Hydroxypropyl cellulose with low degree of substitution and method for producing same

Abstract

Provided is a method for producing L-HPC having high flowability and good bondability. A method for producing hydroxypropyl cellulose having a low degree of substitution, the method comprising at least: a step for obtaining alkali cellulose by bringing powdered pulp into contact with an alkali metal hydroxide solution; a step for obtaining a reaction product by reacting the alkali cellulose with propylene oxide; a dissolution step for mixing the reaction product with water without adding an acid; a step for neutralizing an alkali metal hydroxide contained in the reaction product; a step in which a reaction product after the neutralization step is washed, dehydrated, and dried to obtain a dried hydroxypropyl cellulose having a low degree of substitution; and a step for pulverizing the dried hydroxypropyl cellulose having a low degree of substitution.

Description

TECHNICAL FIELD

[0001] The present application relates to low-substituted hydroxypropyl cellulose and a method for producing the same. BACKGROUND

[0002] Solid preparations such as pharmaceuticals or health foods disintegrate due to water absorption and swelling of a disintegrant contained therein. As the disintegrant, for example, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose and calcium salt thereof, starch and derivatives thereof, and the like can be exemplified, and in the pharmaceutical field, low-substituted hydroxypropyl cellulose (hereinafter, also referred to as "L-HPC") is widely used as a non-ionic disintegrant and a binder.

[0003] In solid preparations, tablets are formed by compression of powders into a certain shape, and are manufactured by a tablet machine. From the viewpoint of preventing clogging of a hopper of a tablet machine used for the manufacturing, it is desirable to use L-HPC having high fluidity in the manufacturing of tablets.

[0004] As a method for producing L-HPC having high fluidity, a method is known in which wood pulp is dipped into caustic soda and is pressed to obtain alkali cellulose, the obtained alkali cellulose is subjected to etherification reaction, and then the reaction product of the etherification reaction is dissolved in water not containing acid, and thereafter the alkali is completely neutralized by acid (Patent Document 1).

[0005] PRIOR ART DOCUMENTS

[0006] PATENT DOCUMENTS

[0007] Patent Document 1: Japanese Patent Application Laid-Open No. 11-322802 SUMMARY

[0008] PROBLEMS ADDRESSED BY THE INVENTION

[0009] However, it is known that L-HPC obtained by the method described in Patent Document 1 has high fluidity, but has poor formability when formed into tablets, that is, the binding property of L-HPC particles to each other in tablets is poor. On the other hand, when L-HPC having high binding property is desired to be produced, there is a problem that the fluidity is decreased. Thus, since fluidity and binding property are properties opposite to each other, it is difficult to satisfy both high fluidity and good binding property.

[0010] The present application has been achieved in order to eliminate the drawbacks of the prior art, and aims to provide a method for producing L-HPC having high fluidity and good binding property.

[0011] SOLUTIONS FOR ADDRESSING THE PROBLEMS

[0012] The present inventors have conducted intensive studies in order to achieve the above object, and as a result, have found that, by subjecting alkali cellulose obtained by bringing powdered pulp into contact with an alkali metal hydroxide solution to etherification reaction, and mixing the reaction product with water without adding acid in the dissolving step, it is surprisingly possible to obtain L-HPC having high fluidity but also good bonding properties, thereby completing the present invention.

[0013] According to the present invention, there are provided a method for producing low-substituted hydroxypropyl cellulose and low-substituted hydroxypropyl cellulose.

[0014] [1] A method for producing low-substituted hydroxypropyl cellulose, comprising at least:

[0015] a step of bringing powdered pulp into contact with an alkali metal hydroxide solution to obtain alkali cellulose;

[0016] a step of reacting the alkali cellulose with propylene oxide to obtain a reaction product;

[0017] a dissolving step of mixing the reaction product with water without adding acid;

[0018] a step of neutralizing alkali metal hydroxide contained in the reaction product;

[0019] a step of washing, dehydrating, and drying the reaction product after the neutralizing step to obtain dried low-substituted hydroxypropyl cellulose; and

[0020] a step of pulverizing the dried low-substituted hydroxypropyl cellulose.

[0021] [2] The method for producing low-substituted hydroxypropyl cellulose according to [1], wherein

[0022] The amount of water used in the dissolving step is 2.0 to 3.5 as the mass ratio of water to cellulose in the powdered pulp.

[0023] [3] The method for producing low-substituted hydroxypropyl cellulose according to [1] or [2], wherein

[0024] In the dissolving step, the mixing temperature is 30 to 40°C.

[0025] [4] A low-substituted hydroxypropyl cellulose having a hydroxypropoxy group content of 5 to 16 mass%, in a case where all particles are classified into a fine particle, a spherical particle including a first spherical particle and a second spherical particle, and a fibrous particle including a long fibrous particle and a short fibrous particle by a dynamic image analysis method, a volume fraction of the spherical particle with respect to all particles is 60 to 90%, and a ratio of a volume fraction of the second spherical particle with respect to the first spherical particle (second spherical particle / first spherical particle) is 0.90 to 1.35, wherein

[0026] the fine particle is a particle having a fiber length of less than 40 μm,

[0027] the spherical particle includes the first spherical particle having an elongation, which is a ratio of a fiber diameter to a fiber length, of 0.5 or more among the particles having a fiber length of 40 μm or more, and the second spherical particle having an elongation of less than 0.5, an aspect ratio of 0.5 or more as a ratio of a minimum Feret diameter to a maximum Feret diameter, and a circularity of 0.7 or more as a ratio of a circumference (P EQPC ) of a circle having an area identical to a projection area of the particle to an actual circumference (P real ) of the particle,

[0028] the long fibrous particle includes the first long fibrous particle having an aspect ratio of less than 0.5 among the particles having a fiber length of 200 μm or more and an elongation of less than 0.5, and the second long fibrous particle having an aspect ratio of 0.5 or more and a circularity of less than 0.7,

[0029] the short fibrous particle includes the first short fibrous particle having an aspect ratio of less than 0.5 among the particles having a fiber length of 40 μm or more and less than 200 μm and an elongation of less than 0.5, and the second short fibrous particle having an aspect ratio of 0.5 or more and a circularity of less than 0.7.

