172] [Physical Properties 5] (Dynamic friction angle of cellulose powder) The powder kinetic friction angle of cellulose powder was calculated using a powder bed shear force measuring device (NS-S300 (product name), manufactured by Nano Seeds Co., Ltd.). Specifically, cellulose powder was filled into a shear cell (φ15 mm, upper and lower cell lengths: 34 mm, 5 mm), and the top surface of the powder bed was flattened. Then, using the measuring device, a shear test was performed at a shear rate of 50 μm / s with indentation target loads of 20 N, 30 N, and 40 N as indentation control conditions. When the target load was reached, indentation was stopped, and lateral sliding was initiated, after which the static and kinetic friction coefficients were measured. For analysis, the elapsed time (s) of the measurement was plotted on the horizontal axis against the shear force (N) on the vertical axis to determine the maximum shear force and the indentation load value at that time. The results were plotted on a graph with the vertical axis representing shear stress and the horizontal axis representing normal stress, and the angle of the line connecting these points with the origin relative to the X-axis was calculated as the powder kinetic friction angle. The values ​​are shown as the average of two measurements.

[0173] [Physical Properties 6] (Loose bulk density of cellulose powder) The loose bulk density of the cellulose powder was measured by the following method. The cellulose powder was filled into a 25 mL cylindrical metal container using a Scott volumeter (Model ASTM B-329-85, manufactured by Tsutsui Scientific Instruments Co., Ltd.). 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 of two measurements.

[0174] [Physical Properties 7] (Compressibility of cellulose powder) The compressibility of the cellulose powder was measured by the following method. The compacted bulk density was measured using a powder property evaluation device (Powder Tester, manufactured by Hosokawa Micron Corporation). A sieve with a mesh size of 710 μm and a metal funnel with an inner diameter of 0.8 cm were used, and the vibration was set to 2.0 (power supply: AC 100 V, 60 Hz). The loose bulk density was measured using the method described above, and the compressibility, defined by the following formula, was calculated. The value is the average of two measurements.

[0175] [Compression ratio (%)] = ([hardened bulk density (g / cm 3 )]-[Loose bulk density (g / cm 3 )]) / [hardened bulk density (g / cm 3 )] x 100

[0176] [Physical Properties 8] (Primary particle ratio of cellulose powder) The primary particle ratio of cellulose powder was calculated using a dry image analyzer (Malvern Morphorogi G3S) and image processing software. Specifically, 10,000 particles were photographed and analyzed to determine the equivalent circle diameter and aspect ratio of each particle. From the results, particle images with equivalent circle diameters ranging from 30 μm to 90 μm and aspect ratios less than the average aspect ratio of the 10,000 particles + 0.1 were selected. For each sampled particle image, the brightness dispersion values ​​selected from the range of 1 to 26 were defined as primary particles, and those selected from the range of 26 to 100 were defined as secondary particles. The primary particle ratio (%) was calculated by multiplying the number of primary particles by the total number of particles × 100.

[0177] [Physical Properties 9] (L / D of primary particles of cellulose powder) Using a dry image analyzer (Malvern Morphorogi G3S) and image processing software, images of primary particles were extracted in the same manner as described above. The long diameter (L) / short diameter (D) ratio was calculated from the long diameter (L) and short diameter (D) obtained from each extracted particle image, and the average value of all the extracted primary particle images was calculated as the L / D ratio of the primary particles of the cellulose powder.

[0178] <Evaluation method> [Production of 370mg tablets] 603.2 g of ascorbic acid (manufactured by Watanabe Chemical Co., Ltd., used after sieving through a 2 mm mesh sieve; average particle size of the resulting ascorbic acid was 320 μm), 108.8 g of spray-dried lactose (manufactured by DFE Pharma Co., Ltd., SuperTab 11SD (trade name)), and 80 g of each cellulose powder were placed in a plastic bag and mixed by shaking for 3 minutes. Next, 8 g of calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) was added to the mixed powder and mixed for an additional 30 seconds to obtain the final formulated powder. The final composition of the final formulated powder was ascorbic acid / spray-dried lactose / each cellulose powder / calcium stearate = 75.4 / 13.6 / 10 / 1 by mass.

[0179] Next, the final formulated powder was compressed using a rotary tableting machine (Kikusui Seisakusho Co., Ltd., 12-barrel) to obtain tablets weighing approximately 370 mg. The formulated powder was supplied by an open feeder and compressed using a 9 mm diameter, R mortar and pestle at a turntable rotation speed of 54 rpm. The compression pressure was adjusted appropriately so that the tablet hardness would be 40 N or more.

