CN108883129B - Tablet containing spherical adsorbent carbon for oral administration - Google Patents

Tablet containing spherical adsorbent carbon for oral administration Download PDF

Info

Publication number
CN108883129B
CN108883129B CN201780019126.5A CN201780019126A CN108883129B CN 108883129 B CN108883129 B CN 108883129B CN 201780019126 A CN201780019126 A CN 201780019126A CN 108883129 B CN108883129 B CN 108883129B
Authority
CN
China
Prior art keywords
tablet
additive
oral administration
spherical
gum
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201780019126.5A
Other languages
Chinese (zh)
Other versions
CN108883129A (en
Inventor
町佳树
神谷洋平
小野佐市
小西麻由
嶋田紘尚
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kureha Corp
Original Assignee
Kureha Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kureha Corp filed Critical Kureha Corp
Publication of CN108883129A publication Critical patent/CN108883129A/en
Application granted granted Critical
Publication of CN108883129B publication Critical patent/CN108883129B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/06—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of pills, lozenges or dragees
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/44—Elemental carbon, e.g. charcoal, carbon black
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms

Abstract

The purpose of the present invention is to provide a tablet containing spherical adsorbent carbon for oral administration having sufficient strength. The problem can be solved by the following tablets: a tablet comprising the spherical adsorbent carbon for oral administration of the present invention and a binding additive, wherein the spherical adsorbent carbon for oral administration is coated with the binding additive, and each spherical adsorbent carbon for oral administration is bonded via the coated binding additive, and the hardness of the tablet is 105N or more.

