WO2019202968A1 - 易服用性顆粒剤及びその製造方法 - Google Patents
易服用性顆粒剤及びその製造方法 Download PDFInfo
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- WO2019202968A1 WO2019202968A1 PCT/JP2019/014580 JP2019014580W WO2019202968A1 WO 2019202968 A1 WO2019202968 A1 WO 2019202968A1 JP 2019014580 W JP2019014580 W JP 2019014580W WO 2019202968 A1 WO2019202968 A1 WO 2019202968A1
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- Prior art keywords
- granule
- granules
- water
- easy
- thickener
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
- A61K9/5057—Gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
Definitions
- the present invention relates to an easy-to-use granule containing granules, a method for producing the same and the like.
- the formulation is a dosage form such as a liquid or jelly.
- the active ingredient is high, masking of the taste is difficult, and the active ingredient such as the drug is unstable in water. Therefore, it is difficult to obtain such a dosage form.
- Patent Document 1 discloses a particle composition containing a sugar alcohol and a water-insoluble polymer, which is useful for a solid preparation, and an easy-to-use solid preparation containing the particle composition and a gelling agent that exhibits slipperiness upon contact with water. Compositions, and easy-to-use solid preparations containing the composition are described.
- Patent Document 2 discloses a particle composition for an easy-to-use solid preparation containing a gelling agent that exhibits slipperiness upon contact with sugar alcohol and water, and part or all of the surface of the particle composition is the The particle composition, an easily takeable solid preparation containing the composition, and the like, which are coated with a gelling agent, are described.
- the easy-to-use preparation containing the particle composition described in Patent Document 1 and Patent Document 2 described above is a solid preparation produced by compression molding such as tableting.
- Patent Document 3 discloses granules having improved dosing properties, that is, granules having reduced feeling of roughness in the oral cavity during taking, and tablets obtained by compressing the granules with a tableting machine. Is described.
- the granule is composed of components that are sparingly soluble in water or saliva (active ingredients and / or excipients, etc.) and components that become viscous liquids when added with water (hydroxypropylmethylcellulose, hydroxypropylcellulose and A binder and / or a disintegrant such as hydroxypropyl starch).
- the granule is prepared by mixing these components in advance, adding water thereto and kneading, and further granulating the kneaded product by an extrusion granulator and drying it. It is manufactured by.
- the object of the present invention is to solve such problems in the prior art, and at least a part of the surface thereof is coated with a substance (thickener) that becomes a viscous liquid when water or the like is added.
- a substance thickener
- easy-to-take generally means that it is easy to swallow (easy to swallow) as a property / characteristic of an oral preparation.
- the present inventors have completed the present invention having the following modes as a result of diligent research.
- the present invention provides the following modes more specifically.
- An easily takeable granule comprising a granule containing sugar or sugar alcohol and having at least a part of its surface coated with a thickener.
- the easily takeable granule of aspect 1 containing an active ingredient.
- the easily takeable granule according to aspect 2 comprising an active ingredient as a component separate from the granule.
- the easily takeable granule according to the aspect 2 or 3 further comprising an active ingredient in the granule coated with the thickener.
- the present invention by covering at least a part of the surface of a granule (granulated product) containing sugar or sugar alcohol with a thickener, it is possible to improve the ease of taking the granule containing the granule. That is, when such granules come into contact with moisture inside and outside the oral cavity, the granules are easily collected, become a gel having low adhesion to the oral cavity and appropriate hardness, and as a result, taking the granule of the present invention A feeling improves and it becomes easy to drink (it is easy to swallow).
- the thickener is not localized in granules (granulated material) containing sugar or sugar alcohol, but is widely distributed on the surface, so even if the amount of thickener used is increased, it can be put in the mouth.
- the granules containing the granules are less likely to adhere to the oral cavity.
- granules are granulated preparations for oral administration
- powders are powdered preparations for oral administration.
- a granule is generally (i) a powdery active ingredient added with an excipient, binder, disintegrant or other additive, mixed and homogenized, and then by an appropriate method.
- Additives such as excipients to active ingredients prepared in advance and mix, and homogenize
- the powder refers to a mixture obtained by adding an excipient or other additive to an active ingredient and mixing them.
- the first aspect of the present invention is a granule containing sugar or sugar alcohol (may be a granule consisting of only sugar or sugar alcohol), wherein at least a part of the surface thereof is coated with a thickener.
