JP2017165972A - Cellulose powder - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a cellulose powder having suppressed burnt deposit during drying, less in black debris, thereby capable of contributing percent defective of tablets and further having largely improved coloring property with medicines having an amino group at a terminal and suitable for an excipient for compression molding.SOLUTION: There is provided a cellulose powder having average polymerization degree of 100 to 300, weight average particle diameter of more than 30 μm and 250 μm or less, apparent specific volume of 2.0 cm/g or more and less than 4.0 cm/g and organic carbon amount derived from residual impurities defined by total organic carbon amount (%) during 1% NaOH extraction-all organic carbon amount (%) during pure water extraction of 0.002 to 0.060%.SELECTED DRAWING: None

Description

  The present invention relates to a cellulose powder used in pharmaceutical, food and industrial applications. More specifically, in pharmaceutical use, the burning at the time of drying is suppressed, there are few black foreign substances, and as a result, it can contribute to the reduction of the defective rate of tablets, and further the colorability with a drug having an amino group at the terminal is greatly improved. The present invention relates to a cellulose powder suitable for an excipient for compression molding and a molded body comprising the same.

In the formulation of tablets and the like, thorough hygiene management is performed for the purpose of preventing adverse health effects. Raw materials used for tablets are sieved during the manufacturing process to prevent foreign substances from entering the tablets themselves, and to remove tablets in which foreign substances are recognized by visual inspection of the final product. However, there may be consumer complaints due to black spots and spots derived from natural raw materials, and the raw materials for tablets are required to strictly control foreign materials derived from natural raw materials.
The following are known as cellulose powders used as excipients for compression molding.

Japanese Patent Publication No.40-26274 Japanese Patent Publication No.56-2047 International Publication No. 2006/115198 Pamphlet JP-A-57-212231

Foreign substances in the cellulose powder include impurities derived from natural raw materials and those in which the cellulose itself is discolored. As a cause of discoloration of cellulose itself, burning at the time of drying can be considered, but a method for reducing the burning at the time of drying has not been known.
The present invention provides a compression molding composition that has reduced charring during drying, has less black foreign matter, and as a result can contribute to a reduction in the defective rate of tablets, and further has greatly improved coloring with a drug having an amino group at the terminal. The object is to provide a cellulose powder suitable for the form.

As a result of intensive studies in view of the above-mentioned present situation, the present inventors have made specific production conditions when producing cellulose powder, so that scorching during drying is suppressed and there are few black foreign substances, resulting in a defective rate of tablets. The present invention has been achieved by finding that it can contribute to reduction, and that coloration with a drug having an amino group at the terminal can be reduced. That is, the present invention is as follows.
(1) The average degree of polymerization is 100 to 300, the weight average particle size is larger than 30 μm, 250 μm or less, the apparent specific volume is 2.0 cm ³ / g to less than 4.0 cm ³ / g, and 1% NaOH is extracted. Total organic carbon amount (%)-cellulose powder having an organic carbon amount derived from residual impurities defined by total organic carbon amount (%) at the time of extraction with pure water of 0.002 to 0.060%,
(2) pore volume within a particle is 0.1 cm ³ / g or more, the cellulose powder of less than 0.265 cm ³ / g (1),
(3) The cellulose powder according to (1), wherein 0 to 20 black visual foreign matters are contained in 50 g of the cellulose powder.
(4) A molded article containing the cellulose powder of (1) or (3),
(5) The molded body according to (4), wherein the molded body is a tablet containing one or more active ingredients.
(6) Natural cellulosic material with a hydrochloric acid concentration of 0.05 to 0.15%, a hydrolysis temperature of 125 to 150 ° C., and a hydrolysis time exceeding 110 minutes and 150 minutes or less, or a hydrochloric acid concentration of 0.15% To 0.4%, a hydrolysis temperature of 125 to 150 ° C., and a hydrolysis time of 50 to 150 minutes, and then the resulting dispersion is spray dried at an inlet temperature of 150 to 300 ° C. Average polymerization degree 100-300, weight average particle diameter larger than 30 μm, 250 μm or less, apparent specific volume 2.0 cm ³ / g to less than 4.0 cm ³ / g, and total organic carbon amount during 1% NaOH extraction ( %)-A method for producing the cellulose powder, wherein a cellulose powder having a residual impurity-derived organic carbon content of 0.002 to 0.060% defined by the total organic carbon content (%) at the time of extraction with pure water is obtained.
(7) A molded article comprising one or more active ingredients, one or more additives selected from sugars, sugar alcohols, starches, and disintegrants, and cellulose powder, having a hardness of 50 to 100 N, A molded article having a tensile strength of 0.1 to 5.5 MPa, a friability of 0 to 0.5%, and a molded article diameter swelling ratio in acetone of 0 to 3.3%;
(8) A molded article according to (7) containing 5 to 90% by weight of cellulose powder,
(9) The total organic carbon content derived from residual impurities in the molded product residue extracted through acetone washing, ethanol washing, pure water washing, and ethanol washing is 0.002 to 0.060% (7) or The molded article of (8).
(10) The total organic carbon amount derived from residual impurities in the cellulose powder extracted through acetone washing, ethanol washing, pure water washing, and ethanol washing of the molded body is 0.002 to 0.060% (7) or The molded article of (8).

  The cellulose powder of the present invention has the effect of suppressing burning at the time of drying, less black foreign matter, and consequently contributing to the reduction of the defective rate of tablets, and further reducing the colorability with a drug having an amino group at the terminal. .

The present invention will be described in detail below.
The cellulose powder of the present invention has an average degree of polymerization of 100-300, preferably 150-300, more preferably 180-250. It is preferable that the average degree of polymerization is 100 or more because moldability is improved, and it is preferable that the average degree of polymerization is 300 or less because the fluidity and disintegration of the powder are excellent without exhibiting fiber properties. An average degree of polymerization of 100-300 is preferred because the balance of moldability, disintegration, and fluidity is particularly excellent.

  The cellulose powder of the present invention needs to have a weight average particle size of more than 30 μm and 250 μm or less. When the thickness exceeds 30 μm, handling is improved without increasing adhesion and cohesion, fluidity is excellent, and when the thickness is 250 μm or less, separation and segregation from the active ingredient does not occur, and the content uniformity of the preparation is improved. This is preferable because there is no risk of deterioration. Preferably, it is larger than 30 μm and 180 μm or less.

Cellulose powder of the present invention has an apparent specific volume of 2.0 cm ³ / g or more, needs to be less than 4.0 cm ³ / g. When the apparent specific volume is 2.0 cm ³ / g or more, the moldability is improved, and when it is less than 4.0 cm ³ / g, the disintegration property and the fluidity are improved. In addition, since it is difficult to recover elasticity without exhibiting fiber properties, it tends to be excellent in moldability. Preferably it is 2.2-3.8 cm < ³ > / g, Most preferably, it is 2.2-2.9 cm < ³ > / g.

The cellulose powder of the present invention preferably has a tapping apparent density of 0.30-0.60 g / cm ³ . More preferably 0.35-0.58g / cm ^3, particularly preferably 0.4-0.55g / cm ^3. A tapping apparent density of 0.60 g / cm ³ or less is preferable because moldability is improved.

  The cellulose powder of the present invention preferably has an angle of repose of 36 ° or more and less than 44 °, which is an index of the fluidity of the powder, from the viewpoint of content uniformity. More preferably, it is 36 degrees-42 degrees.

The cellulose powder of the present invention preferably has substantially no intraparticle pore volume, which is different from the porous cellulose aggregate of WO 2006/115198. The value of pore volume within a particle of the cellulose powder of the present invention measured according to the publication of the assay, 0.1 cm ³ / g or more, preferably less than 0.265 cm ³ / g. By substantially eliminating the intraparticle pores, the contact area with the drug is reduced, and coloring with the drug having an amino group at the terminal becomes difficult, which is preferable.

  In the cellulose powder of the present invention, the amount of organic carbon derived from impurities remaining in the cellulose raw material needs to be 0.002% -0.060%. By setting it to 0.060% or less, the cellulose particles are less likely to be burned during drying, which is preferable. The content of 0.002% or more is preferable because coloring due to a reaction with a drug having an amino group at the terminal is reduced.

  The amount of organic carbon derived from residual impurities in the present invention refers to the total amount of organic carbon (TOC) extracted from cellulose powder (5 g) with pure water (80 mL), and 1% hydroxylation from cellulose powder (5 g). It is defined as the difference from the amount of TOC extracted with an aqueous sodium solution (80 mL). The amount of TOC extracted with a 1% sodium hydroxide aqueous solution reflects the amount of alkali-soluble components and pure water-soluble components contained in the cellulose powder. By subtracting the TOC amount extracted with pure water, that is, the pure water-soluble component, from this TOC amount, the alkali-soluble component in the cellulose powder is obtained, and this correlates with the amount of organic carbon derived from residual impurities.