[0030] EFFECTS OF THE INVENTION

[0031] According to the present application, it is possible to provide an L-HPC having both high flowability and good binding property. In a case where the L-HPC obtained by the production method of the present application is used for the production of a pharmaceutical tablet, since the L-HPC obtained by the production method of the present application has high flowability, it is possible to prevent clogging of the powder in a hopper. In addition, since the L-HPC obtained by the production method of the present application has high binding property, it is possible to reduce the amount of the L-HPC added in the tablet, and it is possible to make the tablet small-sized. BRIEF DESCRIPTION OF DRAWINGS

[0032] FIG. 1A flowchart showing a summary of the method for classifying "all particles" of L-HPC into "fine particles", "first long fibrous particles", "second long fibrous particles", "first short fibrous particles", "second short fibrous particles", "first spherical particles", and "second spherical particles" is shown. DETAILED DESCRIPTION

[0033] Hereinafter, the present application will be described in detail.

[0034] In the present specification, "bonding property" means an index of bonding of L-HPC to each other at the time of molding L-HPC into a tablet, and high bonding property means that a tablet of L-HPC has a property of easily maintaining a shape with respect to an external force, and low bonding property means that a tablet of L-HPC has a property of not easily maintaining a shape with respect to an external force.

[0035] The production method of L-HPC of the present application at least comprises: a step of obtaining alkali cellulose by bringing powdered pulp into contact with an alkali metal hydroxide solution; a step of obtaining a reaction product by reacting the alkali cellulose with propylene oxide; a dissolution step of mixing the reaction product with water without adding acid; a step of neutralizing the alkali metal hydroxide contained in the reaction product; a step of obtaining dried low-substituted hydroxypropyl cellulose by washing, dehydrating, and drying the reaction product after the neutralization; and a step of pulverizing the dried low-substituted hydroxypropyl cellulose.

[0036] <Step of obtaining alkali cellulose>

[0037] The alkali cellulose is obtained by bringing powdered pulp into contact with an alkali metal hydroxide solution.

[0038] The powdered pulp of the raw material can use any one of wood pulp and non-wood pulp such as linter pulp, but from the viewpoint of GMO (genetically modified organism) non-use, pulp derived from wood is preferred. As the tree species of wood, coniferous trees such as pine, spruce, hemlock, and broad-leaved trees such as eucalyptus and maple can be used. The powdered pulp generally includes cellulose and water. Therefore, in the present application, the solid content in the pulp is converted into the cellulose content. The solid content in the pulp, that is, the cellulose content can be calculated from the dry matter content calculated by the test method for pulp-dry matter content according to JIS P8203:2010. The dry matter content is the ratio of the mass of a sample dried at 105 ± 2°C until the constant mass is reached to the mass before drying, expressed in mass %.

[0039] The alkali metal hydroxide solution is not particularly limited as long as it can produce alkali cellulose from the pulp, but from the viewpoint of economy, an aqueous sodium hydroxide solution or an aqueous potassium hydroxide solution is preferred. From the viewpoint of uniformity of the alkali cellulose and reaction efficiency, the concentration of the alkali metal hydroxide in the alkali metal hydroxide solution is preferably 20 to 60% by mass, more preferably 20 to 50% by mass.

[0040] From the viewpoint of reaction efficiency of propylene oxide, the content of the alkali metal hydroxide in the alkali cellulose is preferably 5 to 35% by mass. The content of the alkali metal hydroxide in the alkali cellulose can be determined by neutralization titration of the alkali cellulose using an acid such as sulfuric acid having a known concentration.

[0041] The temperature at which the powdered pulp is brought into contact with the alkali metal hydroxide solution is preferably 20 to 80°C. The time at which the powdered pulp is brought into contact with the alkali metal hydroxide solution is preferably 5 to 120 minutes.

[0042] It is preferred that inert gas replacement in the reaction machine (preferably nitrogen or helium) be performed after the production of the alkali cellulose, but it can also be performed before the production of the alkali cellulose, and the inert gas replacement can be performed again after the production of the alkali cellulose.

[0043] <Process of obtaining reaction product>

[0044] Next, the process of reacting the alkali cellulose obtained in the previous process with propylene oxide to obtain a reaction product is described.

[0045] The amount of propylene oxide added is preferably 0.05 to 0.5 parts by mass with respect to 1 part by mass of anhydrous cellulose. As the method of adding propylene oxide, any of the methods of adding the entire amount of propylene oxide at once, the method of adding in several portions, the method of continuously adding, and the like can be used. The reaction temperature of this process is preferably 40 to 80°C. The reaction time of this process is preferably 1 to 5 hours. This process is preferably performed in an inert gas (nitrogen or helium) atmosphere.

[0046] <Process of dissolving>

[0047] Next, the process of dissolving the reaction product obtained in the previous process by mixing it with water without adding an acid is described.

[0048] In this process, the L-HPC is dissolved by putting the reaction product obtained in the previous process and water into a mixer and mixing them.

[0049] From the viewpoint of obtaining L-HPC having both high fluidity and good bonding properties, the amount of water mixed with the reaction product is preferably 2.0 to 3.5, and more preferably 2.5 to 3.5, in terms of mass ratio, relative to the cellulose in the powdered pulp used to produce the reaction product for the dissolving step. When the mass ratio of the water mixed is less than 2.0, the fluidity of the L-HPC can possibly decrease. In addition, when the mass ratio of the water mixed exceeds 3.5, the bonding properties of the L-HPC can possibly decrease.

[0050] The mixing temperature is preferably 30 to 40°C. In addition, the mixing temperature referred to herein is the jacket temperature of the mixer. The mixing time is preferably 10 minutes to 5 hours.

[0051] The mixer is not particularly limited as long as it can control the jacket temperature, and for example, a double shaft kneader with a jacket, a reaction machine with a jacket and an internal stirrer, or the like can be used.

[0052] <Neutralization Step>

[0053] Next, the step of neutralizing the alkali metal hydroxide contained in the reaction product is described.

[0054] In this step, the alkali metal hydroxide contained in the reaction product obtained in the dissolving step is neutralized by adding an acid to the reaction product, and L-HPC is precipitated.

[0055] As the acid used, inorganic acids such as hydrochloric acid, sulfuric acid, and nitric acid, and organic acids such as formic acid and acetic acid can be exemplified, but from the viewpoint of corrosion or toxicity, hydrochloric acid or acetic acid is preferred.