Description

Tablet containing spherical adsorbent carbon for oral administration
Technical Field
The present invention relates to a tablet containing spherical adsorbent carbon for oral administration. According to the present invention, a tablet having excellent hardness can be provided.
Background
Spherical adsorbent carbon for oral administration can be orally administered to adsorb harmful substances in the digestive tract, thereby treating kidney and liver dysfunction (patent document 1). In order for the spherical adsorbing carbon for oral administration to exert a pharmacological action of adsorbing a harmful substance, it is important to maintain the spherical shape of the spherical adsorbing carbon for oral administration and to maintain the pore structure thereof. The spherical adsorbent carbon for oral administration is sold, for example, under the trade names of "KREMEZIN (registered trademark) capsule 200 mg" and "KREMEZIN (registered trademark) fine particles subpackaged with 2 g" (hereinafter referred to as "KREMEZIN").
KREMEZIN is administered to patients with renal diseases at 6g per 1 day, and is administered in 3 times, so that 2g of KREMEZIN is administered per time. The fine particle size of 2g of KREMEZIN is about 4cm3The volume to be taken is never small. Thus, the administration time is 4cm3In the case of the fine granule (2), the spherical activated carbon is not dissolved in water, so that gritty sensation remains in the oral cavity and a patient who feels a foul feeling is also present.
On the other hand, in the case of the KREMEZIN capsule, gritty sensation in the oral cavity does not occur. However, since dead volume (dead volume) other than spherical activated carbon is generated in the capsule, the volume of the capsule is larger than that of the fine granulesThe product increased by a factor of about 1.5 (about 6 cm)3). Specifically, the volume is about 0.613cm3The capsules of (a) must be taken ten capsules at a time, and there are also patients who complain of large amounts of the capsules.
In addition, in order to eliminate the gritty feeling of the fine granules, or because the dosage of the capsules is large, a lot of patients who cannot take the fine granules and the capsules without taking a large amount of water exist. Among patients with renal disease or renal failure, there are patients who limit the amount of water intake, and these patients need to take as small an amount of water as possible at the same time when taking fine granules or capsules, and thus the patients who originally need to take a large amount of water are greatly affected.
Documents of the prior art
Patent document
Patent document 1: japanese examined patent publication No. 62-11611
Patent document 2: japanese patent laid-open No. 2006 and 8602
Patent document 3: international publication No. 2012/121202
Disclosure of Invention
Problems to be solved by the invention
In order to solve the above problems, it is considered to form spherical adsorbent carbon for oral administration into a tablet. However, unlike general drugs, spherical adsorbent carbon for oral administration cannot be tabletted by compression or the like (patent document 2). That is, since the spherical adsorbent carbon for oral administration is very hard, lacks deformability, and is brittle, as in the case of glass, the spherical adsorbent carbon for oral administration is broken and cannot maintain the spherical shape when subjected to tablet compression molding.
The present inventors have found the following facts: a tablet containing spherical adsorbent carbon for oral administration that is practically usable can be produced by kneading an additive for particle preparations that exhibits a film-forming ability (patent document 3). However, the strength of the obtained tablet was insufficient.
Accordingly, an object of the present invention is to provide a tablet containing spherical adsorbent carbon for oral administration having sufficient strength.
Technical scheme
The present inventors have conducted intensive studies on tablets containing spherical adsorbent carbon for oral administration (for example, spherical activated carbon) having sufficient strength, and as a result, have surprisingly found that the above problems can be solved by a tablet in which the spherical adsorbent carbon for oral administration is coated with a specific binding additive, and each of the spherical adsorbent carbon for oral administration is bonded via the coated binding additive, and which exhibits a hardness of 105N or more. It has also been found that: the tablet can be obtained by coating the spherical adsorbent carbon for oral administration with a binder additive, adding a solvent to the coated spherical adsorbent carbon for oral administration, and then compression-molding.
The present invention has been completed based on this finding.
Accordingly, the present invention relates to a tablet and a method for producing the same, wherein: [1] a tablet comprising spherical adsorbent carbon for oral administration and at least one binding additive selected from the group consisting of: propylene glycol alginate, gum ghatti, carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, guar gum, glucomannan, copovidone, gelatin, tamarind gum, tara gum, corn starch, tragacanth gum, sodium hyaluronate, hydroxyethyl cellulose, hydroxypropyl methylcellulose, pullulan, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, cross-linked starch phosphate, locust bean gum, wintersweet powder, fully pregelatinized starch, oxidized starch, and partially pregelatinized starch,
the spherical adsorbent carbon for oral administration is coated with the binding additive, each spherical adsorbent carbon for oral administration is bonded via the coated binding additive, and the hardness of the tablet is 105N or more;
[2] the tablet according to [1], wherein,
the spherical adsorption carbon for oral administration is spherical activated carbon;
[3] the tablet according to [2], wherein,
the average particle size of the spherical activated carbon is 0.02-1 mm;
[4] the tablet according to any one of [1] to [3], wherein,
when the volume ratio of the additive for bonding of five prisms each having 1mm on each side from the upper surface to the lower surface, which are positioned at the center and the end of a straight line extending from the center to the four sides when the tablet is observed from the upper surface, is analyzed by an X-ray CT microscope from the upper surface to the lower surface, 1mm of each of the five prisms3The ratio of the maximum value to the minimum value of the volume fraction of the additive for bonding of (2) is 100 or less;
[5] the tablet according to any one of [1] to [3], wherein,
in each of the divided bodies obtained by dividing the flat length of the tablet into three equal parts, when the volume ratio of a cube, which is located at the center of the flat length and at the center of the tablet as viewed from the upper surface and is formed by 2mm on each side, is analyzed by an X-ray CT microscope, the relative standard deviation of the volume ratios of the cubes of the three divided bodies is 5% or less; and
[6] the tablet according to any one of [1] to [3], wherein,
when the volume ratio of the additive for bonding of five prisms each having 1mm on each side from the upper surface to the lower surface, which are positioned at the center and the end of a straight line extending from the center to the four sides when the tablet is observed from the upper surface, is analyzed by an X-ray CT microscope from the upper surface to the lower surface, 1mm of each of the five prisms3The ratio of the maximum value to the minimum value of the volume ratio of the binding additive of (1) is 100 or less, and when the volume ratio of a cube formed by 2mm on each side, which is located at the center of the length in the flat direction and at the center of the tablet as viewed from the upper surface, is analyzed by an X-ray CT microscope in each divided body obtained by dividing the length of the tablet in the flat direction into three parts, the relative standard deviation of the volume ratios of the cubes of the three divided bodies is 5% or less; and
[7] a method for producing a tablet, comprising the steps of:
(1) spraying or dripping a solution containing at least one binding additive selected from the group consisting of propylene glycol alginate, gum ghatti, carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, guar gum, glucomannan, copovidone, gelatin, tamarind gum, tara gum, corn starch, tragacanth gum, sodium hyaluronate, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, pullulan, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, cross-linked starch phosphate, locust bean gum, wintersweet powder, fully pregelatinized starch, oxidized starch, and partially pregelatinized starch on the spherical adsorbent carbon for oral administration, and coating the spherical adsorbent carbon for oral administration with the binding additive;
(2) a compression molding step of adding a solvent to the coated oral administration spherical adsorbent carbon, and then performing compression molding to obtain a molded body; and
(3) the obtained molded article was dried.
Advantageous effects
According to the tablet containing spherical adsorbent carbon for oral administration (for example, spherical activated carbon) of the present invention, a tablet having excellent hardness can be provided. According to the tablet of the present invention, compared with a capsule, a tablet having a reduced volume and improved taking properties can be provided. That is, in the case of capsules, the volume is about 0.613cm3The capsule of (a) must take ten capsules at a time, and there are also patients who complain of a large dose, to which the tablet of the present invention can reduce the volume to 65% of the volume in the case of capsules (about 4 cm)3) The serviceability is improved. Further, the tablet of the present invention can provide a tablet which is improved in the drawbacks of gritty feeling and the like in terms of taking properties as compared with fine granules. According to the tablet of the present invention, it is possible to provide a tablet which can sufficiently exert the function of an adsorbent for oral administration without breaking the pore structure while maintaining the spherical shape of the spherical adsorbent carbon for oral administration.
Drawings
Fig. 1 is a diagram schematically showing the positions of three cubes for analyzing the volume fraction of a tablet in the tablet of the present invention from the upper surface (a) and the side surface (B).
Fig. 2 is an analysis image of an X-ray CT microscope (nano3DX) showing the local presence of the additive in the tablet (a) obtained by the production method of the present invention and the tablet (B) obtained by a conventional kneading method.
Fig. 3 is a diagram schematically showing the positions of five prisms for analyzing the volume fraction of the additive in the tablet of the present invention from the upper surface (a) and the side surface (B).
Fig. 4 is a graph showing changes in the volume ratio of the additive in the tablet of the present invention analyzed by an X-ray CT microscope from the upper surface to the lower surface.
FIG. 5 is a photograph showing that the spherical activated carbon (A) obtained by the kneading method remains in the stirring and granulating machine and (B) adheres to the molding die.
Fig. 6 is a graph and a photograph showing the division of the additive and the spherical activated carbon when the volume ratio of the additive was calculated by the analysis software ImageJ based on the brightness information of 256 levels.
Detailed Description
[1] tablets containing spherical adsorbent charcoal for oral administration
The tablet containing spherical adsorbent carbon for oral administration of the present invention contains spherical adsorbent carbon for oral administration and at least one binding additive selected from the group consisting of: propylene glycol alginate, gum ghatti, carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, guar gum, glucomannan, copovidone, gelatin, tamarind gum, tara gum, corn starch, tragacanth gum, sodium hyaluronate, hydroxyethyl cellulose, hydroxypropyl methylcellulose, pullulan, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, cross-linked starch phosphate, locust bean gum, wintersweet powder, fully pregelatinized starch, oxidized starch, and partially pregelatinized starch. The spherical adsorbent carbon for oral administration is coated with the binding additive, and each spherical adsorbent carbon for oral administration is bonded via the coated binding additive, and the hardness of the tablet is 105N or more.
Spherical adsorbent charcoal for oral administration
The spherical adsorbent carbon for oral administration is not particularly limited as long as it is a spherical adsorbent carbon for oral administration that can be used for medical purposes, and is preferably a spherical active carbon for oral administration, that is, a spherical active carbon that can be used for medical purposes. In the present specification, a description will be given of an example of spherical adsorbent carbon for oral administration using a spherical activated carbon.
For example, the average particle size of the spherical activated carbon contained in the tablet of the present invention is not particularly limited, but is preferably 0.02 to 1mm, more preferably 0.03 to 0.90mm, and still more preferably 0.05 to 0.80 mm. The particle diameter (diameter) of the spherical activated carbon is preferably in the range of 0.01 to 2mm, more preferably 0.02 to 1.5mm, and still more preferably 0.03 to 1 mm.
"spherical activated carbon" means an activated carbon having a BET specific surface area of 100m2A BET specific surface area of the spherical activated carbon used in the present invention is preferably 500 m/g or more2A value of at least g, more preferably 700m2(ii) at least g, more preferably 1300m2A value of 1650m or more, particularly 1650m2More than g.
In order to maintain the pore structure and exert pharmacological effects such as adsorption of harmful substances, the form of the spherical adsorbent carbon for oral administration (for example, spherical activated carbon) contained in the tablet is preferably a spherical form that maintains the spherical adsorbent carbon for oral administration. That is, since the adsorption capacity, for example, the selective adsorption rate of the toxic substance is influenced by the diameter, the average particle diameter, the specific surface area, and the pore volume within a specific pore diameter range, it is desirable to maintain the spherical shape that does not damage the spherical adsorbent carbon for oral administration and affects the diameter or the average particle diameter, and to maintain the pore structure that affects the specific surface area and the pore volume. Further, by maintaining the spherical shape, side effects such as constipation can be prevented.
Additives for binding
The binding additive for tablets of the present invention comprises: propylene glycol alginate, gum ghatti, carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, guar gum, glucomannan, copovidone, gelatin, tamarind gum, tara gum, corn starch, tragacanth gum, sodium hyaluronate, hydroxyethyl cellulose, hydroxypropyl methylcellulose, pullulan, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, cross-linked starch phosphate, locust bean gum, wintersweet powder, fully pregelatinized starch, oxidized starch, partially pregelatinized starch, or a combination thereof. The spherical adsorbent carbon for oral administration is coated with a binding additive which makes the tablet of the present invention, in which the spherical adsorbent carbon for oral administration is bound, have a hardness of 105N or more.