In the cellulose powder of the present invention, the amount of organic carbon derived from residual impurities as defined in the present invention is within a specific range, so both the component that burns with heat during drying and the component that reacts with a drug having an amino group at the terminal are included. Since it is reduced, it is difficult to burn when dried, and as a result, the reactivity with a drug having an amino group at the terminal can be reduced. The amount of organic carbon derived from residual impurities is a very small amount of components in the cellulose powder, but surprisingly, it has been found that the larger the amount, the more likely it is burnt during drying.
At the same time, it has also been found that those having a small amount of organic carbon derived from residual impurities are likely to be colored by reacting with a drug having an amino group at the terminal. This probably means that a small amount of organic charcoal derived from residual impurities means that many components are extracted during hydrolysis. This is thought to be due to discoloration of the extracted component by heating and increasing the reactivity with the drug. When the amount of organic carbon derived from residual impurities is within the range of the present invention, the ease of scorching of cellulose particles at a spray drying temperature of 150 to 300 ° C., which is commonly used, is greatly reduced, and the occurrence of scorching foreign matter can be suppressed.
From the above, it was found that when the amount of organic carbon derived from residual impurities is within the range specified in the present invention, scorching during drying can be suppressed, and coloring with a drug having an amino group at the terminal can be dramatically improved. . The coloration with drugs having an amino group at the end increased as the number of black foreign bodies increased, but this seems to be related to the reaction with the drug having an amino group at the end even when burned by drying. It is.

  The cellulose powder of the present invention can be obtained by hydrolyzing a natural cellulosic material at a higher temperature than before. That is, after reaching a predetermined reaction temperature with a hydrochloric acid concentration of 0.05 to 0.15%, a reaction temperature of 125 to 150 ° C. Exceeding to 0.4%, reaction temperature 125-150 ° C. After reaching the predetermined reaction temperature, hydrolysis is performed for 50 minutes to 150 minutes or less, so that residual impurities are extracted from the cellulose particles with hot water during hydrolysis. Impurities inside the cellulose particles that correlate with the amount of organic carbon derived from can be increased, and the impurities extracted in the subsequent washing are removed, so the amount of organic carbon derived from impurities remaining in the cellulose particles after drying is reduced. It becomes possible to reduce.

  As a result of examining the hydrolysis temperature in detail, surprisingly, when the hydrochloric acid concentration is 0.05 to 0.15%, the hydrolysis temperature is 125 ° C. or more and the hydrolysis time exceeds 110 minutes, or the hydrochloric acid concentration In the case of more than 0.15 to 0.4%, when the hydrolysis temperature is 125 ° C. or more and the hydrolysis time is 50 to 150 minutes, the amount of organic carbon derived from residual impurities remaining in the cellulose particles after drying is dramatically increased. It was found that the amount of organic carbon derived from residual impurities in a specific range specified in the present invention was reduced. This is because impurities that correlate with the amount of organic carbon derived from residual impurities inside the cellulose particles are more easily extracted at 125 ° C. or higher as the hydrochloric acid concentration is higher or the reaction time is longer within the range specified in the present application. I think that the. That is, at 125 ° C. or higher, the higher the concentration of hydrochloric acid or the longer the reaction time, the lower the amount of organic carbon derived from residual impurities remaining in the cellulose particles after drying. The amount of organic carbon derived from impurities can be within a specific range defined in the present application.

  It is preferable that the volume average particle diameter of the cellulose dispersion after hydrolysis is 70 to 150 μm by performing a stirring treatment under the above hydrolysis conditions. The cellulose dispersion is dehydrated, washed several times with pure water, neutralized with alkali, and then dehydrated again to obtain a cellulose cake having a solid content of 20 to 50% by weight.

  In the cellulose powder of the present invention, the cellulose cake is made into a cellulose slurry having a solid content of 10-25% by weight with pure water, and the volume average particle size of the cellulose dispersion before drying is set to 40 μm or more and less than 50 μm by stirring treatment or the like. Thereafter, spray drying is preferred. When the volume average particle size of the cellulose dispersion before drying is 40 μm or more, the fluidity of the cellulose powder after drying is improved, and when it is less than 50 μm, the fiber property is hardly expressed and the fluidity is improved.

  As the spray drying temperature, a commonly used inlet temperature of 150 to 300 ° C. can be used. Although the cellulose particles tend to burn easily when the inlet temperature is high, the cellulose powder of the present invention has a characteristic that it is harder to burn than the conventional cellulose powder even in this temperature range.

  Agitation during the reaction or in the subsequent step has an effect of shortening the cellulose fiber. When the stirring force is increased, the volume average particle diameter of the particles can be decreased, and when the stirring force is decreased, the volume average particle diameter can be increased. By appropriately controlling the stirring force so as to obtain a desired volume average particle diameter, the volume average particle diameter of the cellulose particles can be within the range of the present invention.

  The magnitude of the stirring force can be controlled by changing the size and shape of the stirring tank, the size and shape of the stirring blade, the number of rotations, the number of baffle plates, and the like.

  The IC (electric conductivity) of the cellulose dispersion before drying after washing and adjusting the pH is preferably 200 μS / cm or less. If it is 200 μS / cm or less, the dispersibility of the particles in water will be improved, and the disintegration will be good. Preferably it is 150 μS / cm or less, more preferably 100 μS / cm or less. When preparing the cellulose dispersion, water containing a small amount of an organic solvent may be used as long as the effect of the present invention is not impaired in addition to water.

  The natural cellulosic material referred to in the present invention is a vegetable fiber material derived from natural products containing cellulose, such as wood, bamboo, cotton, ramie, etc., and has a cellulose I type crystal structure. It is preferable. From the viewpoint of production yield, it is particularly preferable that these are refined pulps, and the α-cellulose content is desirably 85% or more.

The cellulose powder of the present invention preferably has a water absorption capacity of 1.8-3.0 cm ³ / g. When it is 1.8 cm ³ / g or more, the moldability is improved, and it is preferable, and when it is 3.0 cm ³ / g or less, the fiber property is hardly expressed, and the fluidity and disintegration property are preferable.

  The cellulose powder of the present invention preferably has 0 to 20 black visual foreign substances contained in 50 g of cellulose powder. A smaller number of foreign substances is preferable because reactivity with a drug having an amino group at the terminal is reduced.

  The molded product as used in the present invention refers to a molded product containing the cellulose powder of the present invention and processed by appropriately selecting a known method such as mixing, stirring, granulation, tableting, sizing and drying. Examples of molded articles include solid preparations such as tablets, powders, fine granules, granules, extracts, pills, capsules, troches, and poultices when used for pharmaceuticals. The present invention includes not only pharmaceuticals but also foods such as confectionery, health foods, texture improvers, dietary fiber reinforcing agents, solid foundations, bath preparations, animal drugs, diagnostic agents, agricultural chemicals, fertilizers, ceramic catalysts, etc. include.

  The amount of the molded body referred to in the present invention is not particularly limited as long as it contains the cellulose powder of the present invention, but it is preferably 1-99.9% by weight based on the weight of the molded body. If it is 1% by weight or more, the molded product can be prevented from being worn or destroyed, and sufficient physical properties can be imparted. Preferably, it is 3% by weight or more, preferably 5% by weight or more. If it is 99.9% by weight or less, sufficient efficacy of the active ingredient can be obtained.

  In addition to the cellulose powder of the present invention, the molded product referred to in the present invention includes an active ingredient, a disintegrant, a binder, a fluidizing agent, a lubricant, a corrigent, a fragrance, a colorant, and a sweetener as necessary. It is also free to contain other additives such as surfactants.

  Disintegrants include croscarmellose sodium, carmellose, carmellose calcium, carmellose sodium, celluloses such as low-substituted hydroxypropylcellulose, carboxymethyl starch sodium, hydroxypropyl starch, rice starch, wheat starch, corn starch, potato Starches, starches such as partially pregelatinized starch, crospovidone and the like can be mentioned.

  Binders include sugars such as sucrose, glucose, lactose, fructose, sugar alcohols such as mannitol, xylitol, maltitol, erythritol, sorbitol, gelatin, pullulan, carrageenan, locust bean gum, agar, konjac mannan, xanthan gum, tamarind Water-soluble polysaccharides such as gum, pectin, sodium alginate, gum arabic, crystalline cellulose, powdered cellulose, celluloses such as hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, starches such as pregelatinized starch and starch paste, polyvinylpyrrolidone, Synthetic polymers such as carboxyvinyl polymer and polyvinyl alcohol, calcium hydrogen phosphate, calcium carbonate, synthetic hydrotalcite, aluminate silicate Inorganic acids such as Neshiumu like.

  Examples of the fluidizing agent include hydrous silicon dioxide and light anhydrous silicic acid. Examples of the lubricant include magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid ester, talc and the like. Examples of the corrigent include glutamic acid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaric acid, malic acid, ascorbic acid, sodium chloride, 1-menthol and the like.

  Examples of the fragrances include oranges, vanilla, strawberry, yogurt, menthol, fennel oil, cinnamon oil, spruce oil, mint oil, and green tea powder. Examples of the colorant include food colors such as Food Red No. 3, Food Yellow No. 5, and Food Blue No. 1, copper chlorophyllin sodium, titanium oxide, riboflavin, and the like. Examples of sweeteners include aspartame, saccharin, dipotassium glycyrrhizinate, stevia, maltose, maltitol, starch syrup, and amacha powder. Examples of the surfactant include phospholipid, glycerin fatty acid ester, polyethylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, and the like.

  The active ingredient as used in the present invention means pharmaceutical medicinal ingredients, agricultural chemical ingredients, fertilizer ingredients, feed ingredients, food ingredients, cosmetic ingredients, pigments, fragrances, metals, ceramics, catalysts, surfactants, etc., in powder form, It may be any shape such as crystalline, oily, or solution. Further, it may be coated for the purpose of elution control, bitterness reduction and the like. The cellulose powder of the present invention is particularly effective for active ingredients having an unpleasant odor.

