WO2006085497A1 - Comprimé à désintégration orale - Google Patents

Comprimé à désintégration orale Download PDF

Info

Publication number
WO2006085497A1
WO2006085497A1 PCT/JP2006/301951 JP2006301951W WO2006085497A1 WO 2006085497 A1 WO2006085497 A1 WO 2006085497A1 JP 2006301951 W JP2006301951 W JP 2006301951W WO 2006085497 A1 WO2006085497 A1 WO 2006085497A1
Authority
WO
WIPO (PCT)
Prior art keywords
weight
starch
orally disintegrating
disintegrating tablet
cold water
Prior art date
Application number
PCT/JP2006/301951
Other languages
English (en)
Japanese (ja)
Inventor
Kazuki Mimura
Ken Kanada
Kiyohisa Ouchi
Original Assignee
Kissei Pharmaceutical Co., Ltd.
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 Kissei Pharmaceutical Co., Ltd. filed Critical Kissei Pharmaceutical Co., Ltd.
Priority to JP2007502589A priority Critical patent/JP5004236B2/ja
Publication of WO2006085497A1 publication Critical patent/WO2006085497A1/fr

Links

Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/06—Antiabortive agents; Labour repressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Definitions

  • the present invention relates to a tablet that rapidly disintegrates in the oral cavity and a method for producing the same.
  • an orally disintegrating tablet prepared by dispensing a suspension of an active ingredient into a bowl and freeze-drying is known (for example, see Patent Document 1).
  • the orally disintegrating tablets that require equipment are inconvenient to handle because of their low hardness.
  • JP-A-8-291051 discloses the production of an orally disintegrating tablet prepared by compression-molding a granulated product containing an active ingredient, a water-soluble binder and a water-soluble excipient, followed by humidification and drying. Although a method has been disclosed, this method requires special manufacturing equipment (see, for example, Patent Document 2).
  • WO95 / 20380 discloses an orally disintegrating preparation that is prepared by combining granulated and compression-molded saccharides with low moldability and saccharides with high moldability, and then humidifying and drying to increase hardness. (For example, see Patent Document 3).
  • W097 / 47287 includes an orally disintegrating tablet comprising a combination of a sugar alcohol or saccharide having an average particle size of 30 ⁇ m or less, an active ingredient and a disintegrant, and having an appropriate hardness and disintegration. It is disclosed (for example, see Patent Document 4).
  • the D-mannitol used here has a problem of causing tableting troubles such as binding and cabbing due to large friction with the metal wall during compression molding. There is a need for special manufacturing equipment such as applying tablets and tableting.
  • WO2000 / 57857 contains spray-dried D-mannitol and crospovidone.
  • An orally disintegrating tablet having moderate hardness and disintegration prepared by directly tableting a mixture is disclosed (for example, see Patent Document 5).
  • Japanese Patent Laid-Open No. 2001-163770 discloses an appropriate hardness and disintegration property obtained by directly compressing a tableting powder containing a co-ground product of a mixture containing a saccharide and a disintegrant and an unpowdered saccharide product.
  • An orally disintegrating tablet having the above has been disclosed (for example, see Patent Document 6).
  • D-mannitol is used as an excipient and an orally disintegrating tablet is prepared according to these methods, there is a problem that tableting troubles such as binding still tend to occur during compression molding. I'm going.
  • Patent Document 1 U.S. Pat.No. 4,371,516
  • Patent Document 2 Japanese Patent Laid-Open No. 2001-163770
  • Patent Document 3 International Publication No. 95/20380 Pamphlet
  • Patent Document 4 International Publication No. 97/47287 Pamphlet
  • Patent Document 5 Pamphlet of International Publication No. 2000/57857
  • Patent Document 6 Japanese Patent Laid-Open No. 2001-163770
  • An object of the present invention is to provide an orally disintegrating tablet that has an appropriate hardness and quick disintegration, and can be industrially produced by a general production facility.
  • the present invention provides:
  • Sugar or sugar alcohol power At least selected from lactose and D_mannitol Orally disintegrating tablet according to [1], wherein
  • a method for producing an orally disintegrating tablet comprising mixing a disintegrant with a product and compression molding;
  • [21] a) active ingredient, b) sugar or sugar alcohol, c) partially alpha-monified starch with cold water soluble content of 10-20% by weight, and d) portion with cold water soluble content of less than 10% by weight
  • a method for producing an orally disintegrating tablet comprising granulating a mixture containing alpha-monified starch while adding water, mixing the resulting granulated product with a disintegrant, and compressing the mixture; About.
  • any active ingredient that can be administered orally without particular limitation can be used.
  • active ingredients include, for example, antiparkinsonian drugs, antihyperlipidemic drugs, antidiabetic drugs, bronchial asthma drugs, allergic disease drugs, imminent flow premature birth drugs, dysuria drugs, etc.
  • active ingredients include, for example, antiparkinsonian drugs, antihyperlipidemic drugs, antidiabetic drugs, bronchial asthma drugs, allergic disease drugs, imminent flow premature birth drugs, dysuria drugs, etc.
