Cellulose powder and molded article

Abstract

Provided are a cellulose powder and a molded article using the cellulose powder, the molded article having excellent hardness and wear while maintaining good disintegrability while reducing mass variation, and being capable of obtaining a smaller molded article without changing the amount of an active ingredient such as a drug, and a molded article using the cellulose powder. The present invention provides: a cellulose powder which has a ratio Y (Cv / D50) of a water absorption rate Cv to an average particle diameter D50 of 0.12 g2 / (s [mu] m) or more, an apparent density X of 0.135 g / cm3 or less, and a molded article containing one or more active ingredients and the cellulose powder of any one of the active ingredients, and which is characterized in that: the ratio Y (Cv / D50) is 0.12 g2 / (s [mu] m) or more; the ratio Y (Cv / D50) of the water absorption rate Cv to the average particle diameter D50 of the cellulose powder and the apparent density X satisfy formula (1-1) [Y > = 1.5 X-0. 06].

Description

Technical Field

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

[0002] Cellulose powders, such as crystalline cellulose and powdered cellulose, have long been widely used as excipients in the pharmaceutical, food, and other chemical industries to produce shaped articles containing active ingredients. These cellulose powders are particularly demanded to have good moldability and to facilitate administration by miniaturizing the shaped articles without changing the dosage of the active ingredient, such as the 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 for providing the absorbent article. Specifically, the absorbent article includes an absorbent body containing water-absorbent resin particles, wherein the tap density of the water-absorbent resin particles is 0.500 g / cm 3 The change in tap 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 above.

[0004] Patent Document 2 discloses a cellulose powder that exhibits excellent compression moldability, uniformly retains adhesive components during granulation, achieves a narrow particle size distribution, shortens the disintegration time of the shaped body, and imparts stable disintegration properties over time. Specifically, the cellulose powder is disclosed to have a particle size distribution with a sharpness of 1.5 to 2.9, and a total organic carbon content derived from residual impurities of greater than 0.07% and less than 0.25%. Prior art literature Patent Literature

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

[0006] However, Patent Document 1 discloses resin particles having at least one structural unit selected from the group consisting of (meth)acrylic acid and its salts as a material having an excellent permeation rate for a liquid mainly composed of water and capable of retaining the liquid, but does not investigate cellulose powder.

[0007] Patent Document 2 discloses only a molded article obtained by a wet tableting method, and does not investigate a direct tableting method. Furthermore, no research has been conducted on miniaturization of the molded article.

[0008] The present invention has been developed in view of the above-mentioned circumstances and provides a cellulose powder having excellent hardness and abrasiveness while reducing mass variation and maintaining good disintegration properties, and a molded body using the cellulose powder, which can produce a smaller molded body without changing the amount of active ingredients such as drugs. Means for solving problems

[0009] That is, the present invention includes the following aspects. [1] A cellulose powder characterized by a water absorption rate Cv relative to an average particle size D 50 The ratio Y(Cv / D 50 ) is 0.12g 2 / (s·μm) or more, The bulk density X is 0.135g / cm 3 the following. [2] A cellulose powder characterized in that the water absorption rate Cv is relative to the average particle size D 50 The ratio Y(Cv / D 50 ) and the bulk density X satisfy the following formula (1-1): Y≥1.5×X-0.06……Formula (1-1). [3] The cellulose powder of [2], wherein the water absorption rate Cv is relative to the average particle size D 50 The ratio Y(Cv / D 50 ) is 0.12g 2 / (s·μm) or more, The bulk density X is 0.135g / cm 3 the following. [4] The cellulose powder according to any one of [1] to [3], wherein the cohesive force F is greater than the average particle size D. 50 Ratio F / D 50 It is 0.01N% / μm or more. [5] The cellulose powder according to any one of [1] to [4], wherein the powder has a dynamic friction angle of 30° or greater. [6] The cellulose powder according to any one of [1] to [5], wherein the primary particle ratio is 20% or more. [7] The cellulose powder according to any one of [1] to [6], wherein the L / D of the primary particles is 2.0 or more. [8] The cellulose powder according to any one of [1] to [7], wherein the compressibility is 40% or more. [9] The cellulose powder according to any one of [1] to [8], wherein the average degree of polymerization is 100 or more and 450 or less.

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

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

[10] , wherein the water absorption rate Cv is 2.0 g 2 / s or more and 12.0g 2 / s or less.

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

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

[13] A shaped body comprising one or more active ingredients and the cellulose powder according to any one of [1] to

[12] .

[14] The shaped article of

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

[15] The formed article of

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

[16] The shaped article according to any one of

[13] to

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

[0010] The cellulose powder of the above embodiment can provide a cellulose powder having excellent hardness and abrasiveness while reducing quality variations and maintaining good disintegrability, and can produce smaller molded bodies without changing the amount of active ingredients such as drugs. DETAILED DESCRIPTION

[0011] <Cellulose powder> One embodiment of the present invention (hereinafter referred to as "this embodiment") relates to a cellulose powder that satisfies "a water absorption rate Cv relative to an average particle size D 50 The ratio Y(Cv / D 50 ) is 0.12g 2 / (s·μm) or more, and the bulk density X is 0.135g / cm 3 Below”, or “water absorption rate Cv relative to average particle size D 50 The ratio Y(Cv / D 50 ) and the relationship between the bulk density X satisfies Y≥1.5×X-0.06".

[0012] The cellulose powder of this embodiment, having the above-mentioned structure, can reduce quality variations, maintain good disintegration properties, and obtain a smaller molded body with excellent hardness and abrasiveness without changing the amount of active ingredients such as drugs.

[0013] Cellulose powder in this specification is generally referred to as crystalline cellulose, powdered cellulose, etc., and is suitable for use as a pharmaceutical additive or food additive. Among them, crystalline cellulose is preferred as the cellulose powder. Known crystalline cellulose includes, for example, microcrystalline cellulose described in the 9th edition of the Official Standards of Food Additives, crystalline cellulose described in the Japanese Pharmacopoeia (18th revised edition), and crystalline cellulose described in the United States Pharmacopoeia, the European Pharmacopoeia, and the like.

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

[0015] The average degree of polymerization of the cellulose powder is measured by the method shown below. As a sample, accurately weigh about 1.3g of cellulose powder (about 0.25g in the case of powdered cellulose) and place it in a 125mL conical flask. Accurately add 25mL of water and 25mL of 1mol / L copper ethylenediamine test solution. Immediately introduce nitrogen, seal it, and use an oscillator to mix and dissolve it. Accurately measure an appropriate amount of the liquid, and test it at 25±0.1℃ according to the viscosity determination method 1〈2.53〉 using a capillary viscometer with a viscometer constant (K) of about 0.03 to determine the dynamic viscosity ν. Separately, accurately measure 25mL of water and 25mL of 1mol / L copper ethylenediamine test solution, and use the same method to test the mixed solution using a capillary viscometer with a viscometer constant (K) of about 0.01 to determine the dynamic viscosity ν0. The relative viscosity ηrel of the cellulose powder is calculated according to the following formula.

[0016] ηrel=ν / ν0

[0017] The product [η]C, the limiting viscosity [η] (mL / g) and the concentration C (g / 100 mL), was determined from the relative viscosity ηrel according to Tables 1 and 2 below, and the average degree of polymerization P was calculated according to the following formula. In the following formula, MT is the weight (g) of the cellulose powder measured on a dry basis.

[0018] P=95〔η〕C / MT

[0019] [Table 1] By relative viscosity η rel Find the table of the product of limiting viscosity and concentration [n] C

[0020] [Table 2] By relative viscosity η rel Table for finding the product of limiting viscosity and concentration [n] C (continued)

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

[0022] [Average particle size D 50 ] The average particle size D of the cellulose powder of this embodiment 50 It is preferably 15 μm to 300 μm, more preferably 20 μm to 200 μm, further preferably 25 μm to 150 μm, further preferably 25 μm to 100 μm, and particularly preferably 25 μm to 70 μm. 50 On the other hand, if the average particle size D of the cellulose powder is greater than the above lower limit, the fluidity tends to be improved. 50 When the content is below the upper limit, the mixture tends to be easily and uniformly mixed with active ingredients such as drugs.

[0023] It should be noted that the average particle size D of the cellulose powder 50 It is a particle size at 50% cumulative volume measured by a laser diffraction / scattering particle size distribution analyzer (LA-950V2 model (trade 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 preferably 2.0 g 2 / s above 12.0g 2 / s or less, more preferably 3.0g 2 / s above 10.0g 2 / s or less, more preferably 4.5g 2 / s above 10.0g 2 By setting the water absorption rate Cv within the above range, high compression moldability can be exhibited.

[0025] The water absorption rate Cv of the cellulose powder is measured by the method shown below. First, a Teflon (registered trademark) container was filled with about 5.0 g of cellulose powder that passed through a 500 μm mesh and vibrated under the conditions of 300 times, 18 mm stroke, and 198 g weight. The vibrated cellulose powder was fully immersed in 300 mL of pure water at a speed of 0.5 mm / s until saturated. The square of the pure water penetration rate (g / min) during the measurement period until saturation was reached was measured using a commercially available water absorption rate meter (Penetoanalyzer PNT-N (trade name), manufactured by Hosokawa Micron Co., Ltd.). 2 ) The square of the penetration rate until saturation is reached (g 2 The relationship between the water absorption rate (g) and the measurement time is linearized by the least square method. The slope of the linearized graph is the water absorption rate (g 2 / s). Specifically, it can be measured using the method described in the Examples below.

[0026] [Water absorption rate Cv relative to average particle size D 50 Ratio Cv / D 50 ] Cv / D 50 The water absorption rate Cv(g 2 / s) divided by the average particle size D 50 (μm) is calculated. In the cellulose powder of this embodiment, the water absorption rate Cv (g 2 / s) relative to the average particle size D 50 (μm) ratio Cv / D 50 , preferably 0.12g 2 / (s·μm) or more, more preferably 0.13g 2 / (s·μm) or more, more preferably 0.14g 2 / (s·μm) or more, more preferably 0.153g 2 / (s·μm) or more, particularly preferably 0.154g 2 / (s·μm) or more. By making Cv / D 50 The above lower limit is above, which strengthens the hydrogen bonds between the cellulose particles in the cellulose powder and improves the plastic deformability. As a result, high compression moldability can be achieved. That is, by increasing the Cv / D of the cellulose powder of this embodiment to 50 By controlling the particle size above the above lower limit, good formability can be ensured regardless of the particle shape. On the other hand, Cv / D 50 The upper limit of the amount is not particularly limited, but may be, for example, 0.50 g. 2 / (s·μm), can also be 0.30g 2 / (s·μm), can also be 0.25g 2 / (s·μm), can also be 0.24g 2 / (s·μm).

[0027] [Bulk density] The cellulose powder of this embodiment preferably has a bulk density of 0.135 g / cm 3 Below, more preferably 0.130 g / cm 3 By making the bulk density below the above upper limit, sufficient mechanical strength can be imparted to the molded article. On the other hand, the lower limit of the bulk density is not particularly limited, but may be, for example, 0.03 g / cm 3 , can also be 0.05g / cm 3 , can also be 0.07g / cm 3 , can also be 0.08g / cm 3 .

[0028] The bulk density of the cellulose powder is measured by the method shown below. A 25 mL cylindrical metal container was filled with cellulose powder using a Scot volumetric meter (ASTM B-329-85, manufactured by Tsutsui Rikagaku Instruments Co., Ltd.). The cellulose powder in the 25 mL cylindrical metal container was leveled and the mass (g) of the cellulose powder in the container was divided by 25 mL to calculate the bulk density (g / cm 3 ). Specifically, it can be measured using the method described in the Examples below.

[0029] In the cellulose powder of this embodiment, the water absorption rate Cv is relative to the average particle size D 50 The ratio Y(Cv / D 50 )(g 2 / (s·μm)) and bulk density X(g / cm 3 ) relationship, preferably satisfies the following formula (1-1), more preferably satisfies the following formula (1-2). By making Cv / D 50 The range of the bulk density satisfying the above relationship strengthens the hydrogen bonds between the cellulose particles in the cellulose powder and improves the plastic deformability. As a result, high compression moldability can be achieved. That is, by adjusting the Y(Cv / D) of the cellulose powder of this embodiment to 50 ) and the bulk density (X) are controlled within the range of the above relationship, good formability can be guaranteed regardless of the shape of the particles.

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

[0031] From the perspective of having more excellent formability and being able to form tablets with good hardness and disintegration properties, the cellulose powder of this embodiment has a Y (Cv / D 50 ) and the bulk density X, preferably satisfies the formula (1-1) or (1-2) and satisfies X≤0.135, preferably satisfies the formula (1-1) or (1-2) and satisfies 0.12≤Y, and more preferably satisfies the formula (1-1) or (1-2) and satisfies X≤0.135 and 0.12≤Y at the same time.

[0032] In the cellulose powder of this embodiment, the water absorption rate Cv is relative to the average particle size D 50 The ratio Y(Cv / D 50 ) and the bulk density X, preferably satisfies the following formula (2-1), more preferably satisfies the following formula (2-2), and even more preferably satisfies the following formula (2-3). 50 ) and the bulk density X, preferably satisfies any one of the following formulas (2-1) to (2-3) and satisfies X≤0.135, preferably satisfies any one of the following formulas (2-1) to (2-3) and satisfies 0.12≤Y, and more preferably satisfies any one of the following formulas (2-1) to (2-3) and satisfies both X≤0.135 and 0.12≤Y.

[0033] Y≤-2.0×X+0.53……Formula (2-1) Y≤-2.0×X+0.50……Formula (2-2) Y≤-2.0×X+0.47……Formula (2-3)

[0034] In the cellulose powder of this embodiment, the water absorption rate Cv is relative to the average particle size D 50 The ratio Y(Cv / D 50 ) and the bulk density X, preferably satisfies the following formula (3-1), more preferably satisfies the following formula (3-2), and even more preferably satisfies the following formula (3-3). 50 ) and the bulk density X, preferably satisfies any one of the following formulas (3-1) to (3-3) and satisfies X≤0.135, preferably satisfies any one of the following formulas (3-1) to (3-3) and satisfies 0.12≤Y, and more preferably satisfies any one of the following formulas (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……Formula (3-2) Y≥-4.4×X+0.50……Formula (3-3)

[0036] In the cellulose powder of this embodiment, the water absorption rate Cv is relative to the average particle size D 50 The ratio Y(Cv / D 50 The relationship between ) and the bulk density X preferably satisfies the following formula (4-1), more preferably satisfies the following formula (4-2), further preferably satisfies the following formula (4-3), and further preferably satisfies the following formula (4-4). 50 ) and the bulk density X, preferably satisfies any one of the following formulas (4-1) to (4-4) and satisfies X≤0.135, preferably satisfies any one of the following formulas (4-1) to (4-4) and satisfies 0.12≤Y, and more preferably satisfies any one of the following formulas (4-1) to (4-4) and satisfies both X≤0.135 and 0.12≤Y.