  For example, as a medicinal medicinal component, for example, aspirin, aspirin aluminum, acetaminophen, etenzamide, sazapyrine, salicylamide, lactylphenetidine, isothibenzyl hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, dipheterol hydrochloride, triprolidine hydrochloride, tripelenamine hydrochloride, Tonsilamine hydrochloride, phenetazine hydrochloride, methodirazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline teocrate, promethazine methylene disalicylate, carbinoxamine maleic acid dichlormamine hydrochloride , D-chlorpheniramine maleate, difephosphate Roll, aloclamide hydrochloride, cloperastine hydrochloride, pentoxyberine citrate (carbetapentane citrate), tipepidine citrate, dibutate sodium, dextromethorphan hydrobromide, dextromethorphan / phenolphthalic acid, tipepidine hibenzate, Fendizoic acid cloperastine, phosphate codeine, dihydrocodeine phosphate, noscapine hydrochloride, noscapine, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, potassium guaiacolsulfonate, guaifenesin, sodium benzoate caffeine, caffeine, anhydrous caffeine, Vitamin B1 and derivatives thereof and salts thereof, vitamin B2 and derivatives thereof and salts thereof, vitamin C and derivatives thereof and salts thereof, hesperidin Derivatives thereof and salts thereof, vitamin B6 and derivatives thereof and salts thereof, nicotinamide, calcium pantothenate, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum / aminoacetic acid Salt (aluminum glycinate), aluminum hydroxide gel (as dry aluminum hydroxide gel), dry aluminum hydroxide gel, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, water Coprecipitation product of aluminum oxide / calcium carbonate / magnesium carbonate, coprecipitation product of magnesium hydroxide / potassium aluminum sulfate, magnesium carbonate, magnesium aluminate metasilicate, ranitidine hydrochloride, Cimetidine, famotidine, naproxen, diclofenac sodium, piroxicam, azulene, indomethacin, ketoprofen, ibuprofen, diphenidol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, promethazine hydrochloride, meclizine hydrochloride, dimenhydrinate, diphenhydramine tannate, phenocendine tannate Pyralin, diphenhydramine fumarate, promethazine methylene disalicylate, spocollamine hydrobromide, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, methyl atropine bromide, methyl anisotropine bromide, methyl spocollamine bromide, methyl bromide -1-hyostiamine, methylbenactidium bromide, belladonna extract, isopropy iodide , Diphenylpiperidinomethyldioxolane iodide, papaverine hydrochloride, aminobenzoic acid, cesium oxalate, ethyl piperidylacetylaminobenzoate, aminophylline, diprofylline, theophylline, sodium bicarbonate, fursultiamine, isosorbide nitrate, ephedrine, cephalexin, ampicillin , Sulfixazole, sucralfate, allylisopropylacetylurea, bromvalerylurea, etc. , Gooh, Beast (including Yutan), Shajin, Syoukyo, Sojitsu, Clove, Chimpi, Sandalwood, Earth Dragon, Chikutsutsu Carrots, carrots, valerians, buttonpis, salamanders and their extracts, insulin, vasopressin, interferon, urokinase, seratopeptidase, somatostatin, etc. “Japanese Pharmacopoeia”, “External group”, “USP”, “NF The medicinal medicinal ingredients described in “EP” can be used, and one kind selected from the above may be used alone, or two or more kinds may be used in combination.

  The amount of the active ingredient contained in the molded product of the present invention is preferably 0.01 to 99% by weight based on the weight of the molded product. If the active ingredient is 0.01% by weight or more, sufficient medicinal effects can be expected. Moreover, if it is 99 weight% or less, the amount of excipient | filler is sufficient, can prevent the abrasion of a molded object, destruction, etc., and can provide a satisfying physical property to a molded object.

  The tablet referred to in the present invention contains the cellulose powder of the present invention and other additives as necessary, and can be obtained by any of the direct tableting method, granule compression method, and terminal method. A tablet obtained by direct tableting is particularly preferred.

  When the molded product of the present invention, preferably a tablet, contains one or more active ingredients and one or more additives selected from sugars, sugar alcohols, starches, and disintegrants, the cellulose powder of the present invention is used. When blended, the hardness is 50 to 100 N, the tensile strength is 0.1 to 5.5 MPa, the friability is 0 to 0.5%, and the molded article in acetone, preferably the diameter swelling rate of the tablet is 0 to 3.3. % Shaped bodies, preferably tablets. As a compounding quantity of the cellulose powder in a molded object, Preferably a tablet, 5-90 weight% is preferable. The range of 5 to 90% by weight is preferable because the above physical properties can be balanced.

  When the cellulose powder of the present application is blended into a molded product, preferably a tablet, the hardness, tensile strength, and friability are as described above, and the molded product in acetone, preferably the tablet has a diameter swelling ratio of 0 to 3.3%. It can be a shaped body, preferably a tablet. Preferably, it exceeds 2.0 and is 3.3%. It is preferable that the diameter swelling rate of the molded body in acetone, preferably the tablet is in the range of 0 to 3.3%, since the balance of hardness, tensile strength and friability can be obtained.

The diameter swelling rate of the molded body, preferably the tablet, in acetone is the rate of change of the molded body (tablet) diameter (mm) before and after the molded body, preferably the tablet is immersed in acetone (25 ° C.) for 60 seconds. Defined and calculated by the following formula.

Molded body (tablet) diameter swelling ratio (%) = [(molded body (tablet) diameter after acetone immersion−molded body (tablet) diameter before acetone immersion) / molded body (tablet) diameter before acetone immersion] × 100

  If the diameter swelling rate of the molded body in acetone, preferably the tablet is 0 to 3.3%, rapid disintegration and dissolution can be imparted to the molded body, preferably the tablet. The disintegration time specified by the Japanese Pharmacopoeia is 20 minutes or less, preferably 10 minutes or less, more preferably 1 minute or less, and particularly preferably 30 seconds or less. Further, the amount of the total organic carbon derived from the residual impurities in the molded product residue extracted from the molded product, preferably the tablet through acetone washing, ethanol washing, pure water washing, and ethanol washing, or the total organic carbon derived from residual impurities in the cellulose powder. The amount is preferably 0.002 to 0.060%. A range of 0.002 to 0.060% is preferable in terms of reactivity with foreign substances and drugs and disintegration.