  • One or more selected components are used.
  • antiparkinsonian drug include L-dopa, strength belgorin and the like.
  • antihyperlipidemic agent include bezafibrate, furofibrate, symfibrate and the like.
  • antidiabetic agent include mitiglinide calcium hydrate, nateglinide and the like.
  • bronchial asthma therapeutic agent examples include ozadarel hydrochloride and the like.
  • allergic disease therapeutic agent examples include tranilast.
  • ritodrine hydrochloride is an example of the treatment for threatened premature birth.
  • urination disorder therapeutic agent examples include silodosin.
  • the preferred active ingredient is mitiglinide Calcium hydrate, ritodrine hydrochloride, silodosin or strength bergolin.
  • the content of the active ingredient varies depending on the type of the tablet. Usually, about 0.01 to about 50 parts by weight, preferably about 0. 01 to about 20 parts by weight.
  • the content of mitiglinide calcium hydrate is about 1 to about 20 parts by weight per tablet; L 00 parts by weight.
  • sugars or sugar alcohols used in the orally disintegrating tablet of the present invention those having high water solubility and low moldability are preferably used.
  • sugars or sugar alcohols include, for example, sugars such as lactose, gnolecose, sucrose, and fructose; and sugar alcohols such as D-mannitol, xylitol, maltitol, sorbitol, and lactose or D_mannitol strength S, It is preferable because it has a good sweetness when taken, and D_mannito nore is particularly preferable because it has a refreshing feeling and easily obtains an appropriate hardness and quick disintegration.
  • sugars or sugar alcohols can be used in combination of two or more as required.
  • sugars and sugar alcohols can be used in combination.
  • the sugar or sugar alcohol content is about 10 to about 95 parts by weight, preferably about 30 to about 90 parts by weight, more preferably 100 parts by weight of the tablet. About 50 to about 90 parts by weight.
  • the content of sugar and sugar alcohol can be used in any ratio.
  • the “cold water soluble content (% by weight)” can be measured as follows.
  • partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight ⁇ Means partially alpha-ized dendron that is 10 to 20% by weight of the portion contained in the supernatant liquid when the cold water soluble component is measured according to the above measurement method.
  • partially partially modified starch having a cold water-soluble content of less than 10% by weight means that when the cold water-soluble content is measured according to the above measurement method, the portion that dissolves in water is 10% by weight. Means less alpha alpha starch.
  • the partially alpha-ized starch used in the orally disintegrating tablet of the present invention is obtained by physically modifying cereal starches such as corn, wheat, and rice, and the kind thereof is not particularly limited. However, partially alpha-ized starch prepared from corn starch is preferred.
  • Partially alpha-ized starch having a cold water soluble content of 10 to 20% by weight used in the orally disintegrating tablet of the present invention is a commercially available partially alpha-ized starch such as Star chl500 ( Nippon Colorcon, cold water soluble component: 10 to 20% by weight) can be used.
  • partially alpha-ized starch with a cold water-soluble content of less than 10% by weight used in combination with “partially alpha-ized starch with a cold-water soluble content of 10 to 20% by weight”
  • PCS manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: less than 10% by weight
  • LYCATAB C manufactured by Rocket
  • partially alpha-ized starch having a cold water-soluble content of 10 to 20% by weight and “partially alpha-ized starch having a cold water-soluble content of less than 10% by weight” are known methods, for example, Manufactured according to the method described in JP-B-59-47600, JP-A-4-318001, etc. I'll do it for you.
  • the cold water soluble content of the "partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight" used in the orally disintegrating tablet of the present invention is preferably about 12 to about 18% by weight. More preferably about 14 to about 16% by weight.
  • the cold water soluble content of the “partially alpha-monoized starch having a cold water soluble content of less than 10% by weight” used in the orally disintegrating tablet of the present invention is preferably about 1 to about 8% by weight, More preferably from about 1 to about 6% by weight, and even more preferably from about 1 to about 3% by weight.
  • the content of partially-alphatized starch having a cold water soluble content of 10 to 20% by weight is usually about 0.5 to about about 100 parts by weight of the tablet. If it is 30 parts by weight and less than 0.5 part by weight relative to 100 parts by weight of the tablet, a sufficient tableting failure improving effect cannot be obtained, and if it exceeds 30 parts by weight, rapid disintegration cannot be obtained.
  • the preferred content of partially alpha-monified starch having a cold water soluble content of 10 to 20% by weight is about 1 to about 20 parts by weight, more preferably about 2 to about 15 parts by weight per 100 parts by weight of the tablet. Part.