- the easy-to-use granule can further contain an active ingredient and the like, but there are cases where it contains only the granule (granulated product) (corresponding to the granule itself of the present invention).
- the easy-to-take granules can further contain an active ingredient.
- "granule” includes "powder” in addition to the pharmacopoeia "granule”.
- Said easy-to-take granules can contain an active ingredient as a component (component) separate from granules containing sugar or sugar alcohol.
- the active ingredient may be contained in granules coated with a thickener.
- the active ingredient in the easy-to-use granules, may or may not be further contained as a separate component from the granules.
- the granule of the present invention at least a part of the surface of the granule containing sugar or sugar alcohol, preferably substantially the entire surface thereof is coated with a thickener, whereby the granule containing the granule is easily taken. Improved or improved.
- substantially the entire surface of the granule containing sugar or sugar alcohol is coated with the thickener.
- the sugar or sugar alcohol includes any substance known to those skilled in the art, for example, one or more selected from the group consisting of mannitol, lactose, sorbitol, maltitol, xylitol, erythritol, lactitol, maltose, and isomalt. I can do it.
- the “thickener” means a substance that becomes a viscous liquid when water or the like is added. As described in the examples of the present specification, at least a part of the surface of the granule containing sugar or sugar alcohol is coated with the thickener, so that the adhesion is low when the granule is exposed to water. In addition, when the granule of the present invention is taken with water or without water, the feeling of taking is improved and it is easy to swallow (easy to swallow). Has properties.
- granule 100 ⁇ 3000N / m 2 preferably has a hardness of 300 ⁇ 2500N / m 2, and, 500 J / m 3 In the following, it is preferably in the form of a gel exhibiting adhesion of 450 J / m 3 or less.
- the thickener is not particularly limited.
- one or more water-soluble substances selected from the group consisting of sodium carboxymethylcellulose (also referred to as “carmellose sodium”), xanthan gum, sodium alginate, carrageenan, guar gum, and gelatin.
- the water-soluble polymer may be a natural product or a synthetic product.
- the granule of the present invention and / or the granule contained therein include other optional ingredients known to those skilled in the art such as the above thickener, binder, disintegrant and excipient. It may be included.
- a water-insoluble polymer can be further included.
- the water-insoluble polymer any substance known to those skilled in the art can be used as long as the object can be achieved, and it may be a natural product or a synthetic product.
- the water-insoluble polymer examples include microfibrous cellulose, crystalline cellulose, powdered cellulose and various cellulose derivatives known to those skilled in the art. Among these, microfibrous cellulose or crystalline cellulose is particularly preferable.
- Microfibrous cellulose is a cellulose that is generally produced from plant fibers and has a fiber diameter (short diameter) or thickness of several nanometers to 1 ⁇ m. This means that the surface area is remarkably increased, the hydrophilicity that is inherent in cellulose is remarkably increased, and a three-dimensional network structure is formed by entanglement of microfibers. To do.
- Such a dried product of microfibrous cellulose can be obtained directly in the dry state by any conventionally known technique, for example, by directly pulverizing the cellulose fiber in the dry state with a ball mill (Japanese Patent Laid-Open No. Sho 56-56). 100801).
- the water-suspended microfibrous cellulose composed of the microfibrous cellulose microfibrillated with a high-pressure homogenizer in the aqueous dispersion of cellulose fibers is subjected to solvent substitution in the substitution step, and then the solvent is removed by the drying step.
- a dried product of fine fibrous cellulose can be obtained by pulverizing in the pulverizing step (Japanese Patent Laid-Open No. 2009-203559).
- microfibrous cellulose is a fiber aggregate having an average fiber length of about 0.01 to 2 mm and an average fiber diameter of about 0.001 to 1 ⁇ m, preferably an average fiber diameter of about 0.01 to 0.00. Mention may be made of microfibrous cellulose that is 1 ⁇ m.
- a microfibrous cellulose (with a water content of 10 to 35% solids) is a product name “CELISH” series (average fiber diameter of about 0.01 to 0.1 ⁇ m), Daicel Finechem Co., Ltd.
- Various grades of products are sold.