[0056] The amount of acid used is the equivalent amount required to neutralize the alkali metal hydroxide contained in the alkali cellulose used to produce the reaction product. The acid can also be used in the form of a mixed solution (aqueous solution) mixed with water.

[0057] The neutralization temperature is preferably 30 to 40°C. Since this step can also be performed using the same mixer as the dissolving step described above, the neutralization temperature means the jacket temperature of the reaction machine or the mixer described above.

[0058] <Step of Washing, Dewatering, and Drying>

[0059] Next, the step of washing, dewatering, and drying the reaction product after the neutralization step to obtain dried low-substituted hydroxypropyl cellulose is described.

[0060] The washing and dewatering can be performed, for example, by dewatering using a dewatering machine after bringing the precipitate into contact with water.

[0061] From the viewpoint of washing, the temperature of the water used for washing is preferably 50°C or higher. From the viewpoint of economy, the amount of water used is preferably 30 to 300 times by mass relative to the cellulose in the powdered pulp used for generating the reaction product for the dissolving step.

[0062] As the dewatering machine, a batch-type centrifugal dewatering machine, a press dewatering machine, or the like can be used. The centrifugal effect of the batch-type centrifugal dewatering machine is only required to be sufficient for dewatering, but from the viewpoint of productivity, the centrifugal acceleration is preferably 500 G or higher.

[0063] Next, the L-HPC obtained by washing and dewatering is dried to obtain dried low-substituted hydroxypropyl cellulose.

[0064] Drying can be performed using a drier. As the drier, a fluidized bed drier, an air flow drier, a box-type drier, a vibration drier, a natural convection low-temperature drier, a forced air low-temperature drier, a cabinet drier, or the like can be exemplified. From the viewpoint of drying efficiency, the drying temperature is preferably 60°C to 120°C. From the viewpoint of productivity, the drying time is preferably 0.5 to 36 hours.

[0065] <Crushing Step>

[0066] Next, the step of crushing the dried low-substituted hydroxypropyl cellulose is described.

[0067] Crushing can be performed using a crusher. As the crusher, for example, an impact crusher such as a hammer mill, an impact mill, a screen-type refiner (Victory Mill), or the like, or a compression crusher such as a roll mill, a ball mill, or the like can be exemplified. From the viewpoint of energy efficiency, an impact crusher is preferred.

[0068] It is further preferred to sieve the crushed L-HPC to remove coarse powder that is not sufficiently crushed. The mesh of the sieve is preferably 45 to 250 μm, and more preferably 75 to 150 μm.

[0069] The L-HPC obtained by the production method of the present application is described.

[0070] The hydroxypropoxy content of the L-HPC is 5 to 16 mass%, preferably 6 to 15 mass%, and more preferably 7 to 14 mass%. In the case where the hydroxypropoxy content is less than 5 mass%, the swelling rate of the L-HPC becomes low, and in the case of use in tablets and the like, the disintegrability can be insufficient. On the other hand, in the case where the hydroxypropoxy content exceeds 16 mass%, the L-HPC sometimes becomes water-soluble. Furthermore, the hydroxypropoxy content of the L-HPC can be measured by the method described in the "Low Substituted Hydroxypropyl Cellulose" of the 18th revised edition of the Japanese Pharmacopoeia.

[0071] In the present specification, the low-substituted hydroxypropyl cellulose is classified into four types of particles, "long fibrous particles", "short fibrous particles", "spherical particles", and "fine particles". Furthermore, the long fibrous particles are classified into "first long fibrous particles" and "second long fibrous particles", the short fibrous particles are classified into "first short fibrous particles" and "second short fibrous particles", and the spherical particles are classified into "first spherical particles" and "second spherical particles". A flowchart summarizing the method for classifying these particles is shown as FIG. 1

[0072] The volume fraction of each of the particles in the L-HPC can be calculated by measuring the shape parameters such as the fiber length (LEFI), the fiber diameter (DIFI), the elongation, the aspect ratio, and the circularity, using a dynamic image analysis method. The dynamic image analysis method refers to a method of calculating the particle size or the particle shape by continuously capturing the image of a particle dispersed in a fluid such as a gas or a solvent and performing binarization and analysis. For example, a dynamic image analysis particle size distribution measuring device QICPIC / R16 (manufactured by SYMPATEC) can be used for the measurement.

[0073] All of the particles A are classified into particles C having a fiber length (Length of Fiber: LEFI) of 40 μm or more and fine particles B having a fiber length of less than 40 μm. The LEFI is defined as the length between both ends of a particle, and is the longest path from one side to the other side in the outline of the particle. Furthermore, the detection limit of the QICPIC / R16 with the M7 lens mounted is 4.7 μm, and therefore particles of less than 4.7 μm are not detected, but since the volume fraction of particles having an LEFI of less than 4.7 μm is extremely small in the entire L-HPC, it can be ignored for the purpose of the present application.

[0074] ​Particles C with a LEFI of 40 μm or more are divided into first spherical particles S1 with an elongation of 0.5 or more, which is the ratio of fiber diameter (DIFI) to LEFI (DIFI / LEFI), and particles D with an elongation of less than 0.5. DIFI is defined as the minor diameter of the particle, calculated by dividing the projected area of ​​the particle by the sum of the lengths of all branches of the fiber.

[0075] Particles D with a LEFI greater than 40 μm and an elongation less than 0.5 are divided into particles E (with an aspect ratio less than 0.5, calculated as the ratio of the maximum Feret diameter (Fmax) to the minimum Feret diameter (Fmin)) and particles F (with an aspect ratio greater than 0.5). The aspect ratio of any particle is a value greater than 0 and less than 1. The Feret diameter is the distance between two parallel tangents enclosing the particle. The maximum Feret diameter (Fmax) is the maximum diameter achieved when the direction changes from 0° to 180°, and the minimum Feret diameter (Fmin) is the minimum diameter achieved when the direction changes from 0° to 180°.

[0076] Particles E with a LEFI of 40 μm or more, an elongation of less than 0.5, and an aspect ratio of less than 0.5 are divided into first long fibrous particles LF1 with a LEFI of 200 μm or more and first short fibrous particles SF1 with a LEFI of less than 200 μm.