The tablet of the present invention is characterized by containing the above-mentioned additive for binding as an additive, but may contain an additive other than the additive for binding (hereinafter, sometimes referred to as "other additive"). That is, the tablet of the present invention may contain a sticking additive and other additives as additives, or may contain only a sticking additive as an additive. In other words, the additive used in the present invention may be formed of a bonding additive or other additives, or may be formed of a bonding additive.
(other additives)
Additives that can be used as additives other than the additive for adhesion (other additives) will be described below.
Generally, additives used in pharmaceuticals are described in "pharmaceutical additives book 2016", and examples thereof include: excipient, lubricant, disintegrant, surfactant, binder, etc. The functions of the excipient, the lubricant, the disintegrant, and the binder are not necessarily singular, and for example, crystalline cellulose classified as an excipient often functions as a disintegrant, and also functions as a binder for improving moldability in the direct compression method. Therefore, the respective functions of the excipient, the lubricant, the disintegrant, and the binder may be repeated in some cases. Examples of the excipient, lubricant, disintegrant, and binder are described below, and additives not classified as these additives may be used as other additives.
The excipient is mainly an additive for extending (bulking agent) or diluting (diluting agent), and specifically, there can be mentioned: starch, calcium hydrogen phosphate, synthetic aluminum silicate, or magnesium trisilicate, etc.
The binder is an additive for providing a binding force to the main agent and the extender and molding the same, and is an additive for maintaining the dosage form, preventing damage in the packaging step and during transportation, and improving the mechanical strength. Specifically, there may be mentioned: crystalline cellulose, low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose, powdered cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, starch, fully pregelatinized starch, partially pregelatinized starch, dextrin, acacia, sodium alginate, tragacanth, purified gelatin, polyvinyl alcohol, or povidone, and the like.
Further, the disintegrant is an additive for wetting in the digestive tract to disintegrate the preparation and disperse it into fine particles when the tablet is taken. Specifically, there may be mentioned: carboxymethyl cellulose, carboxymethyl cellulose calcium, low-substitution hydroxypropyl cellulose, hydroxypropyl methyl cellulose, powdered cellulose, starch, sodium carboxymethyl starch, hydroxypropyl starch, and the like.
The lubricant is an additive having a function of improving various properties such as flowability, filling property, adhesion property, and moldability of the powder in tableting, and is an additive for improving the quality and production efficiency of tablets. Specifically, there may be mentioned: sucrose fatty acid ester, talc, magnesium stearate, stearic acid, or the like.
Examples of the surfactant include: alkylallyl polyether alcohol, higher alcohol sulfate, N-cocoyl-L-arginine ethyl ester DL-pyrrolidone carboxylate, sodium N-cocoyl-N-methylaminoethyl sulfonate, cholesterol, self-emulsifying glyceryl monostearate, sucrose fatty acid ester, squalane, stearyl alcohol, polyethylene glycol 40stearate (polyoxyl 40stearate), cetyl alcohol, cetomacrogol 1000, diethyl sebacate, sorbitan fatty acid ester, sorbitan sesquioleate, sodium dodecylbenzenesulfonate, sorbitan trioleate, nonylphenoxy polyoxyethylene ethane sulfate ammonium solution, polyoxyethylene octylphenyl ether, oleylamine polyoxyethylene, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene sorbitan monolaurate, sodium lauryl sulfate, polyoxyethylene sorbitan monolaurate, polyoxyethylene lauryl sulfate, polyoxyethylene octylphenyl ether, oleylamine polyoxyethylene, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, Polyoxyethylene sorbitol beeswax, polyoxyethylene nonylphenyl ether, polyoxyethylene (20) polyoxypropylene (20) glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (124) polyoxypropylene (39) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (10) polyoxypropylene (4) hexadecyl ether, polyoxyethylene (2E.O.) sodium lauryl ether sulfate (70%), polyoxyethylene 35 castor oil, polysorbate 20, polysorbate 60, polysorbate 80, polyethylene glycol 400, sorbitan monooleate, glyceryl monostearate, sorbitan monolaurate, N-coconut oil fatty acid L-arginine ethyl ester DL-pyrrolidone carboxylate, lauryl dimethyl amine oxide liquid, Lauryl pyrrolidone, sodium lauryl sulfate, lauric acid diethanolamide, sodium lauroyl sarcosinate, lauroyl lauryl alcohol (lauromarogol), polyoxyethylene lauryl ether sodium phosphate or polyoxyethylene oleyl ether phosphate (8MOL), and the like.
(content of Additives for binding)
The weight ratio of the spherical adsorbent carbon for oral administration (for example, spherical activated carbon) to the binding additive is not particularly limited as long as the effects of the present invention can be obtained, and the content of the binding additive in the tablet of the present invention is preferably 1 wt% or more, more preferably 1.5 wt% or more, and still more preferably 2 wt% or more. If the amount of the binder additive is too small, the hardness of the resulting tablet may be reduced. The upper limit of the additive for adhesion is not limited, and the additive for adhesion is preferably 35% by weight or less, more preferably 30% by weight or less, and still more preferably 25% by weight or less. If the amount of the binder additive is too large, the volume of the tablet may increase, and the dosage of the tablet may increase. From the viewpoint that the hardness of the obtained tablet is easily 105N or more, the content of the binder additive in the tablet of the present invention is preferably 1 to 35 wt% (or may be 1 to 30 wt% or 1 to 25 wt%), more preferably 1.5 to 30 wt% (or may be 1.5 to 25 wt% or 1.5 to 20 wt%), and still more preferably 2 to 25 wt% (or may be 2 to 20 wt% or 2 to 17 wt%).
The tablet of the present invention may contain other additives as additives, and the weight ratio of the binding additive to the other additives is not particularly limited as long as the effect of the present invention can be obtained, but the other additives are preferably 10000 parts by weight or less, more preferably 1000 parts by weight or less, further preferably 100 parts by weight or less, and most preferably 50 parts by weight or less with respect to 100 parts by weight of the binding additive. If the amount of the other additives is too large, the hardness of the resulting tablet may be lowered. The lower limit of the weight ratio is not particularly limited, and the content of the other additive may be, for example, 0.1 part by weight or more, 1 part by weight or more, or 10 parts by weight or more, based on 100 parts by weight of the binder additive.
(wrap)
In the tablet of the present invention, spherical adsorbent carbon (for example, spherical activated carbon) for oral administration is coated with the binding additive, and the spherical activated carbon is bound via the coated binding additive.
Hardness
The hardness of the tablet of the present invention is not particularly limited as long as it is 105N or more, and is preferably 110N or more, in some cases 120N or more, in some cases 140N or more, in some cases 160N or more, in some cases 180N or more, and in some cases 200N or more. By setting the hardness to 105N or more, the dosage form can be maintained, and breakage during packaging and transportation can be more effectively prevented. The upper limit of the hardness is not particularly limited, and may be, for example, 500N or less, 400N or less, or 350N or less. The range of the hardness is not particularly limited, and examples thereof include: 105 to 500N, 105 to 400N, 105 to 350N, 110 to 500N, 110 to 400N, 110 to 350N, 120 to 500N, 120 to 400N, 120 to 350N, 140 to 500N, 140 to 400N, 140 to 350N, 160 to 500N, 160 to 400N, 160 to 350N, 180 to 500N, 180 to 400N, 180 to 350N, 200 to 500N, 200 to 400N, 200 to 350N, and the like.
Other problems caused by the kneading method, means for solving the problems, and effects thereof
When the kneading method, which is a conventional method, is used, the obtained tablet has insufficient strength, and the following problems are involved. That is, in the case of producing tablets by kneading, the yield of the spherical activated carbon is low. In addition, the uniformity of the spherical adsorbent carbon for oral administration and the binder additive in the tablets obtained by the kneading method was low. In addition, the adsorption amount of DL- β -aminoisobutyric acid in the tablet obtained by the kneading method may be decreased as compared with the granule or capsule.
The present inventors have conducted intensive studies on tablets having a high yield of spherical adsorbent carbon for oral administration and a high uniformity of spherical adsorbent carbon for oral administration and a binder additive, and a process for producing the same, and as a result, they have surprisingly found the following facts: by spraying or dropping a solution containing a binding additive onto spherical adsorbent carbon for oral administration and producing tablets by compression molding, the yield of spherical adsorbent carbon for oral administration is dramatically improved, and tablets having dramatically improved uniformity of spherical adsorbent carbon for oral administration and binding additive are obtained. More specifically, the following description will be made of the uniformity of the volume ratio of the tablet and the uniformity of the local presence of the additive.
According to the method for producing a tablet containing a spherical adsorbent carbon for oral administration (for example, a spherical activated carbon), the yield of the spherical adsorbent carbon for oral administration to be used can be improved. In addition, the tablet containing the spherical adsorbent carbon for oral administration obtained by the production method of the present invention prevents the spherical adsorbent carbon for oral administration and the binding additive from being locally present, and improves the uniformity of the spherical adsorbent carbon for oral administration and the binding additive. Thus, the hardness of the resulting tablet is improved. The tablet can exhibit excellent adsorption ability of DL- β -aminoisobutyric acid. That is, according to the method for producing a tablet of the present invention, as compared with the kneading method described in patent document 3, the yield of the spherical adsorbent carbon for oral administration in the method for producing a tablet can be improved, the hardness can be improved, and the adsorption ability of DL- β -aminoisobutyric acid can be expected to be improved.
Uniformity of volume ratio of tablet
The volume fraction within the tablet of the invention is preferably uniform. That is, in comparison with a tablet containing a general compound as an active ingredient, since the tablet of the present invention contains spherical adsorbent carbon for oral administration (for example, spherical activated carbon) as an active ingredient, it is apparent from fig. 1 and the like that there are gaps between the spherical adsorbent carbons for oral administration. Consider that: if there are dense voids and coarse voids, the hardness, wear resistance, and the like of the tablet decrease. In other words, consider that: if the volume ratio of the spherical adsorbent carbon for oral administration and the additive in the tablet is not uniform, the hardness, the degree of abrasion, and the like of the tablet are reduced. That is, the volume ratio of the tablet is uniform, whereby the hardness, the degree of abrasion, and the like of the tablet can be further improved.
The uniformity of the volume ratio of the tablet of the present invention can be specified, for example, by the following method. That is, the uniformity of the tablet can be judged to be high in the following cases: when the volume ratio of a cube, which is located at the center of the flat direction length and at the center of the tablet as viewed from the top surface and is formed by 2mm on each side, is analyzed by an X-ray CT microscope for each divided body obtained by dividing the flat direction length of the tablet into three equal parts, the relative standard deviation of the cube volume ratios of the three divided bodies is 5% or less.
As shown in fig. 1, the tablet has a flat shape except for a round pellet shape. Fig. 1(a) shows a flat tablet as viewed from the upper surface, and fig. 1(B) shows a flat tablet as viewed from the side surface. When the tablet is viewed from the top surface, the tablet often has a circular, elliptical, rectangular, or rectangular shape as shown in fig. 1(a), but the tablet usually has a symmetrical form, and "a cube at the center of the tablet when viewed from the top surface" can be specified as shown by the square broken line in fig. 1 (a). When the flat tablet is viewed from the side, the flat length in the flat direction may be divided into three equal divided bodies as shown in fig. 1(B), and the "cube located at the center of the flat length" may be specified in each divided body as shown by the broken line. Therefore, "three cubes formed of 2mm on each side located at the center of the length in the flat direction and at the center of the tablet as viewed from the upper surface" can be specified. In the case where the tablet is a pellet in a spherical shape, the flat direction may be set to any direction, and the "center of the length in the flat direction" and the "center of the tablet as viewed from the upper surface" and the like may be specified.
For the three cubes, the volume fraction of each cube can be calculated by analyzing with an X-ray CT microscope. Then, the relative standard deviation of the volume ratios of the three cubes obtained was calculated, and when the relative standard deviation was 5% or less, it was judged that the uniformity of the tablet was high.
In the case where the length of the tablet in the flat direction is less than 6mm, three cubes each formed by 2mm on each side may partially overlap. However, even when three cubes are superimposed, the relative standard deviation of the volume ratios of the three divided bodies can be calculated, and when the relative standard deviation is 5% or less, it can be judged that the uniformity of the tablet is high.
The relative standard deviation of the volume ratio is preferably 4.7% or less, and more preferably 4.5% or less. The smaller the relative standard deviation, the more the uniformity is improved, and the hardness, abrasion degree, and the like of the tablet can be improved. Therefore, the lower limit of the relative standard deviation of the volume fraction is preferably 0% or more, and practically may be 0.1% or more, 0.5% or more, and 0.7% or more. The relative standard deviation of the volume fraction may be, for example, 0.1 to 5%, or 0.5 to 4.7%, or 0.7 to 4.5%. Uniformity of local Presence of additives