[0180] [Production of 410mg tablets] 544.4 g of ascorbic acid (manufactured by Watanabe Chemical Co., Ltd., used after sieving through a 2 mm mesh sieve; average particle size of the resulting ascorbic acid was 320 μm), 167.6 g of spray-dried lactose (manufactured by DFE Pharma Co., Ltd., SuperTab 11SD (trade name)), and 80 g of each cellulose powder were placed in a plastic bag and mixed by shaking for 3 minutes. Next, 8 g of calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) was added to the mixed powder and mixed for an additional 30 seconds to obtain the final formulated powder. The final composition of the final formulated powder was ascorbic acid / spray-dried lactose / each cellulose powder / calcium stearate = 68 / 21 / 10 / 1 by mass ratio.

[0181] Next, the final formulated powder was tableted using a rotary tablet press (Kikusui Seisakusho Co., Ltd., 12-barrel) to obtain tablets weighing approximately 410 mg. The formulated powder was supplied by an open feeder and tableted using a 9 mm diameter, R mortar and pestle at a turntable rotation speed of 54 rpm. The tableting pressure was appropriately adjusted so that the tablet hardness would be 40 N or more.

[0182] [Production of 470mg tablets] 200 g of ethenzamide (Yamamoto Chemical Industry Co., Ltd., C grade), 245 g of spray-dried lactose (DFE Pharma Co., Ltd., SuperTab 11SD (trade name)), 50 g of each cellulose powder, and 5 g of light anhydrous silicic acid (Nippon Aerosil Co., Ltd., AEROSIL 200 (trade name)) were placed in a plastic bag and mixed by shaking for 3 minutes. Next, 5 g of magnesium stearate (Taihei Chemical Industry Co., Ltd.) was added to the mixed powder and mixed for an additional 30 seconds to obtain the final formulated powder. The final composition of the final formulated powder was ethenzamide / spray-dried lactose / each cellulose powder / light anhydrous silicic acid / magnesium stearate = 40 / 49 / 10 / 1 / 1 by mass.

[0183] The final formulated powder was then compressed using a single punch tableting machine (manufactured by Ichikawa Seiki Co., Ltd.) to obtain tablets weighing approximately 470 mg. The formulated powder was compressed using a mortar and pestle with a diameter of 8 mm and an R at a rate of 30 tablets per minute. The compression pressure was adjusted appropriately so that the tablet hardness was 100 N or more.

[0184] [Rating 1] (Tablet mass variation (mass%)) The mass of 10 tablets obtained was measured, and the average mass and standard deviation (g) of the mass were calculated. The mass variation was evaluated using the coefficient of variation (mass %; hereinafter, the coefficient of variation is also referred to as mass CV) defined by the following formula. The smaller the coefficient of variation, the smaller the variation can be evaluated to be, and tablets with a mass CV of 1.0 mass % or less were evaluated to have good variation.

[0185] [Mass CV (mass%)]=[Standard deviation (g)] / [Average mass (g)]×100

[0186] [Rating 2] (Tablet hardness (N)) The tablets were broken by applying a load in the diameter direction of the tablet using a Schleungel hardness tester (Model 6D (trade name), manufactured by Freund Corporation), and the load (N) at that time was measured and expressed as an average value for 10 tablets.

[0187] [Rating 3] (Collapse time (seconds)) A disintegration test was conducted in accordance with the 18th edition of the Japanese Pharmacopoeia, General Test Method, Tablet Disintegration Test Method. The disintegration time of the tablets was measured in pure water at 37°C using a disintegration tester (Toyama Sangyo Co., Ltd., NT-40HS model (product name), without disc). The disintegration time was expressed as the average value of 6 tablets. Tablets with a disintegration time of 1800 seconds or less were evaluated as having excellent disintegrability.

[0188] [Rating 4] (Friability (%)) The weight (Wa) (g) of 18 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, any fine powder adhering to the tablets was removed, and the weight (Wb) (g) was measured again. The friability was calculated using the following formula.

