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WO2010117035A1 - Complexe et son procédé de fabrication ; granules et comprimés - Google Patents

Complexe et son procédé de fabrication ; granules et comprimés Download PDF

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Publication number
WO2010117035A1
WO2010117035A1 PCT/JP2010/056363 JP2010056363W WO2010117035A1 WO 2010117035 A1 WO2010117035 A1 WO 2010117035A1 JP 2010056363 W JP2010056363 W JP 2010056363W WO 2010117035 A1 WO2010117035 A1 WO 2010117035A1
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WO
WIPO (PCT)
Prior art keywords
ibuprofen
complex
composite
aluminum hydroxide
tablet
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.)
Ceased
Application number
PCT/JP2010/056363
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English (en)
Japanese (ja)
Inventor
武利 伊藤
佑理子 石田
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.)
Lion Corp
Original Assignee
Lion 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 Lion Corp filed Critical Lion Corp
Priority to JP2011508387A priority Critical patent/JP5578171B2/ja
Priority to KR1020117022839A priority patent/KR20120010228A/ko
Publication of WO2010117035A1 publication Critical patent/WO2010117035A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • 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
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/1611—Inorganic 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
    • A61K9/2009—Inorganic 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
    • A61K9/2072—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
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy

Definitions

  • the present invention relates to a composite in which the dissolution property of ibuprofen is improved and the bitterness is masked, a method for producing the same, and a granule and a tablet containing the composite.
  • Ibuprofen is widely used for antipyretic analgesics and cold medicines, but has a bitter taste and has a problem in ingestion.
  • Bitter taste masking has generally been improved by coating and granulation of ibuprofen particles.However, there is a problem that elution of ibuprofen decreases when coating and granulation are performed at a level that provides sufficient masking properties. there were. Therefore, the effect may be delayed for headaches that need to be corrected as soon as possible. This tendency is particularly noticeable when tablets are dissolved in the oral cavity and taken without water, such as orally disintegrating tablets and chewable tablets, and it is extremely possible to achieve both practical dissolution and bitterness masking properties. It was difficult.
  • the present invention has been made in view of the above circumstances, and an object thereof is to provide a composite containing ibuprofen, a method for producing the same, and a granule and a tablet containing the composite containing ibuprofen, which are compatible with the dissolution property and bitterness masking property of ibuprofen.
  • the present inventors have found that the elution and bitterness masking properties of ibuprofen can be achieved by using a composite containing amorphous ibuprofen and aluminum hydroxide. It has been found and the present invention has been made. Furthermore, it has been found that by using this complex in combination with thaumatin and / or crospovidone having a median diameter of less than 30 ⁇ m, a significant bitterness masking effect of ibuprofen can be obtained, and the present invention has been made. is there.
  • the present invention provides the following composite, a production method thereof, a granule and a tablet.
  • a composite comprising ibuprofen or a salt thereof and aluminum hydroxide, wherein ibuprofen is amorphous ibuprofen.
  • [2] The composite according to [1], wherein aluminum hydroxide is dispersed in an ibuprofen solution comprising ibuprofen or a salt thereof and a solvent, and then the solvent is distilled off.
  • a complex containing ibuprofen a method for producing the same, and a granule and a tablet containing the same, which can achieve both dissolution properties and bitterness masking properties of ibuprofen.
  • FIG. 2 is a chart showing thermal analysis (DSC) results of particles of Example 1.
  • the composite of the present invention contains ibuprofen or a salt thereof and aluminum hydroxide, and ibuprofen is amorphous ibuprofen.
  • ibuprofen or its salt examples include ibuprofen (2- (4-isobutyphenyl) propionic acid) and its salts such as sodium, potassium, magnesium, calcium, ammonium, methylglucamine, and salts with amino acids such as lysine. Can be mentioned. Ibuprofen or a salt thereof is effective as an antipyretic analgesic, but has a problem in dissolution and has a bitter taste.
  • the compounding amount of ibuprofen in the complex and the preparation (granulate and tablet) is appropriately selected based on the OTC drug approval reference amount so that the daily dose is 450 mg.
  • Aluminum hydroxide serves as a support for amorphized ibuprofen.
  • aluminum hydroxide it is preferable to use aluminum hydroxide having an oil absorption of 1 mL / g or more, more preferably 1.2 mL / g or more. If the oil absorption is less than 1 mL / g, the amorphous stability may be insufficient.