- crystalline cellulose As a typical example of crystalline cellulose, commercially available products such as Avicel (FMC Corporation), Theolas (Asahi Kasei Chemicals Co., Ltd.), and Bibapua (Lettengmeier) can be exemplified. Chemical), ARBOCEL (Letttenmeier), Solka Flock (Kimura Sangyo).
- the easy-to-use granule of the present invention has uses as various foods such as supplementary foods, functional nutritional foods and health foods, and uses as pharmaceuticals.
- any substance known to those skilled in the art can be selected as the active ingredient (active ingredient) contained in the easy-to-take granules of the present invention depending on each of the above uses.
- various nutritional components such as proteins, sugars, lipids and minerals; various vitamins and their derivatives; health food materials such as various extracts derived from microorganisms, plants or animals; and sourness
- Various foods, sweeteners, excipients, surfactants, lubricants, adjuvants, acidulants, sweeteners, flavoring agents, fragrances, colorants, stabilizers, etc. based on Article 10 of the Food Sanitation Law It can contain other optional ingredients acceptable as food ingredients (food additives) listed in the list of specified additives or existing additives, and general food and beverage additives
- Examples of the use and types of the above-mentioned medicinal ingredients include, for example, central nervous system drugs, peripheral nervous system drugs, sensory organ drugs, vaginal cardiovascular drugs, respiratory organ drugs, digestive organ drugs, hormone drugs, urine Reproductive organ drugs, other individual organ system drugs, vitamins, nourishing tonics, blood and body fluid drugs, other metabolic drugs, cell utilization drugs, oncology drugs, radiopharmaceuticals, allergy drugs, other Drugs for tissue cell function, herbal medicines, Kampo medicines, other herbal medicines and medicines based on Kampo medicines, antibiotic drugs, chemotherapeutic agents, biological drugs, drugs against parasites, drugs against other pathogenic organisms, antiseptic drugs, Diagnostic drugs, public health drugs, in-vitro diagnostic drugs, and the like.
- the thickness of the coating layer by the thickener is, for example, about 0.01 to 250 microns, and the sugar or sugar in the granule
- the alcohol and thickener are usually 50 to 99% by weight and 0.01 to 30% by weight, respectively, preferably 60 to 99% by weight and 0.05 to 20% by weight, respectively.
- the content and type of the above-mentioned active ingredient and other optional ingredients contained in the granule or granule of the present invention are appropriately determined by those skilled in the art according to the purpose of use of the granule and the characteristics of those ingredients. I can do it.
- the active ingredient is contained in an amount of 0.01 to 80% by weight, preferably 0.1 to 50% by weight, based on the whole granule.
- Each of these components is included in any shape and form known to those skilled in the art, such as granules, particles, or powder, and preferably in the form of granules.
- the easy-to-use granule of the present invention and the granule containing sugar or sugar alcohol, at least a part of which is coated with a thickener, are prepared by adding water or It can be produced by a method including a step of granulating a composition containing sugar or sugar alcohol using an aqueous solution of the substance.
- the wet granulation method is a method of forming a composite by dispersing and drying each component in the presence of water.
- the wet granulation method include spray drying, tumbling granulation, stirring granulation, And spraying methods such as fluidized bed granulation, freeze-drying method, extrusion granulation, kneading granulation and the like, and these can be produced by any method known to those skilled in the art.
- the concentration of the aqueous solution of the thickener can be appropriately selected by those skilled in the art, but usually an aqueous solution of 0.01 to 20% by weight, preferably 0.1 to 15% by weight is used.
- a step of granulating by spraying an aqueous solution of a thickener on a composition containing sugar or sugar alcohol, or a composition containing sugar or sugar alcohol or the like can be granulated by a manufacturing method including a step of adding an aqueous solution of a thickener to a product and granulating it. .
- a manufacturing method including a step of adding an aqueous solution of a thickener to a product and granulating it.
- the active ingredient and other ingredients are also included in the granule, by adding at any stage such as before the granulation step or during the granulation step, the above The composition containing these additional components is appropriately prepared.
- the granule of the present invention can be produced.
- granulation obtained by granulation, and active ingredients are dry-granulated by any method / means known to those skilled in the art (for example, granules and active ingredients are mixed to form a sheet) And crushing the compression-formed product to form granules).
- the granule and the active ingredient are not granulated, and the active ingredient (regardless of whether the active ingredient is a granule or a powder) is added to and mixed with the granule. Good.