[0077] Particles F with a length-to-diameter ratio (LEFI) of 40 μm or more, an elongation of less than 0.5, and an aspect ratio of 0.5 or more are divided into second spherical particles S2 with a circularity of 0.7 or more, and particles G with a circularity of less than 0.7. Circularity is measured using the area of ​​the particle's projected surface (A). p The circumference of circles with the same area (P) EQPC ) and the actual particle's perimeter (P real The ratio of ) is defined by the following formula.

[0078] [Mathematical Expression 1]

[0079]

[0080] The circularity of any one particle is a value over 0 and under 1. The smaller the circularity, the more irregular the shape of the particle. The EQPC is defined as the Diameter of a Circle of Equal Projection Area, that is, the diameter of a circle having an area equal to the projection area of the particle, also called the Heywood diameter.

[0081] The LEFI of the particle G having a circularity of less than 0.7 and an aspect ratio of 0.5 or more, and an elongation of less than 0.5 of 40 μm or more is classified into the second long-fiber-like particle LF2 having an LEFI of 200 μm or more and the second short-fiber-like particle SF2 having an LEFI of less than 200 μm.

[0082] <Volume of the microparticles>

[0083] The volume (V m ) of the microparticles in the L-HPC can be calculated by assuming the microparticles as spheres having a diameter of EQPC and by the following equation.

[0084] V m = (π / 6) x (EQPC) 3 x N m

[0085] where N m is the number of the microparticles in the sample, and EQPC is the median EQPC corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the microparticles.

[0086] <Volume of the first long-fiber-like particles>

[0087] The volume (V LF1 ) of the first long-fiber-like particles in the L-HPC can be calculated by assuming the first long-fiber-like particles as cylinders having a base with a diameter of DIFI and a height of LEFI and by the following equation.

[0088] V LF1 = (π / 4) x (DIFI) 2 x (LEFI) x N LF1

[0089] where N LF1 is the number of the first long-fiber-like particles in the sample, DIFI is the median DIFI corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the first long-fiber-like particles, and LEFI is the median LEFI corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the first long-fiber-like particles.

[0090] Volume of the second long fibrous particles

[0091] Volume of the second long fibrous particles (V LF2 ) in the L-HPC can be calculated by assuming the second long fibrous particles as a cylinder having a base diameter of DIFI and a height of LEFI and by the following equation.

[0092] V LF2 = (π / 4) x (DIFI) 2 x (LEFI) x N LF2

[0093] where N LF2 is the number of the second long fibrous particles in the sample, DIFI is the median DIFI corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the second long fibrous particles, and LEFI is the median LEFI corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the second long fibrous particles.

[0094] Volume of the first short fibrous particles

[0095] Volume of the first short fibrous particles (V SF1 ) in the L-HPC can be calculated by assuming the first short fibrous particles as a cylinder having a base diameter of DIFI and a height of LEFI and by the following equation.

[0096] V SF1 = (π / 4) x (DIFI) 2 x (LEFI) x N SF1

[0097] where N SF1 is the number of the first short fibrous particles in the sample, DIFI is the median DIFI corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the first short fibrous particles, and LEFI is the median LEFI corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the first short fibrous particles.

[0098] Volume of the second short fibrous particles

[0099] Volume of the second short fibrous particles (V SF2 ) in the L-HPC can be calculated by assuming the second short fibrous particles as a cylinder having a base diameter of DIFI and a height of LEFI and by the following equation.

[0100] V SF2 = (π / 4) x (DIFI) 2 x (LEFI) x N SF2

[0101] wherein N SF2 is the number of the second short-fiber-like particles in the sample, DIF is the median DIF corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the second short-fiber-like particles, and LEF is the median LEF corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the second short-fiber-like particles.

[0102] <Volume of the first spherical particles>

[0103] The volume V S1 of the first spherical particles in the L-HPC can be calculated by assuming the first spherical particles as a sphere having a diameter of EQPC and by the following equation.

[0104] V S1 = (π / 6) x (EQPC) 3 x N S1

[0105] wherein N S1 is the number of the first spherical particles in the sample, and EQPC is the median EQPC corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the first spherical particles.

[0106] <Volume of the second spherical particles>

[0107] The volume V S2 of the second spherical particles in the L-HPC can be calculated by assuming the second spherical particles as a sphere having a diameter of EQPC and by the following equation.

[0108] V S2 = (π / 6) x (EQPC) 3 x N S2

[0109] wherein N S2 is the number of the second spherical particles in the sample, and EQPC is the median EQPC corresponding to the 50% cumulative value of the cumulative particle size distribution curve on a number basis of the second spherical particles.

[0110] <Volume of all particles>

[0111] The volume V total of all particles in the L-HPC can be calculated according to the volumes V m , V LF1 , V LF2 , V SF1 , V SF2 , V S1 , and V S2 defined in the above and by the following equation.

[0112] V total = V m + V LF1 + V LF2 + V SF1 + V SF2 + V S1 + V S2

[0113] Volume fraction of each particle

[0114] The volume fraction of each particle in the L-HPC with respect to the total particles can be calculated according to the volume of each particle V m , V LF1 , V LF2 , V SF1 , V SF2 , V S1 , V S2 and the volume of the total particles V total respectively, by the following equations.

[0115] Volume fraction R m (%) = V m / V total x 100

[0116] Volume fraction R LF1 (%) = V LF1 / V total x 100

[0117] Volume fraction R LF2 (%) = V LF2 / V total x 100

[0118] Volume fraction R SF1 (%) = V SF1 / V total x 100

[0119] Volume fraction R SF2 (%) = V SF2 / V total x 100

[0120] Volume fraction R S1 (%) = V S1 / V total x 100

[0121] Volume fraction R S2 (%) = V S2 / V totalx 100

[0122] In the case where all the particles of the L-HPC are classified into the fine particles, the spherical particles including the first spherical particles and the second spherical particles, and the fibrous particles including the long fibrous particles and the short fibrous particles, the volume fraction of the spherical particles with respect to all the particles is preferably 60 to 90%, more preferably 66 to 88%. In the case where the volume fraction of the spherical particles with respect to all the particles is less than 60%, the flowability of the L-HPC is poor, and in the case where the volume fraction exceeds 90%, the bonding property of the L-HPC is insufficient.