[0037] Y≤X+0.25……Formula (4-1) Y≤X+0.21……Formula (4-2) Y≤X+0.18……Formula (4-3) Y≤X+0.16……Formula (4-4)

[0038] In the cellulose powder of this embodiment, the water absorption rate Cv is relative to the average particle size D 50 The ratio Y(Cv / D 50 ) and the bulk density X, preferably satisfies two or more relationships selected from the group consisting of the above-mentioned formulas (1-1) to (1-2), the above-mentioned formulas (2-1) to (2-3), the above-mentioned formulas (3-1) to (3-3), and the above-mentioned formulas (4-1) to (4-4). In addition, in the cellulose powder of this embodiment, the water absorption rate Cv relative to the average particle size D 50 The ratio Y(Cv / D 50) and the bulk density X, preferably satisfies two or more of the relationship formulas in 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; it is also preferably satisfied with two or more of the relationship formulas in 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 0.12≤Y; it is more preferably satisfied with two or more of the relationship formulas in 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 simultaneously satisfies X≤0.135 and 0.12≤Y.

[0039] From the perspective of having more excellent formability and being able to form tablets with good hardness and disintegration properties, the cellulose powder of this embodiment has a Y (Cv / D 50) and the bulk density X, preferably, any one of the formulas (1-1) to (1-2) is satisfied, X≤0.135 and 0.12≤Y are satisfied at the same time; more preferably, any one of the formulas (1-1) to (1-2) is satisfied, X≤0.135, 0.12≤Y and any one of the formulas (2-1) to (2-3) are satisfied at the same time; further preferably, any one of the formulas (1-1) to (1-2) is satisfied, X≤0.135, 0.12≤Y, any one of the formulas (2-1) to (2-3) and any one of the formulas (3-1) to (3-4) are satisfied at the same time. -3), or simultaneously satisfies any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, any one of the formulas (2-1) to (2-3), and any one of the formulas (4-1) to (4-4); further preferably, simultaneously satisfies any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, any one of the formulas (2-1) to (2-3), any one of the formulas (3-1) to (3-3), and the formulas (4-1) to (4-4). Among them, it is preferred that the formula (1-1), X≤0.135, 0.12≤Y and the formula (2-3) are satisfied at the same time; it is more preferred that the formula (1-1), X≤0.135, 0.12≤Y, the formula (2-3) and the formula (3-2) are satisfied at the same time; it is further preferred that the formula (1-1), X≤0.135, 0.12≤Y, the formula (2-3) and the formula (3-3) are satisfied at the same time, or the formula (1-1), X≤0.135, 0.12≤Y, the formula (2-3) and the formula (4-4) are satisfied at the same time; it is even more preferred 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 at the same time.

[0040] From the perspective of having more excellent formability and being able to form tablets with good hardness and disintegration properties, the cellulose powder of this embodiment has a Y (Cv / D 50) and the bulk density X, preferably satisfying any one of the formulas (1-1) to (1-2), X≤0.135 and 0.12≤Y at the same time; more preferably satisfying any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, and any one of the formulas (3-1) to (3-3) at the same time; further preferably satisfying any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, any one of the formulas (3-1) to (3-3) and the formulas (4-1) to (4-3) at the same time. -4), or simultaneously satisfies any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, any one of the formulas (3-1) to (3-3), and any one of the formulas (2-1) to (2-3); further preferably, simultaneously satisfies any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, any one of the formulas (2-1) to (2-3), any one of the formulas (3-1) to (3-3), and the formulas (4-1) to (4-4). Among them, it is preferred that the formula (1-1), X≤0.135, 0.12≤Y and the formula (3-2) are satisfied at the same time; it is more preferred that the formula (1-1), X≤0.135, 0.12≤Y and the formula (3-3) are satisfied at the same time; it is further preferred that the formula (1-1), X≤0.135, 0.12≤Y, the formula (3-3) and the formula (2-3) are satisfied at the same time; it is even more preferred that the formula (1-1), X≤0.135, 0.12≤Y, the formula (3-3), the formula (2-3) and the formula (4-4) are satisfied at the same time.

[0041] From the perspective of having more excellent formability and being able to form tablets with good hardness and disintegration properties, the cellulose powder of this embodiment has a Y (Cv / D 50) and the bulk density X, preferably, any one of the formulas (1-1) to (1-2), X≤0.135 and 0.12≤Y are satisfied at the same time; more preferably, any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y and any one of the formulas (4-1) to (4-4) are satisfied at the same time; further preferably, any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, any one of the formulas (4-1) to (4-4) and any one of the formulas (2-1) to (2 -3), or simultaneously satisfies any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, any one of the formulas (4-1) to (4-4), and any one of the formulas (3-1) to (3-3); further preferably, simultaneously satisfies any one of the formulas (1-1) to (1-2), X≤0.135, 0.12≤Y, any one of the formulas (4-1) to (4-4), any one of the formulas (2-1) to (2-3), and the formulas (3-1) to (3-3). Among them, it is preferred that the formula (1-1), X≤0.135, 0.12≤Y and the formula (4-4) are satisfied at the same time; it is more preferred that the formula (1-1), X≤0.135, 0.12≤Y, the formula (4-4) and the formula (2-3) are satisfied at the same time, or the formula (1-1), X≤0.135, 0.12≤Y, the formula (4-4) and the formula (3-2) or (3-3) are satisfied at the same time; it is further preferred that the formula (1-1), X≤0.135, 0.12≤Y, the formula (4-4), the formula (2-3) and the formula (3-2) or (3-3) are satisfied at the same time; it is particularly preferred that the formula (1-1), X≤0.135, 0.12≤Y, the formula (4-4), the formula (2-3) and the formula (3-3) are satisfied at the same time.

[0042] The Y(Cv / D 50) and the 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) at the same time; 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) at the same time, or 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 (4-1) to (4-4) at the same time; further 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 the formulas (4-1) to (4-4) at the same time. Among them, it is preferred to satisfy the formula (1-1) and the formula (2-3) at the same time; it is more preferred to satisfy the formula (1-1), the formula (2-3) and the formula (3-2) at the same time; it is further preferred to satisfy the formula (1-1), the formula (2-3) and the formula (3-3) at the same time, or to satisfy the formula (1-1), the formula (2-3) and the formula (4-4) at the same time; it is even more preferred to satisfy the formula (1-1), the formula (2-3), the formula (3-3) and the formula (4-4) at the same time.

[0043] The Y(Cv / D 50 ) and the 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) at the same time; 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) at the same time, or 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 (4-1) to (4-4) at the same time; further 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 the formulas (4-1) to (4-4) at the same time. Among them, it is preferred to satisfy the formula (1-1) and the formula (3-2) at the same time; it is more preferred to satisfy the formula (1-1) and the formula (3-3) at the same time; it is further preferred to satisfy the formula (1-1), the formula (3-3) and the formula (2-3) at the same time, or to satisfy the formula (1-1), the formula (3-3) and the formula (4-4) at the same time; it is even more preferred to satisfy the formula (1-1), the formula (2-3), the formula (3-3) and the formula (4-4) at the same time.

[0044] The Y(Cv / D 50 ) and the 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) at the same time; more preferably satisfies the formula (1-1) and the formula (4-1) at the same time; further preferably satisfies the formula (1-1) and the formula (4-2) at the same time; further preferably satisfies the formula (1-1) and the formula (4-3) at the same time; and particularly preferably satisfies the formula (1-1) and the formula (4-4) at the same time.

[0045] [Cohesion F] The cellulose powder of this embodiment preferably has a cohesive force F of 30 N% to 100 N%, more preferably 45 N% to 90 N%, even more preferably 50 N% to 80 N%, and even more preferably 55 N% to 80 N%. By setting the cohesive force F within this range, the cohesive force of the cellulose powder is increased, and a molded body with reduced wear during the molded body manufacturing process can be obtained.

[0046] The cohesive force F of the cellulose powder is measured by the method shown below. First, fill the shear groove ( The upper and lower groove lengths are: 34 mm and 5 mm), and the upper surface of the powder layer is leveled. Then, a powder layer shear force measuring device (NS-S300 type (trade name), manufactured by Nano Seeds Co., Ltd.) is used, and the target pressure load of 20N is used as the pressure control condition, and a shear test is performed at a shear rate of 50 μm / second. When the target load is reached, the pressure is stopped, and after starting lateral sliding, the static friction coefficient and the dynamic friction coefficient are measured. During the analysis, the measured elapsed time (s) is used as the horizontal axis and the load (N) applied to the shear surface is used as the vertical axis for fitting, the maximum and minimum values of the shear surface load are obtained, and the cohesive force defined by the following formula is calculated.

[0047] [Cohesion F (N%)] =([maximum shear load (N)] - [minimum shear load (N)]) / [maximum shear load (N)] × 100

[0048] The cohesive force F of the cellulose powder can be specifically measured by the method described in the Examples below.

[0049] [Cohesive force F relative to average particle size D 50 Ratio F / D 50 ] In the cellulose powder of this embodiment, the cohesive force F is proportional to the average particle size D 50 Ratio F / D50 It is preferably 0.01 N% / μm or more, more preferably 0.8 N% / μm or more, further preferably 0.9 N% / μm or more, further 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 the value is above the lower limit, the cohesive force of the cellulose powder increases, and a molded body with less wear can be obtained during the production process of the molded body. By controlling the shape of the cellulose particles in the cellulose powder, F / D 50 It can be equal to or greater than the above lower limit. On the other hand, F / D 50 The upper limit of is not particularly limited, but may be 3.0 N% / μm, 2.5 N% / μm, 2.4 N% / μm, 2.3 N% / μm, or 2.2 N% / μm.

[0050] [Powder dynamic friction angle] The cellulose powder of this embodiment preferably has a powder dynamic friction angle of 30° or greater, more preferably 40° or greater, even more preferably 43° or greater, even more preferably 49° or greater, particularly preferably 50° or greater, and most preferably 51° or greater. By setting the powder dynamic friction angle to be above the lower limit, the friction between the cellulose powder particles is increased, and a molded body with reduced wear can be obtained during the molded body manufacturing process. On the other hand, the upper limit of the powder dynamic friction angle is not particularly limited, but may be 70°, 65°, 60°, or 57°.

[0051] The powder dynamic friction angle of cellulose powder is measured by the method shown below. First, fill the shear groove ( Upper and lower groove lengths: 34mm, 5mm), and level the upper surface of the powder layer. Then, a powder layer shear force measuring device (NS-S300 type (trade name), manufactured by Nano Seeds Co., Ltd.) was used, and the target pressure loads of 20N, 30N, and 40N were used as pressure control conditions, and a shear test was performed at a shear rate of 50μm / second. When the target load was reached, the pressure was stopped, and after lateral sliding began, the static friction coefficient and the dynamic friction coefficient were measured. During the analysis, the measured elapsed time (s) was first fitted as the horizontal axis and the shear force (N) as the vertical axis to obtain the maximum value of the shear force and the pressure load value at this time. The results were fitted into a graph with the vertical axis as the shear stress and the horizontal axis as the vertical stress, and the angle of the straight line connecting the origin and these points relative to the X-axis was calculated as the powder dynamic friction angle.

[0052] [Compression ratio] The cellulose powder of this embodiment preferably has a compressibility of 40% or greater, more preferably 45% or greater, even more preferably 50% or greater, even more preferably 53% or greater, and particularly preferably 55% or greater. By setting the compressibility above the lower limit, a cellulose powder that is easily compressible can be obtained, exhibiting high compression moldability. On the other hand, the upper limit of the compression rate is not particularly limited, but may be 70%, 65%, or 62%.

[0053] The compressibility of the cellulose powder was measured by the method shown below. First, the tap density was measured using a powder property evaluation device (Powder Tester, manufactured by Hosokawa Micron Co., Ltd.). A sieve with a pore size of 710 μm and a metal funnel with an inner diameter of 0.8 cm were used, and the vibration condition was VIBRATION 2.0 (power supply: AC100 V, 60 Hz). The bulk density was measured using the method described above, and the compressibility was calculated using the following formula.

[0054] [Compression ratio (%)] =([tap density (g / cm 3 )]-[Bulk density (g / cm 3 )]) / [Tap density (g / cm 3 )]×100

[0055] [Structure of particles] As the cellulose powder of the present embodiment, the type with a higher proportion of primary particle structure is preferred. It should be noted that the structure formed by the aggregation of the primary particles is called a secondary aggregation structure. Whether there are primary particles or secondary aggregation structures can be determined by a dry image analysis device (Malvern Morphorogi G3S) when the particles are photographed at 5 times the angle, and it can be confirmed from the resulting image whether there are primary particles or secondary aggregation structures with clear boundaries of primary particles. In the cellulose powder of the present embodiment, by focusing on the shape of the cellulose primary particles and controlling the proportion of the primary particle structure particles to a specific range, it was confirmed for the first time that it has high formability and wear prevention effects. The primary particle structure is closely related to the formability of the formed body. The more primary particles there are, the higher the plastic deformability during compression, and then the entanglement of particles is easy to occur, so it can play a role in high formability and wear prevention effects.

[0056] The ratio of primary particles to the total number of cellulose powder particles (primary particle ratio) can be measured by the method shown below. Using a dry image analyzer (Malvern Morphorogi G3S), 10,000 particles were photographed and image analysis was performed to determine the equivalent area circular particle size and aspect ratio of each particle. Based on the result, particle images with an equivalent area circular particle size in the range of 30 μm to 90 μm and an aspect ratio of less than the average value of the aspect ratio of 10,000 particles + 0.1 were extracted. The particle shapes in the selected particle images were visually confirmed one by one, and the particle monomers were determined to be primary particles and the particle aggregations were determined to be secondary particles. The proportion of particle images determined to be primary particles in the extracted particle images was calculated as the primary particle rate. It should be noted that image processing software can also be used to confirm the particle shape in the particle image. As a simple method, the range of brightness dispersion values selected from the extracted particle images, ranging from 1 to 26, is defined as primary particles, and the range of brightness dispersion values selected from 26 to 100 is defined as secondary particles. The primary particle rate (%) can be calculated by dividing the number of primary particles by the total number of particles × 100. In this embodiment, the method using the aforementioned image processing software was employed.

[0057] In the present invention and this specification, a cellulose powder in which 20% or more of the total number of particles consists of primary particles, i.e., a cellulose powder having a primary particle fraction of 20% or more, is referred to as a "cellulose powder having a high primary particle fraction." It should be noted that in the cellulose powder of this embodiment, particles having a primary particle fraction 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 fraction is not particularly limited, but may be 50% or even 45%.

[0058] The cellulose powder of this embodiment exhibits high moldability due to the high proportion of primary particles, which facilitates particle entanglement. This characteristic allows the use of the cellulose powder of this embodiment to reduce the amount of cellulose powder required to produce a molded article, enabling the production of a smaller molded article without changing the amount of active ingredients such as drugs.