The total amount of organic carbon derived from residual impurities in the molded product (preferably tablet) residue is extracted from the molded product residue with pure water (80 mL), and the total organic carbon (TOC) content of the molded product residue and the molded product residue It is defined as the difference (%) from the amount of TOC with respect to the molded product residue extracted from the inside with 1% aqueous sodium hydroxide solution (80 mL). When the molded product residue is cellulose powder, the molded product residue is sufficiently washed with pure water, so the total organic carbon content (%) at the time of extraction of the molded product residue with pure water is close to zero. The total amount of organic carbon derived from the residual impurities of the body residue is approximately equal to the total amount of organic carbon (%) during 1% NaOH extraction. If the total amount of organic carbon (%) during extraction with pure water is detected, it is considered that impurities are not sufficiently removed by washing with pure water, or residual acetone and ethanol are not sufficiently removed by drying. Therefore, the amount of pure water to be extracted is increased within a range of 1.3 to 2 times, or the drying temperature is adjusted within a range of 100 to 120 ° C. and the drying time is adjusted within a range of 3 to 5 hours. The total amount of organic carbon derived from residual impurities in the molded product residue extracted through acetone washing, ethanol washing, pure water washing, and ethanol washing can be confirmed by the following procedure.
(I) Put 120 g of the molded body into a 500 ml beaker, add 300 g of acetone, and stir with a stirrer until the molded body piece is not recognized, and then suction filter (use Buchner funnel, filter paper for quantitative analysis, 5C, 110 mm in diameter). . In the case where the molded piece is recognized, the mixture is subjected to ultrasonic treatment for 10 minutes and then stirred for 30 minutes. Repeat until no shaped pieces are found.
(Ii) Add 100 mL of ethanol to the residue on the filter paper, stir the residue well with a spatula and suction filter (repeat this operation three times). The poorly water-soluble component is removed by the operations (i) and (ii).
(Iii) Put the residue of (ii) in 1000 mL of pure water, and stir with a stirrer for 10 minutes, followed by suction filtration.
(Iv) The residue of (iii) is put into 600 ml of pure water, stirred with a stirrer for 10 minutes, and then suction filtered.
(V) Put the residue of (iv) in 1000 mL of pure water and heat at 80 to 100 ° C. for 30 minutes while stirring with a stirrer. After cooling to 20-30 ° C., 5 μg / L of α-amylase is added and stirred at 37 ° C. for 30 minutes, followed by suction filtration.
(Vi) Add 150 mL of ethanol to the residue of (v), stir the residue well with a spatula and suction filter (repeat this operation 3 times). Water-soluble components and starches are removed by the operations (iii) to (vi). The water-soluble components include saccharides and sugar alcohols and can be quantified by a known method.
(Vii) The residue on the filter paper is scraped off from the filter paper, put in a petri dish, dried at room temperature (20-30 ° C.) until the ethanol odor disappears, and then dried at 100 ° C. for 3 hours to obtain a measurement sample.
(Viii) About 2 g of dried residue is put into a measurement cell, and an absorption spectrum is measured by near infrared spectroscopy (device name: InfraAlyzer 500, manufacturer name: BRAN + LUBBE). When the peak of the second derivative value of the NIR absorption spectrum is detected at 1692 nm, the cellulose powder content (C;%) in the molded product residue is calculated according to the following equation.
C (%) = NIR second derivative spectrum intensity value × 316583 + 95.588
When there is a peak of the second derivative value of the NIR absorption spectrum at 1692 nm, a residue of crospovidone is contained in addition to the cellulose powder. The above formula is used to specify the content of cellulose powder in the dry residue. Instead of the shaped body of (i), three composition powders of cellulose powder / crospovidone = 100/0, 50/50, 0/100 are prepared, and the dry residue is removed through the operations (i) to (vii). The NIR second-order differential spectrum intensity is measured using InfraAlyzer 500 (manufacturer name: BRAN + LUBBE), and the coefficient of the above equation can be obtained from a three-point calibration curve.
When the peak of the second derivative value of the NIR absorption spectrum is not detected at 1692 nm, the total organic carbon (TOC) amount extracted from the dry residue with pure water (80 mL) is 0.0% with respect to the dry residue. The dry residue consists only of cellulose powder. When it exceeds 0.0%, disintegrants other than starch and crospovidone may be contained. Therefore, in order to remove them, the dry residue is dispersed with 50 mL of pure water and passed through a sieve having an opening of 10 μm. After removing particles other than cellulose powder, the filtrate is evaporated to dryness to obtain a dry residue (ix). Nevertheless, if the total organic carbon content (%) at the time of extraction of the residue with pure water exceeds 0.0%, it is dispersed with 50 mL of pure water (sonication or homogenizer treatment may be performed if necessary). The supernatant centrifuged at 2000 G is evaporated to dryness to give a dry residue (ix).
(Ix) <When the peak of the second derivative value of the NIR absorption spectrum is detected at 1692 nm in (viii)>
Weigh the dry residue (A; g, 4 to 4.5 g as a guide), put it in 80 ml of 1% NaOH, stir with a stirrer for 5 minutes, and filter with suction. Collect the filtrate and measure the volume (X; mL). The filtrate was acidified with hydrochloric acid (pH 2-3), and the total organic carbon content (TOC _{1% NaOH} ; mg / L) was measured with a total organic carbon meter (manufactured by Shimadzu Corporation, using TOC-VCSH, TC-IC method). To do. Since the residue is thoroughly washed with pure water, the total amount of organic carbon (%) at the time of extraction with pure water can be regarded as zero. Therefore, the amount of organic carbon derived from residual impurities in the cellulose powder contained in the residue is 1%. It becomes equal to the total organic carbon amount (%) at the time of NaOH extraction. Calculate according to the following.
-Cellulose powder residue amount (B; g) in the residue extracted from the molded product = A x C / 100
-Total organic carbon amount (Y; mg) in cellulose powder residue = (TOC _{1% NaOH /} 1000) x X-0.4 / 100 x (AB) x 1000
The above coefficient 0.4 is obtained when 2.5 g of crospovidone powder is formed from the molded product of (i), and the dry residue obtained through the processing up to (vii) is used to extract all of the extracted product with 80 ml of 1% NaOH. The amount of organic carbon (%).
・ Total organic carbon content (%) derived from residual impurities in the molded product residue extracted through acetone cleaning, ethanol cleaning, pure water cleaning, and ethanol cleaning.
= Y / (1000 × B) × 100 = Y / (10 × B)
<When the peak of the second derivative value of the NIR absorption spectrum is not detected at 1692 nm in (viii)>
Weigh the dry residue (A _H2O for extraction with pure water; g, A 1% NaOH for extraction with 1% aqueous _NaOH ; g), add 80 mL of pure water or 1% aqueous NaOH, and add in a beaker. After stirring for 5 minutes (using a stirrer), the dry residue is removed by suction filtration (using quantitative analysis filter paper, 5C, diameter 110 mm) to obtain a filtrate. The volume of the total amount of the filtrate was measured (the total amount when pure water was used was V _H2O , the total amount when 1% NaOH was used was V _{1% NaOH} ; mL), then acidified (pH 2-3) with hydrochloric acid, Total organic carbon content (TOC; mg / L) was measured with an organic carbon meter (manufactured by Shimadzu Corporation, using TOC-VCSH, TC-IC method). The TOC when pure water is used is TOC _H2O , and the TOC when 1% NaOH is used is TOC _{1% NaOH} . The amount of organic carbon derived from residual impurities in the molded product residue is calculated by the following equation.
-Total organic carbon amount (%) derived from residual impurities in molded product residue = 1% Total organic carbon amount during NaOH extraction (%)-Total organic carbon amount during pure water extraction (%)
-Total organic carbon content (%) during 1% NaOH extraction:
= [(TOC _{1% NaOH} (mg / L) / 1000) × V _{1% NaOH} (mL)] / A _{1% NaOH} × 1000 (mg) × 100
・ Total organic carbon content during pure water extraction (%):
= [(TOC _{H 2 O} (mg / L) / 1000) × V _{H 2 O} (mL)] / A _{H 2 O} × 1000 (mg) × 100

  In the case of sugar-coated tablets, the cellulose powder of the present invention is a sugar-coating reinforcing agent, an extrudability improving agent in extrusion granulation, crushing granulation, fluidized bed granulation, high-speed agitation granulation, granulation aid in rolling fluid granulation, etc. It can also be used in wet granulation for the purpose, etc., and it is possible to prepare granules and granules for tableting. A dry granulation method may be used for preparing the granules for tableting. Further, the tableting granules obtained by a known method can be tableted by adding the cellulose powder of the present invention and compression molding (late method). The cellulose powder of the present invention has high water absorption and contributes to increase the granulation yield by reducing the generation of coarse particles because the granulation rate can be slowed even when granulating a pharmaceutical active ingredient with high water solubility. To do. Further, since the cellulose powder of the present invention has a low particle density, the granulated product is bulky and contributes to obtaining granules for tableting with high compression moldability. Further, it can be blended into a powder for the purpose of preventing blocking and improving fluidity, or blended into a capsule for the purpose of improving fillability.

EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, these do not restrict | limit the scope of the present invention. In addition, the measuring method of each physical property in an Example and a comparative example is as follows.
1) Average degree of polymerization (-)
Value measured by the copper ethylenediamine solution viscosity method described in the 15th revised Japanese Pharmacopoeia, confirmation test (3) for crystalline cellulose.
2) Loss on drying (%)
1 g of the powder was dried at 105 ° C. for 3 hours, and the weight loss was expressed as a percentage by weight.
3) Volume average particle diameter of cellulose particles in cellulose dispersion (μm)
The particle size of the cellulose dispersion after hydrolysis or the cellulose dispersion before drying was determined by the following procedure. The cellulose dispersion was dropped on a microscope table, placed on a slide glass and dried, and then an optical microscope image was taken using a microscope. The optical microscope was subjected to image analysis processing (manufactured by Interquest Co., Ltd., apparatus: Hyper700, software: Imagehyper), and the long side of the rectangle with the smallest area among the rectangles circumscribing the particles was determined, and the cumulative number of particles was 50%. The diameter was defined as the average particle diameter. Image analysis processing was performed on at least 100 particles.
4) Weight average particle diameter (μm) of cellulose powder
The weight average particle size of the powder sample is determined by sieving 10 g of the sample for 10 minutes using a low-tap type sieve shaker (Sieve Shaker A type manufactured by Hira Kogakusho) or JIS standard sieve (Z8801-1987). Measured and expressed as 50% cumulative weight particle size.
5) Apparent specific volume (cm ³ / g)
A powder sample is roughly packed in a 100 cm ³ glass graduated cylinder over 2-3 minutes using a quantitative feeder, etc., and the upper surface of the powder layer is leveled with a soft brush like a brush and the volume is read. Was divided by the weight of the powder sample. The weight of the powder was appropriately determined so that the volume was about 70-100 cm ³ .
6) Apparent tapping density (g / cm ³ )
Using a commercially available powder property measuring machine (made by Hosokawa Micron, powder tester PT-R type), 100cm ³ cup is filled with powder, tapped 180 times, and then the volume of the cup is filled into the cup and the remaining powder layer Divided by the weight of
7) Amount of organic carbon derived from residual impurities (%)
Add pure water or 80% 1% NaOH aqueous solution to cellulose powder (W; mg, 5000 mg as a guide), stir for 5 minutes in a beaker (use stirrer), and then suction filtration (quantitative analysis filter paper, 5C, 110 mm diameter) ) To remove the cellulose powder to obtain a filtrate. The volume of the total amount of the filtrate was measured (the total amount when using water was V _H2O , the total amount when using _{1% NaOH} was V _{1% NaOH} ; mL), then acidified (pH 2-3) with hydrochloric acid, The total organic carbon content (TOC; mg / L) was measured with a carbon meter (manufactured by Shimadzu Corporation, using TOC-VCSH, TC-IC method). The TOC when pure water is used is TOC _H2O , and the TOC when 1% NaOH is used is TOC _{1% NaOH} . The amount of organic carbon derived from residual impurities was calculated by the following equation.
・ Residual impurity-derived organic carbon amount (%) = 1% Total organic carbon amount during NaOH extraction (%) − Total organic carbon amount during pure water extraction (%)
-Total organic carbon content (%) during 1% NaOH extraction:
= [(TOC _{1% NaOH} (mg / L) / 1000) × V _{1% NaOH} (mL)] / W (mg) × 100
・ Total organic carbon content during pure water extraction (%):
= [(TOC _H2O (mg / L) / 1000) x _VH2O (mL)] / W (mg) x 100
8) Water absorption capacity (cm ³ / g)
Pure water is added dropwise to 2 g of cellulose powder (in terms of dry matter), and if necessary, the amount of pure water dropped from the point where water oozes out on the surface while kneading with a spatula so that the cellulose powder blends with the dropped water. (V) was determined. The water absorption capacity was calculated by the following formula. The average value of triplicate measurements was used.
The water absorption capacity ^{(cm 3 / g) = V} / 2
9) Angle of repose (°)
When using a Sugihara-type angle of repose measuring instrument (slit size depth 10 x width 50 x height 140 mm, protractor installed at a position of 50 mm width) and dropping cellulose powder into the slit at a rate of 3 g / min with a quantitative feeder The dynamic self-fluidity of was measured. The angle of repose is the angle between the bottom of the apparatus and the cellulose powder forming layer.
10) Foreign substance amount (pieces / 50g)
50 g of the cellulose powder of the present invention was sieved by hand for 5 minutes, and the entire amount remaining on the 75 μm sieve was spread thinly on blue drawing paper, and the number of black foreign matters was counted visually for 15 minutes using a loupe.
11) Reactivity of cellulose powder and drug having amino group at its terminal A mixture of equal amounts of cellulose powder and aminophylline was stored in a sealed bottle (50 cm ³ ) at 60 ° C. for 30 days. About the said equal amount mixture after a preservation | save, the value of L, a, and b was calculated | required with the following formula | equation by the spectroscopic colorimeter (SE-2000, Nippon Denshoku Industries). It is considered that the lower the whiteness decrease, the lower the reactivity.
Whiteness = 100 − [(100−L) ² + (a ² + b ² )] ^0.5
L: Brightness a: Saturation (green to red) b: Saturation (blue to yellow)
12) Intraparticle pore volume (cm ³ / g)
The pore distribution was determined by mercury porosimetry using an Autopore 9520 type (trade name) manufactured by Shimadzu Corporation. Each sample powder used for the measurement was dried under reduced pressure at room temperature for 15 hours. From the obtained pore distribution, the total volume in the range of pore diameters of 0.1 to 15 μm was defined as the intraparticle pore volume based on the measurement at an initial pressure of 20 kPa.
13) Hardness [N]
Using a Schleingel hardness meter (Freund Sangyo Co., Ltd., 6D type), a cylindrical shaped product or tablet was loaded in the diameter direction of the cylindrical shaped product or tablet, and the load when it was broken was measured. The number average of five samples is shown. A cylindrical molded body of 100% cellulose powder was produced as follows. 0.5 g of a sample is put in a mortar (manufactured by Kikusui Seisakusho, using material SUK2, 3), and is 10 MPa with a flat paddle (manufactured by Kikusui Seisakusho, using material SUK2, 3) with a diameter of 1.13 cm (bottom area is 1 cm2). Compressed and held the stress for 10 seconds to produce a cylindrical molded body (the compressor used was PCM-1A manufactured by Aiko Engineering, and the compression speed was about 10 cm / min). The practical hardness is 50 N or more for a tablet having a diameter of 8 mm, and 70 N or more for a tablet having a diameter of 9 mm or more.
14) Tensile strength [MPa]
Tablet hardness: H [N], tablet diameter (maximum diameter for caplet tablets, etc.): D [mm], tablet thickness: T [mm] were obtained and calculated according to the following formula.
Tensile strength [MPa] = 2 × H ÷ (3.14 × D × T)
15) Tablet friability [%]
Measure the weight (Wa) of 20 tablets, put it in a tablet friability tester (PTFR-A, manufactured by PHARMA TEST), rotate at 25 rpm for 4 minutes, remove fine powder adhering to the tablets, and again The weight was measured (Wb) and calculated from equation (7).
Friction = 100 × (Wa−Wb) / Wa
In order to make a tablet that can withstand practical use, the friability needs to be 0.5% or less.