- Average particle diameter Measured using a laser diffractometer (LA-960, HORIBA). Each measurement was performed three times, and the average value thereof was taken as the measurement result.
- Moisture Using a halogen moisture meter (HB43 type, METTLER TOLEDO Co., Ltd.), 5 g of granules containing sugar or sugar alcohol were heated to 105 ° C. and measured until the moisture change rate was 0.05% / min or less. .
- a halogen moisture meter HB43 type, METTLER TOLEDO Co., Ltd.
- Hardness and adhesion Measured with a texture analyzer (TA.XT.plus, Stable Micro Systems).
- the jigs are 20-8probe (20mm ⁇ probe, height 8mm, resin) and F-245 (measuring container, diameter 40mm, height), which are food measuring jigs for people with difficulty in swallowing that comply with Consumer Affairs Agency standards. 15 mm) was used.
- Hardness after gelation Four adult men and women took the granule without water and evaluated the hardness after gelation according to the following five-level evaluation criteria, and the average values were listed in the table . 1: Very soft, not different from water 2: Soft 3: Moderate hardness 4: Slightly hard 5: Very hard
- Adhesion feeling Four adult men and women took the granule without water, and evaluated the adhesion feeling according to the following five-level evaluation criteria, and the average values were listed in the table. 1: Not felt, very weak 2: Feel a little, weak 3: Feel clear 4: Slightly strong 5: Very strong
- Lactose (GranuLac 200, Meggle) 187.0g, Hydroxypropylmethylcellulose (ISP) 1.0g and Hydroxypropyl starch (HPS-101W, Freund Sangyo Co., Ltd.) 11.0g are mixed, and 25mL of purified water is added. Kneaded. This kneaded product was granulated with an extrusion granulator (Multigran MG-55-2 type, Dalton Co., Ltd.) and then dried with a dryer to obtain a granulated product. The obtained granulated product had the following physical property values. Moisture value: 1.25%, average particle size: 973 ⁇ m
- Lactose (GranuLac 200, Meggle) 184.0g, Hydroxypropylcellulose (HPC-SSL, Nippon Soda Co., Ltd.) 4.0g and Hydroxypropyl starch (HPS-101W, Freund Sangyo Co., Ltd.) 11.0g are mixed, and 20mL Of purified water was added and kneaded. This kneaded product was granulated with an extrusion granulator (Multigran MG-55-2 type, Dalton Co., Ltd.) and then dried with a dryer to obtain a granulated product. The obtained granulated product had the following physical property values. Moisture value: 0.50%, average particle size: 1009 ⁇ m
- N-acetylglucosamine (Marine Sweet YSK, Yaizu Suisan Kogyo Co., Ltd.) was added to 240.0 g of the granules produced in Example 1 and mixed well. Then, it was molded with a dry granulator (TF-LABO, Freund Sangyo Co., Ltd.), and granulated with an oscillator type granulator to obtain a granulated product.
- the obtained granulated product (granule) had the following physical property values. Moisture value: 0.60%, average particle size: 579 ⁇ m
- Mannitol (PEARLITOL, Roquette) 558.0g and carmellose sodium (CMC Daicel, Daicel Finechem Co., Ltd.) 40.65g were mixed, and 1.35g of carmellose sodium (CMC Daicel, Daicel Finechem Co., Ltd.) dissolved in water.
- the mixture was granulated with a stirring granulator (high speed mixer FS-GS-5, Fukae Powtech Co., Ltd.) while adding 90 g of CMCNa aqueous solution adjusted to 1.5% by weight. Then, it dried with the dryer and obtained the granulated material by sizing.
- Lactose (GranuLac 200, Meggle) 291.0 g and carmellose sodium (CMC Daicel, Daicel FineChem) 9.0 g were mixed, and purified water 40 g was added and kneaded. This kneaded product was granulated with an extrusion granulator (Multigran MG-55-2 type, Dalton Co., Ltd.) and then dried with a dryer. Then, the granulated material was obtained by sizing. The obtained granulated product had the following physical property values. Moisture value: 0.94%, average particle size: 783 ⁇ m
- Table 1 shows the measurement results of hardness and adhesion and the sensory evaluation results of the granulated products (granules) obtained in Examples 1 and 2 and Comparative Examples 1 and 2.