[0123] In addition, the ratio of the volume fraction of the second spherical particles with respect to the first spherical particles (second spherical particles / first spherical particles, i.e., R S2 / R S1 ) is 0.90 to 1.35. In the case where the ratio of the volume fraction of the second spherical particles with respect to the first spherical particles (second spherical particles / first spherical particles) is less than 0.90, the bonding property of the L-HPC is insufficient, and in the case where the ratio of the volume fraction exceeds 1.35, the flowability is poor.

[0124] From the viewpoints of the bonding property and the flowability, the average particle diameter of the L-HPC based on the dry laser method is preferably 10 to 100 μm, more preferably 30 to 90 μm, and further preferably 40 to 70 μm. In addition, the average particle diameter means the diameter corresponding to the 50% cumulative value of the cumulative particle size distribution curve based on the volume, and can be measured, for example, using a laser diffraction type particle size distribution measuring device Mastersizer 3000 (manufactured by Malvern).

[0125] From the viewpoint of the flowability, the uniformity of the L-HPC is preferably 2.0 to 2.9, more preferably 2.1 to 2.8, and further preferably 2.2 to 2.7. The uniformity can be calculated from the values of the diameter (D 60 ) corresponding to the 60% cumulative value of the cumulative particle size distribution curve based on the volume and the diameter (D 10 ) corresponding to the 10% cumulative value of the cumulative particle size distribution curve based on the volume, using the following equation.

[0126] Uniformity = D 60 / D 10

[0127] In addition, D 60 or D 10 may be measured, for example, using a laser diffraction type particle size distribution measuring device Mastersizer 3000 (manufactured by Malvern). It can be said that the smaller the uniformity, the more excellent the flowability of the powder.

[0128] From the viewpoint of fluidity, the compressibility of the L-HPC is preferably 20 to 29%, more preferably 21 to 28%, and further preferably 22 to 27%. The compressibility can be calculated from the values of the bulk density (BD L ) and the tap density (BD T ) by the following equation.

[0129] Compressibility (%) = {(BD T - BD L ) / BD T} x 100

[0130] It can be said that the smaller the compressibility, the more excellent the fluidity of the powder.

[0131] The bulk density refers to the density of the state of sparse packing, and can be measured by, for example, using a powder property evaluation device, Powder Tester PT-S (manufactured by Hosokawa Micron), supplying the material uniformly from above (at 23 cm) to a cylindrical container (material: stainless steel) having a diameter of 5.05 cm and a height of 5.05 cm (volume: 100 mL), and weighing after scraping the upper surface flat.

[0132] The tap density refers to the density when the cylindrical container is tightly packed by applying tapping. By tapping, it means an operation of tightly packing the sample by repeatedly dropping the cylindrical container filled with the sample from a certain height to apply a slight impact to the bottom. In practice, as in the measurement of the bulk density, the sample is filled into the cylindrical container, and after weighing after scraping the upper surface flat, the lid is fitted on the cylindrical container, and after the sample is added to the upper edge of the lid, 180 times of tapping is performed at a tapping height of 1.8 cm. After the tapping is completed, the lid is removed, the sample is scraped flat at the upper surface of the cylindrical container, and weighed, and the density in this state is taken as the tap density.

[0133] From the viewpoint of fluidity, the repose angle of the L-HPC is preferably 20 to 55°, more preferably 25 to 50°, and further preferably 30 to 45°. In addition, the repose angle can be calculated by, for example, using a powder property evaluation device, Powder Tester PT-S (manufactured by Hosokawa Micron), flowing the powder from a height of 75 mm on a disc-shaped table of 80 mm, and measuring the angle of the piled powder with the table. It can be said that the smaller the repose angle, the more excellent the fluidity of the powder.

[0134] From the viewpoint of fluidity, the L-HPC preferably has a scoop angle of 40 to 60°, more preferably 45 to 55°. In addition, the scoop angle is measured, for example, using a powder property evaluation device, Powder Tester PT-S (Mikrolab Co., Ltd.). A metal spatula (scoop) having a width of 22 mm is gently lifted from a layer filled with the powder, and after the angle of the powder remaining on the scoop with the scoop is measured, the scoop is subjected to an impact, and the angle of the powder remaining on the scoop with the scoop is again measured. The scoop angle can be calculated using these values and by the following equation.

[0135] Scoop angle = (angle before impact + angle after impact) / 2

[0136] It can be said that the smaller the scoop angle, the more excellent the fluidity of the powder.

[0137] The L-HPC preferably has a fluidity index of 70 or more. The fluidity index is an index for fluidity evaluation proposed by Carr and described in (R.L. Carr, Chem. Eng, 72, Jan. 18, 163, Feb. 1, 69 (1965), 76 Oct. 13, 7 (1969)), and in detail, in "Shinshin Zokuho Fuboku Shishitsu Zokushu [Powder Society of Japan / Japan Powder Industry Technology Association, Nikkei Technology Books, 1985]", p. 151. The fluidity index can be calculated by measuring the uniformity, compressibility, repose angle, and scoop angle described above, calculating the index for each, and summing them. The larger the fluidity index, the higher the fluidity.

[0138] From the viewpoint of reducing the amount of L-HPC added to a pharmaceutical tablet, the L-HPC preferably has a bonding property of 85 N or more.

[0139] In addition, for the bonding property of the L-HPC in the present application, after the L-HPC is conditioned by being stored in a 25°C desiccator (relative humidity of about 11%) with a saturated lithium chloride aqueous solution for 1 week to make the dry loss (amount of moisture) 2.8 to 4.0 mass%, a tablet is manufactured by using a tableting machine (for example, HANDTAB 200 (manufactured by Shibuya Seimitsu Co., Ltd.)) provided with a circular flat-type pest having a diameter of 12 mm, and compressing and molding at a tabletting pressure of 10 kN (about 88.5 MPa). The hardness of the tablet is measured as the maximum breaking strength at the time of tablet breakage by using a tablet hardness tester (for example, TBH-125 (manufactured by ERWEKA Co., Ltd.)) to apply a load at a speed of 1 mm / sec in the diameter direction of the tablet.

[0140] The dry loss (moisture content) of the L-HPC can be measured by the method described in "General Test Methods 2.41 Dry Loss Test Method" of the 18th revised edition of the Japanese Pharmacopoeia.

[0141] [Examples]

[0142] Hereinafter, examples and comparative examples are shown to specifically describe the present application, but the present application is not limited to the following examples.