Example 1
2 kg of commercially available KP pulp (polymerization degree 840, level-off polymerization degree 145) is shredded and placed in 30 L of 0.05% aqueous hydrochloric acid solution, and a low-speed stirrer (Ikebukuro Sakai Kogyo Co., Ltd., 30 LGL reactor, blade diameter of about The mixture was hydrolyzed at 145 ° C. for 115 minutes with stirring (stirring speed: 234 rpm). The obtained acid-insoluble residue was filtered using a Nutsche, the filter residue was further washed four times with 70 L of pure water, neutralized with ammonia water, added to a 90 L plastic bucket, pure water was added, and three-one motor ( A cellulose dispersion with a concentration of 19% was prepared (pH: 7.5, IC; 54 μS / cm) while stirring (stirring speed: 500 rpm) with HEIDON, type BLh1200, 8 M / M, blade diameter of about 10 cm.

  This was spray-dried (liquid supply rate 6 L / hr, inlet temperature 180 to 220 ° C., outlet temperature 50 to 70 ° C.) to obtain cellulose powder A (loss on drying: 3.5%). Table 1 shows the physical properties of the cellulose powder A.

(Example 2)
2 kg of commercially available KP pulp (polymerization degree 840, level-off polymerization degree 145) is shredded and placed in 30 L of a 0.10% hydrochloric acid aqueous solution, and a low speed stirrer (Ikebukuro Sakai Kogyo Co., Ltd., 30 LGL reactor, blade diameter of about The mixture was hydrolyzed at 135 ° C. for 120 minutes with stirring (stirring speed: 234 rpm). The obtained acid-insoluble residue was filtered using a Nutsche, the filter residue was further washed four times with 70 L of pure water, neutralized with ammonia water, added to a 90 L plastic bucket, pure water was added, and three-one motor ( A cellulose dispersion with a concentration of 20% was prepared (pH: 7.1, IC; 45 μS / cm) while stirring (stirring speed: 500 rpm) with HEIDON, type BLh1200, 8 M / M, blade diameter of about 10 cm.

  This was spray-dried (liquid supply rate: 6 L / hr, inlet temperature: 180 to 220 ° C., outlet temperature: 50 to 70 ° C.) to obtain cellulose powder B (loss on drying: 3.0%). Table 1 shows the physical properties of the cellulose powder B.

(Example 3)
2 kg of commercially available KP pulp (polymerization degree 840, level-off polymerization degree 145) is shredded and placed in 30 L of a 0.39% hydrochloric acid aqueous solution, and a low-speed stirrer (Ikebukuro Sakai Kogyo Co., Ltd., 30 LGL reactor, blade diameter of about The mixture was hydrolyzed at 128 ° C. for 145 minutes with stirring (stirring speed: 234 rpm). The obtained acid-insoluble residue was filtered using a Nutsche, the filter residue was further washed four times with 70 L of pure water, neutralized with ammonia water, added to a 90 L plastic bucket, pure water was added, and three-one motor ( A cellulose dispersion having a concentration of 18% was prepared (pH: 7.5, IC; 40 μS / cm) while stirring (stirring speed: 500 rpm) with HEIDON, type BLh1200, 8 M / M, blade diameter of about 10 cm.

This was spray-dried (liquid supply speed 6 L / hr, inlet temperature 180 to 220 ° C., outlet temperature 50 to 70 ° C.) to obtain cellulose powder C (loss on drying 3.3%). Table 1 shows the physical properties of the cellulose powder C.
Example 4
2 kg of commercially available KP pulp (polymerization degree 840, level-off polymerization degree 145) is shredded and placed in 30 L of a 0.39% hydrochloric acid aqueous solution, and a low-speed stirrer (Ikebukuro Sakai Kogyo Co., Ltd., 30 LGL reactor, blade diameter of about The mixture was hydrolyzed at 126 ° C. for 55 minutes with stirring (stirring speed: 234 rpm). The obtained acid-insoluble residue was filtered using a Nutsche, the filter residue was further washed four times with 70 L of pure water, neutralized with ammonia water, added to a 90 L plastic bucket, pure water was added, and three-one motor ( A cellulose dispersion with a concentration of 19% was prepared (pH: 7.8, IC: 35 μS / cm) while stirring (stirring speed: 500 rpm) with HEIDON, type BLh1200, 8 M / M, blade diameter of about 10 cm.

  This was spray-dried (liquid supply rate: 6 L / hr, inlet temperature: 180 to 220 ° C., outlet temperature: 50 to 70 ° C.) to obtain cellulose powder D (loss on drying: 3.5%). Table 1 shows the physical properties of the cellulose powder D.

  In the cellulose powders of Examples 1 to 4, since the amount of organic carbon derived from residual impurities was in a specific range, the number of foreign matters was dramatically reduced. In addition, the whiteness of the aminophylline equivalent mixture after storage at 60 ° C. for 30 days was 95% or more, which was higher than the comparative example.

(Comparative Example 1)
2 kg of commercially available SP pulp (polymerization degree 1030, level-off polymerization degree 220) was shredded and hydrolyzed under the conditions of 30 L of 0.14N (0.49%) hydrochloric acid aqueous solution at 121 ° C. for 1 hour. The obtained acid-insoluble residue was filtered using a Nutsche, and the filter residue was further washed with 70 L of pure water four times, neutralized with ammonia water, put into a 90 L plastic bucket, and stirred with a three-one motor. A 17% cellulose dispersion was obtained (pH; 6.4, IC; 64 μS / cm).
After spray drying (liquid supply rate 6 L / hr, inlet temperature 180 to 220 ° C., outlet temperature 70 ° C.), coarse particles were removed with a 325 mesh sieve to remove cellulose powder E (loss on drying 4.1%, JP-B 40-26274). Equivalent to Example 1). Table 1 shows the physical properties of the cellulose powder E.