  • the upper limit of the oil absorption amount is not particularly limited, but if the oil absorption amount is too large, there may be a problem in the productivity of the composite, and 7 mL / g or less is preferable.
  • the blending amount of ibuprofen in the complex and preparation (granule and tablet) is preferably 1 / 0.5 to 7, more preferably 1/1 to 4 by mass ratio represented by ibuprofen / aluminum hydroxide.
  • the carrier for the amorphized ibuprofen Although it is preferable to use only aluminum hydroxide as the carrier for the amorphized ibuprofen, other carrier components and aluminum hydroxide can be used in combination as long as the effects of the present invention are not impaired.
  • other carrier components include light anhydrous silicic acid and calcium carbonate.
  • the amount of aluminum hydroxide in the carrier is preferably 70 to 100% by mass, more preferably 85 to 100% by mass.
  • the amount of ibuprofen in the supported components is preferably 70 to 100% by mass, more preferably 85 to 100% by mass.
  • Non-steroidal anti-inflammatory agents such as nitrazepam, triazolam, phenobarbital, and amibarbital; hypnotics and sedatives such as phenytoin, metalbital, primidone, clonazepam, carbamazepine, and valproic acid; meclizine hydrochloride, dimenhydrinate Antidepressants; antidepressants such as imiplanin, noxiptylline, phenelzine; haloperidol, meprobamate, chlordiazepoxide, diazebam, oxa
  • Vitamins dimethicone, famotidine, ranitidine, cimetidine, nizatidine, metoclopramide, famotidine, omeprazole, sulpiride, trepibutone, sucralfa Gastrointestinal diseases therapeutic agents such as caffeine, dicoumarol, cinnarizine, clofibrate, gefarnate, brobenesid, mercaptopurine, methotrexate, ursodeoxycholic acid, dihydroergotamine mesylate, glucuronolactone, ⁇ - Bioactive substances such as aminobutyric acid, chondroitin, sodium chondroitin sulfate, lactoferrin, milk protein, cysteine, collagen; starch, pregelatinized starch, sucrose, gelatin, gum arabic powder, methylcellulose, carmellose, carmellose calcium, carmellose sodium , Hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyr
  • the complex is a method in which aluminum hydroxide is dispersed or dissolved in an ibuprofen solution composed of ibuprofen or a salt thereof and a solvent, and then the solvent is distilled off.
  • An aluminum hydroxide gel is added to ibuprofen or a salt thereof, and the mixture is melted by heating. It can be obtained by, for example, a method of cooling after cooling and solidifying. In this way, ibuprofen or a salt thereof is once dissolved, and reprecipitated using aluminum hydroxide as a carrier, whereby ibuprofen is non-crystallized and a composite in which amorphous ibuprofen is supported on aluminum hydroxide is obtained. Non-crystallization can be confirmed from the fact that a diffraction peak derived from an ibuprofen crystal is not observed with a thermal analysis (DSC) diffractometer.
  • DSC thermal analysis
  • the method of distilling off the solvent is preferable, and the solvent for dissolving ibuprofen or a salt thereof is not particularly limited as long as it can dissolve ibuprofen or a salt thereof, but a solvent such as ethanol, methanol, acetone, acetonitrile, water, aqueous sodium hydroxide, etc. Can be used alone or in combination of two or more.
  • the concentration of ibuprofen in the ibuprofen solution is not particularly limited as long as it can be dissolved, but is 0.1 to 50% by mass.
  • the mass ratio represented by ibuprofen / aluminum hydroxide is preferably 1 / 0.5 to 7, and more preferably 1/1 to 4. If the amount of aluminum hydroxide relative to ibuprofen is less than 0.5, the amorphous stability may be insufficient, and the dissolution property may be poor. Further, since the amount of ibuprofen in the composite decreases when the amount of aluminum hydroxide increases, the amount of particles may increase in order to obtain an effective amount of ibuprofen.
  • the obtained liquid is evaporated.
  • the method for distilling off the solvent is not particularly limited, and a known method such as an evaporator can be used.
  • the obtained composite can be pulverized, granulated, or sized as it is or as necessary to obtain composite particles having a predetermined particle diameter.
  • the volume average particle diameter of the particles is preferably from 0.1 to 800 ⁇ m, more preferably from 1 to 600 ⁇ m.
  • the measurement of the average particle diameter in this invention uses the particle size distribution measuring apparatus by a laser diffraction scattering method.
  • the composite is usually “as it is, or, if necessary, within the range where the effects of the present invention are not impaired, and / or a granulated product to which other components are added” , Composite particles) ”.
  • the ratio of the composite is appropriately selected in the range of 30 to 100% by mass in the composite particle, more preferably 50 to 100% by mass, and still more preferably 70 to 100% by mass.
  • the component quoted by [0014] is mentioned, for example.