  • a partially alpha-ized starch having a cold water-soluble content of 10 to 20% by weight and a partially alpha-ized starch having a cold water-soluble content of less than 10% by weight When used in combination, the ratio of partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight to partially alpha-monified starch having a cold water soluble content of less than 10% by weight is 1: It is used in the range of 0 to about 1: about 9, preferably about 2: about 1 to about 1: about 9.
  • Examples of the disintegrant used in the orally disintegrating tablet of the present invention include crospovidone and corn starch, and crospovidone is preferred.
  • the content of the disintegrant varies depending on the type of disintegrating tablet, but is usually about 0.5 to about 30 parts by weight with respect to 100 parts by weight of the tablet. More specifically, the content of crospovidone is about 0.5 to about 10 parts by weight, preferably about 1 to about 7 parts by weight, based on 100 parts by weight of the tablet.
  • the content of corn starch is about 3 to about 20 parts by weight, preferably about 5 to about 20 parts by weight per 100 parts by weight of the tablet.
  • the orally disintegrating tablet of the present invention has various additives, such as excipients, binders, lubricants, and sweeteners used in the preparation of the preparation, as long as the effects of the invention are not hindered.
  • excipients include rice starch, crystalline cellulose, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, calcium lactate, and ethyl cellulose.
  • binder examples include hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polybutyl pyrrolidone, methyl cellulose, polybutyl alcohol, sodium alginate, aminoalkyl methacrylate copolymer, polyethylene glycol and the like.
  • lubricant for example, magnesium stearate, calcium stearate, talc, light anhydrous key acid, sucrose fatty acid ester, sodium stearyl fumarate and the like can be mentioned.
  • sweeteners include aspartame (registered trademark), saccharin sodium, dipotassium glycyrrhizin, stevia, thaumatin, and acesulfame K.
  • Examples of the acidulant include citrate, tartaric acid, malic acid, ascorbic acid and the like.
  • the foaming agent include sodium hydrogen carbonate, sodium carbonate, calcium carbonate and the like.
  • Examples of the corrigent include L-aspartic acid, sodium chloride, magnesium chloride, sodium citrate, calcium citrate, sodium L-glutamate, and sodium bicarbonate.
  • Examples of the fragrances include orange oil, lemon oil, menthol, and various fragrance powders.
  • Examples of the colorant include edible pigments such as edible yellow No. 5, edible red No. 2, and edible blue No. 2, yellow ferric oxide, ferric oxide, and caramel pigment.
  • the orally disintegrating tablet of the present invention comprises: a) an active ingredient, b) a sugar or sugar alcohol, and c) cold water, a partially alpha-gelatinized starch having a soluble content of 10 to 20% by weight.
  • a disintegrant may be added, mixed, and compression molded.
  • the method for producing an orally disintegrating tablet of the present invention is characterized in that the granulated product contains partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight.
  • the active ingredient in the granulated product can be contained in any amount, and as long as the effect of the invention is not hindered, the sugar or sugar alcohol and the moiety.
  • Add and mix active ingredients and disintegrant to granulated product made from alpha-ized starch However, it is also possible to manufacture by compression molding.
  • the disintegrability can be enhanced by adding a partially alpha-integrated starch having a cold water-soluble content of less than 10% by weight to the granulated product. Adjust the disintegration time in the oral cavity to a preferred time by appropriately increasing or decreasing the amount of partially alpha-ized starch that is 20% by weight and the amount of partially alpha-ized starch that is soluble in cold water less than 10% by weight. Can do.
  • Examples of the granulation method used for the orally disintegrating tablet of the present invention include, for example, a fluidized bed granulation method, a high-speed stirring granulation method, an extrusion granulation method, a rolling granulation method, and a rolling fluid granulation method.
  • the fluidized bed granulation method and the high-speed stirring granulation method are preferably used.
  • the orally disintegrating tablet of the present invention can be produced, for example, as follows.
  • the orally disintegrating tablet of the present invention comprises a mixture of a) an active ingredient and b) a sugar or a sugar alcohol while spraying partially alpha-monified starch having a cold water soluble content of 10 to 20% by weight.
  • a disintegrant to the granulated product, mixing it, and compressing it.
  • a part of the partially alpha-monified starch having a cold water soluble content of 10 to 20% by weight is mixed with the active ingredient and sugar or sugar alcohol, and the remaining partially alpha-ized starch is mixed. It can also be granulated while spraying.
  • the orally disintegrating tablet of the present invention comprises a mixture containing a) an active ingredient, b) a sugar or sugar alcohol, and c) partially alpha-unified starch having a cold water soluble content of less than 10% by weight. It can be produced by granulating while partially spraying partially alpha-monified starch having a soluble content of 10 to 20% by weight, adding a disintegrant to the granulated product, mixing, and compression molding.