- Table 1 shows the measurement results of hardness and adhesion of the granules (granules and granules) obtained in Examples 3 to 25 and Comparative Examples 3 to 5.
- the present invention greatly contributes to research and development related to easy-to-use granules.
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Abstract
Description
ることにより製造されている。
[態様1]
糖又は糖アルコールを含みその表面の少なくとも一部が増粘剤によって被覆された顆粒、を含む易服用性顆粒剤。
[態様2]
更に有効成分を含む、態様1記載の易服用性顆粒剤。
[態様3]
該顆粒と別個の構成要素として有効成分を含む、態様2記載の易服用性顆粒剤。
[態様4]
増粘剤によって被覆されている顆粒内に更に有効成分を含む、態様2又は3に記載の易服用性顆粒剤。
[態様5]
該顆粒の表面の実質的に全体が増粘剤によって被覆されている、態様1~4のいずれか一項に記載の易服用性顆粒剤。
[態様6]
増粘剤がカルボキシメチルセルロースナトリウム、キサンタンガム、アルギン酸ナトリウム、カラギーナン、グァーガム、及びゼラチンから成る群から選択される一つ以上の水溶性高分子を含む、態様1~5のいずれか一項に記載の易服用性顆粒剤。
[態様7]
水溶性高分子がカルボキシメチルセルロースナトリウムである、態様6に記載の易服用性顆粒剤。
[態様8]
糖又は糖アルコールがマンニトール、乳糖、ソルビトール、マルチトール、キシリトール、エリスリトール、ラクチトール、マルトース及びイソマルトから成る群から選択される一つ以上を含む、態様1~7のいずれか一項に記載の易服用性顆粒剤。
[態様9]
該顆粒が、更に、水不溶性高分子を含む、態様1~8のいずれか一項に記載の易服用性顆粒剤。
[態様10]
水不溶性高分子が微小繊維状セルロースである態様9記載の易服用性顆粒剤。
[態様11]
微小繊維状セルロースにおける平均繊維長0.01~2mm及び平均繊維径0.001~1μmである、態様10記載の易服用性顆粒剤。
[態様12]
顆粒が水に触れると100~3000N/m2の硬さを有し、且つ、500J/m3以下の付着性を示すゲル状となる、態様1~11のいずれか一項に記載の易服用性顆粒剤。
[態様13]
増粘剤の水溶液を用いて、糖または糖アルコールを含む組成物を造粒する工程を含む、態様1~12のいずれか一項に記載の易服用性顆粒剤の製造方法。
[態様14]
造粒して得られた顆粒及び有効成分を乾式造粒する工程を含む、態様13記載の易服用性顆粒剤の製造方法。
(1)平均粒子径:100~2000μm、(2)水分:0.2~5.0重量%。
以下の実施例及び比較例で得た各顆粒剤(顆粒)について、各物性値を以下の条件・方法で測定した。
更に、以下の実施例に於ける官能評価は以下の通り実施した。
まとまり感:成人男女4名が顆粒剤を水なしで服用し、まとまり感について以下の5段階の評価基準にしたがって評価し、表には平均値を記載した。
1: 感じない、非常に弱い
2: 少し感じる、弱い
3: はっきり感じる
4: やや強い
5: 非常に強い
1: 水と変わらない、非常にやわらかい
2: やわらかい
3: 適度な硬さ
4: やや硬い
5: 非常に硬い
1: 感じない、非常に弱い
2: 少し感じる、弱い
3: はっきり感じる
4: やや強い
5: 非常に強い
日本薬局方記載の「溶出試験法」(回転バスケット法)に従い、溶出液に水を用いて測定した。溶出液へのアセトアミノフェンの溶出率は、紫外可視吸光度測定法により、試験液の波長243nmにおける吸光度を、アセトアミノフェン(アセトアミノフェン、岩城製薬株式会社)を溶出液に含まれるアセトアミノフェンの濃度と同程度の濃度となるように水に溶解させて調製した標準溶液の波長243nmにおける吸光度と比較して測定した。
マンニトール(PEARLITOL、Roquette社)145.5gおよびカルメロースナトリウム (CMCダイセル、ダイセルファインケム株式会社)4.5gを流動層造粒機 (FL-LABO、フロイント産業株式会社)に加え、精製水を3.8g/minの速度で噴霧し造粒することで造粒物を得た。得られた造粒物は以下の物性値を有していた。
水分値:0.65%、平均粒子径:285μm
マンニトール(PEARLITOL、Roquette社)90g、ヒドロキシプロピルセルロース(HPC-SSL、日本曹達株式会社)2gおよびヒドロキシプロピルスターチ(HPS-101W、フロイント産業株式会社)5.5gを乳鉢内で混合し、15mLの精製水を加えて混練した。この混練物を目開き500μmの篩に押し当て粒状にした後、乾燥機で乾燥することで造粒物を得た。得られた造粒物は以下の物性値を有していた。