  • a solution or dispersion of a coating agent selected from ethylcellulose, triacetin, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinylpyrrolidone, pregelatinized starch and gelatin is separately sprayed and It is good also as a coating particle by drying and coating. Thereby, interaction with other components, etc. can be reduced.
  • the concentration of the coating agent in the solution or dispersion is preferably 0.1 to 50% by mass, and more preferably 1 to 20% by mass.
  • the granulating apparatus used for coating is not particularly limited, and a Wurster type fluidized bed granulator or the like is appropriately selected.
  • the supply air temperature during flow is preferably 40 to 90 ° C, and the exhaust temperature is preferably 20 to 40 ° C.
  • the drying temperature and time are not particularly limited, and the drying is performed at 40 to 80 ° C. for about 1 to 120 minutes.
  • the amount of the coating agent can be performed within a range that does not significantly impair the effects of the present invention.
  • the composite or composite particle of the present invention can be blended to prepare a granule or tablet preparation containing the composite.
  • the tablet is an orally disintegrating tablet, an orally dissolving tablet, or a chewable tablet that can be chewed and taken in the mouth, the effect of the present invention is remarkably exhibited.
  • complex is suitably selected according to the intake amount of the said ibuprofen or its salt, and aluminum hydroxide. For example, in the case of 2 tablets at a time and the mass ratio of ibuprofen to aluminum hydroxide (ibuprofen / aluminum hydroxide) is 1/1, the amount of the complex per tablet is 150 mg.
  • thaumatin and / or crospovidone having a median diameter of less than 30 ⁇ m is blended, whereby the bitterness of ibuprofen is remarkably suppressed by the synergistic effect with the complex or the composite particle. Show the effect.
  • the combined use of thaumatin and crospovidone having a median diameter of less than 30 ⁇ m further suppresses the bitter taste of ibuprofen.
  • Saumatine is a type of protein, also known as thaumatin. Although thaumatin is usually mixed with powder, when ibuprofen is granulated, it may be mixed in the granulated particles.
  • the amount of thaumatin is preferably 0.01 to 50 parts by weight, more preferably 0.01 to 1.0 parts by weight, and particularly preferably 0.01 to 0.10 parts by weight with respect to 100 parts by weight of ibuprofen. . Within this range, the effect of suppressing bitterness can be obtained effectively.
  • crospovidone having a median diameter of less than 30 ⁇ m examples include Kollidon CL-F, CL-SF, CL-M manufactured by BASF, and polyplastidone INF-10 manufactured by ISP. Further, crospovidone having a median diameter of 30 ⁇ m or more can be pulverized according to a conventional method. The lower limit of the median diameter is not particularly set, but is usually preferably 1 ⁇ m or more.
  • the amount of crospovidone having a median diameter of less than 30 ⁇ m is preferably 0.1 to 150 parts by weight, more preferably 0.5 to 120 parts by weight, and particularly preferably 1 to 100 parts by weight with respect to 100 parts by weight of ibuprofen. Within this range, the effect of suppressing bitterness can be obtained effectively.
  • the components to be added to the preparation can be used singly or in appropriate combination of two or more, as long as the effects of the present invention are not impaired. be able to.
  • the following are mentioned as other components.
  • excipients include cellulose and derivatives thereof, starch and derivatives thereof, saccharides, sugar alcohols, and the like. More specifically, crystalline cellulose, lactose, sucrose, mannitol, erythritol, corn starch, potato starch, hydroxy And propyl starch.
  • binder examples include hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, gelatin, dextrin, starch, pregelatinized starch and the like.
  • disintegrant examples include carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropyl cellulose, low-substituted carboxymethyl starch sodium, and crospovidone having a median diameter of 30 ⁇ m or more.
  • lubricant examples include magnesium stearate, calcium stearate, sucrose fatty acid ester, anhydrous silicic acid, light anhydrous silicic acid, sodium stearyl fumarate and the like.
  • the preparation can be made into a granule by mixing a complex and an optional component, and then wrapping the mixture, and the mixture can be compression molded with a rotary tableting machine, a single-punch tableting machine, or the like.
  • a sugar coating or a pigment-containing coating can be appropriately formed into tablets.
  • Example 1 100 g of crystalline ibuprofen was dissolved in 200 g of ethanol. 50 g of dry aluminum hydroxide gel was added thereto to make a uniform slurry, and then the solvent was distilled off with a rotary evaporator. When the crystallinity of the residue was evaluated with a thermal analyzer manufactured by Rigaku Denki Co., Ltd., no melting peak derived from ibuprofen crystals was observed, and ibuprofen was amorphous. The residue was sieved with a sieve of 150 to 355 ⁇ m to obtain particles with a volume average particle diameter of 200 ⁇ m. In addition, the chart which shows the thermal analysis (DSC) result of the particle