  • the orally disintegrating tablet of the present invention comprises a mixture containing a) an active ingredient, b) a sugar or sugar alcohol, and c) a partially alpha-monified starch having a cold water soluble content of 10 to 20% by weight. It is possible to produce the product by granulating it with the addition of, adding a disintegrant to the granulated product, mixing it, and compression molding. [0038] Manufacturing method 4
  • the orally disintegrating tablet of the present invention comprises: a) an active ingredient, b) sugar or sugar alcohol, c) partially alpha-starch starch having a soluble content of 10 to 20% by weight of cold water, and d) less than 10% by weight
  • a) an active ingredient b) sugar or sugar alcohol
  • c) partially alpha-starch starch having a soluble content of 10 to 20% by weight of cold water and d) less than 10% by weight
  • the ability to produce a mixture containing partially alpha-monoized starch having a soluble content of cold water by adding water, adding a disintegrant to the granulated product, mixing, and compression-molding S can.
  • both sugar and sugar alcohol may be mixed with the active ingredient and granulated, but either one is granulated.
  • the other may be added and mixed after granulation.
  • a mixture containing an active ingredient and a sugar alcohol is granulated, and a sugar and a disintegrant are added to and mixed with the resulting granulated product, thereby preventing tableting troubles during compression molding.
  • the orally disintegrating tablet of the invention can be prepared.
  • compression molding can be performed using a single-punch tableting machine, a rotary tableting machine, or the like.
  • the pressure for tableting is usually 2 to 60 kN / cm 2 , preferably 6 to 30 kN / cm 2 .
  • the orally disintegrating tablet of the present invention thus obtained exhibits moderate hardness and rapid or powerful disintegration or solubility in the oral cavity.
  • the orally disintegrating time of the orally disintegrating tablet of the present invention is a force that varies depending on the size and thickness of the tablet, and is usually within 60 seconds, and preferably within 40 seconds.
  • the hardness of the orally disintegrating tablet of the present invention is usually 30 N or more, preferably 5
  • the orally disintegrating tablet of the present invention rapidly disintegrates or dissolves in the oral cavity, it can be easily taken by elderly people and children who have difficulty swallowing.
  • the orally disintegrating tablet of the present invention is easy to handle because it has sufficient hardness not to be damaged in the distribution process.
  • the orally disintegrating tablet of the present invention can be easily produced without causing problems such as tableting troubles in the production process, it is suitable for industrial production.
  • starches corn starch, partially alpha-monified starch and alpha-monified starch, and cold water soluble content of dextrin were measured according to the following method.
  • Example:! ⁇ 11 and comparative example:! ⁇ 8 The hardness of the tablets produced by! ⁇ 8 was measured with a hardness meter (TS-75N, Oka Measured by Tasei). The test was conducted with 3 tablets and the average value was determined. The results are shown in Table 2 and Table 3.
  • Examples 1 to 11 In the tableting process of 11 and Comparative Examples 1 to 8, the appearance of the tablet was determined from the appearance of the upper and lower surfaces of the tablet, the presence of binding was determined from the appearance of the tablet side surface, and the cabbage was removed from the occurrence of delamination of the tablet. The presence or absence was observed. In addition, if the powder adheres to the mortar wall or the frictional state (occurrence of abnormal noise) is severe, tableting is prohibited. The results are shown in Table 2 and Table 3.
  • Granulation was performed while spraying this dispersion with a spray nozzle.
  • Granulated material sieved with No. 18 sieve 374g, crospovidone (Polyplasdone XL-10, ISP) 20g, light anhydrous anhydrous (Adsolidar 101, Freund Sangyo) 2g and magnesium stearate (made by Taihei Chemical Sangyo) 4g was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton).
  • a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablet weight 200 mg, 8 ⁇ ⁇ circular, table rotation speed 30 mm, tableting pressure 7.8, 11.7 press 15.61 Tablets were produced under the conditions of 111 2 .
  • D-mannitol Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 zm
  • Starchl500 partially alpha-unified starch
  • 70 g are mixed at high speed.
  • the mixture was mixed for 2 minutes using a granulator (FM-VG-10, manufactured by Paurek).
  • This mixture was put into a fluidized bed granulator / dryer (LAB-1, manufactured by Norec), and 21 g of partially alpha-integrated starch (Starchl500, manufactured by Nippon Colorcon, cold water soluble content: 15.8% by weight) was added to 180 g of purified water.
  • Granulation was performed while spraying this dispersion with a spray nozzle.
  • the mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton).
  • the tableting mixture was mixed with a tablet weight of 200 mg, 8 ⁇ ⁇ circle, table rotation speed 30 mm, tableting pressure 11.7, 15.6 and 19.5 kN / Tablets were made under conditions of cm 2 .