[0059] Furthermore, since powders with primary particle structures can be formed with low compressive forces during molding, the percentage of primary particles in the powder is closely related not only to moldability and abrasiveness, but also to the disintegration of the molded article and the dissolution of the active ingredient. Reducing the compressive force during molding can maintain the interstices between primary particles in the molded article. In other words, by using the cellulose powder of this embodiment with a high percentage of primary particles, a molded article containing a large number of interstices between cellulose primary particles can be obtained.

[0060] When a molded article containing numerous interstices between cellulose primary particles is exposed to water, water quickly penetrates between the primary particles, promoting particle disintegration. Furthermore, when the active ingredient is retained within the interstices between the cellulose primary particles, contact between the active ingredient and water is facilitated, promoting the dissolution of the active ingredient. In other words, by using the cellulose powder of this embodiment to produce a molded article, both the disintegration of the molded article and the dissolution of the active ingredient can be improved.

[0061] Furthermore, the cellulose primary particles have high compression moldability and an anti-abrasion effect and are easily dispersed in water. Therefore, by using the cellulose powder of this embodiment, a molded article having an excellent balance between moldability and disintegrability can be obtained.

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

[0063] Furthermore, the gaps between the cellulose primary particles in the molded article contribute to increasing the mixing rate with other ingredients such as the active ingredient. Therefore, by using the cellulose powder of this embodiment to produce a molded article, mixing uniformity can be improved and concentration variations can be significantly reduced.

[0064] Furthermore, the cellulose powder of this embodiment has a high proportion of primary particles, a low bulk density, and a light weight, resulting in high dynamic fluidity. Therefore, by using the cellulose powder of this embodiment, it is possible to reduce quality variations in molded articles.

[0065] [L / D of primary particles] In the cellulose powder of this embodiment, the ratio L / D of the major diameter (L) to the minor diameter (D) of the primary particles is preferably 2.0 or greater, more preferably 2.5 or greater, even more preferably 3.0 or greater, even more preferably 3.5 or greater, and particularly preferably 3.8 or greater. By setting the L / D of the primary particles to be above the above lower limit, entanglement between the elongated particles is promoted during compression molding of the cellulose powder, thereby exhibiting high compression moldability. On the other hand, the upper limit of L / D of the primary particles of the cellulose powder of the present embodiment is not particularly limited, but may be 6.0 or 5.0.

[0066] The L / D of the primary particles of the cellulose powder is measured by the method shown below. Using a dry image analyzer (Malvern Morphorogi G3S), primary particle images were extracted using the same method as described above. The major diameter (L) / minor diameter (D) ratio was calculated based on the major diameter (L) and minor diameter (D) obtained from the extracted particle images. The average value of the total extracted primary particle images was calculated as the L / D ratio of the primary particles of the cellulose powder.

[0067] [Method for producing cellulose powder] The method for producing the cellulose powder according to the present embodiment will be described below. In the production of the cellulose powder of this embodiment, for example, a dispersion of a natural cellulosic material (hereinafter also referred to as a "cellulose dispersion") is first obtained, containing cellulose primary particles having an average particle size of 10 μm or greater and less than 300 μm, an average width of 2 μm or greater and 30 μm or less, and an average thickness of 0.5 μm or greater and 5 μm or less. This shape of the cellulose primary particles in the cellulose dispersion promotes entanglement between the primary particles of the cellulose powder 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 entangle during the drying process, resulting in the formation of a secondary aggregate structure of the cellulose powder particles, making it difficult to maintain the primary particle structure. In this regard, the cellulose powder of this embodiment focuses on the structure of cellulose primary particles and, by controlling this structure within a specific range, demonstrates for the first time that it can promote high plastic deformability and inter-particle entanglement during compression molding of the cellulose powder. This enhanced plastic deformability and inter-particle entanglement facilitates moldability in molded articles compared to conventional methods, enabling the production of smaller molded articles without increasing the amount of active ingredients, such as drugs.

[0069] Based on the above problems, in the production of the cellulose powder of the present embodiment, a cellulose dispersion having a cellulose concentration of 0.5% by mass to 40% by mass is preferably prepared because the more primary particles in the cellulose dispersion, the easier it is to obtain a secondary aggregate structure.

[0070] Then, the obtained cellulose dispersion is dried to obtain the cellulose powder of the present embodiment.

[0071] Natural cellulose-based materials may be plant-based or animal-based. Examples of natural cellulose-based materials include wood, bamboo, wheat straw, rice straw, cotton, ramie, bagasse, kenaf, sugar beet, sea squirt, bacterial cellulose, and other cellulose-containing natural sources. Natural cellulose-based materials have a cellulose I-type crystal structure. As a raw material, one of the above-mentioned natural cellulose-based materials may be used, or a mixture of two or more thereof may be used.

[0072] Purified pulp is also preferred. The pulp purification method is not particularly limited, and any pulp, such as dissolving pulp, kraft pulp, or NBKP pulp, can be used. Wood-derived pulp is preferred due to its high α-cellulose purity, ease of availability, and stable supply.

[0073] Among them, wood pulp is preferably one having a leveling-off degree of polymerization of 130 to 250 as measured by a copper ethylenediamine solution method, a whiteness of 90% to 99%, an S10 of 5% to 20%, and an S18 of 1% to 10%. By making the leveling-off degree of polymerization above the above lower limit, formability is easily exhibited. On the other hand, by making the degree of polymerization below the above upper limit, it is easier to control the average width and average thickness of the cellulose primary particles within a specific range. By making the whiteness above the above lower limit, the appearance of the cellulose powder can be improved. The higher the whiteness, the better, but the maximum is usually around 99%. By making S10 and S18 within the above range, formability and yield are improved. Here, the natural cellulose material may be hydrolyzed with raw materials such as pulp or may not be hydrolyzed. In particular, when hydrolysis is performed, it may be acid hydrolysis, alkali oxidative decomposition, thermal hydrolysis, or steam explosion. Any of these hydrolysis methods may be used alone, or two or more of them may be used in combination.

[0074] In the above-mentioned preparation method, water is preferably used as a medium for dispersing the solid component containing natural cellulose material in an appropriate medium. In addition, as a medium, there is no particular limitation as long as it can be used in industry even if it is not water. For example, a mixture of water and an organic solvent can be used. As the organic solvent, for example, alcohols such as methanol, ethanol, isopropanol, butanol, 2-methylbutanol, and benzyl alcohol; hydrocarbons such as pentane, hexane, heptane, and cyclohexane; ketones such as acetone and methyl ethyl ketone. In particular, the organic solvent is preferably a substance used for pharmaceuticals, and substances classified as solvents in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.) can be listed. Water or an organic solvent can be used alone, or two or more can be used in combination. It is also possible to first disperse in one medium, remove the medium, and then disperse in a different medium.

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

[0076] The cellulose primary particles in this application specification refer to particles having a size ranging from 1 μm to 500 μm, which are newly formed by dividing the fibers constituting a natural cellulosic material, or by subjecting the natural cellulosic material to mechanical treatments such as pulverization and grinding, or chemical treatments such as hydrolysis.

[0077] As methods for reducing the average particle size of cellulose primary particles to less than 300 μm, for example, mechanical treatments such as crushing and grinding; well-known separation treatments such as cyclone separation, centrifugal separation, and screening; and methods of appropriately combining the two, etc. By appropriately adjusting the treatment volume, shear force (affected by the rotation speed, blade shape, blade size, etc.), centrifugal force, mesh size, and other conditions known to generally affect the treatment, it is possible to reduce the average particle size of cellulose primary particles to less than 300 μm. In addition, for example, when performing chemical treatments such as acid hydrolysis, by appropriately changing the acid concentration, temperature, and other conditions at that time, or by appropriately changing other conditions known to affect the above-mentioned mechanical treatments and separation treatments, it is also possible to reduce the average particle size of cellulose primary particles to less than 300 μm.

[0078] Usually, when hydrolysis is carried out, if the acid and alkali concentrations and the reaction temperature of the hydrolysis solution are increased, there is a tendency for the cellulose polymerization degree to decrease and the average particle size of the cellulose particles in the dispersion to become smaller. In addition, strengthening the stirring force of the solution also tends to reduce the average particle size of the cellulose particles in the dispersion. Therefore, the polymerization degree and the average particle size of the cellulose particles can be controlled within the required range by adjusting the polymerization degree of the raw cellulose and the stirring force in the hydrolysis or dispersion process of the natural cellulose material. The stirring force depends on the width, height, volume, blade type, blade diameter and stirring speed of the stirring layer. Therefore, although it is difficult to specify a specific range, it is preferred that the product of the blade diameter (m) and the stirring speed (rpm) is 5 or more and 2000 or less, more preferably 10 or more and 1000 or less, and further preferably 10 or more and 700 or less.

[0079] In the method for producing cellulose powder of this embodiment, the hydrolysis of the raw cellulose is preferably carried out at a relatively low concentration of acid or alkali, a relatively high reaction temperature, and a relatively short reaction time. By drying the cellulose dispersion prepared under such reaction conditions, (Cv / D 50 ) is 0.12g 2 / (s·μm) or more, bulk density is 0.135g / cm 3 For example, the cellulose powder can be hydrolyzed in a hydrochloric acid solution containing 0.05% by mass to 0.3% by mass, preferably 0.1% by mass to 0.3% by mass, and more preferably 0.1% by mass to 0.2% by mass, at a temperature of 85°C to 150°C, preferably 100°C to 135°C, and more preferably 105°C to 130°C. The reaction time of the hydrolysis reaction can be appropriately set depending on the amount of the raw cellulose, the amount of the 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] As a method for making the average width of the cellulose primary particles be 2 μm to 30 μm and the average thickness be 0.5 μm to 5 μm, there is no particular limitation as long as the cellulose primary particles are mainly torn in the longitudinal direction. As such a method, specifically, for example, wood pulp is subjected to a high-pressure homogenizer treatment and the like, and mechanical treatments such as grinding or separation treatments are performed as needed, or a method of appropriately combining the two can be cited. When the high-pressure homogenizer treatment is performed, although it also depends on the processing volume, the pressure range can be appropriately adjusted to about 10 MPa to 200 MPa. In addition, for example, pulp having an average width of cellulose primary particles of 2 μm to 30 μm and an average thickness of 0.5 μm to 5 μm can also be screened.

[0081] The cellulose dispersion preferably has a concentration of 0.5% by mass to 40% by mass. Obtaining a cellulose dispersion that satisfies this condition allows the cellulose powder particles to maintain a primary particle structure. This results in high plastic deformability during compression, which in turn promotes entanglement between primary particles.

[0082] The cellulose concentration in the cellulose dispersion is measured by the method shown below. 5 g of the cellulose dispersion was placed on aluminum foil equipped with an infrared moisture meter (Model FD-240, manufactured by Kett Scientific Laboratory Co., Ltd.) and dried by heating with infrared radiation. The moisture content (%) obtained by the mass change due to water evaporation was used to calculate the cellulose concentration in the cellulose dispersion using the following formula.

[0083] [Cellulose concentration in cellulose dispersion (%)] = 100 - [Water content (%)]

[0084] By preparing a cellulose dispersion in which the cellulose primary particles have an average particle size of 10 μm or greater and less than 300 μm, an average width of 2 μm or greater and 30 μm or less, and an average thickness of 0.5 μm or greater and 5 μm or less, and preferably a cellulose concentration of 0.5% by mass or greater and 40% by mass or less in the cellulose dispersion, the primary particle structure is easily maintained during drying of the cellulose dispersion. Furthermore, since the cellulose primary particles having a specific average particle size, average width, and average thickness are easily bent, the high plastic deformability of the cellulose primary particles and the entanglement between the primary particles are promoted during compression molding of the cellulose powder, resulting in a molded article exhibiting high moldability and anti-wear effects.

[0085] When the average particle size of the cellulose primary particles is less than the above upper limit and the shape of the cellulose primary particles is within a specific range, the cellulose primary particles are more easily bendable, the plastic deformability during compression molding is improved, and entanglement between the primary particles is further promoted. On the other hand, when the average particle size of the cellulose primary particles is greater than the above lower limit, the formation of fine particles can be prevented, the spaces between the cellulose primary particles in the molded article can be more effectively maintained, and a molded article with better disintegration and dissolution properties can be obtained.

[0086] By setting the average width of the cellulose primary particles below the upper limit, the cellulose primary particles are more easily bendable, exhibiting enhanced plastic deformability during compression molding, and further promoting entanglement between the primary particles. On the other hand, by setting the average width of the cellulose primary particles above the lower limit, the interstices between the cellulose primary particles in the molded article are more effectively maintained, resulting in a molded article with improved disintegration and dissolution properties.

[0087] By setting the average thickness of the cellulose primary particles below the upper limit, the cellulose primary particles are more easily bent, exhibit higher plastic deformability during compression molding, and promote entanglement between the primary particles. A lower lower limit for the average thickness of the cellulose primary particles is preferred because it facilitates particle entanglement, but is typically around 0.5 μm.

[0088] By setting the average width and average thickness of the cellulose primary particles to be greater than the aforementioned lower limits, the formation of fine particles can be prevented, the gaps between the cellulose primary particles in the molded article can be more effectively maintained, and the disintegration and dissolution properties can be further improved.

[0089] The method for producing a cellulose dispersion as used herein is not particularly limited. Examples include i) a method of producing a cellulose dispersion by treating one or more natural cellulosic materials to obtain cellulose primary particles; ii) a method of producing a cellulose dispersion by fractionating the cellulose dispersion described in i) above, treating each of the particles separately, and then mixing the particles; iii) a method of producing a cellulose dispersion by fractionating the cellulose dispersion described in i) or ii) above, treating each of the particles separately, and then mixing the particles; and iv) a method of producing a cellulose dispersion by mixing two or more separately prepared cellulose primary particles. From the perspective of economic efficiency, the method i) is preferred. The treatment method may be either wet or dry. Products obtained by the wet or dry processes may be mixed before drying, or products obtained by the wet or dry processes may be combined.

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

[0091] Examples of the pulverization method include a screen-type pulverization method using a screen mill, a hammer mill, or the like; a blade rotary shearing screen-type pulverization method using a flash mill, or the like; an airflow-type pulverization method using a jet mill, or the like; a ball-type pulverization method using a ball mill, a vibrating ball mill, or the like; and a blade stirring-type pulverization method.

[0092] Examples of the grinding method include grinding methods using stirring blades such as portable mixers, stand mixers, and side mixers, which use single-direction rotating blades, multi-shaft rotating blades, reciprocating rotating blades, vertically movable blades, rotating and vertically movable blades, and pipeline-type blades; jet-type stirring and grinding methods such as pipeline mixers; grinding methods using high-shear homogenizers, high-pressure homogenizers, and ultrasonic homogenizers; and grinding methods using shaft-rotating extrusion methods such as kneaders.