The distribution of the additive in the tablet of the present invention is preferably uniform, that is, the volume fraction uniformity of the additive in the tablet of the present invention is preferably superior to that in a conventional tablet containing spherical activated carbon. For example, as shown in fig. 2(B), in a tablet containing spherical activated carbon obtained by a conventional kneading method, the additive is unevenly distributed in a portion close to the surface of the upper portion of the tablet (the additive is shown by white), and the uniformity of the additive is low. Consider that: in the case of an offset of the additive, the hardness or abrasion of the tablet, etc. decreases. In other words, consider that: if the volume ratio of the additive is not uniform in the tablet, the hardness, the degree of abrasion, and the like of the tablet decrease. That is, the volume ratio of the additive is uniform, whereby the hardness, the degree of abrasion, and the like of the tablet can be further improved.
The uniformity of the volume fraction of the additive of the present invention can be specified, for example, by the following method. The uniformity of the distribution of the additive can be judged to be high in the following cases: when the volume ratio of the additive of five prisms each having 1mm on each side from the upper surface to the lower surface, which are positioned at the center and the end of a straight line extending from the center to the four sides in the case of observing the tablet from the upper surface, was analyzed by an X-ray CT microscope from the upper surface to the lower surface, each 1mm of the five prisms3The ratio of the maximum value to the minimum value of the additive volume ratio of (2) is 100 or less. That is, in the tablet of the present invention, the ratio of the maximum value to the minimum value of the additive volume ratio in the five prisms is 100 or less. On the other hand, in the conventional tablet, the ratio of the maximum value to the minimum value of the additive volume ratio in five prisms exceeds 100, and therefore the hardness, the abrasion degree, and the like of the tablet are reduced.
As shown in fig. 3, the tablet has a flat shape except for a round pellet shape. Fig. 3(a) shows a flat tablet as viewed from the upper surface, and fig. 3(B) shows a flat tablet as viewed from the side surface. When the tablet is viewed from the top surface, the tablet often has a circular, elliptical, quadrangular, or rectangular shape as shown in fig. 3(a), but the tablet usually has a symmetrical shape, and "a prism at the center when viewed from the top surface" can be specified as shown by a broken line of a C square in fig. 3 (a). In addition, "a prism located at an end of a straight line extending from the center to four directions" shown by N, E, S in fig. 3(a) and a dotted line of a W square may be specified. When the flat tablet is viewed from the side, the prism is located from the upper surface to the lower surface in the flat direction of the tablet, as shown by the broken line in fig. 3 (B). Therefore, "a prism at the center portion in the case of viewing from the upper surface" and "a prism at the end of a straight line extending from the center of the tablet to four directions" can be specified.
For the five prisms, the additive volume fraction for each prism was calculated by X-ray CT microscopy from the top surface to the bottom surface. Furthermore, it is possible to calculate every 1mm at any position of the prism3The volume ratio of the additive (2) was determined to be 1mm per unit3The maximum value and the minimum value of the additive volume ratio of (1).
In the present invention, at each 1mm3When the ratio of the maximum value to the minimum value of the additive volume ratio of (2) is 100 or less, it can be judged that the uniformity of the distribution of the additive is high, but the ratio of the maximum value to the minimum value is preferably 99 or less, more preferably 98 or less, and further preferably 96 or less. The smaller the ratio of the maximum value to the minimum value, the more the uniformity of the additive is improved, and the hardness, the degree of abrasion, and the like of the tablet can be improved. Therefore, the lower limit of the ratio of the maximum value to the minimum value is preferably 1 or more, and practically may be 2 or more, 4 or more, or 6 or more. The ratio of the maximum value to the minimum value may range from 1 to 100, 2 to 99, 4 to 98, and 6 to 96, for example.
Depending on the shape of the tablet, the height of the prism at the N, E, S and W positions may be lower than that of the prism at the C position, and in this case, the height can be measured every 1mm by finding3The "ratio of the maximum value to the minimum value of the volume ratio of the additive" can be calculated as the volume ratio of the additive from the upper surface to the lower surface of the volume ratio of the additive of (1).
(X-ray CT microscope)
The X-ray CT microscope for analyzing the volume fraction of the tablet and the volume fraction of the additive in the present invention is an apparatus as follows: the inside of a sample such as a material or a tablet can be observed in a planar (2D) or a stereoscopic (3D) manner with a high resolution of a submicron order. The fine structure of a material, a tablet, or the like can be analyzed with high resolution. For example, as described in the present example, the volume ratio of the tablet formed of the spherical activated carbon and the additive may be analyzed, or only the volume ratio of the additive may be analyzed.
As the X-ray CT microscope, commercially available "nano 3 DX" (high resolution 3 DX-ray microscope: Kabushiki Kaishi, Ltd.) and "three-dimensional measurement X-ray CT apparatus TDM series: Katsuku Kabushiki Kaishi" having a high resolution of 1 μm or less can be used, and the volume ratio of the tablet or the volume ratio of the additive can be calculated by using software attached to the apparatus, image processing software ImageJ, or the like.
Method for producing [2] tablet
The method for producing a tablet of the present invention comprises the steps of:
(1) spraying or dripping a solution containing at least one binding additive selected from the group consisting of propylene glycol alginate, gum ghatti, carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, guar gum, glucomannan, copovidone, gelatin, tamarind gum, tara gum, corn starch, tragacanth gum, sodium hyaluronate, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, pullulan, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, cross-linked starch phosphate, locust bean gum, wintersweet powder, fully pregelatinized starch, oxidized starch, and partially pregelatinized starch onto spherical adsorbent carbon (e.g., spherical activated carbon) for oral administration, and coating the spherical adsorbent carbon for oral administration with the binding additive;
(2) a compression molding step of adding a solvent to the coated oral administration spherical adsorbent carbon, and then performing compression molding to obtain a molded body; and
(3) the obtained molded article was dried.
The "binding additive" used in the method for producing a tablet of the present invention may be the binding additive described in the section of [1] tablet containing spherical adsorbent carbon for oral administration.
A coating step (1)
Coating step (1): a solution containing at least one binding additive selected from the group consisting of propylene glycol alginate, gum ghatti, carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, guar gum, glucomannan, copovidone, gelatin, tamarind gum, tara gum, corn starch, tragacanth gum, sodium hyaluronate, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, pullulan, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, cross-linked starch phosphate, locust bean gum, wintersweet powder, fully pregelatinized starch, oxidized starch, and partially pregelatinized starch is sprayed onto spherical adsorbent carbon for oral administration (for example, spherical activated carbon), and the spherical adsorbent carbon for oral administration is coated with the binding additive. As the coating method, a spray method is used. Examples of the spraying method include: a top spray pattern, a tangential spray pattern, a bottom spray pattern, a side spray pattern, or the like.
For example, in the case of the top spray method, a spray solution is prepared by dissolving a binder additive and other additives in a solvent. Then, for example, spherical adsorbent carbon for oral administration is charged into a rotary fluidized coating apparatus or a fluidized bed granulator, and a spray liquid is sprayed from above.
The solvent used for the spray liquid is not particularly limited, and all organic solvents usable as pharmaceutical additives can be used, and examples thereof include: water, acetic acid, acetone, anisole, 1-butanol, 2-butanol, N-butyl acetate, t-butyl methyl ether, cumene, dimethyl sulfoxide, ethanol, ethyl acetate, diethyl ether, ethyl formate, formic acid, heptane, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methyl ethyl ketone, 2-methyl-1-propanol, pentane, 1-pentanol, 1-propanol, 2-propanol, propyl acetate, tetrahydrofuran, acetonitrile, chlorobenzene, chloroform, cyclohexane, 1, 2-dichloroethylene, dichloromethane, N-dimethylacetamide, N-dimethylformamide, 1, 4-dioxane, 2-ethoxyethanol, ethylene glycol, formamide, hexane, methanol, 2-methoxyethanol, N-butyl acetate, N-methyl acetate, N-dimethylformamide, N-dimethylformamide, 1, 4-dioxane, 2-ethoxyethanol, ethylene glycol, formamide, Methyl butyl ketone, methyl cyclohexane, N-methyl pyrrolidone, nitromethane, pyridine, sulfolane, tetralin, toluene, 1, 2-trichloroethylene, xylene, or the like. The surfactant is not particularly limited, and examples thereof include: alkylallyl polyether alcohol, higher alcohol sulfate, N-cocoyl-L-arginine ethyl ester DL-pyrrolidone carboxylate, sodium N-cocoyl-N-methylaminoethyl sulfonate, cholesterol, self-emulsifying glyceryl monostearate, sucrose fatty acid ester, squalane, stearyl alcohol, polyethylene glycol 40stearate, cetyl alcohol, cetomacrogol 1000, diethyl sebacate, sorbitan fatty acid ester, sorbitan sesquioleate, sodium dodecylbenzenesulfonate, sorbitan trioleate, nonylphenoxy polyoxyethylene ethane sulfate ammonium solution, polyoxyethylene octylphenyl ether, oleylamine polyoxyethylene, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene sorbitan monolaurate, sodium lauryl ether, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan, Polyoxyethylene sorbitol beeswax, polyoxyethylene nonylphenyl ether, polyoxyethylene (20) polyoxypropylene (20) glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (124) polyoxypropylene (39) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (10) polyoxypropylene (4) hexadecyl ether, polyoxyethylene (2E.O.) sodium lauryl ether sulfate (70%), polyoxyethylene 35 castor oil, polysorbate 20, polysorbate 60, polysorbate 80, polyethylene glycol 400, sorbitan monooleate, glyceryl monostearate, sorbitan monolaurate, N-coconut oil fatty acid L-arginine ethyl ester DL-pyrrolidone carboxylate, lauryl dimethyl amine oxide liquid, Lauryl pyrrolidone, sodium lauryl sulfate, lauric acid diethanolamide, sodium lauroyl sarcosinate, lauroyl lauryl alcohol (lauromarogol), polyoxyethylene lauryl ether sodium phosphate or polyoxyethylene oleyl ether phosphate (8MOL), and the like.
The amount of the binder additive to the solvent is not particularly limited as long as the binder additive is substantially uniformly coated on the spherical adsorbent carbon for oral administration (for example, spherical activated carbon), and the binder additive is preferably 0.01 to 100 w/v%, more preferably 0.1 to 50 w/v%, and still more preferably 1 to 15 w/v% to the solvent.
Step (2) of compression Molding
The compression molding step (2) is a step of adding a solvent to the coated adsorbent spherical carbon for oral administration (for example, spherical activated carbon), and then compression molding the mixture. For example, a solvent is added to the coated spherical adsorbent carbon for oral administration, and the mixture is compression-molded and then dried to obtain a tablet having a hardness of 105N or more.
Examples of the solvent include an organic solvent, water, and a mixture thereof. The volume ratio of the organic solvent to water in the mixed liquid of the organic solvent and water is not particularly limited, but is preferably 5:95 to 95:5, more preferably 15:85 to 85:15, and still more preferably 30:70 to 70: 30. When the amount is within the above range, water can permeate into the binder additive for coating the spherical adsorbent carbon for oral administration.
(organic solvent)
The organic solvent usable in the production method is not particularly limited as long as the effects of the present invention can be obtained, and examples thereof include: acetic acid, acetone, anisole, 1-butanol, 2-butanol, N-butyl acetate, t-butyl methyl ether, cumene, dimethyl sulfoxide, ethanol, ethyl acetate, diethyl ether, ethyl formate, formic acid, heptane, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methyl ethyl ketone, 2-methyl-1-propanol, pentane, 1-pentanol, 1-propanol, 2-propanol, propyl acetate, tetrahydrofuran, acetonitrile, chlorobenzene, chloroform, cyclohexane, 1, 2-dichloroethylene, dichloromethane, N-dimethylacetamide, N-dimethylformamide, 1, 4-dioxane, 2-ethoxyethanol, ethylene glycol, formamide, hexane, methanol, 2-methoxyethanol, N-butyl acetate, N-butyl methyl ether, cumene, dimethyl sulfoxide, ethyl alcohol, 2-propanol, propyl acetate, tetrahydrofuran, acetonitrile, chlorobenzene, chloroform, 1, 2-dichloroethylene, dichloromethane, N-dimethylacetamide, methyl butyl ketone, methyl cyclohexane, N-methyl pyrrolidone, nitromethane, pyridine, sulfolane, tetralin, toluene, 1, 2-trichloroethylene, xylene, or the like. Drying step (3)
In the method for producing a tablet of the present invention, the obtained molded body is dried. The drying method is not limited as long as the solvent of the molded article is evaporated, and examples thereof include: freeze drying, drying under reduced pressure, air-blowing drying, natural drying, or heating drying.
For example, in the case of heat drying, the heating temperature is not particularly limited, and is, for example, preferably 50 to 200 ℃ and preferably 80 to 180 ℃. The heating time is also not particularly limited, but is preferably 10 minutes to 3 hours, and more preferably 30 minutes to 2 hours.
However, when the heating temperature is high, the heating time can be shortened, and the heating temperature and the heating time can be appropriately determined by those skilled in the art.
The moisture content of the tablet obtained in the drying step (3) is not particularly limited, but is preferably 0.01 to 20% by weight, and more preferably 0.1 to 10% by weight.
Examples
The present invention will be specifically described below with reference to examples, but the scope of the present invention is not limited to these examples.
Production example 1: production of porous spherical carbonaceous Material
The porous spherical carbonaceous material was obtained in the same manner as in example 1 of Japanese patent application No. 3522708 (Japanese patent application laid-open No. 2002-308785). The specific operation is as follows.
68kg of petroleum pitch (softening point: 210 ℃, quinoline insoluble content: 1 wt% or less, H/C atomic ratio: 0.63) and 32kg of naphthalene were charged into a pressure-resistant vessel having an internal volume of 300L and equipped with a stirring blade, and melt-mixed at 180 ℃ and then cooled to 80 to 90 ℃ to extrude the mixture, thereby obtaining a tape-shaped molded article. Then, the belt-shaped formed body is crushed so that the ratio of the diameter to the length is about 1 to 2.
The crushed material was put into an aqueous solution prepared by dissolving 0.23 wt% of polyvinyl alcohol (degree of saponification: 88%) and heating the solution to 93 ℃, and after the crushed material was dispersed by stirring to be spheroidized, the aqueous solution of polyvinyl alcohol was replaced with water to be cooled, and the resultant was cooled at 20 ℃ for 3 hours to solidify asphalt and precipitate naphthalene crystals, thereby obtaining a slurry of a spherical asphalt molded body.