  • this tableting mixture was tablet weight 200 mg, 8 ⁇ ⁇ circular, table rotation speed 30 mm, tableting pressure 11.7 and 15.6 kN m 2 Tablets were made under the conditions of
  • PCS Partially alpha starch
  • D-mannitol Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 zm
  • PCS partially alpha-ized starch
  • F 8 agitation granulator
  • LAB-1 fluidized bed granulator / dryer
  • D-mannitol Mannit P, Towa Kasei Kogyo Co., Ltd., average particle size 45 zm
  • PCS partially-modified starch
  • PCS cold water soluble content: 1.2 wt%
  • D-mannitol Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 zm
  • FM-VG-10 high-speed mixing and agitation granulator
  • This pulverized product was put into a fluidized bed granulator / dryer (LAB-1, manufactured by Norec), and granulated while spraying purified water with a spray nozzle.
  • D_Mannitol Mannit P, Towa Kasei Kogyo Co., Ltd., average particle size 45 zm
  • corn starch corn starch (Nihon Shokuhin Kako Co., Ltd., cold water soluble content: 0.1 wt%) 9
  • the mixture was mixed for 2 minutes using a stirring granulator (FM-VG-10, manufactured by Paurek). This mixture was put into a fluid bed granulator / dryer (LAB-1, Norec) and granulated while spraying purified water with a spray nozzle. 374g of granulated material sieved with No.
  • D-mannitol Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 / im
  • alpha starch (UNI-PURE, manufactured by National Starch & Chemical) 70g are mixed at high speed with agitation granulator (FM-VG-10) , Manufactured by Paurek) for 2 minutes.
  • This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paurek), and 21 g of alpha-gelatinized starch (UNI-PURE, manufactured by National Starch & Chemical) is dispersed in 180 g of purified water, and this dispersion is sprayed. Granulation was carried out while spraying with sizzle.
  • D_mannitol Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 ⁇ ⁇ ) 563 / 5 ⁇ and alpha starch (Amcoll C, manufactured by Nissho Chemical Co., Ltd.) 80 g -V G-10, manufactured by Parek) for 2 minutes.
  • This mixture is put into a fluidized bed granulator / dryer (LA B-1, manufactured by Baurek).
  • 1 lg of alpha-monified starch (Amicol C, Nissho Chemical) is dispersed in 180 g of purified water, and this dispersion is sprayed. Granulation was carried out while spraying with Nozure. Granulated material sieved with No.
  • Granulation was performed while spraying the dispersion with a spray nozzle.
  • the mixture was mixed for 2 minutes using a type mixer (DV-1, manufactured by Dalton).
  • rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablet weight 200mg, 8 ⁇ circle, table rotation speed 30 ⁇ m, tableting pressure 11.7 ⁇ 15.61 ⁇ 111 papermaking tablets in two conditions.
  • PCS Partially alpha starch
  • Total 200.0 mg / tablet 17.5 g of ritodrine hydrochloride, D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 4 5 zm) 546 g and partially alpha-unified starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., soluble in cold water) Min: 1. 2 wt%) 7 ( ⁇ was mixed for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Baurec).
  • FM-VG-10 high-speed mixing and agitation granulator
  • PCS Partially alpha starch
  • FM-VG-10 high-speed mixing and agitation granulator
  • alpha-starch starch (Starchl500, Nippon Colorcon, cold water soluble content: 15.8% by weight) 21 ⁇ of purified water 18 ( Then, the resulting dispersion was sprayed with a spray nozzle and granulated, and 372 g of the granulated product sieved with No. 18 sieve, 20 g of crospovidone (Polyplasdone X L-10, ISP), light anhydrous 2 g of caustic acid (Adsolidar 101, manufactured by Freund Corporation) and 6 g of magnesium stearate (produced by Taihei Chemical Industry) were mixed for 2 minutes using a V-type mixer (DV-1, Dalton).
  • crospovidone Polyplasdone X L-10, ISP
  • light anhydrous 2 g of caustic acid (Adsolidar 101, manufactured by Freund Corporation)
  • 6 g of magnesium stearate produced by Taihei Chemical Industry
  • the tablet weight is 200 mg, 8 ⁇ ⁇ circular, table rotation speed 30 mm, tableting pressure 11.7 and 15.6 kN m 2 Made.
  • PCS Partially alpha starch
  • This tableting mixture was tableted using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8 ⁇ ⁇ circle, table rotation speed 30 mm, tableting pressure 19.5 kN / cm 2 Made.
  • a rotary tableting machine Correct 12HUK, manufactured by Kikusui Seisakusho
  • PCS Partially alpha starch
  • Total 200.0 mg / 1 tablet 17.5 g of mitiglinide calcium hydrate, D_mannitol (Mannit P, Towa Kasei Kogyo) , Average particle size 45 ⁇ ) 542.5g and partially alpha starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2% by weight) 70 ⁇ , high-speed mixing and agitation granulator (FM-VG-10, For 2 minutes.
  • PCS partially alpha starch
  • This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paurek), and 21 g of partially alpha-monoized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2% by weight) is dispersed in 180 g of purified water. Then, this dispersion was granulated while spraying with a spray nozzle. 372g of granulated material sieved by No.
  • LAB-1 fluidized bed granulator / dryer
  • PCS partially alpha-monoized starch
  • the orally disintegrating tablet of the present invention has sufficient hardness not to be damaged in the distribution process and rapidly disintegrates or dissolves in the oral cavity, so that it is taken by elderly people and patients who have difficulty swallowing children. It is useful as an easy-to-use dosage form.

Abstract

La présente invention a pour objet un comprimé à désintégration orale rapide qui présente une dureté adéquate et qui peut être produit à échelle industrielle, ainsi qu'une méthode de production dudit comprimé. La présente invention a notamment pour objet un comprimé à désintégration orale qui comprend a) un principe actif, b) un sucre ou un polyol sucré, c) un amidon partiellement gélifié contenant entre 10 et 20 % en masse de matières solubles dans l'eau froide, et d) un agent délitant. Ledit comprimé peut être produit par mélange de l'agent délitant avec un mélange en granules constitué du principe actif a), du sucre ou du polyol sucré b) et de l'amidon partiellement gélifié contenant entre 10 et 20 % en masse de matières solubles dans l'eau froide c), suivi d'un moulage par compression.
PCT/JP2006/301951 2005-02-09 2006-02-06 Comprimé à désintégration orale WO2006085497A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2007502589A JP5004236B2 (ja) 2005-02-09 2006-02-06 口腔内崩壊錠

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005-032978 2005-02-09
JP2005032978 2005-02-09

Publications (1)

Publication Number Publication Date
WO2006085497A1 true WO2006085497A1 (fr) 2006-08-17

Family

ID=36793069

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/301951 WO2006085497A1 (fr) 2005-02-09 2006-02-06 Comprimé à désintégration orale

Country Status (2)

Country Link
JP (3) JP5004236B2 (fr)
WO (1) WO2006085497A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008032767A1 (fr) * 2006-09-14 2008-03-20 Astellas Pharma Inc. Comprimé se désintegrant oralement et procédé de fabrication de celui-ci
WO2010001063A1 (fr) * 2008-07-04 2010-01-07 Roquette Freres Mannitol orodispersible
JP2013544849A (ja) * 2010-12-02 2013-12-19 アプタリス ファーマテク，インコーポレイテッド 迅速分散顆粒、口腔内崩壊錠、および方法
JP2015134838A (ja) * 2015-05-07 2015-07-27 ニプロ株式会社 口腔内崩壊剤及びその製造方法
WO2016051782A1 (fr) * 2014-09-30 2016-04-07 キッセイ薬品工業株式会社 Préparation pour voie orale dans laquelle le goût amer d'un médicament au goût amer est masqué
JP2019031491A (ja) * 2017-08-08 2019-02-28 日本ケミファ株式会社 糖尿病治療剤
JP2021098710A (ja) * 2015-06-18 2021-07-01 エステトラ ソシエテ プリーヴ ア レスポンサビリテ リミテ エステトロール成分を含有する口腔内崩壊性投与単位

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7001332B2 (ja) * 2016-03-29 2022-01-19 小林製薬株式会社 造粒物
JP6800596B2 (ja) * 2016-03-29 2020-12-16 小林製薬株式会社 錠剤
WO2021095092A1 (fr) * 2019-11-11 2021-05-20 大塚製薬株式会社 Comprimé à dissolution orale

Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06502194A (ja) * 1991-07-22 1994-03-10 ラボラトワール　プログラファルム 急速崩壊性多粒子状錠剤
JPH0692857A (ja) * 1988-09-09 1994-04-05 Bristol Myers Squibb Co 直接圧縮シクロホスファミド錠剤
JPH06508836A (ja) * 1991-06-26 1994-10-06 セプラコア，インコーポレーテッド 光学的に純粋なｒ（＋）オンダンセトロンを使用する嘔吐、吐き気および他の障害の治療のための方法および組成物
JPH06509073A (ja) * 1991-06-26 1994-10-13 セプラコア，インコーポレーテッド 光学的に純粋なｓ（−）オンダンセトロンを使用する嘔吐、吐き気および他の障害の治療のための方法および組成物
WO1995020380A1 (fr) * 1994-01-31 1995-08-03 Yamanouchi Pharmaceutical Co., Ltd. Moulage comprime a solubilite intra-orale et son procede de production
JPH11269202A (ja) * 1998-02-03 1999-10-05 Cerestar Holding Bv 圧縮錠剤及び硬ゼラチンカプセル用結合剤、崩壊剤及び増量剤としての、自由に流動する直接圧縮でんぷん
WO2000057857A1 (fr) * 1999-03-25 2000-10-05 Yuhan Corporation Comprimé à administrer oralement se désagrégeant rapidement
JP2001039894A (ja) * 1999-06-26 2001-02-13 Cerestar Holding Bv 圧縮タブレットのための結合剤および崩壊剤として使用される時の賦形剤の性質の増強剤としての直接圧縮性の澱粉
JP2001163770A (ja) * 1999-12-08 2001-06-19 Yansen Kyowa Kk 口腔内速崩壊型錠剤及びその製造方法
JP2001513545A (ja) * 1997-08-22 2001-09-04 スミスクライン・ビーチャム・コーポレイション 急速崩壊性メチルセルロース錠
JP2001513752A (ja) * 1996-09-12 2001-09-04 ロシュ ダイアグノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング 迅速崩壊ペレット
JP2002505269A (ja) * 1998-03-06 2002-02-19 エウランド インターナショナル ソシエタ ペル アチオニ 急速崩壊錠剤
JP2002524410A (ja) * 1998-09-08 2002-08-06 スミスクライン・ビーチャム・コーポレイション リプスタチン誘導体−可溶性繊維錠剤
WO2003049680A2 (fr) * 2001-12-05 2003-06-19 Peirce Management, Llc Compositions contenant des antihistaminiques sedatifs et des antihistaminiques non sedatifs
JP2003212757A (ja) * 2001-10-01 2003-07-30 Ind-Swift Ltd 徐放性マクロライド製剤
WO2003066029A2 (fr) * 2002-02-07 2003-08-14 Pharmacia Corporation Forme pharmaceutique destinee a etre administree par voie mucosale
US20050232988A1 (en) * 2004-04-19 2005-10-20 Venkatesh Gopi M Orally disintegrating tablets and methods of manufacture

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4600579A (en) * 1983-06-07 1986-07-15 Mallinckrodt, Inc. N-acetyl-p-aminophenol compositions containing partially gelatinized starch and method for preparing same
JP2000273039A (ja) * 1999-01-20 2000-10-03 Taisho Pharmaceut Co Ltd 口腔内崩壊性組成物
CN1186098C (zh) * 1999-02-15 2005-01-26 住友制药株式会社 在口腔中迅速崩解的片剂
JP2003055197A (ja) * 2001-06-07 2003-02-26 Tanabe Seiyaku Co Ltd 機能性粒子含有口腔内速崩壊性製剤
AU2003209475A1 (en) * 2002-03-07 2003-09-16 Vectura Limited Fast melt multiparticulate formulations for oral delivery
JP4408340B2 (ja) * 2002-03-22 2010-02-03 武田薬品工業株式会社 速崩壊性固形製剤
ATE454132T1 (de) * 2003-01-21 2010-01-15 Nippon Shinyaku Co Ltd Rasch in der mundhöhle schmelzende tablette
JP4551627B2 (ja) * 2003-02-28 2010-09-29 東和薬品株式会社 口腔内崩壊錠剤の製造方法
JP2005015477A (ja) * 2003-06-06 2005-01-20 Takeda Chem Ind Ltd 固形製剤
CA2588293C (fr) * 2004-11-24 2013-07-02 Teva Pharmaceutical Industries Ltd. Compositions de rasagiline delitantes oralement

Patent Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0692857A (ja) * 1988-09-09 1994-04-05 Bristol Myers Squibb Co 直接圧縮シクロホスファミド錠剤
JPH06508836A (ja) * 1991-06-26 1994-10-06 セプラコア，インコーポレーテッド 光学的に純粋なｒ（＋）オンダンセトロンを使用する嘔吐、吐き気および他の障害の治療のための方法および組成物
JPH06509073A (ja) * 1991-06-26 1994-10-13 セプラコア，インコーポレーテッド 光学的に純粋なｓ（−）オンダンセトロンを使用する嘔吐、吐き気および他の障害の治療のための方法および組成物
JPH06502194A (ja) * 1991-07-22 1994-03-10 ラボラトワール　プログラファルム 急速崩壊性多粒子状錠剤
WO1995020380A1 (fr) * 1994-01-31 1995-08-03 Yamanouchi Pharmaceutical Co., Ltd. Moulage comprime a solubilite intra-orale et son procede de production
JP2001513752A (ja) * 1996-09-12 2001-09-04 ロシュ ダイアグノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング 迅速崩壊ペレット
JP2001513545A (ja) * 1997-08-22 2001-09-04 スミスクライン・ビーチャム・コーポレイション 急速崩壊性メチルセルロース錠
JPH11269202A (ja) * 1998-02-03 1999-10-05 Cerestar Holding Bv 圧縮錠剤及び硬ゼラチンカプセル用結合剤、崩壊剤及び増量剤としての、自由に流動する直接圧縮でんぷん
JP2002505269A (ja) * 1998-03-06 2002-02-19 エウランド インターナショナル ソシエタ ペル アチオニ 急速崩壊錠剤
JP2002524410A (ja) * 1998-09-08 2002-08-06 スミスクライン・ビーチャム・コーポレイション リプスタチン誘導体−可溶性繊維錠剤
WO2000057857A1 (fr) * 1999-03-25 2000-10-05 Yuhan Corporation Comprimé à administrer oralement se désagrégeant rapidement
JP2001039894A (ja) * 1999-06-26 2001-02-13 Cerestar Holding Bv 圧縮タブレットのための結合剤および崩壊剤として使用される時の賦形剤の性質の増強剤としての直接圧縮性の澱粉
JP2001163770A (ja) * 1999-12-08 2001-06-19 Yansen Kyowa Kk 口腔内速崩壊型錠剤及びその製造方法
JP2003212757A (ja) * 2001-10-01 2003-07-30 Ind-Swift Ltd 徐放性マクロライド製剤
WO2003049680A2 (fr) * 2001-12-05 2003-06-19 Peirce Management, Llc Compositions contenant des antihistaminiques sedatifs et des antihistaminiques non sedatifs
WO2003066029A2 (fr) * 2002-02-07 2003-08-14 Pharmacia Corporation Forme pharmaceutique destinee a etre administree par voie mucosale
US20050232988A1 (en) * 2004-04-19 2005-10-20 Venkatesh Gopi M Orally disintegrating tablets and methods of manufacture

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
ACTA SCIENTIARUM, vol. 24, no. 3, 2002, pages 649 - 655 *
DATABASE CAPLUS [online] 2002, XP003000940, accession no. STN Database accession no. (2002:222514) *
DATABASE CAPLUS [online] 2003, XP003000941, accession no. STN Database accession no. (2003:284438) *
MAJALAH FARMASI INDONESIA, vol. 12, no. 4, 2001, pages 166 - 171 *
SINCHAIPANID N. ET AL.: "PREPARATION AND EVALUATION OF VARIOUS STARCHES IN TABLET DISINTEGRATION", WARASAN PHESATCHASAT, vol. 22, no. 2, 1995, pages 68 - 75, XP003000942 *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101516403B (zh) * 2006-09-14 2013-10-02 安斯泰来制药株式会社 口腔崩解片及其制备方法
JP5332615B2 (ja) * 2006-09-14 2013-11-06 アステラス製薬株式会社 口腔内崩壊錠及びその製造法
WO2008032767A1 (fr) * 2006-09-14 2008-03-20 Astellas Pharma Inc. Comprimé se désintegrant oralement et procédé de fabrication de celui-ci
US9839610B2 (en) 2008-07-04 2017-12-12 Roquette Freres Orodispersible mannitol
WO2010001063A1 (fr) * 2008-07-04 2010-01-07 Roquette Freres Mannitol orodispersible
FR2933299A1 (fr) * 2008-07-04 2010-01-08 Roquette Freres Mannitol orodispersible
JP2011526612A (ja) * 2008-07-04 2011-10-13 ロケット・フルーレ 口腔内崩壊性マンニトール
US10105314B2 (en) 2008-07-04 2018-10-23 Roquette Freres Orodispersible mannitol
JP2013544849A (ja) * 2010-12-02 2013-12-19 アプタリス ファーマテク，インコーポレイテッド 迅速分散顆粒、口腔内崩壊錠、および方法
JPWO2016051782A1 (ja) * 2014-09-30 2017-07-13 キッセイ薬品工業株式会社 苦味を有する薬剤の苦味をマスキングした経口投与製剤
WO2016051782A1 (fr) * 2014-09-30 2016-04-07 キッセイ薬品工業株式会社 Préparation pour voie orale dans laquelle le goût amer d'un médicament au goût amer est masqué
JP2015134838A (ja) * 2015-05-07 2015-07-27 ニプロ株式会社 口腔内崩壊剤及びその製造方法
JP2021098710A (ja) * 2015-06-18 2021-07-01 エステトラ ソシエテ プリーヴ ア レスポンサビリテ リミテ エステトロール成分を含有する口腔内崩壊性投与単位
JP7140355B2 (ja) 2015-06-18 2022-09-21 エステトラ ソシエテ プリーヴ ア レスポンサビリテ リミテ エステトロール成分を含有する口腔内崩壊性投与単位
JP2019031491A (ja) * 2017-08-08 2019-02-28 日本ケミファ株式会社 糖尿病治療剤

Also Published As

Publication number Publication date
JP2012107049A (ja) 2012-06-07
JP5004236B2 (ja) 2012-08-22
JPWO2006085497A1 (ja) 2008-06-26
JP2014001233A (ja) 2014-01-09
JP5342028B2 (ja) 2013-11-13

Similar Documents

Publication Publication Date Title
JP5693635B2 (ja) 苦味をマスキングした口腔内崩壊錠、およびその製造方法
JP5342028B2 (ja) 口腔内崩壊錠
JP6092936B2 (ja) 口腔内崩壊錠の製造方法
JP4749668B2 (ja) 高い均質性を有する口内分散性錠剤及びその調製方法
JP5074190B2 (ja) 口腔内速崩壊性錠剤
JP5332615B2 (ja) 口腔内崩壊錠及びその製造法
KR101386022B1 (ko) 건식 직타 속붕괴성 정제
WO2005037319A1 (fr) Composition de comprime se desagregeant rapidement dans la bouche
WO2000078292A1 (fr) Preparations solides a desintegration rapide
EP2429586A1 (fr) Excipient se désintégrant par voie orale
WO2007018192A1 (fr) Comprimé pouvant être désintégré par voie orale
HU201867B (en) Process for producing in water dispergatable tablets
JP2016174616A (ja) 崩壊性組成物及び易崩壊性圧縮成型物
WO2006068166A1 (fr) Substance granulee par voie seche et procede pour la produire
US20110014286A1 (en) Mixture for producing rapidly disintegrating tablets
JPWO2009054432A1 (ja) 口腔内速崩壊性医薬組成物およびその製造方法
JP5062872B2 (ja) 不快な味を低減した口腔内崩壊錠剤
WO2003072140A1 (fr) Preparations moulees par compression presentant des proprietes de desintegration rapide
JP6989064B1 (ja) 固形製剤及びその製造方法
JP2001131091A (ja) 固形製剤用添加物
WO2023182332A1 (fr) Composition d'additifs pour comprimés orodispersible
JP2005194225A (ja) 胃内崩壊性錠剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2007502589

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06713094

Country of ref document: EP

Kind code of ref document: A1

WWW Wipo information: withdrawn in national office

Ref document number: 6713094

Country of ref document: EP