(Comparative Example 2)
A commercially available KP pulp (polymerization degree 840, level-off polymerization degree 145) was hydrolyzed in a 0.7% aqueous hydrochloric acid solution at 125 ° C. for 150 minutes, and then the hydrolysis residue was neutralized, washed and filtered to obtain a wet cake. After sufficiently grinding in a kneader, ethanol having a volume ratio of 1 was added, and the mixture was squeezed and filtered and then air-dried. The dry powder was pulverized with a hammer mill, and coarse particles were removed with a 40 mesh sieve to obtain cellulose powder F (dry weight 3.0%, corresponding to Example 1 of JP-A-56-2047). Table 1 shows the physical properties of the cellulose powder F.

(Comparative Example 3)
A cellulose powder G was obtained in the same manner as in Example 2 except that the hydrochloric acid concentration was 0.49%. Table 1 shows the physical properties of the cellulose powder G.

(Comparative Example 4)
A cellulose powder H was obtained in the same manner as in Example 2 except that the hydrolysis time was 160 minutes. Table 1 shows the physical properties of the cellulose powder H.

(Comparative Example 5)
A cellulose powder I was obtained in the same manner as in Example 2 except that the hydrolysis time was 100 minutes. Table 1 shows the physical properties of the cellulose powder I.

(Comparative Example 6)
Cellulose powder J was obtained in the same manner as in Example 2 except that the hydrolysis temperature was 90 ° C. Table 1 shows the physical properties of the cellulose powder J.

（実施例５）
エテンザミド：２５０ｇ、セルロース粉末Ｂ：５００ｇ、噴霧乾燥乳糖：２２０ｇ（スーパータブ、ＤＭＶ製）、アルファー化デンプン「Ｓｗｅｌｓｔａｒ」ＰＤ−１（旭化成ケミカルズ製）：３０ｇを３分間ポリ袋中で混合し、植物性ステアリン酸マグネシウム（太平化学産業）：１０ｇを加え、さらにポリ袋中にて３０秒混合した。ロータリー打錠機（「クリーンプレス・コレクト１２ＨＵＫ」（商品名）菊水製作所製）で打錠し、打錠圧１２ｋＮで重量２００ｍｇ、直径８ｍｍ、１２Ｒの錠剤をオープンフィーダー、ターンテーブル回転数５４ｒｐｍにて作製した。得られた錠剤の物性を表２に示す。
（実施例６）
セルロース粉末Ｂをセルロース粉末Ｃとする以外は、実施例５と同様に操作した。得られた錠剤の物性を表２に示す。
（比較例８〜９）
セルロース粉末Ｂをセルロース粉末Ｆ又はＧとする以外は、実施例５と同様に操作した。得られた錠剤の物性を表２に示す。

(Comparative Example 7)
Cellulose powder K was obtained in the same manner as in Example 2 except that the hydrolysis temperature was 160 ° C. Table 1 shows the physical properties of the cellulose powder K.

(Example 5)
Ethenzamid: 250 g, cellulose powder B: 500 g, spray-dried lactose: 220 g (Supertub, manufactured by DMV), pregelatinized starch “Swelstar” PD-1 (manufactured by Asahi Kasei Chemicals): 30 g are mixed in a plastic bag for 3 minutes, Magnesium stearate (Taihei Chemical Industry): 10 g was added and further mixed in a plastic bag for 30 seconds. Tableting with a rotary tableting machine ("Clean Press Collect 12HUK" (trade name) manufactured by Kikusui Seisakusho), tableting pressure 12kN, weight 200mg, diameter 8mm, 12R tablets open feeder, turntable rotation speed 54rpm Produced. Table 2 shows the physical properties of the obtained tablets.
(Example 6)
The same operation as in Example 5 was performed except that the cellulose powder B was changed to the cellulose powder C. Table 2 shows the physical properties of the obtained tablets.
(Comparative Examples 8-9)
The same operation as in Example 5 was performed except that the cellulose powder B was changed to the cellulose powder F or G. Table 2 shows the physical properties of the obtained tablets.

The cellulose powder of the present invention is suppressed in scorching at the time of drying, has few black foreign matters, and as a result, can contribute to reducing the defective rate of tablets, and further can reduce coloring with a drug having an amino group at the terminal. .

As a result of intensive studies in view of the above-mentioned present situation, the present inventors have made specific production conditions when producing cellulose powder, so that scorching during drying is suppressed and there are few black foreign substances, resulting in a defective rate of tablets. The present invention has been achieved by finding that it can contribute to reduction, and that coloration with a drug having an amino group at the terminal can be reduced. That is, the present invention is as follows.
(1) When the average degree of polymerization is 100 to 300, the weight average particle size is larger than 30 μm, 250 μm or less, the apparent specific volume is 2.0 cm ³ / g to less than 4.0 cm ³ / g, and 1% NaOH aqueous solution is extracted Total organic carbon amount (%)-cellulose powder having an organic carbon amount derived from residual impurities defined by total organic carbon amount (%) at the time of extraction with pure water of 0.002 to 0.060%,
(2) pore volume within a particle is 0.1 cm ³ / g or more, the cellulose powder of less than 0.265 cm ³ / g (1),
(3) The cellulose powder according to (1), wherein 0 to 20 black visual foreign matters are contained in 50 g of the cellulose powder.
(4) A molded article containing the cellulose powder of (1) or (3),
(5) The molded body according to (4), wherein the molded body is a tablet containing one or more active ingredients.
(6) Natural cellulosic material with a hydrochloric acid concentration of 0.05 to 0.15%, a hydrolysis temperature of 125 to 150 ° C., and a hydrolysis time exceeding 110 minutes and 150 minutes or less, or a hydrochloric acid concentration of 0.15% To 0.4%, a hydrolysis temperature of 125 to 150 ° C., and a hydrolysis time of 50 to 150 minutes, and then the resulting dispersion is spray dried at an inlet temperature of 150 to 300 ° C. , Average polymerization degree 100-300, weight average particle diameter larger than 30 μm, 250 μm or less, apparent specific volume 2.0 cm ³ / g to less than 4.0 cm ³ / g, and total organic carbon amount during extraction with 1% NaOH aqueous solution (%)-A method for producing a cellulose powder, wherein the amount of organic carbon derived from residual impurities defined by the total amount of organic carbon (%) during extraction with pure water is 0.002 to 0.060%.
(7) A molded article comprising one or more active ingredients, one or more additives selected from sugars, sugar alcohols, starches, and disintegrants, and cellulose powder, having a hardness of 50 to 100 N, A molded article having a tensile strength of 0.1 to 5.5 MPa, a friability of 0 to 0.5%, and a molded article diameter swelling ratio in acetone of 0 to 3.3%;
(8) A molded article according to (7) containing 5 to 90% by weight of cellulose powder,
(9) The total organic carbon content derived from residual impurities in the molded product residue extracted through acetone washing, ethanol washing, pure water washing, and ethanol washing is 0.002 to 0.060% (7) or The molded article of (8).
(10) The total organic carbon amount derived from residual impurities in the cellulose powder extracted through acetone washing, ethanol washing, pure water washing, and ethanol washing of the molded body is 0.002 to 0.060% (7) or The molded article of (8).