After most of the water was removed by filtration, naphthalene in the asphalt molded body was extracted and removed by n-hexane about 6 times the weight of the spherical asphalt molded body. The porous spherical asphalt obtained as described above was heated to 235 ℃ while introducing heated air using a fluidized bed, and then was maintained at 235 ℃ for 1 hour to be oxidized, thereby obtaining a hot-infusible porous spherical oxidized asphalt.
Then, the porous spherical activated carbon was obtained by activating the porous spherical oxidized pitch at 900 ℃ for 170 minutes in a nitrogen atmosphere containing 50 vol% of water vapor using a fluidized bed, and further subjected to oxidation treatment at 470 ℃ for 3 hours and 15 minutes in a mixed gas atmosphere of nitrogen and oxygen having an oxygen concentration of 18.5 vol% using a fluidized bed, followed by reduction treatment at 900 ℃ for 17 minutes in a nitrogen atmosphere using a fluidized bed, to obtain a porous spherical carbonaceous material. The porous spherical carbonaceous material obtained in this way was used as a spherical activated carbon in the following pharmacological test examples.
The main characteristics of the obtained carbonaceous material are as follows.
1300m specific surface area2(BET method);
pore volume of 0.08mL/g
(pore volume of pore diameter in the range of 20 to 15000nm determined by mercury intrusion method)
The average particle size is 350 μm;
total acidic groups are 0.67 meq/g;
total basic groups are 0.54 meq/g;
the compressive strength is 31.2 MPa; and
the deformation rate when a pressure of 2MPa was applied was 0.7%.
Production example 2: production of porous spherical carbonaceous Material
A porous spherical carbonaceous material (surface-modified spherical activated carbon) was obtained in the same manner as in example 1 of Japanese patent application laid-open No. 2005-314416. The specific operation is as follows.
220g of deionized water and 58g of methyl cellulose were placed in a 1L separable flask, 105g of styrene, 184g of divinylbenzene having a purity of 57% (57% divinylbenzene and 43% ethylvinylbenzene), 1.68g of 2, 2' -azobis (2, 4-dimethylvaleronitrile) and 63g of 1-butanol as a pore-forming agent were added thereto as appropriate, the inside of the system was replaced with nitrogen gas, the two-phase system was stirred at 200rpm, heated to 55 ℃ and then held in this state for 20 hours. Filtering the obtained resin, drying with rotary evaporator, distilling 1-butanol from the resin with vacuum drier, and drying at 90 deg.C under reduced pressure for 12 hrTo obtain a spherical porous synthetic resin having an average particle diameter of 180 μm. The specific surface area of the porous synthetic resin was about 90m2/g。
100g of the obtained spherical porous synthetic resin was charged into a reaction tube equipped with a porous plate, and was subjected to a non-melting treatment in a vertical tubular furnace. Under the non-melting condition, dry air was flowed from the lower portion toward the upper portion of the reaction tube at 3L/min, and the temperature was raised to 260 ℃ at 5 ℃/h, and then the reaction tube was maintained at 260 ℃ for 4 hours, thereby obtaining a spherical porous oxidized resin. Spherical porous oxide resin was subjected to heat treatment at 600 ℃ for 1 hour in a nitrogen atmosphere, and then subjected to activation treatment at 820 ℃ for 10 hours in a nitrogen atmosphere containing 64.5 vol% of water vapor using a fluidized bed, to obtain spherical activated carbon. Further, the obtained spherical activated carbon was subjected to oxidation treatment at 470 ℃ for 3 hours and 15 minutes in a mixed gas atmosphere of nitrogen and oxygen having an oxygen concentration of 18.5 vol% by a fluidized bed, and then subjected to reduction treatment at 900 ℃ for 17 minutes in a nitrogen atmosphere by a fluidized bed, to obtain a surface-modified spherical activated carbon.
The main properties of the obtained surface-modified spherical activated carbon are as follows.
Specific surface area 1763m2(BET method);
pore volume 0.05mL/g
(pore volume of pore diameter in the range of 20 to 15000nm determined by mercury intrusion method)
Average particle size 111 μm (Dv 50);
total acidic groups are 0.59 meq/g;
total basic groups are 0.61 meq/g;
volume density of 0.50g/cm3；
The compressive strength is 436.5 MPa; and
the deformation rate when a pressure of 2MPa was applied was 0.2%.
Although the present specification does not describe an example in which tablets are produced using the spherical activated carbon obtained in production example 2, tablets of the present invention can be obtained in the same manner as the spherical activated carbon obtained in production example 1.
EXAMPLE 1
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 1 was sprayed. Then, the resultant was dried to obtain 535.5g of a coated article. An ethanol/water mixture (6:4) was added to the coated article at a ratio of 1.2mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 15 mm. The hardness of the resulting tablets was 230N. The composition of the obtained tablets is shown in table 2.
[ Table 1]
Name of composition Compounding amount
Pullulan polysaccharide 30g
Sodium lauryl sulfate 4.5g
Refined water 500mL
[ Table 2]
Compounding amount (% by weight)
Pullulan polysaccharide 5.6
Sodium lauryl sulfate 0.8
EXAMPLE 2
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 3 was sprayed. Then, the resultant was dried to obtain 512.5g of a coated product. The resulting coated article was filled in a Teflon (registered trademark) molding die (diameter 12mm, depth 10.2mm, R16mm), water was added at a ratio of 0.9mL to 1g of the coated article, and then the upper part was lightly compressed by a molding rod attached to a stirrer to trim the tablet surface, followed by drying, thereby obtaining a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 124N. The composition of the obtained tablets is shown in table 4.
[ Table 3]
Name of composition Compounding amount
Pullulan polysaccharide 30g
Refined water 500mL
[ Table 4]
Compounding amount (% by weight)
Pullulan polysaccharide 5.7
EXAMPLE 3
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 5 was sprayed. Then, the resultant was dried to obtain 506.8g of a coated article. An ethanol/water mixture (5:5) was added to the coated article at a ratio of 1.4mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablets was 173N. The composition of the obtained tablets is shown in table 6.
[ Table 5]
Name of composition Compounding amount
Alginic acid propylene glycol ester 30g
Refined water 1100mL
[ Table 6]
Compounding amount (% by weight)
Alginic acid propylene glycol ester 5.7
EXAMPLE 4
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 7 was sprayed. Then, the resultant was dried to obtain 564.4g of a coated article. An ethanol/water mixture (6:4) was added to the coated article at a ratio of 1.1mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 216N. The composition of the obtained tablets is shown in table 8.
[ Table 7]
Name of composition Compounding amount
Indian gum 100g
Refined water 1000mL
[ Table 8]
Compounding amount (% by weight)
Indian gum 16.7
EXAMPLE 5
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 9 was sprayed. Then, the resultant was dried to obtain 530.8g of a coated article. An ethanol/water mixture (2:8) was added to the coated article at a ratio of 1.2mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 137N. The composition of the obtained tablets is shown in table 10.
[ Table 9]
Name of composition Compounding amount
Carboxyvinyl polymer 45g
Refined water 3000mL
[ Table 10]
Compounding amount (% by weight)
Carboxyvinyl polymer 8.3
EXAMPLE 6
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 11 was sprayed. Then, the resultant was dried to obtain 497.8g of a coated article. An ethanol/water mixture (5:5) was added to the coated article at a ratio of 1.1mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 121N. The composition of the obtained tablets is shown in table 12.
[ Table 11]
Name of composition Compounding amount
Sodium carboxymethylcellulose 30g
Refined water 600mL
[ Table 12]
Compounding amount (% by weight)
Sodium carboxymethylcellulose 5.7
EXAMPLE 7
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 13 was sprayed. Then, the resultant was dried to obtain 518.1g of a coated article. An ethanol/water mixture (4:6) was added to the coated article at a ratio of 1.0mL to 1g of the coated article using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 123N. The composition of the obtained tablet is shown in table 14.
[ Table 13]
Name of composition Compounding amount
Xanthan gum 45g
Refined water 3000mL
[ Table 14]
Compounding amount (% by weight)
Xanthan gum 8.3g
EXAMPLE 8
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and spray liquids having the formulations shown in Table 15 were sprayed. Then, the resultant was dried to obtain 537.3g of a coated article. An ethanol/water mixture (1:9) was added to the coated article at a ratio of 1.4mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 171N. The composition of the obtained tablets is shown in table 16. [ Table 15]
Name of composition Compounding amount
Guar gum 60g
Refined water 4000mL
[ Table 16]
Compounding amount (% by weight)
Guar gum 10.7
EXAMPLE 9
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 17 was sprayed. Then, the resultant was dried to obtain 525.2g of a coated article. An ethanol/water mixture (1:9) was added to the coated article at a ratio of 1.3mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 122N. The composition of the obtained tablets is shown in table 18.
[ Table 17]
Name of composition Compounding amount
Glucomannan 45g
Refined water 3000mL
[ Table 18]
Compounding amount (% by weight)
Glucomannan 8.3
EXAMPLE 10
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and spray liquids having the formulations shown in Table 19 were sprayed. Then, the resultant was dried to obtain 622.6g of a coated article. An ethanol/water mixture (1:9) was added to the coated article at a ratio of 0.6mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablets was 162N. The composition of the obtained tablets is shown in table 20.
[ Table 19]
Name of composition Compounding amount
Co-polyvidone 225g
Refined water 1200mL
[ Table 20]
Compounding amount (% by weight)
Co-polyvidone 31.0
EXAMPLE 11
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 21 was sprayed. Then, the resultant was dried to obtain 506.0g of a coated article. An ethanol/water mixture (5:5) was added to the coated article at a ratio of 0.9mL to 1g of the coated article using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 175N. The composition of the obtained tablets is shown in table 22.
[ Table 21]
Name of composition Compounding amount
Gelatin 25g
Refined water 600mL
[ Table 22]
Compounding amount (% by weight)
Gelatin 4.8
EXAMPLE 12
The spherical activated carbon 305g obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray liquid having a formulation shown in Table 23 was sprayed. Then, the resultant was dried to obtain 336.3g of a coated product. An ethanol/water mixture (4:6) was added to the coated article at a ratio of 1.4mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 133N. The composition of the obtained tablets is shown in table 24.
[ Table 23]
Name of composition Compounding amount
Tamarind gum 48.8g
Refined water 1200mL
[ Table 24]
Compounding amount (% by weight)
Tamarind gum 8.9
EXAMPLE 13
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 25 was sprayed. Then, the resultant mixture was dried to obtain 548.3g of a coated product. An ethanol/water mixture (1:9) was added to the coated article at a ratio of 1.2mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 201N. The composition of the obtained tablets is shown in table 26.
[ Table 25]
Name of composition Compounding amount
Tara glue 75g
Refined water 6000mL
[ Table 26]
Figure BDA0001807792810000251
Figure BDA0001807792810000261
EXAMPLE 14
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and spray liquids having the formulations shown in Table 27 were sprayed. Then, the resultant was dried to obtain 557.2g of a coated article. An ethanol/water mixture (1:9) was added to the coated article at a ratio of 1.2mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 114N. The composition of the obtained tablets is shown in table 28.
[ Table 27]
Name of composition Compounding amount
Corn starch 100g
Heated refined water 1400mL
[ Table 28]
Compounding amount (% by weight)
Corn starch 16.7
EXAMPLE 15
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 29 was sprayed. Then, the resultant was dried to obtain 524.0g of a coated article. An ethanol/water mixture (1:9) was added to the coated article at a ratio of 1.1mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 105N. The composition of the obtained tablets is shown in table 30.
[ Table 29]
Name of composition Compounding amount
Tragacanth gum 45g
Refined water 3000mL
[ Table 30]
Compounding amount (% by weight)
Tragacanth gum 8.3
EXAMPLE 16
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 31 was sprayed. Then, the resultant was dried to obtain 543.5g of a coated article. An ethanol/water mixture (4:6) was added to the coated product at a ratio of 1.1mL to 1g of the coated product using a low-pressure molding machine, and the resulting coated product was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 290N. The composition of the obtained tablets is shown in table 32.
[ Table 31]
Name of composition Compounding amount
Hyaluronic acid sodium salt 60g
Refined water 3500mL
[ Table 32]
Compounding amount (% by weight)
Hyaluronic acid sodium salt 10.7
EXAMPLE 17
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and spray liquids having the formulations shown in Table 33 were sprayed. Then, the resultant was dried to obtain 531.9g of a coated article. An ethanol/water mixture (5:5) was added to the coated article at a ratio of 1.2mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 133N. The composition of the obtained tablet is shown in table 34.
[ Table 33]
Figure BDA0001807792810000271
Figure BDA0001807792810000281
[ Table 34]
Compounding amount (% by weight)
Hydroxyethyl cellulose 10.7
EXAMPLE 18
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and spray liquids having the formulations shown in Table 35 were sprayed. Then, the resultant was dried to obtain 543.3g of a coated article. An ethanol/water mixture (4:6) was added to the coated article at a ratio of 1.2mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 343N. The composition of the obtained tablets is shown in table 36.
[ Table 35]
Name of composition Compounding amount
Hydroxypropyl cellulose 75g
Refined water 600mL
[ Table 36]
Compounding amount (% by weight)
Hydroxypropyl cellulose 13.0
EXAMPLE 19
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 37 was sprayed. Then, the resultant was dried to obtain 502.9g of a coated article. An ethanol/water mixture (6:4) was added to the coated article at a ratio of 1.4mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 134N. The composition of the obtained tablets is shown in table 38.
[ Table 37]
Name of composition Compounding amount
Hydroxypropyl methylcellulose 36g
Refined water 600mL
[ Table 38]
Compounding amount (% by weight)
Hydroxypropyl methylcellulose 6.7
EXAMPLE 20
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 39 was sprayed. Then, the resultant was dried to obtain 500.4g of a coated article. An ethanol/water mixture (6:4) was added to the coated article at a ratio of 1.4mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 187N. The composition of the obtained tablets is shown in table 40.
[ Table 39]
Name of composition Compounding amount
Polyvinyl alcohol 50g
Heated refined water 1000mL
[ Table 40]
Compounding amount (% by weight)