[0093] The concentration of the dispersed cellulose particles obtained by the above operation in the dispersion before drying is preferably from 0.5% to 40% by mass, more preferably from 1.0% to 30% by mass, even more preferably from 2.0% to 10% by mass, particularly preferably from 3.0% to 9.0% by mass, even more preferably from 3.5% to 8.0% by mass, and most preferably from 4.0% to 7.0% by mass. By setting the concentration of the dispersed cellulose particles in the dispersion to be above the lower limit, the average particle size of the resulting cellulose particles becomes larger, and the flowability becomes more excellent. On the other hand, by setting the concentration of the dispersed cellulose particles in the dispersion to be below 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 also not particularly limited. For example, freeze drying, spray drying, drum drying, shelf drying, pneumatic drying, vacuum drying, etc. can be enumerated. These drying methods can be used alone or in combination with two or more. The spraying method during spray drying can enumerate a disc type, a pressurized nozzle, a pressurized two-fluid nozzle, a pressurized four-fluid nozzle, etc. These spraying methods can be used alone or in combination with two or more. Wherein, as the drying method, from the viewpoint of economy, preferably spray drying or pneumatic drying.

[0095] During the spray drying, a small amount of a water-soluble polymer or surfactant may be added to reduce the surface tension of the dispersion. A foaming agent or gas may also be added to the dispersion to accelerate the vaporization rate of the medium.

[0096] Examples of water-soluble polymers include hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, methylcellulose, gum arabic, starch paste, and the like, which are listed in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These water-soluble polymers may be used alone or in combination of two or more.

[0097] Examples of the surfactant include phospholipids, fatty acid glycerides, 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, glyceryl monostearate, monooxyethylene sorbitan monopalmitate, monooxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, sorbitan monopalmitate, sodium lauryl sulfate, and the like, which are classified as surfactants in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These surfactants may be used alone or in combination of two or more.

[0098] Examples of foaming agents include tartaric acid, sodium bicarbonate, potato starch, anhydrous citric acid, medicinal soap, sodium lauryl sulfate, lauric acid diethanolamide, lauromacrogol, and the like, which are listed in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These foaming agents may be used alone or in combination of two or more.

[0099] In addition to pharmaceutical additives, bicarbonates that generate gas upon thermal decomposition, such as sodium bicarbonate and ammonium bicarbonate; and carbonates that generate gas upon reaction with an acid, such as sodium carbonate and ammonium carbonate, can also be used. When using these carbonates, they must be used 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. Acids used in pharmaceuticals or foods are preferred, but similar effects can be achieved even with other acids.

[0100] Alternatively, instead of adding a foaming agent, a gas such as nitrogen, carbon dioxide, liquefied petroleum gas, or dimethyl ether may be impregnated into the dispersion.

[0101] These water-soluble polymers, surfactants, and gas-generating substances such as foaming agents may be added before drying, and the timing of their addition is not particularly limited.

[0102] <Application> When the cellulose powder of this embodiment is incorporated into a solid preparation containing an active ingredient, it can reduce mass variation, maintain good disintegration properties, achieve excellent hardness and abrasiveness, and enable miniaturization of the solid preparation without changing the amount of the active ingredient. Therefore, it is particularly suitable for use as an excipient in solid preparations aimed at miniaturization.

[0103] When the cellulose powder of this embodiment is added to a solid preparation containing a poorly water-soluble active ingredient, tableting properties are excellent while reducing mass variation and maintaining good disintegration properties. Therefore, the cellulose powder is particularly suitable for use as an excipient in solid preparations containing poorly water-soluble active ingredients.

[0104] Furthermore, when the cellulose powder of this embodiment is added to a solid preparation containing a liquid or semisolid active ingredient, it can prevent leakage of the liquid or semisolid active ingredient while maintaining good disintegration properties. Therefore, it is particularly suitable for use as an excipient in solid preparations containing liquid or semisolid active ingredients.

[0105] In addition, the cellulose powder of this embodiment is blended to a small amount of the active ingredient, and in particular, the average particle size D 50 When mixing active ingredients with small size and high adhesion and cohesion with other ingredients or using them in solid preparations, it can help the mixing speed of active ingredients and reduce concentration deviation, thus improving tableting properties. Therefore, it is particularly suitable for use in preparations with trace amounts of active ingredients, especially when the average particle size D 50 Mixture of active ingredients with small size and high cohesiveness and ingredients other than active ingredients or use of these as excipients for solid preparations.

[0106] Furthermore, when the cellulose powder of this embodiment is added to a solid preparation containing a sublimable active ingredient, recrystallization caused by the sublimation of the sublimable active ingredient can be prevented, thereby preventing a decrease in commercial value. Therefore, the cellulose powder is particularly suitable for use as an excipient in solid preparations containing sublimable active ingredients.

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

[0108] When the formed body of this embodiment is a tablet, by including the cellulose powder of this embodiment, it is possible to reduce quality deviation, maintain good disintegration properties, and obtain a smaller tablet with excellent hardness and abrasiveness without changing the amount of active ingredients such as drugs.

[0109] The contents of the active ingredient and cellulose powder in the molded article of this embodiment are not particularly limited. Generally, the active ingredient content is 0.001% by mass to 99% by mass, and the cellulose powder content of this embodiment is 1% by mass to 99% by mass, relative to the total mass of the molded article. By ensuring that the active ingredient content is above the lower limit, a therapeutically effective amount can be ensured. Meanwhile, by ensuring that the cellulose powder content of this embodiment is below the upper limit, the cellulose powder content of this embodiment is above the lower limit, resulting in a molded article exhibiting practical hardness, abrasiveness, and disintegration. Furthermore, the active ingredient and cellulose powder can be processed by known methods such as mixing, stirring, granulation, sizing, and tableting to obtain the molded article of this embodiment. Furthermore, the molded article of this embodiment may contain, in addition to the active ingredient and cellulose powder, an excipient, a disintegrant, a binder, a fluidizer, a lubricant, a flavoring agent, a fragrance, a colorant, and a sweetener as needed.

[0110] When the molded article of the present embodiment is used as a pharmaceutical product, for example, tablets, powders, fine granules, granules, extracts, pills, etc. are mentioned. Among them, tablets are preferred. In addition, the molded body of this embodiment is not limited to medicines, but can also be used in foods such as snacks, health foods, taste improvers, dietary fiber enhancers; solid foundations, bath products, animal medicines, diagnostic drugs, pesticides, fertilizers, ceramic catalysts, etc.

[0111] [Active ingredient] Active ingredients include pharmaceutical active ingredients, pesticide ingredients, fertilizer ingredients, feed ingredients, food ingredients, cosmetic ingredients, pigments, spices, metals, ceramics, catalysts, surfactants. In addition, the active ingredient can also be in any form such as solid (powdered, crystalline, etc.), oily, liquid, semi-solid. In addition, it is also possible to apply coating for purposes such as controlling dissolution and reducing bitterness. The active ingredient can be used alone or in combination. The active ingredient can also be dissolved, suspended, or emulsified in a medium for use. Among them, the active ingredient is preferably a pharmaceutical active ingredient or a food active ingredient.

[0112] Examples of pharmaceutical active ingredients include antipyretic, analgesic, and anti-inflammatory drugs, hypnotic sedatives, anti-somnia drugs, anti-vertigo drugs, pediatric analgesics, stomachics, antacids, digestive drugs, cardiotonic drugs, antiarrhythmic drugs, antihypertensive drugs, vasodilators, diuretics, antiulcer drugs, intestinal regulating drugs, osteoporosis therapeutic drugs, antitussive and expectorant drugs, antiasthmatic drugs, antibacterial agents, urinary frequency improving agents, tonics, vitamins, and other orally administered ingredients. These pharmaceutical active ingredients may be used alone or in combination of two or more.

[0113] Specific examples of pharmaceutical active ingredients include aspirin, aluminum aspirin, acetaminophen, salicylamide, disalicylate, salicylamide, lactoethoxyanilide, isoxipentyl hydrochloride, diphenylpyrrolidine hydrochloride, diphenhydramine hydrochloride, diphenylephedrine hydrochloride, triprolidine hydrochloride, tripeliramine hydrochloride, pyrimidinediamine hydrochloride, phenethazine hydrochloride, mephenhydramine hydrochloride, diphenhydramine salicylate, chlorpheniramine diphenyldisulfonate, isobutrazol tartrate, diphenhydramine tannate, diphenylpyrrolidine theochloride, methdrolamine naphthalene disulfonate, promethazine methylene disalicylate, chlorpheniramine maleate, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, diphenylephedrine phosphate, chloropropene hydrochloride, cloperastine hydrochloride, pentoxyverine citrate (toclopramide), chlorpheniramine tartrate, chlorpheniramine tannate, chlorpheniramine tartrate ... las), tipedine citrate, sodium dibunate, dextromethorphan hydrobromide, dextromethorphan phenolphthalein, tipedine, clopidogrel diphenhydramine salt, codeine phosphate, dihydrocodeine phosphate, narcotine hydrochloride, narcotine, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, potassium guaiacol sulfonate, guaiacol glycerol ether, sodium benzoate caffeine, 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, niacinamide, calcium pantothenate, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, di Hydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel (as dry aluminum hydroxide gel), dry aluminum hydroxide gel, aluminum hydroxide magnesium carbonate mixed dry gel, coprecipitation product of aluminum hydroxide sodium bicarbonate, coprecipitation product of aluminum hydroxide calcium carbonate magnesium carbonate, coprecipitation product of magnesium hydroxide potassium aluminum sulfate, magnesium carbonate, magnesium aluminum metasilicate, ranitidine hydrochloride, cimetidine, famotidine, naproxen, diclofenac sodium, piroxicam, azulene, indomethacin, ketoprofen, ibuprofen, diphenidol hydrochloride, diphenylpyrrolidone hydrochloride, diphenhydramine hydrochloride, promethazine hydrochloride, meclizine hydrochloride, dimenhydrinate, diphenhydramine tannate, phenamidine tannate, diphenylpyrrolidone tannate, diphenhydramine fumarate, promethazine methylene disalicylate , Scopolamine Hydrobromide, Oxyclipine Hydrochloride, Dicyclomine Hydrochloride, Methixene Hydrochloride, Methylatropine Bromide, Methyloctyltropine Bromide, Methylscopolamine Bromide, Methyl-1-hyoscine Bromide, Methylbenacylamine Bromide, Belladonna Extract, Isopropylammonium Iodide, Diphenylpiperidinylmethyldioxolane Iodide, Papaverine Hydrochloride, Aminobenzoic Acid, Cesium Oxalate, Piperidinylacetylaminobenzoic Acid Ethyl ester, aminophylline, dihydroxypropylphylline, theophylline, sodium bicarbonate, fursultiamine, isosorbide dinitrate, ephedrine, cephalexin, ampicillin, sulfisoxazole, aluminum sulfate, allyl isopropyl acetylurea, bromoisovaleryl urea, etc., ephedra, bamboo shoots, cherry peel, polygala, licorice, platycodon, plantain, plantain, polygala, fritillaria, fennel, phellodendron, coptis root, zedoary, chamomile,Cassia bark, gentian, bezoar, animal gall (including bear gall), adenophora, ginger, atractylodes, clove, tangerine peel, atractylodes, earthworm, bamboo ginseng, ginseng, valerian, peony bark, sansho and their extracts, insulin, vasopressin, interferon, urokinase, serrapeptase, somatostatin and other pharmaceutical active ingredients listed in the "Japanese Pharmacopoeia", "Japanese Pharmacopoeia Non-Pharmacopoeia Standards", "USP", "NF" and "EP". These pharmaceutical active ingredients can be used alone or in combination of two or more.

[0114] As used herein, a poorly water-soluble active ingredient refers to, for example, a pharmaceutical active ingredient for which 30 mL or more of water is required to dissolve 1 gram of solute, as defined in the 18th edition of the Japanese Pharmacopoeia. If the active ingredient is poorly water-soluble, its effects can be achieved by incorporating it into the molded article of this embodiment, regardless of its sublimation properties or surface polarity.

[0115] Examples of the poorly water-soluble solid active ingredient include acetaminophen, ibuprofen, benzoic acid, ethanolide, caffeine, camphor, quinine, calcium gluconate, dimercaprol, sulfonamide, theophylline, theobromine, riboflavin, methylpropanol, phenobarbital, aminophylline, thiosemicarbazide, quercetin, rutin, salicylic acid, theophylline sodium salt, pyrabital, quinine hydrochloride, irgapyrin, digoxin, griseofulvin, phenacetin and other antipyretic and analgesic drugs, nervous system drugs, sedatives and hypnotics, muscle relaxants, hypotensive drugs, antihistamines, etc.; acetylspiramycin, aminophylline, phenacetin, phenacetin, quinine hydrochloride, irgapyrin, digoxin, griseofulvin, phenacetin and other antipyretic and analgesic drugs; Antibiotics such as benzylpenicillin, erythromycin, kitasamycin, chloramphenicol, triacetyloleandomycin, nystatin, and colistin sulfate; steroid hormones such as methyltestosterone, methylandrostenediol, progestogens, estradiol benzoate, ethinylestradiol, deoxycorticosterone acetate, cortisone acetate, hydrocortisone, hydrocortisone acetate, and prednisolone; non-steroidal egg yolk hormones such as dienestilbestrol, hexestrol, diethylstilbestrol, diethylstilbestrol dipropionate, and chlorfenestrol; other fat-soluble vitamins, and other pharmaceutical active ingredients listed in the "Japanese Pharmacopoeia," "Japanese Pharmacopoeia Non-Pharmacopoeia Drug Standards," "USP," "NF," and "EP." These active ingredients may be used alone or in combination of two or more.

[0116] As the active ingredient that is poorly water-soluble and liquid, for example, can be enumerated the vitamins such as teprenone, indomethacin farnesate, menatetrenone, phytomenadione, vitamin A oil, amyl phenyl alcohol, vitamin D, vitamin E, DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), the oil-soluble flavorings such as coenzyme Q, orange oil, lemon oil, peppermint oil, "Japanese Pharmacopoeia", "Japanese Pharmacopoeia External Drug Standard", "USP", "NF", "EP" etc. The pharmaceutical active ingredient of record etc..Various homologues and derivatives are arranged in vitamin E, but as long as it is liquid at room temperature, there is no particular limitation.Specifically, the homologues and derivatives of vitamin E, for example, have: dl-α-tocopherol, acetic acid dl-α-tocopherol, d-α-tocopherol, acetic acid d-α-tocopherol etc..Can use one selected from above-mentioned alone, also can use two or more.

[0117] Examples of the poorly water-soluble semisolid active ingredient include Chinese herbal medicines or herbal extracts such as earthworm, licorice, cinnamon bark, peony root, peony bark, valerian, sansho, ginger, tangerine peel, ephedra, bamboo shoot, cherry peel, polygala, platycodon, plantago seed, plantain, lycoris, polygala, fritillaria, fennel, phellodendron, coptis root, zedoaria, chamomile, gentian, bezoar, animal gall, adenophora, ginger, atractylodes, clove, tangerine peel, atractylodes macrocephala, bamboo ginseng, ginseng, kudzu root decoction, cassia twig decoction, fragrant persimmon powder, purple hu gui zhi decoction, small purple hu decoction, small green dragon decoction, ophiopogon decoction, pinellia ternata decoction, and ephedra decoction; oyster meat extract, propolis, and propolis extracts. One of the above-mentioned ingredients may be used alone, or two or more may be used in combination.