The total amount of organic carbon derived from residual impurities in the molded product (preferably tablet) residue is extracted from the molded product residue with pure water (80 mL), and the total organic carbon (TOC) content of the molded product residue and the molded product residue It is defined as the difference (%) from the amount of TOC with respect to the molded product residue extracted from the inside with 1% aqueous sodium hydroxide solution (80 mL). When the molded product residue is cellulose powder, the molded product residue is sufficiently washed with pure water, so the total organic carbon content (%) at the time of extraction of the molded product residue with pure water is close to zero. The total organic carbon amount derived from the residual impurities of the body residue is approximately equal to the total organic carbon amount (%) at the time of 1% NaOH aqueous solution extraction. If the total amount of organic carbon (%) during extraction with pure water is detected, it is considered that impurities are not sufficiently removed by washing with pure water, or residual acetone and ethanol are not sufficiently removed by drying. Therefore, the amount of pure water to be extracted is increased within a range of 1.3 to 2 times, or the drying temperature is adjusted within a range of 100 to 120 ° C. and the drying time is adjusted within a range of 3 to 5 hours. The total amount of organic carbon derived from residual impurities in the molded product residue extracted through acetone washing, ethanol washing, pure water washing, and ethanol washing can be confirmed by the following procedure.
(I) Put 120 g of the molded body into a 500 ml beaker, add 300 g of acetone, and stir with a stirrer until the molded body piece is not recognized, and then suction filter (use Buchner funnel, filter paper for quantitative analysis, 5C, 110 mm in diameter). . In the case where the molded piece is recognized, the mixture is subjected to ultrasonic treatment for 10 minutes and then stirred for 30 minutes. Repeat until no shaped pieces are found.
(Ii) Add 100 mL of ethanol to the residue on the filter paper, stir the residue well with a spatula and suction filter (repeat this operation three times). The poorly water-soluble component is removed by the operations (i) and (ii).
(Iii) Put the residue of (ii) in 1000 mL of pure water, and stir with a stirrer for 10 minutes, followed by suction filtration.
(Iv) The residue of (iii) is put into 600 ml of pure water, stirred with a stirrer for 10 minutes, and then suction filtered.
(V) Put the residue of (iv) in 1000 mL of pure water and heat at 80 to 100 ° C. for 30 minutes while stirring with a stirrer. After cooling to 20-30 ° C., 5 μg / L of α-amylase is added and stirred at 37 ° C. for 30 minutes, followed by suction filtration.
(Vi) Add 150 mL of ethanol to the residue of (v), stir the residue well with a spatula and suction filter (repeat this operation 3 times). Water-soluble components and starches are removed by the operations (iii) to (vi). The water-soluble components include saccharides and sugar alcohols and can be quantified by a known method.
(Vii) The residue on the filter paper is scraped off from the filter paper, put in a petri dish, dried at room temperature (20-30 ° C.) until the ethanol odor disappears, and then dried at 100 ° C. for 3 hours to obtain a measurement sample.
(Viii) About 2 g of dried residue is put into a measurement cell, and an absorption spectrum is measured by near infrared spectroscopy (device name: InfraAlyzer 500, manufacturer name: BRAN + LUBBE). When the peak of the second derivative value of the NIR absorption spectrum is detected at 1692 nm, the cellulose powder content (C;%) in the molded product residue is calculated according to the following equation.
C (%) = NIR second derivative spectrum intensity value × 316583 + 95.588
When there is a peak of the second derivative value of the NIR absorption spectrum at 1692 nm, a residue of crospovidone is contained in addition to the cellulose powder. The above formula is used to specify the content of cellulose powder in the dry residue. Instead of the shaped body of (i), three composition powders of cellulose powder / crospovidone = 100/0, 50/50, 0/100 are prepared, and the dry residue is removed through the operations (i) to (vii). The NIR second-order differential spectrum intensity is measured using InfraAlyzer 500 (manufacturer name: BRAN + LUBBE), and the coefficient of the above equation can be obtained from a three-point calibration curve.
When the peak of the second derivative value of the NIR absorption spectrum is not detected at 1692 nm, the total organic carbon (TOC) amount extracted from the dry residue with pure water (80 mL) is 0.0% with respect to the dry residue. The dry residue consists only of cellulose powder. When it exceeds 0.0%, disintegrants other than starch and crospovidone may be contained. Therefore, in order to remove them, the dry residue is dispersed with 50 mL of pure water and passed through a sieve having an opening of 10 μm. After removing particles other than cellulose powder, the filtrate is evaporated to dryness to obtain a dry residue (ix). Nevertheless, if the total organic carbon content (%) at the time of extraction of the residue with pure water exceeds 0.0%, it is dispersed with 50 mL of pure water (sonication or homogenizer treatment may be performed if necessary). The supernatant centrifuged at 2000 G is evaporated to dryness to give a dry residue (ix).
(Ix) <When the peak of the second derivative value of the NIR absorption spectrum is detected at 1692 nm in (viii)>
Weigh the dried residue (A; g, 4 to 4.5 g as a guide), put it in 80 ml of 1% NaOH aqueous solution , stir with a stirrer for 5 minutes, and then suction filter. Collect the filtrate and measure the volume (X; mL). The filtrate was acidified with hydrochloric acid (pH 2-3), and the total organic carbon content (TOC _{1% NaOH} ; mg / L) was measured with a total organic carbon meter (manufactured by Shimadzu Corporation, using TOC-VCSH, TC-IC method). To do. Since the residue is thoroughly washed with pure water, the total amount of organic carbon (%) at the time of extraction with pure water can be regarded as zero. Therefore, the amount of organic carbon derived from residual impurities in the cellulose powder contained in the residue is 1%. It becomes equal to the total organic carbon amount (%) at the time of NaOH aqueous solution extraction. Calculate according to the following.
-Cellulose powder residue amount (B; g) in the residue extracted from the molded product = A x C / 100
-Total organic carbon amount (Y; mg) in cellulose powder residue = (TOC _{1% NaOH /} 1000) x X-0.4 / 100 x (AB) x 1000
The above coefficient 0.4 is obtained when the molded product of (i) is 2.5 g of crospovidone powder, and the dry residue obtained through the treatment up to (vii) is used and extracted with 80 ml of 1% NaOH aqueous solution . Total organic carbon content (%).
・ Total organic carbon content (%) derived from residual impurities in the molded product residue extracted through acetone cleaning, ethanol cleaning, pure water cleaning, and ethanol cleaning.
= Y / (1000 × B) × 100 = Y / (10 × B)
<When the peak of the second derivative value of the NIR absorption spectrum is not detected at 1692 nm in (viii)>
Weigh the dry residue (A _H2O for extraction with pure water; g, A 1% NaOH for extraction with 1% aqueous _NaOH ; g), add 80 mL of pure water or 1% aqueous NaOH, and add in a beaker. After stirring for 5 minutes (using a stirrer), the dry residue is removed by suction filtration (using quantitative analysis filter paper, 5C, diameter 110 mm) to obtain a filtrate. After measuring the volume of the total amount of the filtrate (total amount when using pure water is V _H2O , total amount when using 1% NaOH aqueous solution is V _{1% NaOH} ; mL), acidify with hydrochloric acid (pH 2-3), The total organic carbon amount (TOC; mg / L) was measured with a total organic carbon meter (manufactured by Shimadzu Corporation, using TOC-VCSH, TC-IC method). The TOC when pure water is used is TOC _H2O , and the TOC when 1% NaOH aqueous solution is used is TOC _{1% NaOH} . The amount of organic carbon derived from residual impurities in the molded product residue is calculated by the following equation.
-Total organic carbon derived from residual impurities in molded product residue (%) = Total organic carbon (%) during extraction with 1% NaOH aqueous solution- Total organic carbon (%) during extraction with pure water
-Total organic carbon content (%) during extraction with 1% NaOH aqueous solution :
= [(TOC _{1% NaOH} (mg / L) / 1000) × V _{1% NaOH} (mL)] / A _{1% NaOH} × 1000 (mg) × 100
・ Total organic carbon content during pure water extraction (%):
= [(TOC _{H 2 O} (mg / L) / 1000) × V _{H 2 O} (mL)] / A _{H 2 O} × 1000 (mg) × 100

EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, these do not restrict | limit the scope of the present invention. In addition, the measuring method of each physical property in an Example and a comparative example is as follows.
1) Average degree of polymerization (-)
Value measured by the copper ethylenediamine solution viscosity method described in the 15th revised Japanese Pharmacopoeia, confirmation test (3) for crystalline cellulose.
2) Loss on drying (%)
1 g of the powder was dried at 105 ° C. for 3 hours, and the weight loss was expressed as a percentage by weight.
3) Volume average particle diameter of cellulose particles in cellulose dispersion (μm)
The particle size of the cellulose dispersion after hydrolysis or the cellulose dispersion before drying was determined by the following procedure. The cellulose dispersion was dropped on a microscope table, placed on a slide glass and dried, and then an optical microscope image was taken using a microscope. The optical microscope was subjected to image analysis processing (manufactured by Interquest Co., Ltd., apparatus: Hyper700, software: Imagehyper), and the long side of the rectangle with the smallest area among the rectangles circumscribing the particles was determined, and the cumulative number of particles was 50%. The diameter was defined as the average particle diameter. Image analysis processing was performed on at least 100 particles.
4) Weight average particle diameter (μm) of cellulose powder
The weight average particle size of the powder sample is determined by sieving 10 g of the sample for 10 minutes using a low-tap type sieve shaker (Sieve Shaker A type manufactured by Hira Kogakusho) or JIS standard sieve (Z8801-1987). Measured and expressed as 50% cumulative weight particle size.
5) Apparent specific volume (cm ³ / g)
A powder sample is roughly packed in a 100 cm ³ glass graduated cylinder over 2-3 minutes using a quantitative feeder, etc., and the upper surface of the powder layer is leveled with a soft brush like a brush and the volume is read. Was divided by the weight of the powder sample. The weight of the powder was appropriately determined so that the volume was about 70-100 cm ³ .
6) Apparent tapping density (g / cm ³ )
Using a commercially available powder property measuring machine (made by Hosokawa Micron, powder tester PT-R type), 100cm ³ cup is filled with powder, tapped 180 times, and then the volume of the cup is filled into the cup and the remaining powder layer Divided by the weight of
7) Amount of organic carbon derived from residual impurities (%)
Add pure water or 80% 1% NaOH aqueous solution to cellulose powder (W; mg, 5000 mg as a guide), stir for 5 minutes in a beaker (use stirrer), and then suction filtration (quantitative analysis filter paper, 5C, 110 mm diameter) ) To remove the cellulose powder to obtain a filtrate. The volume of the total amount of the filtrate was measured (the total amount when using water was V _H2O , the total amount when using 1% NaOH aqueous solution was V _{1% NaOH} ; mL), then acidified (pH 2-3) with hydrochloric acid, Total organic carbon content (TOC; mg / L) was measured with an organic carbon meter (manufactured by Shimadzu Corporation, using TOC-VCSH, TC-IC method). The TOC when pure water is used is TOC _H2O , and the TOC when 1% NaOH aqueous solution is used is TOC _{1% NaOH} . The amount of organic carbon derived from residual impurities was calculated by the following equation.
-Organic carbon amount (%) derived from residual impurities = Total organic carbon amount (%) during 1% NaOH aqueous solution extraction-Total organic carbon amount (%) during pure water extraction
-Total organic carbon content (%) during extraction with 1% NaOH aqueous solution :
= [(TOC _{1% NaOH} (mg / L) / 1000) × V _{1% NaOH} (mL)] / W (mg) × 100
・ Total organic carbon content during pure water extraction (%):
= [(TOC _H2O (mg / L) / 1000) x _VH2O (mL)] / W (mg) x 100
8) Water absorption capacity (cm ³ / g)
Pure water is added dropwise to 2 g of cellulose powder (in terms of dry matter), and if necessary, the amount of pure water dropped from the point where water oozes out on the surface while kneading with a spatula so that the cellulose powder blends with the dropped water. (V) was determined. The water absorption capacity was calculated by the following formula. The average value of triplicate measurements was used.
Water absorption capacity (cm ³ / g) = V / 2
9) Angle of repose (°)
When using a Sugihara-type angle of repose measuring instrument (slit size depth 10 x width 50 x height 140 mm, protractor installed at a position of 50 mm width) and dropping cellulose powder into the slit at a rate of 3 g / min with a quantitative feeder The dynamic self-fluidity of was measured. The angle of repose is the angle between the bottom of the apparatus and the cellulose powder forming layer.
10) Foreign substance amount (pieces / 50g)
50 g of the cellulose powder of the present invention was sieved by hand for 5 minutes, and the entire amount remaining on the 75 μm sieve was spread thinly on blue drawing paper, and the number of black foreign matters was counted visually for 15 minutes using a loupe.
11) Reactivity of cellulose powder and drug having amino group at its terminal A mixture of equal amounts of cellulose powder and aminophylline was stored in a sealed bottle (50 cm ³ ) at 60 ° C. for 30 days. About the said equal amount mixture after a preservation | save, the value of L, a, and b was calculated | required with the following formula | equation by the spectroscopic colorimeter (SE-2000, Nippon Denshoku Industries). It is considered that the lower the whiteness decrease, the lower the reactivity.
Whiteness = 100 − [(100−L) ² + (a ² + b ² )] ^0.5
L: Brightness a: Saturation (green to red) b: Saturation (blue to yellow)
12) Intraparticle pore volume (cm ³ / g)
The pore distribution was determined by mercury porosimetry using an Autopore 9520 type (trade name) manufactured by Shimadzu Corporation. Each sample powder used for the measurement was dried under reduced pressure at room temperature for 15 hours. From the obtained pore distribution, the total volume in the range of pore diameters of 0.1 to 15 μm was defined as the intraparticle pore volume based on the measurement at an initial pressure of 20 kPa.
13) Hardness [N]
Using a Schleingel hardness meter (Freund Sangyo Co., Ltd., 6D type), a cylindrical shaped product or tablet was loaded in the diameter direction of the cylindrical shaped product or tablet, and the load when it was broken was measured. The number average of five samples is shown. A cylindrical molded body of 100% cellulose powder was produced as follows. 0.5 g of a sample is put in a mortar (manufactured by Kikusui Seisakusho, using material SUK2, 3), and is 10 MPa with a flat paddle (manufactured by Kikusui Seisakusho, using material SUK2, 3) with a diameter of 1.13 cm (bottom area is 1 cm2). Compressed and held the stress for 10 seconds to produce a cylindrical molded body (the compressor used was PCM-1A manufactured by Aiko Engineering, and the compression speed was about 10 cm / min). The practical hardness is 50 N or more for a tablet having a diameter of 8 mm, and 70 N or more for a tablet having a diameter of 9 mm or more.
14) Tensile strength [MPa]
Tablet hardness: H [N], tablet diameter (maximum diameter for caplet tablets, etc.): D [mm], tablet thickness: T [mm] were obtained and calculated according to the following formula.
Tensile strength [MPa] = 2 × H ÷ (3.14 × D × T)
15) Tablet friability [%]
Measure the weight (Wa) of 20 tablets, put it in a tablet friability tester (PTFR-A, manufactured by PHARMA TEST), rotate at 25 rpm for 4 minutes, remove fine powder adhering to the tablets, and again The weight was measured (Wb) and calculated from equation (7).
Friction = 100 × (Wa−Wb) / Wa
In order to make a tablet that can withstand practical use, the friability needs to be 0.5% or less.