水分値:0.76%、平均粒子径:848μm
マンニトール(PEARLITOL、Roquette社)187.0g、ヒドロキシプロピルメチルセルロース(ISP社)1.0gおよびヒドロキシプロピルスターチ(HPS-101W、フロイント産業株式会社)11.0gを混合し、30mLの精製水を加えて混練した。この混練物を押し出し造粒機(マルチグラン MG-55-2型、株式会社ダルトン)で造粒した後、乾燥機で乾燥することで造粒物を得た。得られた造粒物は以下の物性値を有していた。
水分値:0.64%、平均粒子径:770μm
乳糖(GranuLac 200、Meggle社)187.0g、ヒドロキシプロピルメチルセルロース(ISP社)1.0gおよびヒドロキシプロピルスターチ(HPS-101W、フロイント産業株式会社)11.0gを混合し、25mLの精製水を加えて混練した。この混練物を押し出し造粒機(マルチグラン MG-55-2型、株式会社ダルトン)で造粒した後、乾燥機で乾燥することで造粒物を得た。得られた造粒物は以下の物性値を有していた。
水分値:1.25%、平均粒子径:973μm
乳糖(GranuLac 200、Meggle社)184.0g、ヒドロキシプロピルセルロース(HPC-SSL、日本曹達株式会社)4.0gおよびヒドロキシプロピルスターチ(HPS-101W、フロイント産業株式会社)11.0gを混合し、20mLの精製水を加えて混練した。この混練物を押し出し造粒機(マルチグラン MG-55-2型、株式会社ダルトン)で造粒した後、乾燥機で乾燥することで造粒物を得た。得られた造粒物は以下の物性値を有していた。
水分値:0.50%、平均粒子径:1009μm
水分値:0.39%、平均粒子径:383μm
水分値:0.44%、平均粒子径:409μm
水分値:0.51%、平均粒子径:447μm
水分値:1.33%、平均粒子径:1213μm
水分値:1.24%、平均粒子径:1219μm
水分値:0.45%、平均粒子径:1199μm
水分値:0.31%、平均粒子径:1282μm
水分値:0.52%、平均粒子径:1387μm
水分値:1.21%、平均粒子径:1153μm
水分値:0.34%、平均粒子径:1195μm
水分値:0.34%、平均粒子径:1273μm
水分値:0.45%、平均粒子径:1281μm
水分値:1.24%、平均粒子径:1269μm
水分値:1.62%、平均粒子径:1234μm
水分値:1.67%、平均粒子径:1315μm
水分値:0.71%、平均粒子径:525μm
水分値:0.60%、平均粒子径:579μm
水分値:0.44%、平均粒子径:188μm
水分値:0.75%、平均粒子径:151μm
水分値:0.54%、平均粒子径:156μm
水分値:2.92%、平均粒子径:431μm
水分値:2.61%、平均粒子径:418μm
押出造粒での顆粒製造において、使用する増粘剤が、カルボキシメチルセルロースナトリウム、キサンタンガム、アルギン酸ナトリウム、カラギーナン、グァーガム、及びゼラチンから成る群から選択される一つ以上の水溶性高分子を含む場合、増粘剤の水溶液を用いず、精製水を加えて作製した顆粒でも、水に触れると付着性が低く且つ適度な硬さを有するゲル状となる。
水分値:0.43%、平均粒子径:769μm
水分値:0.94%、平均粒子径:783μm
水分値:0.40%、平均粒子径:762μm
実施例1及び2、比較例1及び2で得た造粒物(顆粒)について、硬さと付着性の測定結果、ならびに官能評価結果を表1に示す。また、実施例3~25、比較例3~5で得た造粒物(顆粒及び顆粒剤)についての硬さと付着性の測定結果を表1に示す。
Claims (14)
- 糖又は糖アルコールを含みその表面の少なくとも一部が増粘剤によって被覆された顆粒、を含む易服用性顆粒剤。
- 更に有効成分を含む、請求項1に記載の易服用性顆粒剤。
- 該顆粒と別個の構成要素として有効成分を含む、請求項2記載の易服用性顆粒剤。
- 増粘剤によって被覆されている顆粒内に更に有効成分を含む、請求項2又は3に記載の易服用性顆粒剤。
- 該顆粒の表面の実質的に全体が増粘剤によって被覆されている、請求項1~4のいずれか一項に記載の易服用性顆粒剤。
- 増粘剤がカルボキシメチルセルロースナトリウム、キサンタンガム、アルギン酸ナトリウム、カラギーナン、グァーガム、及びゼラチンから成る群から選択される一つ以上の水溶性高分子を含む、請求項1~5のいずれか一項に記載の易服用性顆粒剤。
- 水溶性高分子がカルボキシメチルセルロースナトリウムである、請求項6に記載の易服用性顆粒剤。