[0118] The sublimable active ingredient is not particularly limited as long as it has sublimation properties. The sublimable active ingredient may be in a solid, liquid, or semisolid state at room temperature. Examples of sublimable active ingredients include benzoic acid, ethanolide, caffeine, camphor, salicylic acid, phenacetin, ibuprofen, and other sublimable pharmaceutical active ingredients listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia, the USP, the NF, and the EP. These active ingredients may be used alone or in combination of two or more.

[0119] [Other ingredients] As excipients, for example, acrylic starch, L-aspartic acid, aminoethanesulfonic acid, glycine, sugar (powder), gum arabic, gum arabic powder, alginic acid, sodium alginate, pregelatinized starch, pumice particles, inositol, ethyl cellulose, ethylene-vinyl acetate copolymer, sodium chloride, olive oil, kaolin, cocoa butter, casein, fructose, pumice particles, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydrous silicon dioxide, dry yeast, dry aluminum hydroxide gel, dry sodium sulfate, dry magnesium sulfate, agar, agar powder, wood Sugar alcohol, citric acid, sodium citrate, disodium citrate, glycerin, calcium glycerophosphate, sodium gluconate, L-glutamine, clay, clay 3, clay granules, croscarmellose sodium, crospovidone, magnesium aluminum silicate, calcium silicate, magnesium silicate, light silicic anhydride, light liquid paraffin, cinnamon powder, crystalline cellulose, crystalline cellulose sodium carboxymethylcellulose, crystalline cellulose (granules), brown rice koji, synthetic aluminum silicate, synthetic hydrotalcite, sesame oil, wheat flour, wheat starch, wheat germ powder, rice flour, rice starch, potassium acetate, Calcium acetate, cellulose acetate phthalate, safflower oil, white beeswax, zinc oxide, titanium oxide, magnesium oxide, β-cyclodextrin, dihydroxyaminoaluminum acetate, 2,6-di-butyl-4-methylphenol, dimethylpolysiloxane, tartaric acid, potassium hydrogen tartrate, calcined gypsum, sucrose fatty acid ester, aluminum magnesium hydroxide, aluminum hydroxide gel, aluminum hydroxide and sodium bicarbonate coprecipitate, magnesium hydroxide, squalene, stearyl alcohol, stearic acid, calcium stearate, polyoxyethylene stearate, magnesium stearate, hydrogenated soybean oil, purified gelatin, purified Shellac, refined sugar, refined sugar granules, cetostearyl alcohol mixture, polyethylene glycol 1000 monocetyl ether, gelatin, sorbitan fatty acid esters, D-sorbitol, tricalcium phosphate, soybean oil, unsaponifiable soybeans, 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 gum powder, silicon dioxide, calcium lactate, lactose, lactose granules, paraffin 101. White shellac, white vaseline, white clay, white sugar, white sugar starch granules, rye green leaf extract powder, rye malt leaf juice dry powder, honey, paraffin, potato starch, semi-digested starch, human serum albumin, hydroxypropyl starch, hydroxypropyl cellulose, 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) polyoxypropylene (30) glycol, polystyrene Sodium olefin sulfonate, polysorbate 80, polyvinyl acetal diethylaminoacetate, polyvinyl pyrrolidone, polyethylene glycol, maltitol, maltose, D-mannitol, syrup, isopropyl myristate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate granules, magnesium aluminum metasilicate, methylcellulose, cottonseed meal, cottonseed oil, Japan wax, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, medicinal charcoal, peanut oil, aluminum sulfate, calcium sulfate, granular corn starch, liquid paraffin, dl-malic acid, calcium monohydrogen phosphate, calcium hydrogen phosphate, calcium hydrogen phosphate granules, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, sodium dihydrogen phosphate, etc. are classified as excipients in the "Drug Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These excipients can be used alone or in combination of two or more.

[0120] Examples of disintegrants include celluloses such as croscarmellose sodium, carboxymethylcellulose, carboxymethylcellulose calcium, carboxymethylcellulose sodium, and low-substituted hydroxypropylcellulose; 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 cross-linked polyvinylpyrrolidone and cross-linked polyvinylpyrrolidone copolymers, which are classified as disintegrants in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). 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 methyl cellulose; starches such as pregelatinized starch and starch paste; synthetic polymers such as polyvinyl pyrrolidone, carboxyvinyl polymer, and polyvinyl alcohol; and inorganic compounds such as calcium hydrogen phosphate, calcium carbonate, synthetic hydrotalcite, and magnesium aluminum silicate. These binders are classified as binders in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These binders may be used alone or in combination of two or more.

[0122] Examples of fluidizing agents include silicon compounds such as hydrous silicon dioxide and light silicic anhydride, which are classified as fluidizing agents in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These fluidizing agents may be used alone or in combination of two or more.

[0123] Examples of lubricants include magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid esters, and talc, which are classified as lubricants in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These lubricants may be used alone or in combination of two or more.

[0124] Examples of flavoring agents include glutamic acid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaric acid, malic acid, ascorbic acid, sodium chloride, and l-menthol, which are classified as flavoring agents in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These flavoring agents may be used alone or in combination of two or more.

[0125] Examples of flavoring agents include orange, vanilla, strawberry, yogurt, menthol, fennel essential oil, cinnamon essential oil, neroli essential oil, peppermint oil, and green tea powder, which are classified as flavoring agents and fragrances in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These flavoring agents and fragrances may be used alone or in combination of two or more.

[0126] Examples of coloring agents include food coloring agents such as Food Red No. 3, Food Yellow No. 5, and Food Blue No. 1, as well as sodium copper chlorophyllin, titanium oxide, and riboflavin, which are classified as coloring agents in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These coloring agents may be used alone or in combination of two or more.

[0127] Examples of sweeteners include aspartame, saccharin, dipotassium glycyrrhizate, stevioside, maltose, maltitol, starch syrup, and gancha powder, which are classified as sweeteners in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These sweeteners may be used alone or in combination of two or more.

[0128] [Method for producing a molded article] The following describes a method for producing a tablet containing one or more active ingredients and the cellulose powder of this embodiment as a main component. It should be noted that these methods for producing the molded body of this embodiment are merely examples, and the effects of the molded body of this embodiment are not limited to the following methods. An example of a manufacturing method is to mix the active ingredient with the cellulose powder of this embodiment and then compress and mold the mixture. In addition to the active ingredient, other additives may be added as needed. Examples of these other additives include one or more selected from the group consisting of excipients, disintegrants, binders, fluidizers, lubricants, flavoring agents, fragrances, colorants, sweeteners, and solubilizers.

[0129] The order of adding the components is not particularly limited, and examples include: i-1) mixing the active ingredient with the cellulose powder of this embodiment and, if necessary, other additives, and compression molding; and ii-1) pre-treating the active ingredient with an additive such as a fluidizer or lubricant, mixing the cellulose powder of this embodiment and, if necessary, other additives, and then compression molding. Alternatively, a lubricant may be added to the compression-molding mixture obtained by methods i-1) or ii-1), further mixing, and compression molding.

[0130] In particular, when using an active ingredient that is poorly soluble in water, the following production methods can be employed. Examples of production methods include i-2) pulverizing the active ingredient or using it directly, mixing the cellulose powder of this embodiment with other ingredients as needed, and compression molding; and ii-2) dissolving or dispersing the active ingredient in one or more media selected from the group consisting of water, an organic solvent, and a cosolvent, adsorbing the active ingredient onto the cellulose powder of this embodiment or other additives as needed, mixing with the cellulose powder of this embodiment or other additives as needed, distilling off the medium as needed, and compression molding.

[0131] Among them, from the viewpoint of moldability and fluidity, in i-2), it is particularly preferred to pre-treat and mix additives such as a fluidizer with the active ingredient, then mix with the cellulose powder of this embodiment and other components as needed and perform compression molding.

[0132] The crystalline form of the active ingredient before compression molding may be the same as or different from that before formulation. However, from the perspective of stability, the crystalline form of the active ingredient before compression molding is preferably the same as that before formulation.

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

[0134] In particular, in the case of the ii-2) method, since a process of temporarily dissolving or dispersing the poorly soluble or insoluble active ingredient in water is performed, the dissolution of the active ingredient is also improved. In particular, when a liquid dispersion such as polyethylene glycol is used as a dispersion of a pharmaceutical active ingredient, even if the original active ingredient is a crystalline powder, the dispersion formed by dispersing it will form a liquid or semisolid state. Therefore, if it is not a thing with excellent compression moldability and fluidity such as the cellulose powder of the present embodiment, the active ingredient cannot be tableted. In addition, when polyethylene glycol is used as a dispersion of a pharmaceutical active ingredient, when the active ingredient is absorbed into the body, a structure coated with polyethylene glycol will be formed in the blood. Therefore, it is also expected that the active ingredient that is easily metabolized in the liver will have a sustained drug effect.

[0135] The method of adding the components is not particularly limited as long as it is a conventional method. For example, a small suction conveying device, an air conveying device, a bucket conveyor, a pressure conveying device, a vacuum conveyor, a vibrating quantitative feeder, a sprayer, a funnel, etc. can be used to add the components continuously or all at once.

[0136] When the active ingredient is a solution, suspension or emulsion, it is preferably sprayed onto cellulose powder or other additives. This can make the concentration deviation of the active ingredient in the final product smaller. As a spraying method, there can be mentioned a method of spraying the active ingredient solution or active ingredient dispersion using a Tianwei spray device, a pressure nozzle, a two-fluid nozzle, a four-fluid nozzle, a rotating disk, an ultrasonic nozzle, etc.; a method of dripping the active ingredient solution or active ingredient dispersion from a tubular nozzle, etc. When adding the active ingredient solution or active ingredient dispersion, a layering or coating in which the active ingredient is layered on the surface of the cellulose particles in the cellulose powder can be applied, or it can be loaded inside the cellulose powder particles, or the active ingredient solution or active ingredient dispersion can be used as a binder and granulated into a matrix with a mixture of cellulose powder particles or porous cellulose and other additives. Layering and coating can be wet or dry.

[0137] The mixing method is not particularly limited as long as it is a conventional method. For example, methods using a container rotary mixer such as a V-type, W-type, double cone type, or container tumbling mixer; a stirring mixer such as a high-speed stirring type, a universal stirring type, a ribbon type, a kneading (Pug) type, or a Nauta type mixer; a high-speed flow mixer, a drum mixer, or a fluidized bed mixer can be mentioned. In addition, methods using a container vibration mixer such as a vibrator can also be mentioned.

[0138] The compression molding method of the composition is not particularly limited as long as it is a conventional method. Examples include methods of compressing the composition into a desired shape using a mortar and pestle, and methods of pre-compression molding into a sheet and then cutting it into the desired shape. Examples of compression molding machines include roller presses such as static presses, roller briquetting presses, and smooth roller presses; single punch tablet presses; and rotary tablet presses.

[0139] The method for dissolving or dispersing the active ingredient in the medium is not particularly limited as long as it is a conventional dissolution or dispersion method. For example, there can be mentioned stirring and mixing methods using stirring blades such as portable mixers, stereo mixers, side mixers, etc., which are unidirectional rotating, multi-axis rotating, reciprocating, vertical moving, rotating + vertical moving, and pipeline types; jet stirring and mixing methods such as pipeline mixers; gas blowing stirring and mixing methods; mixing methods using high shear homogenizers, high-pressure homogenizers, ultrasonic homogenizers, etc.; container vibration mixing methods using a vibrator, etc.

[0140] There are no particular restrictions on the medium used in the above-mentioned manufacturing method as long as it is a solvent used for medicines. For example, water or an organic solvent can be used. As an organic solvent, for example, alcohols such as methanol, ethanol, isopropanol, butanol, 2-methylbutanol, and benzyl alcohol; hydrocarbons such as pentane, hexane, heptane, and cyclohexane; ketones such as acetone and ethyl methyl ketone, and other substances classified as solvents in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nippo Co., Ltd.) can be cited. These media can be used alone or in combination of two or more. It is also possible to temporarily disperse in one medium, remove the medium, and disperse in different media.

[0141] Examples of water-soluble polymers used as solubilizers include hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, methylcellulose, ethylcellulose, gum arabic, and starch paste, which are listed in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These water-soluble polymers may be used alone or in combination of two or more.

[0142] Examples of oils and fats used as solubilizers include monoglyceride stearate, triglyceride stearate, sucrose stearate, paraffin waxes such as liquid paraffin, carnauba wax, hydrogenated oils such as hydrogenated castor oil, castor oil, stearic acid, stearyl alcohol, polyethylene glycol, and the like, listed in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Co., Ltd.). These oils and fats may be used alone or in combination of two or more.

[0143] Examples of surfactants used as solubilizing agents include phospholipids, fatty acid glycerides, 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, glyceryl monostearate, monooxyethylene sorbitan monopalmitate, monooxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, sorbitan monopalmitate, sodium lauryl sulfate, and the like, which are classified as surfactants in the "Pharmaceutical Additives Dictionary" (published by Yakuji Nippo Sha Co., Ltd.). These surfactants may be used alone or in combination of two or more.

[0144] The tablets referred to in this specification refer to a compact formed by compression molding comprising the cellulose powder of this embodiment, one or more active ingredients, and other additives as needed. The tablet composition incorporating the cellulose powder of this embodiment can achieve a practical hardness by simple methods such as direct tableting, without requiring complex steps. Tablet manufacturing methods, such as dry granulation compression, wet granulation compression, direct powder compression, methods for manufacturing multi-core tablets using a pre-compressed tablet as the core, and methods for manufacturing multi-layer tablets by stacking and re-compressing multiple pre-compressed compacts, can be used as needed.

[0145] The cellulose powder of this embodiment has excellent physical properties such as compression moldability, fluidity, and disintegration required as an excipient. Therefore, it is particularly suitable for tablets containing multiple or large amounts of drugs, which are difficult to obtain tablet hardness and are prone to tablet surface cracks, defects, internal peeling, cracks, and other tablet compression defects. For example, tablets containing over-the-counter drugs, Chinese herbal medicine extract powders, etc.; small tablets; non-circular deformed tablets with edge depressions and other parts that are difficult to apply compression pressure evenly; drugs such as enzymes and proteins that are easily inactivated by pressure and friction with excipients, and tablets containing coated particles. In addition, due to the excellent compression moldability of the cellulose powder of this embodiment, tablets with practical wear resistance can be obtained at a relatively low compression pressure. Therefore, since a gap (aqueduct) can be maintained within the tablet, it is also effective for orally disintegrating tablets that need to disintegrate quickly in the oral cavity.