Polyvinyl alcohol 9.1
EXAMPLE 21
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 41 was sprayed. Then, the resultant was dried to obtain 508.9g of a coated article. An ethanol/water mixture (6:4) was added to the coated article at a ratio of 1.1mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 222N. The composition of the obtained tablets is shown in table 42.
[ Table 41]
Name of composition Compounding amount
Polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer 75g
Refined water 500mL
[ Table 42]
Compounding amount (% by weight)
Polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer 13.0
EXAMPLE 22
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 43 was sprayed. Then, the resultant was dried to obtain 530.8g of a coated article. An ethanol/water mixture (6:4) was added to the coated article at a ratio of 1.4mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablets was 162N. The composition of the obtained tablets is shown in table 44.
[ Table 43]
Name of composition Compounding amount
Phosphoric acid crosslinked starch 50g
Heated refined water 600mL
[ Table 44]
Figure BDA0001807792810000301
Figure BDA0001807792810000311
EXAMPLE 23
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and spray liquids having the formulations shown in Table 45 were sprayed. Then, the resultant was dried to obtain 552.0g of a coated article. An ethanol/water mixture (1:9) was added to the coated article at a ratio of 1.1mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 227N. The composition of the obtained tablets is shown in table 46.
[ Table 45]
Name of composition Compounding amount
Locust bean gum 75g
Refined water 3000mL
[ Table 46]
Compounding amount (% by weight)
Phosphoric acid crosslinked locust bean gum 13.0
EXAMPLE 24
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 47 was sprayed. Then, the resultant was dried to obtain 545.5g of a coated article. An ethanol/water mixture (6:4) was added to the coated article at a ratio of 1.1mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablets was 110N. The composition of the obtained tablets is shown in table 48.
[ Table 47]
Name of composition Compounding amount
Cold plum powder 70g
Refined water 600mL
[ Table 48]
Compounding amount (% by weight)
Cold plum powder 12.3
EXAMPLE 25
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and spray liquids having the formulations shown in Table 49 were sprayed. Then, the resultant was dried to obtain 516.4g of a coated article. An ethanol/water mixture (1:9) was added to the coated article at a ratio of 1.0mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablet was 141N. The composition of the obtained tablets is shown in table 50.
[ Table 49]
Name of composition Compounding amount
Fully pregelatinized starch 35g
Refined water 1100mL
[ Table 50]
Compounding amount (% by weight)
Fully pregelatinized starch 6.5
EXAMPLE 26
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 51 was sprayed. Then, the resultant was dried to obtain 533.3g of a coated product. An ethanol/water mixture (6:4) was added to the coated article at a ratio of 1.4mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablets was 125N. The composition of the obtained tablet is shown in table 52. [ Table 51]
Figure BDA0001807792810000321
Figure BDA0001807792810000331
[ Table 52]
Compounding amount (% by weight)
Oxidized starch 10.7
EXAMPLE 27
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 53 was sprayed. Then, the resultant was dried to obtain 520.7g of a coated article. An ethanol/water mixture (2:8) was added to the coated article at a ratio of 0.9mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 12 mm. The hardness of the resulting tablets was 110N. The composition of the obtained tablets is shown in table 54.
[ Table 53]
Name of composition Fitting togetherMeasurement of
Partially pregelatinized starch 50.0g
Refined water 600mL
[ Table 54]
Compounding amount (% by weight)
Partially pregelatinized starch 9.1
Comparative example 1
20g of spherical activated carbon obtained in production example 1, 1.2g of pullulan, and 0.18g of sodium lauryl sulfate were uniformly dispersed in a beaker, and 24mL of purified water was further added. The resulting mixture was kneaded using a spatula (spatula) in such a manner that a coagulated lump of the additive ( powder) was not formed. The prepared kneaded mass (slurry) was filled in a molding die (diameter 12mm, depth 10.2mm), ground with a spatula, and the upper part was lightly compressed by a molding rod attached to a blender to trim the surface of the tablet. By drying each molding die, a tablet was obtained. The hardness of the tablets was 69N. Comparative example 2
500g of the spherical activated carbon obtained in production example 1 was charged into a rotary fluidized coating apparatus (MP-01), and a spray solution having a formulation shown in Table 55 was sprayed. Then, the resultant was dried to obtain 523.5g of a coated product. An ethanol/water mixture (6:4 and 7:3) was added to the coated article at a ratio of 1.1mL and 1.2mL to 1g using a low-pressure molding machine, and the resulting coated article was molded and dried to obtain a tablet having a diameter of 15 mm.
The hardness of the obtained tablet is shown in table 56. The composition of the obtained tablets is shown in table 57.
[ Table 55]
Name of composition Compounding amount
Pullulan polysaccharide 4g
Sodium lauryl sulfate 2.25g
Refined water 500mL
[ Table 56]
Figure BDA0001807792810000341
*1The molded article was very flexible and difficult to transfer, and therefore, the study was discontinued.
*2There was no study.
[ Table 57]
Compounding amount (% by weight)
Pullulan polysaccharide 0.8
Sodium lauryl sulfate 0.4
Hardness of tablet composition
For the measurement of hardness of the tablet composition, the thickness of a sample of the tablet composition was measured using a tablet hardness tester (TBH320TD, manufactured by ERWEKA), and the measured value was input to the hardness tester and measured at room temperature. The measurement conditions are as follows. The results of hardness measurement are summarized in tables 59 to 64 together with the composition of the tablet. In the table, "main ingredient" means spherical activated carbon.
[ Table 58]
Figure BDA0001807792810000351
This operation was performed with n ═ 1.
[ Table 59]
Figure BDA0001807792810000352
[ Table 60]
Figure BDA0001807792810000353
Figure BDA0001807792810000361
[ Table 61]
Figure BDA0001807792810000362
[ Table 62]
Figure BDA0001807792810000363
[ Table 63]
Figure BDA0001807792810000364
Figure BDA0001807792810000371
[ Table 64]
Figure BDA0001807792810000372
Analysis of recovery Rate
The recovery rate of the coated article in the examples or comparative examples was analyzed. The recovery (%) of the coated article was calculated from the amount of the coated article obtained/theoretical amount of the coated article × 100. The higher the recovery rate, the higher the yield of the spherical adsorbent carbon for oral administration.
EXAMPLE 1
The following table shows the recovery rate of the coated article in example 1. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 65]
Figure BDA0001807792810000373
Figure BDA0001807792810000381
EXAMPLE 2
The following table shows the recovery rate of the coated article in example 2. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 66]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
530.0 512.5 96.7
EXAMPLE 3
The following table shows the recovery rate of the coated article in example 3. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 67]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
530.0 506.8 95.6
EXAMPLE 4
The following table shows the recovery rate of the coated article in example 4. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 68]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
600.0 564.4 94.1
EXAMPLE 5
The following table shows the recovery rate of the coated article in example 5. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 69]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
545.0 530.8 97.4
EXAMPLE 6
The following table shows the recovery rate of the coated article in example 6. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 70]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
530.0 497.8 93.9
EXAMPLE 7
The following table shows the recovery rate of the coated article in example 7. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 71]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
545.0 518.1 95.1
EXAMPLE 8
The following table shows the recovery rate of the coated article in example 8. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 72]
Of coated articlesTheoretical quantity (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
560.0 537.3 95.9
EXAMPLE 9
The following table shows the recovery rate of the coated article in example 9. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 73]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
545.0 525.2 96.4
EXAMPLE 10
The following table shows the recovery rate of the coated article in example 10. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 74]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
725.0 622.6 85.9
EXAMPLE 13
The following table shows the recovery rate of the coated article in example 13. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 75]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
575.0 548.3 95.4
EXAMPLE 15
The following table shows the recovery rate of the coated article in example 15. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 76]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
545.0 524.0 96.1
EXAMPLE 16
The following table shows the recovery rate of the coated article in example 16. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 77]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
560.0 543.5 97.1
In example 17, the following table shows the recovery rate of the coated product in example 17. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 78]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
560.0 531.9 95.0
EXAMPLE 18
The following table shows the recovery rate of the coated article in example 18. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 79]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
575.0 543.3 94.5
EXAMPLE 19
The following table shows the recovery rate of the coated article in example 19. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 80]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
536.0 502.9 93.8
EXAMPLE 22
The following table shows the recovery rate of the coated article in example 22. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 81]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
550.0 530.8 96.5
EXAMPLE 23
The following table shows the recovery rate of the coated article in example 23. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 82]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
575.0 552.0 96.0
EXAMPLE 24
The following table shows the recovery rate of the coated article in example 24. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 83]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
570.0 545.5 95.7
EXAMPLE 25
The following table shows the recovery rate of the coated article in example 25. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 84]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
535.0 516.4 96.5
EXAMPLE 26
The following table shows the recovery rate of the coated article in example 26. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 85]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
560.0 533.3 95.2
EXAMPLE 27
The following table shows the recovery rate of the coated article in example 27. The obtained tablets were analyzed by an X-ray CT microscope, and the results of the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained.
[ Table 86]
Theoretical amount of coating (g) Amount (g) of the obtained coated product Recovery ratio of coated article (%)
550.0 520.7 94.7
Comparative example 1
The tablets obtained in comparative example 1 were analyzed by an X-ray CT microscope, and the volume ratios of the tablets shown in table 87 and the volume ratios of the additives in the tablets shown in table 88 were obtained. Analysis of tablet volume fraction Using X-ray CT microscope
The interior of the two-batch tablets obtained in example 1 and the three-batch tablets obtained in comparative example 1 were analyzed under the following conditions using an X-ray CT microscope nano3DX (manufactured by ltd.
Line source: mo
Voltage: 50kV
Current: 24mA
Pixel size: 8.64 μm/voxel
Number of shots: 1200 sheets
Shooting time: about 3 hours
The volume ratio of each 2mm cube in the upper, middle, and lower portions of the tablet divided into three parts was determined using attached analysis software. The RSDs of the volume ratios of the three cubes of the two batches of tablets obtained from example 1 were 1.0 and 2.4, the tablets of the invention having a high homogeneity (table 87).
The interior of each batch of tablets obtained in examples 2 to 27 was analyzed under the following conditions using an X-ray CT microscope TDM1000H-II (2K) (yokoku corporation).
Line source: w
Voltage: 50kV
Current: 0.085mA
Pixel size: 12.7 μm/voxel
Number of shots: 700 to 1500 sheets (arbitrarily set according to the thickness of the tablet)
Shooting time: 10 minutes
The volume ratio of each 2mm cube in the upper, middle and lower portions of the three-divided tablets was determined using the analysis software ImageJ. (Table 87).
[ Table 87]
Figure BDA0001807792810000451
Figure BDA0001807792810000461
Analysis of additive volume ratio of tablet Using X-ray CT microscope
The tablet obtained in the examples was analyzed under the following conditions using an X-ray CT microscope TDM1000H-II (2K) (yokoku corporation).
Line source: w
Voltage: 40kV (example 1, comparative example 1), 50kV (examples 2 to 27)
Current: 0.095mA (example 1, comparative example 1) and 0.085mA (examples 2 to 27)
Pixel size: 15.9 μm/voxel (example 1), 14.4 μm/voxel (comparative example 1), 12.7 μm/voxel (examples 2 to 27)
Number of shots: 700 to 1500 sheets (arbitrarily set according to the thickness of the tablet)
Shooting time: 30 minutes (example 1, comparative example 1), 10 minutes (examples 2 to 27)
For each of examples 1 to 27 and comparative example 1, the additive volume ratios of C, N, E, S in fig. 3 and five prisms of W were calculated by the analysis software ImageJ. Since the distribution of the number of pixels corresponding to the brightness of the spherical activated carbon is normally distributed based on the information of 256 levels of brightness in the obtained image, a portion of brightness equal to or greater than a value obtained by adding 2.5 times the standard deviation to the average value of brightness is defined as an additive, the ratio of the number of pixels is defined as an additive area ratio, and the ratio of the number of pixels of the additive when the image is integrated in an amount corresponding to a predetermined thickness is defined as an additive volume ratio (fig. 6). The values of the maximum and minimum values of the additive volume ratio in each prism and the ratio of the maximum value to the minimum value in five prisms are shown in table 88. Fig. 4 shows the variation of the additive area ratio and the additive volume ratio from the upper surface to the lower surface at the position C in comparative example 1.
As shown in fig. 4, the additive volume ratio of the tablet obtained by the conventional kneading method greatly varied from the upper surface to the lower surface of the tablet.
[ Table 88]
Figure BDA0001807792810000471
Industrial applicability of the invention
The tablet of the present invention is useful as an adsorbent for oral administration for the treatment or prevention of kidney diseases or an adsorbent for the treatment or prevention of liver diseases.