(Comparative Example 2)
A commercially available KP pulp (polymerization degree 840, level-off polymerization degree 145) was hydrolyzed in a 0.7% aqueous hydrochloric acid solution at 125 ° C. for 150 minutes, and then the hydrolysis residue was neutralized, washed and filtered to obtain a wet cake. After sufficiently grinding in a kneader, ethanol having a volume ratio of 1 was added, and the mixture was squeezed and filtered and then air-dried. The dry powder was obtained cellulose powder F to remove coarse particles crushed 40 mesh screen in a hammer mill (dry weight 3.0%, corresponding to Example 1 of Japanese official Akira 56-2047 JP). Table 1 shows the physical properties of the cellulose powder F.

（実施例５）
エテンザミド：２５０ｇ、セルロース粉末Ｂ：５００ｇ、噴霧乾燥乳糖：２２０ｇ（スーパータブ、ＤＭＶ製）、アルファー化デンプン「Ｓｗｅｌｓｔａｒ」ＰＤ−１（旭化成ケミカルズ製）：３０ｇを３分間ポリ袋中で混合し、植物性ステアリン酸マグネシウム（太平化学産業）：１０ｇを加え、さらにポリ袋中にて３０秒混合した。ロータリー打錠機（「クリーンプレス・コレクト１２ＨＵＫ」（商品名）菊水製作所製）で打錠し、打錠圧１２ｋＮで重量２００ｍｇ、直径８ｍｍ、１２Ｒの錠剤をオープンフィーダー、ターンテーブル回転数５４ｒｐｍにて作製した。得られた錠剤の物性を表２に示す。
（実施例６）
セルロース粉末Ｂをセルロース粉末Ｃとする以外は、実施例５と同様に操作した。得られた錠剤の物性を表２に示す。
（比較例８〜９）
セルロース粉末Ｂをセルロース粉末Ｆ又はＧとする以外は、実施例５と同様に操作した。得られた錠剤の物性を表２に示す。

(Comparative Example 7)
Cellulose powder K was obtained in the same manner as in Example 2 except that the hydrolysis temperature was 160 ° C. Table 1 shows the physical properties of the cellulose powder K.

(Example 5)
Ethenzamid: 250 g, cellulose powder B: 500 g, spray-dried lactose: 220 g (Supertub, manufactured by DMV), pregelatinized starch “Swelstar” PD-1 (manufactured by Asahi Kasei Chemicals): 30 g are mixed in a plastic bag for 3 minutes, Magnesium stearate (Taihei Chemical Industry): 10 g was added and further mixed in a plastic bag for 30 seconds. Tableting with a rotary tableting machine ("Clean Press Collect 12HUK" (trade name) manufactured by Kikusui Seisakusho), tableting pressure 12kN, weight 200mg, diameter 8mm, 12R tablets open feeder, turntable rotation speed 54rpm Produced. Table 2 shows the physical properties of the obtained tablets.
(Example 6)
The same operation as in Example 5 was performed except that the cellulose powder B was changed to the cellulose powder C. Table 2 shows the physical properties of the obtained tablets.
(Comparative Examples 8-9)
The same operation as in Example 5 was performed except that the cellulose powder B was changed to the cellulose powder F or G. Table 2 shows the physical properties of the obtained tablets.

Claims (10)

The average degree of polymerization is 100 to 300, the weight average particle size is more than 30 μm, 250 μm or less, the apparent specific volume is 2.0 cm ³ / g to less than 4.0 cm ³ / g, and the total organic carbon during 1% NaOH extraction Cellulosic powder having an amount of organic carbon derived from residual impurities defined by the amount (%)-total organic carbon amount (%) during extraction with pure water of 0.002 to 0.060%. Is 0.1 cm ³ / g or more pore volume within a particle, cellulose powder according to claim 1 is less than 0.265 cm ³ / g.   The cellulose powder according to claim 1, wherein 0 to 20 black visual foreign matters are contained in 50 g of the cellulose powder.   The molded object containing the cellulose powder of Claim 1 or 3.   The shaped body according to claim 4, wherein the shaped body is a tablet containing one or more active ingredients. Natural cellulosic material with a hydrochloric acid concentration of 0.05 to 0.15%, a hydrolysis temperature of 125 to 150 ° C., and a hydrolysis time of more than 110 minutes to 150 minutes or less, or a hydrochloric acid concentration of more than 0.15% Hydrolysis under conditions of 0.4%, hydrolysis temperature 125-150 ° C., and hydrolysis time 50-150 minutes, and then spray-drying the resulting dispersion at an inlet temperature of 150-300 ° C. to average polymerization degrees 100-300, greater than the weight average particle diameter of 30 [mu] m, 250 [mu] m or less, an apparent specific volume of 2.0 cm ³ / g or more ~4.0cm ³ / under g, and total organic carbon at 1% NaOH extraction (%) - A method for producing a cellulose powder, wherein a cellulose powder having a residual impurity-derived organic carbon content of 0.002 to 0.060% defined by the total organic carbon content (%) at the time of extraction with pure water is obtained. A molded body comprising one or more active ingredients, one or more additives selected from sugars, sugar alcohols, starches, and disintegrants, and cellulose powder, having a hardness of 50 to 100 N and a tensile strength of A molded article having 0.1 to 5.5 MPa, a friability of 0 to 0.5%, and a tablet diameter swelling ratio in acetone of 0 to 3.3%. The molded product according to claim 7, comprising 5 to 90% by weight of cellulose powder.   9. The total organic carbon content derived from residual impurities in a molded product residue extracted through acetone cleaning, ethanol cleaning, pure water cleaning, and ethanol cleaning of the molded product is 0.002 to 0.060%. Molded body. The total organic carbon content derived from residual impurities in cellulose powder extracted through acetone washing, ethanol washing, pure water washing, and ethanol washing of the molded body is 0.002 to 0.060%. Molded body.