[0146] Furthermore, for multilayer tablets or cored tablets formed by compressing multiple components in one or more stages, in addition to imparting hardness and suppressing common tableting defects as described above, the cellulose powder also has the effect of suppressing delamination and cracking between layers. Since the cellulose powder of this embodiment has a high proportion of primary particles, the particles themselves have excellent splittability, making it easy to evenly split the tablets when used in scored tablets, etc. Furthermore, the cellulose powder of this embodiment has a well-developed porous structure, and the cellulose particles themselves have excellent retention of particulate drugs, suspended drugs, and solution-like ingredients. Therefore, tablets using this powder also have excellent retention of particulate drugs, suspensions, and solution-like ingredients. Consequently, the cellulose powder of this embodiment is also effective in preventing the peeling of layered, coated, or sugar-coated layers and reinforcing them in layered or coated tablets made with suspended or solution-like ingredients, as well as sugar-coated tablets made by layering ingredients such as sugar and calcium carbonate in a suspended state on the tablet surface.

[0147] Next, the use of a composition containing one or more active ingredients and cellulose powder will be described. The composition containing a solid, liquid, or semisolid active ingredient and cellulose powder obtained by the above method can be used in a powder or granular form as a solid preparation. Alternatively, the powder or granular composition can be further coated with a coating agent to be used as a coated powder or granular solid preparation. The coated or uncoated powder or granular composition obtained here can be filled into capsules or compressed into a tablet-type solid preparation. Furthermore, capsules or tablets can be coated for use.

[0148] Examples of coating agents include ethyl acrylate-methyl methacrylate copolymer dispersions, acetylated fatty acid glycerides, aminoalkyl methacrylate copolymers, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersions, octyldecyl triglyceride, olive oil, kaolin, cocoa butter, deer nut seed oil, castor wax, caramel, carnauba wax, carboxyvinyl polymers, carboxymethylethyl cellulose, sodium carboxymethyl starch, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, hydrous silicon dioxide, dried aluminum hydroxide gel, dried emulsified white shellac, dried methacrylic acid copolymers, winter plum powder, fish scale powder, gold leaf, silver leaf, triethyl citrate, glycerin, fatty acid glycerides, magnesium silicate, light silicic anhydride, and hydroxypropyl cellulose containing light silicic anhydride. Cellulose, light liquid paraffin, spermaceti, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, synthetic wax, high glucose syrup, hard wax, succinylated gelatin, wheat flour, wheat starch, rice starch, cellulose acetate, vinyl acetate resin, cellulose acetate phthalate, white beeswax, titanium dioxide, magnesium oxide, dimethylaminoethyl methacrylate-methyl methacrylate copolymer, polydimethylsiloxane, polydimethylsiloxane / silica mixture, silica mixture, plaster of Paris, sucrose fatty acid esters, agarwood powder, aluminum hydroxide gel, hydrogenated rosin glyceride, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyethylene glycol stearate, magnesium stearate, refined gelatin, refined shellac, refined white sugar, corn protein, sorbitan sesquioleate, cetyl alcohol , gypsum, gelatin, shellac, sorbitan fatty acid esters, D-sorbitol, D-sorbitol liquid, tricalcium phosphate, talc, calcium carbonate, magnesium carbonate, simple syrup, gold foil, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, terpene resin, starch (soluble), corn syrup, corn oil, triacetin, calcium lactate, white shellac, white sugar, honey, stearin, paraffin, pearl powder, potato starch, hydroxypropyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl succinate acetate, hydroxypropyl cellulose-titanium oxide-polyethylene glycol mixture, hydroxypropyl methylcellulose phthalate, piperonyl butoxide, castor oil, diethyl phthalate, dibutyl phthalate, butyl glycol phthalate, glucose, partially pregelatinized starch, fumaric acid-hard Fatty acid-polyvinyl acetal diethylamino acetate-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 diethylamino acetate, polyvinyl alcohol (partially saponified), polyethylene glycol, terminal hydroxy-substituted methyl polysiloxane silicone resin copolymer, D-mannitol, syrup, beeswax, myristyl alcohol, anhydrous silicic acid hydrate, phthalic anhydride, anhydrous calcium hydrogen phosphate, methacrylic acid copolymer, magnesium aluminum silicate, methylcellulose, 2-methyl-5-vinylpyridine methacrylate-methacrylic acid copolymer,Coating agents listed in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nippo Co., Ltd.), such as Japan wax, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, montanate wax, medicinal charcoal, lauromacrogol, calcium sulfate, liquid coumarone resin, liquid paraffin, dl-malic acid, calcium monohydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, calcium dihydrogen phosphate, and rosin. These coating agents may be used alone or in combination of two or more.

[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 drugs loaded within their pores can be used directly as granules, granulated to form granules, or compressed into tablets. These granules, granules, or tablets can be further coated.

[0150] The method for loading the drug into the pores of the cellulose powder is not particularly limited as long as it is a known method. Examples include: i) mixing with a particulate drug and loading it into the pores; ii) mixing with a powdered drug under high shear to forcibly load it into the pores; iii) mixing with a drug in a solution or dispersion, loading it into the pores, and then drying it as needed; iv) mixing with a sublimable drug and allowing it to sublime and adsorb into the pores by heating or reducing pressure; and v) mixing with a drug before or during heating to load the melt into the pores. These methods may be used alone or in combination of two or more.

[0151] The cellulose powder of this embodiment has a well-developed pore structure and exhibits moderate water and oil retention. Therefore, it can be used not only as an excipient but also as core particles for layering or coating. In this case, the layering or coating process can suppress interparticle cohesion. Layering or coating can be performed using either a dry or wet process.

[0152] Furthermore, when the active ingredient is in the form of a solution, suspension, or emulsion, cellulose powder or a mixture of cellulose powder and other additives can be used as a carrier and then immersed in the active ingredient solution, suspension, or emulsion, similar to a dipping method, to load the active ingredient. Depending on the type and concentration of the active ingredient, such dipping methods are practical for maintaining uniformity of the active ingredient and offer a simpler process than spraying. In addition, when the active ingredient is in the form of a solution, suspension or emulsion, the following method can be used: cellulose powder or a mixture thereof with other additives is used as a carrier, impregnated with the active ingredient solution, suspension or emulsion, and the dispersion is spray-dried to form a composite.

[0153] The cellulose powder or the mixture of the cellulose powder and other additives before and after the addition of the active ingredient solution or active ingredient dispersion may be in a state where the unit particles are individually dispersed or in the form of aggregated granules.

[0154] As a granulation method when granulation is performed in the manufacturing process, for example, dry granulation, wet granulation, heating granulation, spray granulation, and microencapsulation can be cited. As for the wet granulation method, specifically, fluidized bed granulation, stirring granulation, extrusion granulation, crushing granulation, and rolling granulation are effective. The fluidized bed granulation method is to spray a binding liquid onto the flowing powder in a fluidized bed granulation device to granulate. The stirring granulation method is to rotate the stirring blade in the mixing tank while adding the binding liquid, thereby mixing, kneading, and granulating the powder simultaneously in a closed structure. The extrusion granulation method is to force the wet mass kneaded by adding the binding liquid to be extruded from a screen of an appropriate size by a screw type or basket type method for granulation. The crushing granulation method is to shear or crush the wet mass kneaded by adding the binding liquid with the rotating blade of a granulator, and eject it from the peripheral screen by centrifugal force for granulation. The rolling granulation method is to use the centrifugal force of the rotating rotor to roll, and the adhesive liquid sprayed by the spray gun at this time makes spherical particles with uniform particle size grow like a snowball to granulate.

[0155] Methods for drying granules include, for example, hot air heating (shelf drying, vacuum drying, fluidized bed drying), conduction heat transfer (pan type, shelf box type, drum type) and freeze drying. In the hot air heating type, hot air is directly contacted with the material, and water is evaporated away at the same time. In the conduction heat transfer type, the material is heated indirectly through a heat transfer wall. Freeze drying is to first freeze the material at a temperature above -10°C and below -40°C, and then dry it under high vacuum (1.3×10 -5 MPa or above and 2.6×10 -4 MPa or less) to sublimely remove water.

[0156] In summary, as methods for manufacturing tablets, for example, there can be mentioned i) mixing the active ingredient and cellulose powder or mixing one or more active ingredients, cellulose powder and other additives as needed, and then compressing and molding by a conventional method (direct tableting method); ii) mixing the active ingredient, cellulose powder and other additives as needed, granulating into granules, and compressing and molding by a conventional method (wet or dry granulation compression method); iii) mixing the active ingredient, cellulose powder and other additives as needed, granulating into granules, further mixing the cellulose powder and other additives as needed, and compressing and molding by a conventional method (wet or dry granulation and powder compression method), etc.

[0157] The method for adding one or more active ingredients, cellulose powder, other additives or particles is not particularly limited as long as it is a conventional method. For example, they can be added continuously or all at once using a small suction conveying device, an air conveying device, a bucket conveyor, a pressure conveying device, a vacuum conveyor, a vibrating quantitative feeder, a sprayer, a funnel, etc. In addition to tablets formed by compression molding as described above, compositions containing active ingredients and cellulose powder can also be used as granules or powders, particularly for the purpose of improving flowability, anti-blocking properties, and anti-cohesion properties, due to their excellent retention of solid or liquid components. Granules or powders can be prepared, for example, by dry granulation, wet granulation, heat granulation, spray drying, and microencapsulation.

[0158] [Physical properties of tablets] The molded article of this embodiment is prepared by (1) sieving ascorbic acid (manufactured by Watanabe Chemical Co., Ltd.) through a sieve having a mesh size of 2 mm. The average particle size D of the obtained ascorbic acid is 50 320 μm) 603.2 parts by mass, spray-dried lactose (DFE Pharma Co., Ltd., Super Tab 108.8 parts by mass of 11SD (trade name) and 80 parts by mass of the cellulose powder of the present embodiment were placed in a plastic bag and shaken for 3 minutes. Then, 8 parts by mass of calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) were added and mixed for further 30 seconds to obtain a prescription powder (the final composition by mass ratio was ascorbic acid / spray-dried lactose / cellulose powder / calcium stearate = 75.4 / 13.6 / 10 / 1). The obtained prescription powder was fed through an open feeder and tableted using a rotary tablet press (manufactured by Kikusui Seisakusho Co., Ltd., 12 punches) using an R punch with a diameter of 9 mm and a rotary disk speed of 54 rpm to obtain tablets with a mass of about 370 mg; (2) ascorbic acid (manufactured by Watanabe Chemical Co., Ltd.) was sieved with a sieve with a mesh size of 2 mm and used. The average particle size D of the obtained ascorbic acid was 0.0447 ... 50320 μm), 544.4 parts by mass of spray-dried lactose (DFE Pharma Co., Ltd., SuperTab 11SD (trade name)) and 80 parts by mass of the cellulose powder of the present embodiment were placed in a plastic bag and shaken for 3 minutes. Then, 8 parts by mass of calcium stearate (Taihei Chemical Industry Co., Ltd.) were added and mixed for further 30 seconds to obtain a prescription powder (the final composition was ascorbic acid / spray-dried lactose / cellulose powder / calcium stearate = 68 / 21 / 10 / 1 in terms of mass ratio). The obtained prescription powder was fed through an open feeder and tableted using a rotary tablet press (Kikusui Seisakusho Co., Ltd., 12 punches) using an R punch with a diameter of 9 mm and a rotary disk speed of 54 rpm to obtain tablets of about 410 mg; or (3) 200 parts by mass of ethisalicylamide (Yamamoto Chemical Industry Co., Ltd., Grade C), spray-dried lactose (DFE 245 parts by mass of SuperTab 11SD (trade name) manufactured by Pharma Co., Ltd., 50 parts by mass of the cellulose powder according to the present embodiment, and 5 parts by mass of light anhydrous silicic acid (AEROSIL 200 (trade name) manufactured by Nippon Aerosil Co., Ltd.) were placed in a plastic bag and shaken for 3 minutes. Then, 5 parts by mass of magnesium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) were added and mixed for a further 30 seconds to obtain a prescription powder (final composition, by mass ratio: ascorbic acid / spray-dried lactose / cellulose powder / calcium stearate = 40 / 49 / 10 / 1 / 1). The obtained prescription powder was tableted using a single-shot tablet press (manufactured by Ichikawa Seiki Co., Ltd.) using an 8 mm diameter R die at a rate of 30 tablets per minute. The mass variation of the tablets when obtaining tablets of approximately 470 mg is preferably 1.0 mass% or less, more preferably 0.7 mass% or less, even more preferably 0.6 mass% or less, and particularly preferably 0.5 mass% or less. On the other hand, the smaller the mass variation of the tablet, the better. The lower limit is not particularly limited, but is usually about 0.01 mass %. The mass variation of tablets can be measured, for example, using the method described in the Examples below.

[0159] Furthermore, when the molded article 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 higher the hardness of the tablet, the better. Although the upper limit is not particularly limited, it is generally around 150 N. Tablet hardness can be measured, for example, by the method described in the Examples below.

[0160] Furthermore, when the molded article 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. Meanwhile, the shorter the disintegration time, the better. The lower limit is not particularly limited, but is generally about 10 seconds. The disintegration time can be measured, for example, by the method described in the Examples below.

[0161] Furthermore, when the molded article of this embodiment is a tablet produced under the same conditions as above, its abrasiveness 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 abrasiveness, the better. While the lower limit is not particularly limited, it is generally around 0.01% by mass. The degree of wear can be measured, for example, by the method described in Examples below.

[0162] That is, when the formed body of this embodiment is a tablet manufactured under the same conditions as above, the tablet preferably has a tablet mass deviation of less than 1.0 mass%, a tablet hardness of 40N or more, a disintegration time of less than 1800 seconds, and an abrasion rate of less than 0.5 mass%. Example

[0163] The present invention will be described based on its examples. However, the embodiments of the present invention are not limited to the description of these examples. The measuring methods and evaluation methods of various physical properties in Examples and Comparative Examples are as follows.

[0164] <Measurement methods of physical properties> [Physical properties 1] (Average particle size of cellulose powder) Average particle size D of cellulose powder 50 The particle size distribution was determined using a laser diffraction / scattering particle size distribution analyzer (LA-950V2, manufactured by Horiba, Ltd.). Approximately 1.0 g of cellulose powder was loaded onto a powder sample sprayer. The sample was dispersed under conditions of a feed rate of 160 and a compressed air pressure of 0.03 MPa. Scattered light was measured within a range of laser (red) transmittance of 95% to 98%. The particle size at 50% of the cumulative volume was defined as the average particle size D. 50 . It is expressed as the average value of 2 measurements.