- 糖又は糖アルコールがマンニトール、乳糖、ソルビトール、マルチトール、キシリトール、エリスリトール、ラクチトール、マルトース及びイソマルトから成る群から選択される一つ以上を含む、請求項1~7のいずれか一項に記載の易服用性顆粒剤。
- 該顆粒が、更に、水不溶性高分子を含む、請求項1~8のいずれか一項に記載の易服用性顆粒剤。
- 水不溶性高分子が微小繊維状セルロースである請求項9記載の易服用性顆粒剤。
- 微小繊維状セルロースにおける平均繊維長0.01~2mm及び平均繊維径0.001~1μmである、請求項10記載の易服用性顆粒剤。
- 顆粒が水に触れると100~3000N/m2の硬さを有し、且つ、500J/m3以下の付着性を示すゲル状となる、請求項1~11のいずれか一項に記載の易服用性顆粒剤。
- 増粘剤の水溶液を用いて、糖または糖アルコールを含む組成物を造粒する工程を含む、請求項1~12のいずれか一項に記載の易服用性顆粒剤の製造方法。
- 造粒して得られた顆粒及び有効成分を乾式造粒する工程を含む、請求項13記載の易服用性顆粒剤の製造方法。
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US17/045,033 US20210154145A1 (en) | 2018-04-17 | 2019-04-02 | Easy-to-take granular preparation and method for producing same |
JP2020514056A JPWO2019202968A1 (ja) | 2018-04-17 | 2019-04-02 | 易服用性顆粒剤及びその製造方法 |
EP19788597.3A EP3782650A4 (en) | 2018-04-17 | 2019-04-02 | Easy-to-take granular preparation, and method for producing same |
AU2019255672A AU2019255672A1 (en) | 2018-04-17 | 2019-04-02 | Easy-to-take granular preparation, and method for producing same |
KR1020207029197A KR20210002478A (ko) | 2018-04-17 | 2019-04-02 | 복용 용이성 과립제 및 그 제조 방법 |
CN201980026530.4A CN111936168A (zh) | 2018-04-17 | 2019-04-02 | 易服用性颗粒剂及其制造方法 |
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- 2019-04-02 WO PCT/JP2019/014580 patent/WO2019202968A1/ja unknown
- 2019-04-02 US US17/045,033 patent/US20210154145A1/en not_active Abandoned
- 2019-04-02 JP JP2020514056A patent/JPWO2019202968A1/ja active Pending
- 2019-04-02 EP EP19788597.3A patent/EP3782650A4/en not_active Withdrawn
- 2019-04-02 KR KR1020207029197A patent/KR20210002478A/ko not_active Application Discontinuation
- 2019-04-02 CN CN201980026530.4A patent/CN111936168A/zh active Pending
- 2019-04-02 AU AU2019255672A patent/AU2019255672A1/en not_active Abandoned
- 2019-04-12 TW TW108112847A patent/TW202011943A/zh unknown
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US20210154145A1 (en) | 2021-05-27 |
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KR20210002478A (ko) | 2021-01-08 |
EP3782650A1 (en) | 2021-02-24 |
JPWO2019202968A1 (ja) | 2021-04-22 |
CN111936168A (zh) | 2020-11-13 |
TW202011943A (zh) | 2020-04-01 |
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