  • DSC thermal analysis
  • Example 6 After adding 50 g of dry aluminum hydroxide gel to 100 g of crystalline ibuprofen, ibuprofen was melted with stirring in a 90 ° C. water bath. The molten dispersion was put into a stainless steel vat and cooled to room temperature, and the solidified product was pulverized in a mortar. When the crystallinity of the solidified product was evaluated by a thermal analyzer manufactured by Rigaku Corporation, no melting peak derived from ibuprofen crystals was observed, and ibuprofen was amorphous.
  • Comparative Example 6 The particles obtained in Comparative Example 5 were used as core particles, an aqueous dispersion of 20% ethyl cellulose and 3% triacetin was used as a coating solution, and an air supply temperature was 70 using an MP-01 Wurster type fine particle coating apparatus (manufactured by POWREC). Granulation was performed at a temperature of 30 ° C. and an exhaust temperature of 30 ° C., followed by quenching at 80 ° C. for 1 hour to obtain coating particles. The coating rate was 15 parts with respect to 100 parts in total of ibuprofen and dry aluminum hydroxide gel. The coating agent is not listed in the table.
  • Examples 7 to 16 The compositions shown in Tables 3 and 4 were mixed and tableted with a tableting tester at a tableting pressure of 400 kg to obtain an orally disintegrating tablet with a diameter of 10 mm.
  • Examples 17 to 21 The composite particles of Examples 1, 2, 5, 6 and 7 were used as core particles, an aqueous dispersion of 20% ethyl cellulose and 3% triacetin was used as a coating solution, and MP-01 Wurster type fine particle coating apparatus (manufactured by POWREC). The mixture was granulated at a supply temperature of 70 ° C. and an exhaust temperature of 30 ° C., and then quenched at 80 ° C. for 1 hour to obtain coating particles. The coating rate was 15 parts with respect to 100 parts in total of ibuprofen and dry aluminum hydroxide gel. All ibuprofen of these coating particles were amorphous, and both bitterness and dissolution were excellent as in Examples 1-16.
  • Example 22 100 g of crystalline ibuprofen was dissolved in 200 g of ethanol. To this, 100 g of dry aluminum hydroxide gel and 50 g of magnesium aluminate metasilicate were added to form a uniform slurry, and then the solvent was distilled off with a rotary evaporator. When the crystallinity of the residue was evaluated with a thermal analyzer manufactured by Rigaku Denki Co., Ltd., no melting peak derived from ibuprofen crystals was observed, and ibuprofen was amorphous. The residue was sieved with a sieve of 150 to 355 ⁇ m to obtain composite particles having an average particle diameter of 200 ⁇ m.
  • Example 23 A mixture having the following composition was prepared using the composite particles obtained in Example 22, and 422.55 mg of this mixture was tableted with a tableting tester at a tableting pressure of 400 kg to obtain an orally disintegrating tablet with a diameter of 10 mm. .
  • Mixture composition composite particles (Example 22) 187.5 g 150 g of crystalline cellulose (Theolas KG801) Crospovidone (Polyplusdon INF-10) 80g Somachin 0.05g Magnesium stearate 5g Total 422.55g
  • Example 24 Composite particles were obtained in the same manner as in Example 22 except that 100 g of ibuprofen, 200 g of dry aluminum hydroxide gel, and 100 g of magnesium aluminate metasilicate were used. The obtained composite particles were granulated by the same method as in Example 17 to obtain coating particles.
  • Example 25 A mixture having the following composition was prepared using the coating particles obtained in Example 24, and 457.6 mg of this mixture was tableted with a tableting tester at a tableting pressure of 400 kg to obtain an orally disintegrating tablet with a diameter of 10 mm. .
  • Mixture composition coated particles (Example 24) 172.5 g Acetaminophen coating * 85 g 140g D-mannitol Crospopidone (Kollidon CL) 50g Somachin 0.05g Magnesium stearate 10g Total 457.55g * Coated product of acetaminophen; acetaminophen was granulated and coated in the same manner as in Example 17. The coating rate was 15 parts by mass with respect to 100 parts by mass of acetaminophen.
  • Example 26 Composite particles were obtained in the same manner as in Example 18 except that 100 g of ibuprofen, 100 g of dry aluminum hydroxide gel, and 200 g of magnesium aluminate metasilicate were used. The obtained composite particles were granulated by the same method as in Example 17 to obtain coating particles.
  • Example 27 A mixture having the following composition was prepared using the coating particles obtained in Example 26, and 470 mg of this mixture was tableted with a tableting tester at a tableting pressure of 400 kg to obtain an orally disintegrating tablet with a diameter of 10 mm.
  • 345 g of mixture composition coated particles Fructose 100g Crospopidone (Kollidon CL-SF) 20g Somachin 0.05g Sucralose 0.3g Magnesium stearate 5g Fragrance 0.5g Total 470.85g
  • the ibuprofen in the composite particles obtained in Examples 22 to 27 was amorphous, and the bitterness and dissolution were excellent as in Examples 1 to 16.