[0165] [Physical Properties 2] (Average degree of polymerization of cellulose powder) As a sample, accurately weigh about 1.3 g of cellulose powder (about 0.25 g in the case of powdered cellulose) and place it in a 125 mL conical flask. Accurately add 25 mL of water and 25 mL of 1 mol / L copper ethylenediamine test solution. Immediately introduce nitrogen, seal the flask, and use an oscillator to mix and dissolve while shaking. Accurately measure an appropriate amount of this solution and test it at 25±0.1°C according to the viscosity determination method 1 <2.53> using a capillary viscometer with a viscometer constant (K) of about 0.03 to determine the dynamic viscosity ν. Separately, accurately measure 25 mL of water and 25 mL of 1 mol / L copper ethylenediamine test solution, and test the mixture in the same way using a capillary viscometer with a viscometer constant (K) of about 0.01 to determine the dynamic viscosity ν0. The relative viscosity ηrel of the cellulose powder is calculated according to the following formula.

[0166] ηrel=ν / ν0

[0167] Based on the relative viscosity ηrel, the product [η]C of the limiting viscosity [η] (mL / g) and the concentration C (g / 100 mL) was determined from Tables 1 and 2, and the average degree of polymerization P was calculated according to the following formula. In the following formula, MT is the weight (g) of the cellulose powder weighed on a dry basis.

[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 instrument (Peneto Analyzer PNT-N (trade name), manufactured by Hosokawa Micron Co., Ltd.). Specifically, a Teflon (registered trademark) container was filled with about 5.0 g of cellulose powder that passed through a 500 μm mesh, and the container was vibrated under the conditions of 300 times, 18 mm stroke, and 198 g weight. The vibrated cellulose powder was fully immersed in 300 mL of pure water at a speed of 0.5 mm / s until saturated, and the square of the pure water penetration rate (g / min) during the measurement period until saturation was reached was measured using the above-mentioned measuring instrument. 2 ) The square of the penetration rate until saturation is reached (g 2 The relationship between the water absorption rate (g) and the measurement time is linearized by the least square method. The slope of the linearized graph is the water absorption rate (g 2 The results were expressed as the average value of 5 measurements.

[0170] [Physical Properties 4] (Cohesive force F of cellulose powder) The cohesive force of the cellulose powder was calculated using a powder layer shear force measuring device (NS-S300 type (trade name), manufactured by Nano Seeds Co., Ltd.). Specifically, the cellulose powder was filled into the shear groove ( The upper and lower groove lengths are: 34mm, 5mm), and the upper surface of the powder layer is leveled. Then, the target pressure load of 20N is used as the pressure control condition, and the shear test is performed at a shear rate of 50μm / second. When the target load is reached, the pressure is stopped, and after starting lateral sliding, the static friction coefficient and the dynamic friction coefficient are measured. During the analysis, the measured elapsed time (s) is used as the horizontal axis and the load (N) applied to the shear surface is used as the vertical axis for fitting. The maximum and minimum values of the shear surface load are obtained, and the cohesive force defined by the following formula is calculated. It is expressed as the average value of 2 measurements.

[0171] [Cohesion F (N%)] = ([Maximum value of shear surface load (N)] - [Minimum value of shear surface load (N)]) / [Maximum value of shear surface load (N)] × 100

[0172] [Physical Properties 5] (Dynamic friction angle of cellulose powder) The powder layer shear force measuring device (NS-S300 type (trade name), manufactured by Nano Seeds Co., Ltd.) was used to calculate the powder dynamic friction angle of the cellulose powder. Specifically, the cellulose powder was filled into the shear groove ( The upper and lower groove lengths are: 34mm, 5mm), and the upper surface of the powder layer is leveled. Then, using the above-mentioned measuring device, the target pressure loads of 20N, 30N, and 40N are used as the pressure control conditions, and the shear test is performed at a shear rate of 50μm / second. When the target load is reached, the pressure is stopped, and after lateral sliding is started, the static friction coefficient and the dynamic friction coefficient are measured. During the analysis, first fit the measured elapsed time (s) as the horizontal axis and the shear force (N) as the vertical axis to find the maximum value of the shear force and the pressure load value at this time. The result is fitted into a graph with the vertical axis as the shear stress and the horizontal axis as the vertical stress, and the angle of the straight line connecting the origin and these points relative to the X-axis is calculated as the powder dynamic friction angle. It is expressed as the average value of 2 measurements.

[0173] [Physical Properties 6] (Bulk density of cellulose powder) The bulk density of the cellulose powder is measured by the following method. A 25 mL cylindrical metal container was filled with cellulose powder using a Scot volumetric meter (ASTM B-329-85, manufactured by Tsutsui Rikagaku Instruments Co., Ltd.). The cellulose powder in the 25 mL cylindrical metal container was leveled and the mass (g) of the cellulose powder in the container was divided by 25 mL to calculate the bulk density (g / cm3 ). The results are expressed as the average of two measurements.

[0174] [Properties 7] (Compression rate of cellulose powder) The compressibility of the cellulose powder was measured by the method shown below. The tap density was measured using a powder property evaluation device (Powder Tester, manufactured by Hosokawa Micron Co., Ltd.). A sieve with a pore size of 710 μm and a metal funnel with an inner diameter of 0.8 cm were used, and the vibration condition was VIBRATION 2.0 (power supply: AC100 V, 60 Hz). The bulk density was measured using the method described above, and the compressibility was calculated using the following formula. The average of two measurements was used.

[0175] [Compression ratio (%)] =([tap density (g / cm 3 )]-[Bulk density (g / cm 3 )]) / [Tap density (g / cm 3 )]×100

[0176] [Property 8] (Primary particle ratio of cellulose powder) The primary particle rate of cellulose powder was calculated using a dry image analyzer (Malvern Morphorogi G3S) and image processing software. Specifically: First, 10,000 particles were photographed and image analysis was performed to determine the equivalent area circular particle size and aspect ratio of each particle. From the results, particle images with an equivalent area circular particle size in the range of 30 μm to 90 μm and an aspect ratio not exceeding the average value of the aspect ratio of 10,000 particles + 0.1 were extracted. The range selected by the brightness dispersion value of 1 to 26 in the extracted particle images was taken as primary particles, and the range selected by 26 to 100 was taken as secondary particles. The primary particle rate (%) was calculated by the number of primary particles / 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), primary particle images were extracted using the same method as described above. The major diameter (L) and minor diameter (D) values obtained from the extracted particle images were used to calculate the major diameter (L) / minor diameter (D). The average value for the entire extracted primary particle image was calculated as the L / D value for the primary particles of the cellulose powder.

[0178] Evaluation Method [Manufacture of 370 mg tablets] 603.2 g of ascorbic acid (manufactured by Watanabe Chemical Co., Ltd., sieved with a 2 mm mesh sieve. The average particle size of the obtained ascorbic acid is 320 μm), 108.8 g of spray-dried lactose (manufactured by DFE Pharma Co., Ltd., SuperTab11SD (trade name)), and 80 g of each cellulose powder were placed in a plastic bag and shaken for 3 minutes. Then, 8 g of calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) was added to the mixed powder and mixed for a further 30 seconds to obtain the final formula powder. The final composition of the final formula powder was calculated by mass ratio: ascorbic acid / spray-dried lactose / each cellulose powder / calcium stearate = 75.4 / 13.6 / 10 / 1.

[0179] The final formulation powder was then compressed using a rotary tablet press (manufactured by Kikusui Seisakusho Co., Ltd., 12 punches) to obtain tablets weighing approximately 370 mg. The formulation powder was fed through an open feeder and compressed using a 9 mm diameter R die at a turntable speed of 54 rpm. The compression pressure was appropriately adjusted to achieve a tablet hardness of 40 N or greater.

[0180] [Manufacture of 410 mg tablets] 544.4 g of ascorbic acid (manufactured by Watanabe Chemical Co., Ltd., sieved with a 2 mm mesh sieve. The average particle size of the ascorbic acid obtained is 320 μm), 167.6 g of spray-dried lactose (manufactured by DFE Pharma Co., Ltd., SuperTab11SD (trade name)), and 80 g of each cellulose powder were placed in a plastic bag and shaken for 3 minutes. Then, 8 g of calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) was added to the mixed powder and mixed for a further 30 seconds to obtain the final formula powder. The final composition of the final formula powder was calculated by mass ratio: ascorbic acid / spray-dried lactose / each cellulose powder / calcium stearate = 68 / 21 / 10 / 1.

[0181] The final formulation powder was then compressed using a rotary tablet press (manufactured by Kikusui Seisakusho Co., Ltd., 12 punches) to obtain tablets weighing approximately 410 mg. The formulation powder was fed through an open feeder and compressed using a 9 mm diameter R die at a turntable speed of 54 rpm. The compression pressure was appropriately adjusted to achieve a tablet hardness of 40 N or greater.

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

[0183] The final formulation powder was then compressed using a single-shot tablet press (manufactured by Ichikawa Seiki Co., Ltd.) to produce tablets weighing approximately 470 mg. The formulation powder was compressed using an 8 mm diameter R die at a rate of 30 tablets per minute. The compression pressure was appropriately adjusted to achieve a tablet hardness of 100 N or greater.

[0184] [Evaluation 1] (Tablet mass deviation (mass %)) The mass of 10 tablets was measured, and the average mass and mass standard deviation (g) were calculated. The mass variation was evaluated based on the coefficient of variation (mass %; hereinafter also referred to as mass CV) defined by the following formula. A smaller coefficient of variation indicates smaller variation, and a mass CV of 1.0 mass % or less is considered good variation.

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

[0186] [Evaluation 2] (Tablet hardness (N)) The obtained tablets were subjected to a load in the radial direction using a Schleuniger hardness tester (manufactured by Furen Sangyo Co., Ltd., Model 6D (trade name)) and broken, and the load (N) at that time was measured. The value is expressed as an average value of 10 tablets.

[0187] [Evaluation 3] (Disintegration time (seconds)) Disintegration tests were conducted according to the General Test Methods and Tablet Disintegration Test Methods in the 18th Revised Edition of the Japanese Pharmacopoeia. Tablets were placed in a disintegration tester (NT-40HS, manufactured by Toyama Sangyo Co., Ltd., without a disc) to determine the disintegration time in pure water at 37°C. The average value of six tablets was expressed. A disintegration time of 1800 seconds or less was considered excellent disintegration.

[0188] [Evaluation 4] (Wear degree (%)) The weight (Wa) (g) of 18 tablets was measured, and these were placed in a tablet abrasion tester (PT-F30 ERA, manufactured by Pharmatest). After rotating at 25 rpm for 4 minutes, the fine powder adhering to the tablets was removed, and the weight (Wb) (g) was measured again. The abrasion degree was calculated according to the following formula.

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

[0190] [Example 1] (Production of Cellulose Powder A) 3 kg of shredded commercial pulp (average degree of polymerization 1667) and 30 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed mixer (manufactured by Kobelco Eco-Solutions, 50 L GL reactor), stirred at a stirring speed of 62 rpm, hydrolyzed at 117°C for 75 minutes, and neutralized with ammonia water to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to a solid content concentration of 34% by mass to obtain a filter residue. Then, it was placed in a 20 L stainless steel tank, pure water was added, and stirred at a stirring speed of 75 rpm using a mixer (HANWA AGITATOR, manufactured by Hanwa Chemical Industry Co., Ltd., model KP-4003, stirring blade diameter of about 17 cm) to prepare a cellulose dispersion with a solid content concentration of 6.3% by mass. The average particle size of the cellulose particles in the cellulose dispersion was 25 μm. The 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 commercial pulp (average degree of polymerization 1667) and 30 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed mixer (manufactured by Kobelco Eco-Solutions, Ltd., 50 L GL reactor), stirred at a stirring speed of 80 rpm, hydrolyzed at 123 ° C. for 75 minutes, and neutralized with ammonia water to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to a solid content concentration of 37% by mass to obtain a filter residue. Then, it was placed in a 20 L stainless steel tank, pure water was added, and stirred at a stirring speed of 75 rpm using a mixer (HANWA AGITATOR, manufactured by Hanwa Chemical Industry Co., Ltd., with a stirring blade diameter of about 17 cm) to prepare a cellulose dispersion with a solid content concentration of 6.4% by mass. The average particle size of the cellulose particles in the cellulose dispersion was 23 μm. The 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 commercial pulp (average degree of polymerization 1667) and 30 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed mixer (manufactured by Kobelco Eco-Solutions, 50 L GL reactor), stirred at a stirring speed of 90 rpm, hydrolyzed at 113 ° C. for 75 minutes, and neutralized with ammonia water to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to obtain a filter residue. Then, it was placed in a 20 L stainless steel tank, pure water was added, and stirred at a stirring speed of 75 rpm using a mixer (HANWA AGITATOR, manufactured by Hanwa Chemical Industry Co., Ltd., with a stirring blade diameter of about 17 cm) to prepare a cellulose dispersion with a solid content concentration of 6.2% by mass. The average particle size of the cellulose particles in the cellulose dispersion was 27 μm. The 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 chopped commercial 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 (manufactured by Kobelco Eco-Solutions Co., Ltd., 50 L GL reactor), stirred at a stirring speed of 240 rpm, and hydrolyzed at 117 ° C for 75 minutes to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to obtain a solid content concentration of 43% by mass, to obtain a filter residue. Then, it was placed in a stainless steel tank with a capacity of 20 L, pure water was added, and stirred at a stirring speed of 75 rpm by a mixer (HANWA AGITATOR, manufactured by Hanwa Chemical Machinery Co., Ltd., with a stirring blade diameter of about 17 cm) to prepare a cellulose dispersion with a solid content concentration of 5.8% by mass. The cellulose dispersion was further neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 27 μm. The 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 chopped commercial 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 (manufactured by Kobelco Eco-Solutions Co., Ltd., 50LGL reactor), and hydrolyzed at 117°C for 70 minutes while stirring at a stirring speed of 240 rpm to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to obtain a filter residue. Then, it was placed in a 20 L stainless steel tank, pure water was added, and stirred at a stirring speed of 75 rpm using a mixer (HANWAAGITATOR, manufactured by Hanwa Chemical Machinery Co., Ltd., with a stirring blade diameter of about 17 cm) to prepare a cellulose dispersion with a solid content concentration of 5.0% by mass. The cellulose dispersion was further neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 27 μm. The 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 changed to 4.5% by mass.

[0196] [Example 7] (Production of Cellulose Powder G) 3 kg of shredded commercial pulp (average degree of polymerization 1667) and 30 L of 0.045 mol / L aqueous hydrochloric acid solution were placed in a low-speed mixer (50 L GL reactor, manufactured by Kobelco Eco-Solutions Co., Ltd.) and hydrolyzed at 107°C for 65 minutes while stirring at 80 rpm. The mixture was then neutralized with aqueous ammonia to produce an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Buchner funnel to obtain a filter residue. The mixture was then placed in a 20 L stainless steel tank, pure water was added, and the mixture was stirred at 75 rpm using a mixer (HANWA AGITATOR, manufactured by Hanwa Kakoki Co., Ltd., with a stirring blade diameter of approximately 17 cm) to produce a cellulose dispersion having a solids concentration of 6.0% by mass. This cellulose dispersion was spray-dried (dispersion feed rate 21 kg / hour, inlet temperature 180°C to 220°C, outlet temperature 90°C to 110°C) to produce cellulose powder G.