[0189] [Friability (%)] = 100 × (Wa - Wb) / Wa

[0190] [Example 1] (Production of cellulose powder A) 3 kg of shredded commercially available pulp (average degree of polymerization: 1667) and 30 L of 0.045 mol / L hydrochloric acid solution were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 117 °C for 75 minutes while stirring at 62 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 filter to obtain a filtration residue with a solids concentration of 34% by mass. The residue was then placed in a 20 L stainless steel tank, and purified water was added. The mixture was stirred at 75 rpm using a mixer (HANWA AGITATOR, Hanwa Chemical Engineering Co., Ltd., Model KP-4003, impeller diameter: approximately 17 cm) to obtain a cellulose dispersion with a solids concentration of 6.3% by mass. The average particle size of the cellulose particles in the cellulose dispersion was 25 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 18 kg / hour, inlet temperature: 180° C. to 220° C., outlet temperature: 90° C. to 110° C.) to obtain cellulose powder A.

[0191] [Example 2] (Production of cellulose powder B) 3 kg of shredded commercially available pulp (average degree of polymerization: 1667) and 30 L of 0.045 mol / L hydrochloric acid solution were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 123 °C for 75 minutes while stirring at 80 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 filter to obtain a filtration residue with a solids concentration of 37% by mass. The mixture was then placed in a 20 L stainless steel tank, purified water was added, and the mixture was stirred at 75 rpm with a mixer (HANWA AGITATOR, Hanwa Kakoki Co., Ltd., impeller diameter: approximately 17 cm) to obtain a cellulose dispersion with a solids concentration of 6.4% by mass. The average particle size of the cellulose particles in the cellulose dispersion was 23 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 22 kg / hour, inlet temperature: 180° C. to 220° C., outlet temperature: 90° C. to 110° C.) to obtain cellulose powder B.

[0192] [Example 3] (Production of cellulose powder C) 3 kg of shredded commercially available pulp (average degree of polymerization: 1667) and 30 L of 0.045 mol / L hydrochloric acid solution were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 113 °C for 75 minutes while stirring at 90 rpm. The resulting acid-insoluble residue was then neutralized with aqueous ammonia to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche filter to obtain a filtration residue. The mixture was then placed in a 20 L stainless steel tank, purified water was added, and the mixture was stirred at 75 rpm using a mixer (HANWA AGITATOR, Hanwa Kakoki Co., Ltd., impeller diameter: approximately 17 cm) to obtain a cellulose dispersion with a solids concentration of 6.2% by mass. The average particle size of the cellulose particles in the cellulose dispersion was 27 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 21 kg / hour, inlet temperature: 180° C. to 220° C., outlet temperature: 90° C. to 110° C.) to obtain cellulose powder C.

[0193] [Example 4] (Production of cellulose powder D) 2.3 kg of shredded commercially available pulp (average degree of polymerization: 1667) and 35 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 117 °C for 75 minutes while stirring at 240 rpm to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche filter to obtain a filtration residue with a solids concentration of 43% by mass. The mixture was then placed in a 20 L stainless steel tank, purified water was added, and the mixture was stirred at 75 rpm using a mixer (HANWA AGITATOR, Hanwa Kakoki Co., Ltd., stirring blade diameter: approximately 17 cm) to obtain a cellulose dispersion with a solids concentration of 5.8% by mass. The cellulose dispersion was then neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 27 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 22 kg / hour, inlet temperature: 180° C. to 220° C., outlet temperature: 90° C. to 110° C.) to obtain cellulose powder D.

[0194] [Example 5] (Production of cellulose powder E) 2.3 kg of shredded commercially available pulp (average degree of polymerization: 1667) and 35 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed mixer (Kobe Eco Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 117 °C for 70 minutes while stirring at 240 rpm to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche filter to obtain a filtration residue. The mixture was then placed in a 20 L stainless steel tank, purified water was added, and the mixture was stirred at 75 rpm using a mixer (HANWA AGITATOR, Hanwa Kakoki Co., Ltd., stirring blade diameter: approximately 17 cm) to obtain a cellulose dispersion with a solids concentration of 5.0 wt%. The cellulose dispersion was then neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 27 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 22 kg / hour, inlet temperature: 180° C. to 220° C., outlet temperature: 90° C. to 110° C.) to obtain cellulose powder E.

[0195] [Example 6] (Production of Cellulose Powder F) Cellulose powder F was obtained in the same manner as in Example 5, except that the solid content concentration of the cellulose dispersion was 4.5% by mass.