[0143] Example 1

[0144] 8402 g of the powdered pulp (cellulose component: 8000 g) was charged into a 150 L reaction machine equipped with an internal stirrer, and after sufficiently replacing the inside of the reaction machine with nitrogen by reducing pressure and nitrogen sealing, 6300 g of a 35 mass% sodium hydroxide aqueous solution was charged into the reaction machine and stirred at an internal temperature of 60°C for 5 minutes to obtain alkali cellulose containing 15 mass% of sodium hydroxide (mass ratio of sodium hydroxide in the alkali cellulose to anhydrous cellulose: 0.276).

[0145] Next, after sufficiently replacing the inside of the same reaction machine with nitrogen by reducing pressure and nitrogen sealing, 1504 g of propylene oxide was charged, and it was allowed to react at an internal temperature of 60°C for 75 minutes while stirring to obtain a reaction product of 16206 g.

[0146] Next, 671 g of water at 35°C was put into a 5 L kneader having a double shaft stirrer, and the reaction product of 680 g (anhydrous cellulose component: 333.5 g) was dispersed, and L-HPC was dissolved by mixing at a jacket temperature of 35°C for 30 minutes. The amount of water used in the dissolving step was 2.0 as the mass ratio of water to cellulose in the powdered pulp.

[0147] After that, while maintaining the jacket temperature at 35°C, 420.4 g of a 33 mass% acetic acid aqueous solution was put into the kneader to completely neutralize the sodium hydroxide contained in the reaction product, and crude L-HPC was precipitated.

[0148] The entire amount of the obtained crude L-HPC was dispersed in hot water of about 90°C of 15000 g, and after washing and dewatering using a batch centrifugal separator at a rotation speed of 2000 rpm, the entire amount of the obtained dewatered product was again dispersed in hot water of about 90°C of 15000 g, and washing and dewatering were performed using a batch centrifugal separator at a rotation speed of 2500 rpm. The obtained dewatered product was dried at 80°C for 18 hours using a cabinet dryer, and after the dried product was pulverized using a jet mill (Victory Mill VP-1, Hosokawa Micron Corporation), sieving was performed using a sieve having a mesh size of 91 μm to obtain L-HPC.

[0149] For the obtained L-HPC, the hydroxypropoxy group content was measured, the average particle diameter, the uniformity, the compressibility, the repose angle, the angle of repose, the volume fraction of each particle (first long fibrous particle, second long fibrous particle, first short fibrous particle, second short fibrous particle, first spherical particle, second spherical particle, and fine particle), the flowability index, and the bonding property were measured as described below. In addition, the flowability index was calculated from the uniformity, the compressibility, the repose angle, and the angle of repose. The results thereof are shown in Table 1.

[0150] <Measurement of average particle diameter>

[0151] The average particle diameter was measured using a laser diffraction particle size distribution measuring device Mastersizer 3000 (manufactured by Malvern) in a dry method and according to a Fraunhofer diffraction theory under conditions of a dispersion pressure of 2 bar and a scattering intensity of 2 to 10% to measure a diameter corresponding to a 50% cumulative value of a cumulative particle size distribution curve based on volume.

[0152] <Measurement of uniformity>

[0153] The uniformity was measured using a laser diffraction particle size distribution measuring device Mastersizer 3000 (manufactured by Malvern) in a dry method and according to a Fraunhofer diffraction theory under conditions of a dispersion pressure of 2 bar and a scattering intensity of 2 to 10% to measure values of a diameter (D 60 ) corresponding to a 60% cumulative value of a cumulative particle size distribution curve based on volume and a diameter (D 10 ) corresponding to a 10% cumulative value of a cumulative particle size distribution curve based on volume, and was calculated by the following equation.

[0154] Uniformity = D 60 / D 10

[0155] <Measurement of compressibility>

[0156] The compressibility was calculated from values of a loose bulk density and a close bulk density by the following equation.

[0157] Compressibility (%) = {(close bulk density - loose bulk density) / close bulk density} x 100

[0158] The bulk density is the density of a bulk material, and is measured by using a powder property evaluation device, Powder Tester PT-S (manufactured by Mikasa Co., Ltd.), to supply the material uniformly from above (at 23 cm) to a cylindrical container (material: stainless steel) having a diameter of 5.05 cm and a height of 5.05 cm (volume: 100 mL), and weighing the container after scraping the upper surface.

[0159] The tap density is the density of a bulk material that is tightly packed by applying vibration to the cylindrical container. The vibration is an operation of tightly packing the sample by repeatedly dropping the cylindrical container filled with the sample from a certain height to slightly impact the bottom. In practice, as in the measurement of the bulk density, the sample is filled into the cylindrical container, and after weighing the container after scraping the upper surface, the sample is added to the upper edge of a lid fitted on the cylindrical container, and the sample is vibrated for 180 times at a vibration height of 1.8 cm. After the vibration, the lid is removed, the sample is scraped at the upper surface of the cylindrical container and weighed, and the density of the sample in this state is taken as the tap density.

[0160] <Measurement of the angle of repose>

[0161] The angle of repose is calculated by measuring the angle of the powder accumulated on a 80-mm-diameter disc-shaped stage with respect to the stage, using a powder property evaluation device, Powder Tester PT-S (manufactured by Mikasa Co., Ltd.), to flow the powder from a height of 75 mm.

[0162] <Measurement of the angle of the spatula>

[0163] The angle of the spatula is calculated by using a powder property evaluation device, Powder Tester PT-S (manufactured by Mikasa Co., Ltd.), to gently lift a metal spatula (spatula) having a width of 22 mm from a layer filled with the powder, measuring the angle of the powder remaining on the spatula with respect to the spatula, impacting the spatula, and again measuring the angle of the powder remaining on the spatula with respect to the spatula. The angle of the spatula can be calculated using these values by the following equation.

[0164] Angle of spatula = (angle before impact + angle after impact) / 2

[0165] <Measurement of the volume fraction of each particle>

[0166] The volume fraction of each particle (first long fibrous particle, second long fibrous particle, first short fibrous particle, second short fibrous particle, first spherical particle, second spherical particle, fine particle) was measured using a dynamic image type particle size distribution measuring device QICPIC / R16 (manufactured by Sympatec GmbH) equipped with a quantitative feeder VIBRI / L, an air flow type disperser RODOS / L, and a M7 lens, under conditions of a frame rate of 500 Hz, an injector of 4 mm, and a dispersion pressure of 1 bar, and the image of the photographed particle was analyzed by analysis software WINDOX5 Version: 5.9.1.1 to obtain the number-based median EQPC, the number-based median LEFI, the number-based median DIFI, the elongation, the aspect ratio, and the circularity of each particle, which were calculated based on the values and by the aforementioned calculation formula. In addition, the classification at the time of analysis used M7.