[0197] [Comparative Example 1] (Production of Cellulose Powder H) 3 kg of shredded commercial pulp (average degree of polymerization 1296) and 30 L of a 0.045 mol / L aqueous hydrochloric acid solution were placed in a low-speed mixer (30 L GL reactor, manufactured by Ikebukuro Enamel Industry Co., Ltd.) and hydrolyzed at 110°C for 60 minutes while stirring at 210 rpm. The mixture was then neutralized with aqueous ammonia to produce 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 feed rate 20 kg / hour, inlet temperature 180°C to 220°C, outlet temperature 90°C to 110°C) to produce cellulose powder H.

[0198] [Comparative Example 2] (Production of Cellulose Powder I) 3 kg of chopped commercial pulp (average degree of polymerization 1296) and 30 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed stirrer (manufactured by Ikebukuro Enamel Industry Co., Ltd., 30LGL reactor), stirred at a stirring speed of 210 rpm, and hydrolyzed at 120°C for 60 minutes to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to a solid content concentration of 33% by mass to obtain a filter residue. Then, it was placed in a 20 L stainless steel tank, pure water was added, and stirred at a stirring speed of 450 rpm using a stirrer (HANWA AGITATOR, manufactured by Hanwa Chemical Machinery Co., Ltd., with a stirring blade diameter of about 10 cm) to prepare a cellulose dispersion with a solid content concentration of 9.4% by mass. The cellulose dispersion was further neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 26 μm. The 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 chopped commercial pulp (average degree of polymerization 1667) and 30 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed mixer (manufactured by Kobelco Eco-Solutions, Ltd., 50 L GL reactor), stirred at a stirring speed of 90 rpm, hydrolyzed at 123 ° C. for 75 minutes, and neutralized with ammonia water to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to a solid content concentration of 42% by mass to obtain a filter residue. Then, it was placed in a 20 L stainless steel tank, pure water was added, and stirred at a stirring speed of 75 rpm using a mixer (HANWA AGITATOR, manufactured by Hanwa Chemical Industry Co., Ltd., with a stirring blade diameter of about 17 cm) to prepare a cellulose dispersion with a solid content concentration of 6.5% by mass. The average particle size of the cellulose particles in the cellulose dispersion was 22 μm. The 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 a 0.015 mol / L aqueous hydrochloric acid solution were placed in a low-speed mixer (50 L GL reactor, manufactured by Kobelco Eco-Solutions Co., Ltd.) and hydrolyzed at 145°C for 70 minutes while stirring at 234 rpm to produce an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Buchner funnel, washed four times with 70 L of pure water, neutralized with aqueous ammonia, and placed in a 45 L plastic drum. Pure water was added and stirred at 300 rpm using a three-in-one mixer (manufactured by HEIDON, model BL1200, three turbine blades, blade diameter approximately 8 cm) to produce a cellulose dispersion with a concentration of 16%. This dispersion was spray-dried (dispersion feed rate 20 kg / hour, inlet temperature 180°C to 220°C, outlet temperature 90°C to 110°C) to produce 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 aqueous hydrochloric acid solution were placed in a low-speed mixer (50 L GL reactor, manufactured by Kobelco Eco-Solutions Co., Ltd.) and hydrolyzed at 140°C for 110 minutes while stirring at 234 rpm to produce an acid-insoluble residue. The resulting acid-insoluble residue was filtered using a Buchner funnel and washed four times with 70 L of pure water. After neutralization with aqueous ammonia, the filtered residue was placed in a 45 L plastic drum, pure water was added, and a cellulose dispersion having an 18% concentration was prepared while stirring at 300 rpm using a three-in-one mixer (manufactured by HEIDON, model BL1200, three turbine blades, blade diameter approximately 8 cm). This dispersion was spray-dried (dispersion feed rate 31 kg / hour, inlet temperature 180°C to 220°C, outlet temperature 90°C to 110°C) to produce cellulose powder L.

[0202] [Comparative Example 6] (Production of Cellulose Powder M) 3 kg of chopped commercial pulp (average degree of polymerization 1296) and 30 L of 0.045 mol / L hydrochloric acid aqueous solution were placed in a low-speed stirrer (manufactured by Ikebukuro Enamel Industry Co., Ltd., 30LGL reactor), stirred at a stirring speed of 210 rpm, and hydrolyzed at 115°C for 75 minutes to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to a solid content concentration of 33% by mass to obtain a filter residue. Then, it was placed in a 20 L stainless steel tank, pure water was added, and stirred at a stirring speed of 450 rpm using a stirrer (HANWA AGITATOR, manufactured by Hanwa Chemical Machinery Co., Ltd., with a stirring blade diameter of about 10 cm) to prepare a cellulose dispersion with a solid content concentration of 9.8% by mass. The cellulose dispersion was further neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 26 μm. The 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 with an ultracentrifugal pulverizer to obtain a cellulose powder N.

[0204] [Comparative Example 8] (Production of Cellulose Powder O) 2 kg of chopped commercial pulp (average degree of polymerization 1030) was soaked in water and passed through a shredder (micro-cutter head / blade gap: 2.029 mm, impeller speed 9000 rpm) with a water content of about 70%. Pure water was then added to prepare a cellulose dispersion with a concentration of about 2%. The cellulose dispersion was then treated six times with a high-pressure homogenizer (treatment pressure 200 MPa) and centrifuged at a centrifugal force of 19600 m / s. 2 After centrifugation, discard the supernatant to obtain a precipitate. After drying the precipitate at 40°C for 16 hours, about 2 kg of the obtained product was mixed with 30 L of 4N hydrochloric acid aqueous solution and placed in a low-speed mixer (50LGL reactor manufactured by Ikebukuro Enamel Industry Co., Ltd.) while stirring, and hydrolyzed at 40°C for 48 hours to obtain an acid-insoluble residue. The obtained acid-insoluble residue was filtered using a Buchner funnel to obtain a filter residue. Then, it was placed in a 90L plastic barrel and pure water was added, and stirred with a three-in-one mixer to prepare a cellulose dispersion with a solid content concentration of 15% by mass. The cellulose dispersion was further neutralized with ammonia water. The average particle size of the cellulose particles in the cellulose dispersion was 18 μm. The 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] Tables 3 and 4 show the evaluation results of the powder properties of each cellulose powder.

[0206] [Table 3] Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Cellulose powder A B C D E F G Average degree of polymerization [-] 249 231 292 269 253 250 320 <![CDATA[Average particle size D 50 [μm]]]> 38 46 60 42 37 36 50 <![CDATA[Apparent density X [g / cm 3 > 0.08 0.11 0.1 0.09 0.11 0.11 0.13 <![CDATA[Water absorption rate Cv [g 2 / s]]]> 8.7 8.2 8.1 9.7 6.2 8.2 6.5 <![CDATA[Cv / D 50 [g 2 / s·μm]]]> 0.23 0.18 0.13 0.23 0.17 0.23 0.13 1.5X-0.06 0.07 0.11 0.09 0.07 0.17 0.23 0.13 Cohesion F[N%] 58 56 63 69 63 71 62 <![CDATA[F / D 50 [N% / μm]]]> 1.52 1.23 1.04 1.66 1.71 1.95 1.24 Powder dynamic friction angle [°] 51 49 50 51 54 53 52 Compression ratio [%] 63 55 58 60 57 58 60 Primary particle rate [%] 30 27 28 25 36 40 26 L / D of primary particles[-] 4.2 4 4 4.3 3.9 4 3.8

[0207] [Table 4] Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Cellulose powder H I J K L M N O Average degree of polymerization [-] 300 276 225 192 185 270 205 210 <![CDATA[Average particle size D 50 [μm]]]> 47 58 32 45 95 53 16 127 <![CDATA[Apparent density X [g / cm 3 > 0.13 0.18 0.18 0.27 0.31 0.18 0.17 0.26 <![CDATA[Water absorption rate Cv [g 2 / s]]]> 5.3 5.3 3.6 3.6 4.5 7.2 2 2.9 <![CDATA[Cv / D 50 [g 2 / s·μm]]]> 0.11 0.09 0.11 0.08 0.05 0.14 0.13 0.02 1.5X-0.06 0.13 0.21 0.2 0.34 0.4 0.21 0.2 0.33 Cohesion F[N%] 65 40 41 9 26 44 31 27 <![CDATA[F / D 50 [N% / μm]]]> 1.38 0.68 1.28 0.19 0.27 0.82 2 0.21 Powder dynamic friction angle [°] 50 49 49 42 38 49 49 47 Compression ratio [%] 59 49 53 40 30 47 58 33 Primary particle rate [%] 27 11 11 3 3 15 50 19 L / D of primary particles[-] 3.7 3.5 3.7 3.3 3.6 3.6 2.7 3.5

[0208] The evaluation results when each cellulose powder was made into tablets are shown in Tables 5 to 7. It should be noted that the criteria for judging the tablets obtained from each cellulose powder shown in the table are: tablets with an abrasion degree of less than 0.5 mass% are designated as A, tablets with an abrasion degree of 0.5 mass% or more and less than 1.0 mass% are designated as B, and tablets with an abrasion degree of 1.0 mass% or more are designated as C.

[0209] [Table 5]

[0210] [Table 6]

[0211] [Table 7]

[0212] Based on Tables 5 to 7, it can be seen that the water absorption rate Cv is used relative to the average particle size D 50 The ratio Y(Cv / D 50 ) is 0.12g 2 / (s·μm) or more, and the bulk density X is 0.135g / cm 3 The following cellulose powder" or "water absorption rate Cv relative to the average particle size D 50 The ratio Y(Cv / D 50) and the relationship between the bulk density X and Y≥1.5×X-0.06 (the above formula (1-1)) are satisfied. In the tablets of cellulose powders B to E (Examples 2 to 5) of "cellulose powders of the invention", the 410 mg tablets have small deviations in tablet mass, good disintegration properties, and excellent hardness and abrasion properties. In the tablets of 370 mg using cellulose powders A to E (Examples 1 to 5), the deviations in tablet mass are similarly small, good disintegration properties are maintained, and the hardness and abrasion properties are excellent. In the tablets of 470 mg using cellulose powders D and F (Examples 4 and 6), the deviations in tablet mass are similarly small. The difference is small, and while maintaining good disintegration, the hardness and abrasiveness are excellent. This shows that by using cellulose powders A to F (Examples 1 to 6) to produce tablets, tablets with excellent hardness and abrasiveness can be obtained while maintaining the characteristics of small tablet quality deviation and good disintegration. In addition, the tablet size can be further reduced without changing the amount of active ingredients such as drugs. Tablets were produced in the same manner using cellulose powder G (Example 7). As with the case of using cellulose powders A to F (Examples 1 to 6), tablets with small tablet quality deviation, excellent hardness and abrasiveness, and good disintegration were obtained.

[0213] In addition, the average particle size D 50 , average degree of polymerization and Cv / D 50 To the same extent, F / D 50 Comparison of different cellulose powders A and D (Examples 1 and 4) shows that F / D 50 Larger (due to D 50 The cellulose powder D (Example 4) having the same degree of wear, that is, a larger value of cohesive force F, tends to have a smaller wear degree.

[0214] Furthermore, the average particle size D 50 , average degree of polymerization and Cv / D 50 Comparison of cellulose powders D and F (Examples 4 and 6) having similar powder dynamic friction angles and different primary particle ratios reveals that cellulose powder F (Example 6) having a higher powder dynamic friction angle and primary particle ratio exhibits a trend toward better disintegration.

[0215] On the other hand, the water absorption rate Cv relative to the average particle size D 50 The ratio Y(Cv / D 50 ) less than 0.12g 2 / (s·μm), or the bulk density X is greater than 0.135g / cm 3 ", and "water absorption rate Cv relative to the average particle size D 50 The ratio Y(Cv / D 50) and the bulk density X does not satisfy Cv≥1.5×X-0.06” for cellulose powders H to L (Comparative Examples 1 to 5). Although the tablet quality deviation is good in 410 mg tablets, the hardness of the tablets using cellulose powders K and L (Comparative Examples 4 and 5) is less than 40N, which is poor, and the hardness of the tablets using cellulose powders I and J (Comparative Examples 2 and 3) is not less than 0.5% by mass. The hardness of the 370 mg tablets using cellulose powders I to L (Comparative Examples 2 to 5) is less than 40N, which is poor. The abrasion of the 370 mg tablets using cellulose powder H (Comparative Example 1) is 0.5% or more by mass. The abrasion of the 470 mg tablets using cellulose powders L to O (Comparative Examples 5 to 8) is not less than 0.5% by mass. Industrial applicability

[0216] The cellulose powder of this embodiment can provide a cellulose powder that reduces quality variations, maintains good disintegration properties, and has excellent hardness and abrasiveness, and can produce smaller molded bodies without changing the amount of active ingredients such as drugs.

Claims

1. A cellulose powder, characterized in that Water absorption rate Cv relative to average particle size D 50 The ratio Y, that is, Cv / D 50 0.12g 2 / (s·μm) or more, The bulk density X is 0.135g / cm 3 the following.

2. A cellulose powder, characterized in that Water absorption rate Cv relative to average particle size D 50 The ratio Y, that is, Cv / D 50 The relationship with the bulk density X satisfies the following formula (1-1): Y≥1.5×X-0.06……Formula (1-1).

3. The cellulose powder according to claim 2, wherein Water absorption rate Cv relative to average particle size D 50 The ratio Y, that is, Cv / D 50 0.12g 2 / (s·μm) or more, The bulk density X is 0.135g / cm 3 the following. The cellulose powder according to claim 1 or 2, wherein Cohesive force F relative to average particle size D 50 Ratio F / D 50 It is 0.01N% / μm or more. The cellulose powder according to claim 1 or 2, wherein The dynamic friction angle of the powder is above 30°. The cellulose powder according to claim 1 or 2, wherein The primary particle ratio is 20% or more.

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

8. The cellulose powder according to claim 1 or 2, wherein The compression rate is over 40%.

9. The cellulose powder according to claim 1 or 2, wherein The average degree of polymerization is 100 or more and 450 or less.

10. The cellulose powder according to claim 1 or 2, wherein Average particle size D 50 It is 15 μm or more and 300 μm or less. The cellulose powder according to claim 1 or 2, wherein Water absorption rate Cv is 2.0g 2 / s or more and 12.0g 2 / s or less.

12. The cellulose powder according to claim 1 or 2, wherein The cohesive force F is 30 N% or more and 100 N% or less.

13. A formed body, characterized in that Contains one or more active ingredients and the cellulose powder according to claim 1 or 2.

14. The formed body according to claim 13, wherein The active ingredient is a pharmaceutical active ingredient.

15. The formed body according to claim 13, wherein The active ingredient is a food active ingredient. The formed body according to claim 13 , which is a tablet.

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