[0196] [Example 7] (Production of cellulose powder G) 3 kg of shredded commercially available pulp (average degree of polymerization: 1667) and 30 L of 0.045 mol / L hydrochloric acid solution were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 107 °C for 65 minutes while stirring at 80 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 filter to obtain a filtration residue. The mixture was then placed in a 20 L stainless steel tank, purified water was added, and the mixture was stirred at 75 rpm using a mixer (HANWA AGITATOR, Hanwa Chemical Engineering Co., Ltd., impeller diameter: approximately 17 cm) to obtain a cellulose dispersion with a solids concentration of 6.0 wt%. This cellulose dispersion was spray-dried (dispersion feed rate: 21 kg / h, inlet temperature: 180 °C to 220 °C, outlet temperature: 90 °C to 110 °C) to obtain cellulose powder G.

[0197] [Comparative Example 1] (Production of cellulose powder H) 3 kg of shredded commercially available pulp (average degree of polymerization: 1296) and 30 L of 0.045 mol / L hydrochloric acid solution were placed in a low-speed mixer (30 LGL reactor, manufactured by Ikebukuro Horo Kogyo Co., Ltd.) and hydrolyzed at 110°C for 60 minutes while stirring at 210 rpm. The mixture was then neutralized with aqueous ammonia to obtain an acid-insoluble residue with a concentration of 2.9% by mass. The average particle size of the cellulose particles in the acid-insoluble residue was 30 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 20 kg / hour, inlet temperature: 180°C to 220°C, outlet temperature: 90°C to 110°C) to obtain cellulose powder H.

[0198] Comparative Example 2 (Production of Cellulose Powder I) 3 kg of shredded commercially available pulp (average degree of polymerization: 1296) and 30 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed mixer (Ikebukuro Horo Kogyo Co., Ltd., 30 LGL reactor) and hydrolyzed at 120 °C for 60 minutes while stirring at a speed of 210 rpm to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche filter to obtain a filtration residue with a solids concentration of 33% by mass. The mixture was then placed in a 20 L stainless steel tank, purified water was added, and the mixture was stirred at a speed of 450 rpm using a mixer (HANWA AGITATOR, Hanwa Kakoki Co., Ltd., stirring blade diameter: approximately 10 cm) to obtain a cellulose dispersion with a solids concentration of 9.4% by mass. The cellulose dispersion was then neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 26 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 20 kg / hour, inlet temperature: 180° C. to 220° C., outlet temperature: 90° C. to 110° C.) to obtain cellulose powder I.

[0199] Comparative Example 3 (Production of cellulose powder J) 3 kg of shredded commercially available pulp (average degree of polymerization: 1667) and 30 L of 0.045 mol / L hydrochloric acid solution were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 123 °C for 75 minutes while stirring at 90 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 filter to obtain a filtration residue with a solids concentration of 42% by mass. The mixture was then placed in a 20 L stainless steel tank, purified water was added, and the mixture was stirred at 75 rpm with a mixer (HANWA AGITATOR, Hanwa Kakoki Co., Ltd., impeller diameter: approximately 17 cm) to obtain a cellulose dispersion with a solids concentration of 6.5% by mass. The average particle size of the cellulose particles in the cellulose dispersion was 22 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 24 kg / hour, inlet temperature: 180° C. to 220° C., outlet temperature: 90° C. to 110° C.) to obtain cellulose powder J.

[0200] Comparative Example 4 (Production of cellulose powder K) 2.3 kg of shredded commercial pulp (average degree of polymerization 1667) and 35 L of 0.015 mol / L hydrochloric acid solution were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 145 °C for 70 minutes while stirring at 234 rpm to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche filter. The filter residue was washed four times with 70 L of pure water, neutralized with ammonia water, and then placed in a 45 L plastic bucket. The pure water was added and stirred at 300 rpm with a Three-One Motor (Heidon, Type BL1200, three turbine blades, approximately 8 cm blade diameter) to obtain a 16% cellulose dispersion. This was spray-dried (dispersion feed rate 20 kg / h, inlet temperature 180 to 220 °C, outlet temperature 90 to 110 °C) to obtain cellulose powder K.

[0201] Comparative Example 5 (Production of cellulose powder L) 2.3 kg of shredded commercial pulp (average degree of polymerization 1667) and 35 L of 0.024 mol / L hydrochloric acid solution were placed in a low-speed mixer (Kobe Eco-Solutions Co., Ltd., 50 LGL reactor) and hydrolyzed at 140 °C for 110 minutes while stirring at 234 rpm to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche filter. The filter residue was washed four times with 70 L of pure water, neutralized with ammonia water, and then placed in a 45 L plastic bucket with pure water. An 18% cellulose dispersion was obtained by stirring at 300 rpm with a Three-One Motor (Heidon, Type BL1200, three turbine blades, approximately 8 cm blade diameter). This was spray-dried (dispersion feed rate 31 kg / h, inlet temperature 180 to 220 °C, outlet temperature 90 to 110 °C) to obtain cellulose powder L.