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Abstract

Complexe comprenant de l'ibuprofène ou un sel d'ibuprofène et un hydroxyde d'aluminium, l'ibuprofène étant un ibuprofène amorphe
PCT/JP2010/056363 2009-04-09 2010-04-08 Complexe et son procédé de fabrication ; granules et comprimés Ceased WO2010117035A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2011508387A JP5578171B2 (ja) 2009-04-09 2010-04-08 複合体及びその製造方法、ならびに粒状剤及び錠剤
KR1020117022839A KR20120010228A (ko) 2009-04-09 2010-04-08 복합체 및 그 제조 방법, 및 입상제 및 정제

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JP2009-094632 2009-04-09
JP2009094632 2009-04-09

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011213714A (ja) * 2010-03-15 2011-10-27 Taisho Pharmaceutical Co Ltd イブプロフェン含有固形製剤の製造方法
JP2011219470A (ja) * 2010-03-25 2011-11-04 Lion Corp 解熱鎮痛組成物
JP2012229182A (ja) * 2011-04-27 2012-11-22 Sumitomo Chemical Co Ltd 粒状農薬組成物
WO2017115745A1 (fr) 2015-12-28 2017-07-06 エスエス製薬株式会社 Préparation pharmaceutique obtenue par moulage par compression
JP2020083884A (ja) * 2018-11-16 2020-06-04 エスエス製薬株式会社 イブプロフェン含有経口用医薬製剤

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0249720A (ja) * 1988-05-18 1990-02-20 Mitsubishi Kasei Corp 難溶性薬剤組成物
JPH11246404A (ja) * 1998-03-04 1999-09-14 Taiho Yakuhin Kogyo Kk 吸収を改善した医薬組成物
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JP2011213714A (ja) * 2010-03-15 2011-10-27 Taisho Pharmaceutical Co Ltd イブプロフェン含有固形製剤の製造方法
JP2011219470A (ja) * 2010-03-25 2011-11-04 Lion Corp 解熱鎮痛組成物
JP2012229182A (ja) * 2011-04-27 2012-11-22 Sumitomo Chemical Co Ltd 粒状農薬組成物
KR20140027287A (ko) * 2011-04-27 2014-03-06 스미또모 가가꾸 가부시끼가이샤 입상 농약 조성물
KR101944560B1 (ko) 2011-04-27 2019-01-31 스미또모 가가꾸 가부시끼가이샤 입상 농약 조성물
WO2017115745A1 (fr) 2015-12-28 2017-07-06 エスエス製薬株式会社 Préparation pharmaceutique obtenue par moulage par compression
JP2020083884A (ja) * 2018-11-16 2020-06-04 エスエス製薬株式会社 イブプロフェン含有経口用医薬製剤
JP7406349B2 (ja) 2018-11-16 2023-12-27 エスエス製薬株式会社 イブプロフェン含有経口用医薬製剤

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