Claims (4)

1. A tablet comprising spherical adsorbent carbon for oral administration and at least one binding additive selected from the group consisting of: propylene glycol alginate, gum ghatti, carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, guar gum, glucomannan, copovidone, gelatin, tamarind gum, tara gum, corn starch, tragacanth gum, sodium hyaluronate, hydroxyethyl cellulose, hydroxypropyl methylcellulose, pullulan, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, cross-linked starch phosphate, locust bean gum, wintersweet powder, fully pregelatinized starch, oxidized starch, and partially pregelatinized starch,
the binding additive is 1 to 35 wt% of the spherical adsorbent carbon for oral administration,
the spherical adsorbent carbon for oral administration is coated with the binding additive, each spherical adsorbent carbon for oral administration is bonded via the coated binding additive, and the hardness of the tablet is 105N or more,
when the volume ratio of the additive for bonding of five prisms each having 1mm on each side from the upper surface to the lower surface, which are positioned at the center and the end of a straight line extending from the center to the four sides when the tablet is observed from the upper surface, is analyzed by an X-ray CT microscope from the upper surface to the lower surface, 1mm of each of the five prisms3The ratio of the maximum value to the minimum value of the volume fraction of the additive for bonding (2) is 100 or less,
the spherical adsorption carbon for oral administration is spherical activated carbon,
the average particle diameter of the spherical activated carbon is 0.02 to 1 mm.
2. The tablet according to claim 1, wherein,
when the volume ratio of a cube, which is located at the center of the flat direction length and at the center of the tablet when viewed from the top surface and is formed by 2mm on each side, is analyzed by an X-ray CT microscope for each divided body obtained by dividing the flat direction length of the tablet into three equal parts, the relative standard deviation of the volume ratios of the cubes of the three divided bodies is 5% or less.
3. The tablet according to claim 1, wherein,
when the volume ratio of the additive for bonding of five prisms each having 1mm on each side from the upper surface to the lower surface, which are positioned at the center and the end of a straight line extending from the center to the four sides when the tablet is observed from the upper surface, is analyzed by an X-ray CT microscope from the upper surface to the lower surface, 1mm of each of the five prisms3The ratio of the maximum value to the minimum value of the volume fraction of the additive for bonding (2) is 100 or less,
when the volume ratio of a cube, which is located at the center of the flat direction length and at the center of the tablet when viewed from the top surface and is formed by 2mm on each side, is analyzed by an X-ray CT microscope for each divided body obtained by dividing the flat direction length of the tablet into three equal parts, the relative standard deviation of the volume ratios of the cubes of the three divided bodies is 5% or less.
4. A method for producing the tablet according to claim 1, comprising the steps of:
(1) spraying or dripping a solution containing at least one binding additive selected from the group consisting of propylene glycol alginate, gum ghatti, carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, guar gum, glucomannan, copovidone, gelatin, tamarind gum, tara gum, corn starch, tragacanth gum, sodium hyaluronate, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, pullulan, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, cross-linked starch phosphate, locust bean gum, wintersweet powder, fully pregelatinized starch, oxidized starch, and partially pregelatinized starch on the spherical adsorbent carbon for oral administration, and coating the spherical adsorbent carbon for oral administration with the binding additive;
(2) a compression molding step of adding a solvent to the coated oral administration spherical adsorbent carbon, and then performing compression molding to obtain a molded body; and
(3) the obtained molded article was dried.
CN201780019126.5A 2016-04-01 2017-03-29 Tablet containing spherical adsorbent carbon for oral administration Active CN108883129B (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
JP2016-074580 2016-04-01
JP2016074578 2016-04-01
JP2016074580 2016-04-01
JP2016-074578 2016-04-01
PCT/JP2017/013048 WO2017170762A1 (en) 2016-04-01 2017-03-29 Tablet containing spherical adsorptive carbon for oral administration