[0202] Comparative Example 6 (Production of Cellulose Powder M) 3 kg of shredded commercially available pulp (average degree of polymerization: 1296) and 30 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed mixer (Ikebukuro Horo Kogyo Co., Ltd., 30 LGL reactor) and hydrolyzed at 115°C for 75 minutes while stirring at a speed of 210 rpm to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche filter to obtain a filtration residue with a solids concentration of 33% by mass. The mixture was then placed in a 20 L stainless steel tank, purified water was added, and the mixture was stirred at a speed of 450 rpm using a mixer (HANWA AGITATOR, Hanwa Kakoki Co., Ltd., stirring blade diameter: approximately 10 cm) to obtain a cellulose dispersion with a solids concentration of 9.8% by mass. The cellulose dispersion was then neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 26 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 20 kg / hour, inlet temperature: 180° C. to 220° C., outlet temperature: 90° C. to 110° C.) to obtain cellulose powder M.

[0203] Comparative Example 7 (Production of Cellulose Powder N) The cellulose powder H obtained in Comparative Example 1 was pulverized in an ultracentrifugal pulverizer to obtain the cellulose powder N.

[0204] [Comparative Example 8] (Production of cellulose powder O) 2 kg of shredded commercially available pulp (average degree of polymerization 1030) was immersed in water and passed through a cutter mill (microcut head / blade gap: 2.029 mm, impeller rotation speed: 9000 rpm) at approximately 70% moisture content. Pure water was then added to prepare a cellulose dispersion at approximately 2% concentration. This dispersion was then processed six times in a high-pressure homogenizer (treatment pressure: 200 MPa). The resulting dispersion was centrifuged at a centrifugal force of 19,600 m / s², and the supernatant was discarded to obtain a sediment. Approximately 2 kg of the resulting sediment was dried at 40°C for 16 hours. Then, 30 L of 4N aqueous hydrochloric acid was added to a low-speed mixer (Ikebukuro Horo Kogyo Co., Ltd., 50LGL reactor) and hydrolyzed at 40°C for 48 hours with stirring to obtain an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Nutsche filter to obtain a filtration residue. The mixture was then placed in a 90 L plastic bucket, pure water was added, and the mixture was stirred with a 3-1 motor to obtain a cellulose dispersion with a solids concentration of 15% by mass. The cellulose dispersion was then neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 18 μm. This cellulose dispersion was spray-dried (dispersion supply rate: 6 kg / hour, inlet temperature: 180°C to 220°C, outlet temperature: 50°C to 70°C) to obtain cellulose powder O.

[0205] The evaluation results of the powder properties of each cellulose powder are shown in Tables 3 and 4.

[0206] [Table 3]

[0207] [Table 4]

[0208] Tables 5 to 7 show the evaluation results when each cellulose powder was made into tablets. The criteria for judging the tablets obtained from each cellulose powder shown in the table were as follows: tablets with a friability of less than 0.5% by mass were rated A, tablets with a friability of 0.5% by mass or more but less than 1.0% by mass were rated B, and tablets with a friability of 1.0% by mass or more were rated C.

[0209] [Table 5]

[0210] [Table 6]

[0211] [Table 7]

[0212] From Tables 5 to 7, the average particle size D 50 The ratio of water absorption rate Cv to 50 ) is 0.12g 2 / (s·μm) or more, and the loose bulk density X is 0.135 g / cm 3 or "Cellulose powder having an average particle diameter D 50 The ratio of water absorption rate Cv to 50Tablets made using cellulose powders B to E (Examples 2 to 5), which are "cellulose powders in which the relationship between the mass of the cellulose powder and the loose bulk density X satisfies Y≧1.5×X−0.06 (the above formula (1-1))," showed small variations in tablet mass and excellent hardness and friability while maintaining good disintegration properties for 410 mg tablets. 370 mg tablets made using cellulose powders A to E (Examples 1 to 5) also showed small variations in tablet mass and excellent hardness and friability while maintaining good disintegration properties. 470 mg tablets made using cellulose powders D and F (Examples 4 and 6) also showed small variations in tablet mass and excellent hardness and friability while maintaining good disintegration properties. Thus, by producing tablets using cellulose powders A to F (Examples 1 to 6), tablets with small variations in tablet mass and excellent hardness and friability while maintaining good disintegration properties can be obtained. Furthermore, tablets can be made smaller without changing the amount of an active ingredient such as a drug. By producing tablets in the same manner using cellulose powder G (Example 7), tablets with small variations in tablet mass, excellent hardness and abrasion resistance, and good disintegration properties can be obtained, as in the case of using cellulose powders A to F (Examples 1 to 6).

[0213] In addition, the average particle diameter D 50 , average degree of polymerization, and Cv / D 50 are similar, and F / D 50 When comparing cellulose powders A and D (Examples 1 and 4) with different F / D 50 is greater than (D 50 Since the values ​​of cohesive strength F were similar, cellulose powder D (Example 4) (which has a larger value of cohesive strength F) tended to have a smaller friability.

[0214] Furthermore, the average particle size D 50 , average degree of polymerization, and Cv / D 50 When cellulose powders D and F (Examples 4 and 6) were compared, which had similar powder kinetic friction angles and different primary particle ratios, cellulose powder F (Example 6), which had a larger powder kinetic friction angle and primary particle ratio, tended to have better disintegrability.

[0215] On the other hand, “average particle diameter D 50 The ratio of water absorption rate Cv to 50 ) is 0.12g 2 / (s·μm) or the loose bulk density X is 0.135 g / cm 3 "larger than" and "average particle diameter D 50 The ratio of water absorption rate Cv to 50 The relationship between the loose bulk density X and the mass of the cellulose powders H to L (Comparative Examples 1 to 5) did not satisfy Cv≧1.5×X−0.06. For 410 mg tablets, the variation in tablet mass was good. However, for tablets using cellulose powders K and L (Comparative Examples 4 and 5), the hardness was poor, less than 40 N, and for tablets using cellulose powders I and J (Comparative Examples 2 and 3), the hardness was not below 0.5% by mass. For 370 mg tablets using cellulose powders I to L (Comparative Examples 2 to 5), the hardness was poor, less than 40 N. For 370 mg tablets using cellulose powder H (Comparative Example 1), the friability was 0.5% by mass or more. For 470 mg tablets using cellulose powders L to O (Comparative Examples 5 to 8), the friability was not below 0.5% by mass. [Industrial Applicability]

[0216] According to the cellulose powder of this embodiment, it is possible to provide a cellulose powder that has excellent hardness and friability while maintaining small mass variation and good disintegrability, and that can be used to obtain smaller molded bodies without changing the amount of active ingredients such as drugs.

Claims

1. Average particle diameter D ５０ The ratio Y of the water absorption rate Cv to the water absorption rate Cv (Cv / D ５０ The relationship between the loose bulk density X and the cellulose sieve mass satisfies the following formula (1-1): Y≧1.5×X-0.06...Formula (1-1)

2. Average particle diameter D ５０ The ratio Y of the water absorption rate Cv to the water absorption rate Cv (Cv / D ５０ ) is 0.12g ２ / (s μm) or more, Loose bulk density X is 0.135 g / cm ３ The following is cellulose powder.

3. Average particle diameter D ５０ The ratio of cohesive strength F to ５０ The cellulose powder according to claim 1 or 2, wherein the sieving strength is 0.01 N% / μm or more.

4. 3. The cellulose powder according to claim 1 or 2, having a powder dynamic friction angle of 30° or more.

5. 3. The cellulose powder according to claim 1 or 2, having a primary particle ratio of 20% or more.

6. The cellulose powder according to claim 1 or 2, wherein the L / D ratio of the primary particles is 2.0 or more.

7. 3. The cellulose powder according to claim 1, having a compressibility of 40% or more.

8. The cellulose powder according to claim 1 or 2, having an average degree of polymerization of 100 or more and 450 or less.

9. Average particle diameter D ５０ The cellulose powder according to claim 1 or 2, wherein the particle size is 15 μm or more and 300 μm or less.

10. Water absorption rate Cv is 2.0g ２ / s or more 12.0g ２ The cellulose powder according to claim 1 or 2, wherein the viscosity is 1 / s or less.

11. The cellulose powder according to claim 1 or 2, having a cohesive strength F of 30 N% or more and 100 N% or less.

12. one or more active ingredients; The cellulose powder according to claim 1 or 2, A molded body comprising:

13. The molded article according to claim 12, wherein the active ingredient is a pharmaceutical active ingredient.

14. The molded article according to claim 12, wherein the active ingredient is a food active ingredient.

15. The molded article according to claim 12, which is a tablet.

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