[0167] <Calculation of Flowability Index>

[0168] The flowability index was calculated by measuring the uniformity, the compressibility, the repose angle, and the scoop angle described above, obtaining an index for each, and summing them. The greater the flowability index, the higher the flowability. In the present application, in the case where the flowability index is 70 or greater, the flowability is considered to be good.

[0169] <Measurement of Bonding Property>

[0170] The bonding property was measured by storing L-HPC in a 25°C desiccator (relative humidity of about 11%) with saturated lithium chloride aqueous solution for 1 week to adjust the humidity so that the dry loss (moisture content) became 2.8 to 4.0 mass%, using a table type tablet maker HANDTAB200 (manufactured by Seiko Instruments Inc.) provided with a circular flat type pest having a diameter of 12 mm, and compression molding to produce a 450 mg tablet at a tabletting pressure of 10 kN (about 88.5 MPa). The hardness of the tablet was measured using a tablet hardness tester TBH-125 (manufactured by ERWEKA) by applying a load at a speed of 1 mm / sec in the diameter direction of the tablet, and the maximum breaking strength at the time of tablet fracture was measured. The greater the value of the maximum breaking strength, the better the bonding property. In the present application, in the case where the maximum breaking strength is 85 N or greater, the bonding property is considered to be good.

[0171] Example 2

[0172] Example 1 was repeated except that the amount of water used in the dissolving step was changed to 2.5 as the mass ratio of water to cellulose in the powdered pulp. The obtained L-HPC was measured for the hydroxypropoxy group content, the average particle size, the uniformity, the compressibility, the angle of repose, the angle of spatula, the volume fraction of each particle (the first long fibrous particle, the second long fibrous particle, the first short fibrous particle, the second short fibrous particle, the first spherical particle, the second spherical particle, and the fine particle), the flowability index, and the bondability. In addition, the flowability index was calculated from the uniformity, the compressibility, the angle of repose, and the angle of spatula. The results are shown in Table 1.

[0173] Example 3

[0174] Example 1 was repeated except that the amount of water used in the dissolving step was changed to 3.0 as the mass ratio of water to cellulose in the powdered pulp. The obtained L-HPC was measured for the hydroxypropoxy group content, the average particle size, the uniformity, the compressibility, the angle of repose, the angle of spatula, the volume fraction of each particle (the first long fibrous particle, the second long fibrous particle, the first short fibrous particle, the second short fibrous particle, the first spherical particle, the second spherical particle, and the fine particle), the flowability index, and the bondability. In addition, the flowability index was calculated from the uniformity, the compressibility, the angle of repose, and the angle of spatula. The results are shown in Table 1.

[0175] Example 4

[0176] Example 1 was repeated except that the amount of water used in the dissolving step was changed to 3.5 as the mass ratio of water to cellulose in the powdered pulp. The obtained L-HPC was measured for the hydroxypropoxy group content, the average particle size, the uniformity, the compressibility, the angle of repose, the angle of spatula, the volume fraction of each particle (the first long fibrous particle, the second long fibrous particle, the first short fibrous particle, the second short fibrous particle, the first spherical particle, the second spherical particle, and the fine particle), the flowability index, and the bondability. In addition, the flowability index was calculated from the uniformity, the compressibility, the angle of repose, and the angle of spatula. The results are shown in Table 1.

[0177] Comparative Example 1

[0178] The same procedure as in Example 2 was conducted except that, in addition to adding 33 mass% acetic acid aqueous solution 84.1 g to water before dispersing the reaction product into water in the dissolving step, L-HPC was obtained. For the obtained L-HPC, the hydroxypropoxy group content, average particle diameter, uniformity, compressibility, repose angle, angle of repose, volume fraction of each particle (first long fibrous particle, second long fibrous particle, first short fibrous particle, second short fibrous particle, first spherical particle, second spherical particle, and fine particle), flowability index, and bonding property were measured. In addition, the flowability index was calculated from the uniformity, compressibility, repose angle, and angle of repose. The results thereof are shown in Table 1.

[0179] Comparative Example 2

[0180] After a sheet-shaped pulp (moisture content: 7.27 mass%) was dipped into a 35 mass% sodium hydroxide aqueous solution at 20°C, the remaining sodium hydroxide aqueous solution was removed by pressure filtration to obtain a sheet-shaped alkali cellulose containing 16.9 mass% of sodium hydroxide (mass ratio of sodium hydroxide in the alkali cellulose to anhydrous cellulose: 0.353). The sheet-shaped alkali cellulose was cut by a slitter to obtain a chip-shaped alkali cellulose.

[0181] Next, the chip-shaped alkali cellulose 625.9 g (cellulose component: 300 g) was charged into a rotation-type reaction machine, after the inside of the reaction machine was sufficiently replaced with nitrogen by reducing the pressure and sealing with nitrogen, propylene oxide 68.7 g was charged, and the reaction was performed at an internal temperature of 50°C for 180 minutes while stirring to obtain a reaction product 694.6 g.

[0182] Next, water 734.3 g at 35°C was put into a 5L kneader having a double shaft stirrer, after the reaction product 680 g (cellulose component as anhydrous cellulose: 293.7 g) was dispersed, the L-HPC was dissolved by mixing at a jacket temperature of 35°C for 30 minutes. The amount of water used in the dissolving step was 2.5 as a mass ratio of water to cellulose in the sheet-shaped pulp.

[0183] After that, while maintaining the jacket temperature at 35°C, 33 mass% acetic acid aqueous solution 471.0 g was put into the kneader to completely neutralize the sodium hydroxide contained in the reaction product, and crude L-HPC was precipitated.

[0184] The washing, dewatering, and drying processes were carried out in the same manner as in Example 1 to obtain L-HPC. For the obtained L-HPC, the hydroxypropoxy content, average particle size, uniformity, compressibility, angle of repose, angle of spatula, volume fraction of each particle (first long fibrous particle, second long fibrous particle, first short fibrous particle, second short fibrous particle, first spherical particle, second spherical particle, and fine particle), flowability index, and bonding property were measured. In addition, the flowability index was calculated from the uniformity, compressibility, angle of repose, and angle of spatula. The results thereof are shown in Table 1.

[0185] Comparative Example 3

[0186] After the sheet-form pulp (moisture content: 8.86 mass%) was dipped in a 43 mass% sodium hydroxide aqueous solution at 33.5°C, the remaining sodium hydroxide aqueous solution was removed by pressure filtration to obtain sheet-form alkali cellulose containing 24.0 mass% of sodium hydroxide (mass ratio of sodium hydroxide in the alkali cellulose to anhydrous cellulose: 0.594). The sheet-form alkali cellulose was cut by a slitter to obtain a flake-form alkali cellulose.

[0187] Next, the flake-form alkali cellulose 495.8 g (cellulose content: 200 g) was charged into a self-rotating reaction machine, and a reaction was carried out in the same manner as in Comparative Example 2 to obtain a reaction product 551.8 g.

[0188] Next, 1432.8 g of water at 33.5°C was put into a 5L kneader having a double shaft mixer, and after the reaction product 549.3 g (cellulose content as anhydrous cellulose: 199.0 g) was dispersed, L-HPC was dissolved by mixing at a jacket temperature of 33.5°C for 70 minutes. The amount of water used in the dissolving process was 7.2 in terms of the mass ratio of water to cellulose in the sheet-form pulp.

[0189] After that, while maintaining the jacket temperature at 33.5°C, 537.4 g of a 33 mass% acetic acid aqueous solution was put into the kneader to completely neutralize the sodium hydroxide contained in the reaction product, and crude L-HPC was precipitated.

[0190] The washing, dewatering, and drying processes were carried out in the same manner as in Example 1 to obtain L-HPC. For the obtained L-HPC, the hydroxypropoxy content, average particle size, uniformity, compressibility, angle of repose, angle of spatula, volume fraction of each particle (first long fibrous particle, second long fibrous particle, first short fibrous particle, second short fibrous particle, first spherical particle, second spherical particle, and fine particle), flowability index, and bonding property were measured. In addition, the flowability index was calculated from the uniformity, compressibility, angle of repose, and angle of spatula. The results thereof are shown in Table 1.

[0191] [Table 1]

[0192]

[0193] The L-HPCs of Examples 1 to 4 were good in both flowability and bonding property, and in comparison, the flowability of Comparative Examples 1 to 2 was poor, and the flowability and bonding property of Comparative Example 3 were both poor.

[0194] It can be considered that the L-HPCs of Examples 1 to 4 were mixed with water without adding acid in the dissolving step by using powdered pulp as the raw material pulp, and as a result, the fiber morphology of the L-HPCs disappeared more and the proportion of spherical particles increased, and the flowability became good. In addition, the L-HPCs of Examples 1 to 4 maintained the proportion of the entire spherical particles and the ratio of the volume fraction of the second spherical particles to the first spherical particles increased, compared to Comparative Examples 1 to 3. The second spherical particles are a morphology slightly closer to fibers compared to the first spherical particles, and thus it can be considered that since the ratio of the volume fraction of the second spherical particles to the first spherical particles increased, good bonding property was also exhibited. It can be considered that since fragmented pulp was used as the raw material pulp in Comparative Example 2, although the amount of water to be mixed in the dissolving step was set to the same amount as in Example 2, the reaction product on the fragments dissolved and remained in the dissolving step, and as a result, the proportion of spherical particles decreased and the flowability decreased.

[0195] In addition, it was shown according to Examples 1 to 4 that there was a tendency that if the amount of water to be mixed in the dissolving step was increased, the flowability improved, and if the amount of water was decreased, the bonding property improved.

Claims

1. A method for manufacturing low-substituted hydroxypropyl cellulose, characterized in that, At least include: The process of obtaining alkali cellulose by contacting powdered pulp with an alkali metal hydroxide solution; The process of reacting the alkali cellulose with propylene oxide to obtain the reaction product; A dissolution process in which the reaction product is mixed with water without the addition of acid; The process of neutralizing the alkali metal hydroxide contained in the reaction products; The process of washing, dehydrating, and drying the reaction product after the neutralization step to obtain dry, low-substituted hydroxypropyl cellulose; and The process of pulverizing the dried, low-substituted hydroxypropyl cellulose.

2. The method for manufacturing low-substituted hydroxypropyl cellulose according to claim 1, wherein, The amount of water used in the dissolving process is 2.0 to 3.5 by mass ratio of water to cellulose in the powdered pulp.

3. The method for manufacturing low-substituted hydroxypropyl cellulose according to claim 1 or 2, wherein, In the dissolution process, the mixing temperature is 30–40°C.

4. A low-substituted hydroxypropyl cellulose, wherein the hydroxypropoxy group content is 5-16% by mass, and when all particles are classified by dynamic image analysis into microparticles, spherical particles including first spherical particles and second spherical particles, and fibrous particles including long fibrous particles and short fibrous particles, the volume fraction of the spherical particles relative to all particles is 60-90%, and the volume fraction ratio of the second spherical particles to the first spherical particles (second spherical particles / first spherical particles) is 0.90-1.35, characterized in that... The microparticles are particles with a fiber length of less than 40 μm. The spherical particles include a first spherical particle whose elongation is 0.5 or more (the ratio of fiber diameter to fiber length) among the particles with a fiber length of 40 μm or more, and a first spherical particle whose elongation is less than 0.5, whose aspect ratio is 0.5 or more (the ratio of minimum Ferrette diameter to maximum Ferrette diameter), and whose circumference (P) is the area of ​​a circle having the same area as the projected area of ​​the particle. EQPC ) and the actual particle's perimeter (P real The second spherical particle with a roundness of 0.7 or higher. The long fibrous particles include first long fibrous particles with an aspect ratio of less than 0.5 among particles with a fiber length of 200 μm or more and an elongation of less than 0.5, and second long fibrous particles with an aspect ratio of 0.5 or more and a roundness of less than 0.

7. The short fibrous particles include a first short fibrous particle with a fiber length of 40 μm or more and less than 200 μm and an elongation of less than 0.5, wherein the aspect ratio is less than 0.5, and a second short fibrous particle with an aspect ratio of 0.5 or more and a roundness of less than 0.7.

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