Publications (2)

Publication Number Publication Date
CN108883129A CN108883129A (en) 2018-11-23
CN108883129B true CN108883129B (en) 2021-01-08

Family

ID=59964639

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780019126.5A Active CN108883129B (en) 2016-04-01 2017-03-29 Tablet containing spherical adsorbent carbon for oral administration

Country Status (5)

Country Link
JP (1) JP6430679B2 (en)
KR (1) KR102158133B1 (en)
CN (1) CN108883129B (en)
TW (1) TWI693946B (en)
WO (1) WO2017170762A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7438897B2 (en) 2020-08-26 2024-02-27 フタムラ化学株式会社 Tablet type adsorbent for oral administration

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005187405A (en) * 2003-12-25 2005-07-14 Lion Corp Uric acid value inhibitor and purine body adsorbent
WO2012121202A1 (en) * 2011-03-04 2012-09-13 株式会社クレハ Tablet-type composition for oral administration and method for producing same
CN104030287A (en) * 2014-07-09 2014-09-10 四川创越炭材料有限公司 Spherical activated carbon and preparation method thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5595611A (en) * 1979-01-17 1980-07-21 Osamu Otsubo Mannan-coated activated carbon
DE3572440D1 (en) * 1984-06-19 1989-09-28 Basf Ag Gastro-resistant cylindrical pancreatine-microtablets
JPS6211611A (en) 1985-07-10 1987-01-20 ロ−ム株式会社 Manufacture of semiconductor pellet
JP4618409B2 (en) 2004-06-25 2011-01-26 味の素株式会社 Oral uremic toxin adsorbent
JP4875840B2 (en) * 2004-07-30 2012-02-15 トーアエイヨー株式会社 Activated carbon preparation for oral administration
JP2007137802A (en) * 2005-11-16 2007-06-07 Takeda Chem Ind Ltd Method for producing tablet
JP5415837B2 (en) * 2009-06-12 2014-02-12 アサヒグループホールディングス株式会社 Method for producing granules and tablets from a powdery functional substance having inferior compression moldability

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005187405A (en) * 2003-12-25 2005-07-14 Lion Corp Uric acid value inhibitor and purine body adsorbent
WO2012121202A1 (en) * 2011-03-04 2012-09-13 株式会社クレハ Tablet-type composition for oral administration and method for producing same
CN104030287A (en) * 2014-07-09 2014-09-10 四川创越炭材料有限公司 Spherical activated carbon and preparation method thereof

Also Published As

Publication number Publication date
TW201735905A (en) 2017-10-16
KR102158133B1 (en) 2020-09-21
JPWO2017170762A1 (en) 2018-12-13
WO2017170762A1 (en) 2017-10-05
KR20180118785A (en) 2018-10-31
CN108883129A (en) 2018-11-23
TWI693946B (en) 2020-05-21
JP6430679B2 (en) 2018-11-28

Similar Documents

Publication Publication Date Title
JP5701971B2 (en) Tablet-type composition for oral administration and method for producing the same
JP4875001B2 (en) Wet granulation pharmaceutical composition of aripiprazole
CN108367005B (en) Dosage form compositions comprising tyrosine protein kinase inhibitors
CN104434809A (en) Olaparib solid dispersion preparation and preparation method thereof
CN108883130B (en) Tablet containing spherical adsorbent carbon for oral administration and method for producing same
JP3568567B2 (en) High moldability excipient and method for producing the same
CN108883129B (en) Tablet containing spherical adsorbent carbon for oral administration
WO2019012552A4 (en) Compositions of ferric organic compounds
JP6201017B2 (en) Method for producing orally disintegrating tablet excellent in hardness and disintegration, and orally disintegrating tablet produced by the production method
WO2007141806A1 (en) Pharmaceutical formulations comprising oxcarbazepine and methods thereof
JP6073843B2 (en) Method for producing orally disintegrating tablet excellent in hardness and disintegration, and orally disintegrating tablet produced by the production method
Mandal et al. Evaluation of the drug-polymer interaction in calcium alginate beads containing diflunisal
KR101509489B1 (en) Method for preparing solid oral formulation comprising valsartan
Khatik et al. Development of sustained release Aceclofenac lipid matrix tablet using continuous melt granulation technique
CN1692909A (en) Dosmalfate dispersion tablet and its prepn. method
CN116370417A (en) Rasagiline granule composition and pharmaceutical composition thereof
JP6216408B2 (en) Method for preparing very poorly soluble drugs in solid dosage forms
Khan et al. Formulation and Evaluation of Metronidazole Loaded Nanosponges for Topical Delivery
WO2013130785A2 (en) Extended release pharmaceutical formulations of water-soluble active pharmaceutical ingredients and methods for making the same
Dongare et al. Optimization of crystallo-Co-Agglomerates of meloxicam-paracetamol to improve flow properties and dissolution
WO2019012553A1 (en) Process for preparation of compositions of ferric organic compounds
CN1695629A (en) Oral preparation of quick releasing Breviscapini and producing method

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant