WO2022102457A1 - リナグリプチン含有口腔内崩壊錠 - Google Patents

リナグリプチン含有口腔内崩壊錠 Download PDF

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WO2022102457A1
WO2022102457A1 PCT/JP2021/040258 JP2021040258W WO2022102457A1 WO 2022102457 A1 WO2022102457 A1 WO 2022102457A1 JP 2021040258 W JP2021040258 W JP 2021040258W WO 2022102457 A1 WO2022102457 A1 WO 2022102457A1
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Prior art keywords
linagliptin
orally disintegrating
disintegrating tablet
carmellose
tablet
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PCT/JP2021/040258
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English (en)
French (fr)
Japanese (ja)
Inventor
康史 福原
克彦 尾曲
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沢井製薬株式会社
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Priority to JP2022561834A priority Critical patent/JPWO2022102457A1/ja
Publication of WO2022102457A1 publication Critical patent/WO2022102457A1/ja

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3

Definitions

  • the present invention relates to an orally disintegrating tablet containing linagliptin and a method for producing the same.
  • Linagliptin (1-[(4-methyl-quinazoline-2-yl) methyl] -3-methyl-7- (2-butin-1-yl) -8- (3- (R) -amino-piperidine-1-) Il) -xanthine) is a dipeptidyl peptidase-4 (DPP-IV) inhibitor and is used as a therapeutic agent for type II diabetes.
  • Patent Document 1 describes linagliptin or a salt thereof, a first diluent which is mannitol, a second diluent which is pregelatinized starch, a binder which is copovidone, a tablet decomposition substance which is corn starch, and magnesium stearate.
  • a pharmaceutical composition comprising a certain lubricant is disclosed.
  • the linagliptin-containing preparation be an orally disintegrating tablet which is an easy-to-drink dosage form for elderly people and patients who have difficulty swallowing.
  • the orally disintegrating tablet which is easy to take, will lead to the active participation of the patient in the treatment and the improvement of the medication behavior. Has been done.
  • the orally disintegrating tablet needs to have a good taste and other feeling of administration, and if the drug substance has a bitter taste or the like, it is required to mask the bitter taste or the like. Since linagliptin has a strong bitterness when the linagliptin-containing preparation is used as an orally disintegrating tablet, it is necessary to devise a method for masking the bitterness of linagliptin.
  • Patent Document 2 reports a technique of coating particles containing a drug substance with a poorly soluble substance.
  • Patent Document 3 describes a base by melting a mixture of a (meth) acrylate-polymer having an anionic group and a pharmaceutically active substance, extruding the mixture, and finely grinding the extruded product into granules or powder. Disclosed are methods of processing into taste-isolated granules or powders without the addition of sexually active substances.
  • Patent Document 4 by mixing a drug having an unpleasant taste with sucralose, which is a water-soluble sweetener, the discomfort of the drug exhibiting an unpleasant taste when taken is suppressed and the drug is made easier to take.
  • sucralose which is a water-soluble sweetener
  • the above-mentioned conventional bitterness masking method is complicated and time-consuming, such as coating of drug substance-containing fine particles and melting / extrusion / crushing steps, and requires special manufacturing equipment, so that bitterness is easily and efficiently masked. A method is required.
  • Patent No. 5478244 Special Table 6-502194 Gazette Japanese Patent Publication No. 2005-526731 Japanese Unexamined Patent Publication No. 2001-342151
  • One of the objects of the present invention is to provide a linagliptin-containing orally disintegrating tablet capable of sufficiently masking bitterness and a method for producing the same.
  • Orally disintegrating tablets are provided.
  • the additive may contain one or more selected from the group consisting of carmellose calcium, croscarmellose sodium, and carmellose.
  • the additive may be croscarmellose sodium.
  • the additive may contain 0.5 parts by weight or more with respect to 1 part by weight of linagliptin.
  • a linagliptin-containing orally disintegrating tablet capable of sufficiently masking bitterness and a method for producing the same are provided.
  • the linagliptin-containing orally disintegrating tablet according to the present invention and a method for producing the same will be described in detail.
  • the linagliptin-containing orally disintegrating tablet of the present invention and the method for producing the same are not construed as being limited to the contents of the embodiments and examples shown below.
  • the linagliptin-containing orally disintegrating tablet according to one embodiment of the present invention contains linagliptin and a disintegrating agent other than crospopidone.
  • the linagliptin of the present embodiment is 1-[(4-methyl-quinazoline-2-yl) methyl] -3-methyl-7- (2-butyne-1-yl) -8- (3- (R) -amino. -Piperidin-1-yl) -xanthine.
  • the present invention is not limited to this, and linagliptin or a salt thereof or a hydrate thereof may be used.
  • Linagliptin is contained, for example, 5 mg in one of the linagliptin-containing orally disintegrating tablets according to the present invention.
  • the disintegrant of the present embodiment preferably contains one or more selected from the group consisting of carmellose calcium, croscarmellose sodium, carmellose, and sodium starch glycolate. More preferably, the disintegrant comprises one or more selected from the group consisting of carmellose calcium, croscarmellose sodium, and carmellose. The additive is more preferably croscarmellose sodium.
  • the disintegrant of the present embodiment is preferably 0.5 parts by weight or more with respect to 1 part by weight of linagliptin.
  • the disintegrant is preferably contained in an amount of 0.9 parts by weight or more with respect to 1 part by weight of linagliptin.
  • the disintegrant is preferably contained in an amount of 1.8 parts by weight or more with respect to 1 part by weight of linagliptin. It is more preferable that the disintegrant is contained in an amount of 2 parts by weight or more with respect to 1 part by weight of linagliptin.
  • the disintegrant is preferably contained in an amount of 10 parts by weight or less with respect to 1 part by weight of linagliptin.
  • the disintegrant is preferably contained in an amount of 6 parts by weight or less with respect to 1 part by weight of linagliptin.
  • the linagliptin-containing orally disintegrating tablet of the present embodiment contains an additive necessary for forming the orally disintegrating tablet.
  • the additive include excipients, binders, disintegrants other than crospopidone, lubricants, surfactants, sweeteners, flavoring agents, fragrances, coloring agents and the like.
  • the additive one kind may be used alone, or two or more kinds may be used in combination. Further, in the case of two or more kinds, a so-called premix additive, which is granulated by mixing a plurality of additives in advance, may be contained.
  • the additives of the present embodiment are, for example, starches such as corn starch, lactose, sucrose, mannitol, xylitol, erythritol, sorbitol, martitol, calcium citrate, calcium phosphate, crystalline cellulose, magnesium carbonate, calcium carbonate, aluminic acid metasilicate. Excipients such as magnesium, light anhydrous silicic acid, anhydrous calcium hydrogen phosphate, etc .; sucrose, gelatin, gum arabic powder, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, polyethylene glycol, carmellose, crystalline cellulose carmellose.
  • starches such as corn starch, lactose, sucrose, mannitol, xylitol, erythritol, sorbitol, martitol, calcium citrate, calcium phosphate, crystalline cellulose, magnesium carbonate,
  • Excipients such as sodium, carmellose sodium, dextrin, purulan, tragant, sodium alginate, pregelatinized starch; magnesium stearate, calcium stearate, sodium stearyl fumarate, talc, light anhydrous silicic acid, hydrous silicon dioxide, sucrose fatty acid ester , Glue such as hardened oil; interface of glycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene hardened castor oil, polyoxyethylene alkyl ether, sodium lauryl sulfate, polyoxyethylene polyoxypropylene glycol, etc.
  • Sweeteners such as aspartame, saccharin, sodium saccharin, sodium acesulfam, sucralose, taumatin, lacanca extract, sorbitol, sucrose, glucose, martitol; citrate, sodium citrate, tartrate, DL-apple acid, glycine, DL -Excipients such as alanine; fragrances such as strawberry, lemon, lemon lime, orange, l-menthol, peppermint oil; and coloring agents such as yellow iron sesquioxide, iron sesquioxide, edible tar pigment, and natural pigment may be contained. ..
  • the linagliptin-containing orally disintegrating tablet contains linagliptin-derived bitterness by containing carmellose calcium, croscarmellose sodium, carmellose, or sodium starch glycolate as a disintegrant.
  • the linagliptin-containing orally disintegrating tablet can be produced according to a production method known in the pharmaceutical field.
  • the method for producing an orally disintegrating tablet containing linagliptin in the present embodiment is produced by first homogeneously mixing linagliptin and an additive selected from the above, and then tableting the obtained mixture.
  • a mixture containing linagliptin and an additive containing one or more selected from the group consisting of carmellose calcium, croscarmellose sodium, carmellose, and sodium starch glycolate is prepared in advance. Granulated ones may be used.
  • Additives such as excipients, binders, disintegrants capable of suppressing linagliptin-derived bitterness, surfactants, sweeteners, taste-masks, flavors, and colorants are added to the granulated products as needed. It may be contained. Further, a granulated product containing no linagliptin may be used.
  • the granulation method may be any method known in the pharmaceutical field, and may be a stirring granulation method, a fluidized bed granulation method, a rolling granulation method, a compression granulation method, an extrusion granulation method, a melt granulation method, or a spray granulation method. The granulation method and the like can be mentioned. As the granulation method, a stirring granulation method or a fluidized bed granulation method is simple and more preferable.
  • the linagliptin-containing orally disintegrating tablet can be produced by compression molding with a commonly used locking machine.
  • any shape can be adopted, and for example, it can be molded into a tablet shape, an elliptical shape, a spherical shape, or a rod shape.
  • the bitterness derived from linagliptin can be suppressed by adding carmellose calcium, croscarmellose sodium, carmellose, or sodium starch glycolate as a disintegrant.
  • Example 1 Per 5.0 g of linagliptin, anhydrous calcium hydrogen phosphate (GS: Kyowa Chemical Industry) 99.1 g, crystalline cellulose (Theoras PH102: Asahi Kasei) 84.0 g, carmellose calcium (ECG505: Nichirin Chemical Industry) 4.5 g, aspartame ( Ajinomoto) 15.0 g and light anhydrous silicic acid (Aerosil 200: Nippon Aerosil) 0.9 g were mixed in a polyethylene bag. The mixture was sieved through a No. 30 sieve and 1.5 g of magnesium stearate (Taipei Chemical Industry Co., Ltd.) was mixed to obtain a pre-tablet powder.
  • GS Kyowa Chemical Industry
  • the pre-locking powder was tableted with a rotary tableting machine (VELA5: Kikusui Seisakusho) to obtain an orally disintegrating tablet containing 210.0 mg of linagliptin and a thickness of 3.5 mm per tablet.
  • a rotary tableting machine VelA5: Kikusui Seisakusho
  • Example 2 In the oral cavity containing linagliptin at a thickness of 3.5 mm and 210.0 mg per tablet in the same manner as in Example 1 except that carmellose calcium was changed to croscarmellose sodium (Kiccolate ND-2HS: Nichirin Chemical Industry Co., Ltd.). Obtained a disintegrating tablet.
  • Comparative Example 1 210.0 mg per tablet, thickness 3 in the same manner as in Example 1 except that anhydrous calcium hydrogen phosphate (GS: Kyowa Chemical Industry) was added in place of carmellose calcium (ECG505: Nichirin Chemical Industry). An orally disintegrating tablet containing .5 mm linagliptin was obtained.
  • GS Kyowa Chemical Industry
  • ECG505 Nichirin Chemical Industry
  • Table 1 shows the disintegration time (sec), oral disintegration time (sec), and bitterness (sensory evaluation) of Examples 1 and 2 and Comparative Example 1.
  • the linagliptin-containing orally disintegrating tablets according to Examples 1 and 2 to which carmellose calcium or croscarmellose sodium was added as a disintegrant had a disintegration time, an oral disintegration time, and a sensory evaluation. It was good.
  • the linagliptin-containing orally disintegrating tablet according to Comparative Example 1 containing no disintegrant delayed the disintegration time and the orally disintegrating time, and could not suppress the bitterness.
  • Example 3 Per 5.0 g of linagliptin, anhydrous calcium hydrogen phosphate (GS: Kyowa Chemical Industry) 99.1 g, crystalline cellulose (Theoras PH102: Asahi Kasei) 84.0 g, carmellose calcium (ECG505: Nichirin Chemical Industry) 4.5 g, aspartame ( Ajinomoto) 15.0 g and light anhydrous silicic acid (Aerosil 200: Nippon Aerosil) 0.9 g were mixed in a polyethylene bag. The mixture was sieved through a No. 30 sieve and 1.5 g of magnesium stearate (Taipei Chemical Industry Co., Ltd.) was mixed to obtain a pre-tablet powder.
  • GS Kyowa Chemical Industry
  • the pre-locking powder was tableted with a rotary tableting machine (VELA5: Kikusui Seisakusho) to obtain an orally disintegrating tablet containing linagliptin having a thickness of 3.4 mm and 210.0 mg per tablet.
  • a rotary tableting machine VelA5: Kikusui Seisakusho
  • Example 4 An orally disintegrating tablet containing linagliptin having a thickness of 3.4 mm and 210.0 mg per tablet in the same manner as in Example 3 except that the amount of calcium hydrogen phosphate was changed to 9 g and the amount of anhydrous calcium hydrogen phosphate was reduced accordingly.
  • Example 5 An orally disintegrating tablet containing linagliptin having a thickness of 3.4 mm and 210.0 mg per tablet in the same manner as in Example 3 except that the amount of calcium hydrogen phosphate was changed to 20 g and the amount of anhydrous calcium hydrogen phosphate was reduced accordingly.
  • Example 6 Per 3.0 g of linagliptin, 60.36 g of anhydrous calcium hydrogen phosphate (GS: Kyowa Chemical Industry), 50.4 g of crystalline cellulose (Theoras PH102: Asahi Kasei), croscarmellose sodium (Kiccolate ND-2HS: Nichirin Chemical Industry) 1. 5 g, 9.0 g of aspartame (Ajinomoto) and 0.54 g of light anhydrous silicic acid (Aerosil 200: Nippon Aerosil) were mixed in a polyethylene bag. The mixture was sieved through a No.
  • Example 7 Same as Example 3 except that carmellose calcium was changed to croscarmellose sodium (Kiccolate ND-2HS: Nichirin Chemical Industry) and magnesium stearate was changed to 2.0 g, and anhydrous calcium hydrogen phosphate was reduced by that amount.
  • an orally disintegrating tablet containing linagliptin having a thickness of 3.4 mm and 210.0 mg per tablet was obtained.
  • Example 8 210.0 mg per tablet and 3.4 mm thick linagliptin-containing oral disintegration in the same manner as in Example 7, except that croscarmellose sodium was changed to 9 g and anhydrous calcium hydrogen phosphate was reduced by that amount. I got a lock.
  • Example 9 210.0 mg per tablet and 3.4 mm thick linagliptin-containing oral disintegration in the same manner as in Example 7, except that croscarmellose sodium was changed to 20 g and anhydrous calcium hydrogen phosphate was reduced by that amount. I got a lock.
  • Example 10 Per 5.0 g of linagliptin, anhydrous calcium hydrogen phosphate (GS: Kyowa Chemical Industry) 84.1 g, crystalline cellulose (Theoras PH102: Asahi Kasei) 73.0 g, croscarmellose sodium (Kiccolate ND-2HS: Nichirin Chemical Industry) 30. 0 g, 15.0 g of aspartame (Ajinomoto) and 0.9 g of light anhydrous silicic acid (Aerosil 200: Nippon Aerosil) were mixed in a polyethylene bag. The mixture was sieved through a No.
  • Example 2 An orally disintegrating tablet containing linagliptin having a thickness of 3.4 mm and 210.0 mg per tablet was obtained by the same method as in Example 3 except that the carmellose calcium was changed to sodium starch glycolate (Primogel: DFE pharma). rice field.
  • Example 11 210.0 mg per tablet and 3.4 mm thick linagliptin-containing oral disintegration in the same manner as in Comparative Example 2, except that sodium starch glycolate was changed to 10 g and anhydrous calcium hydrogen phosphate was reduced by that amount. I got a lock.
  • Example 12 210.0 mg per tablet and 3.4 mm thick linagliptin-containing oral disintegration in the same manner as in Comparative Example 2, except that sodium starch glycolate was changed to 20 g and anhydrous calcium hydrogen phosphate was reduced by that amount. I got a lock.
  • Example 13 A linagliptin-containing orally disintegrating tablet having a thickness of 3.4 mm and 210.0 mg per tablet was obtained by the same method as in Example 3 except that carmellose calcium was changed to carmellose (NS-300: Nichirin Chemical Industry Co., Ltd.). rice field.
  • Example 14 A linagliptin-containing orally disintegrating tablet having a thickness of 3.4 mm and 210.0 mg per tablet was obtained by the same method as in Example 13 except that carmellose was changed to 10 g and anhydrous calcium hydrogen phosphate was reduced by that amount. rice field.
  • Example 15 A linagliptin-containing orally disintegrating tablet having a thickness of 3.4 mm and 210.0 mg per tablet was obtained by the same method as in Example 13 except that carmellose was changed to 20 g and anhydrous calcium hydrogen phosphate was reduced by that amount. rice field.
  • Example 3 A linagliptin-containing orally disintegrating tablet having a thickness of 3.4 mm and 210.0 mg per tablet was obtained by the same method as in Example 3 except that carmellose calcium was changed to crolideon CL-F (BASF). rice field.
  • Comparative Example 4 A linagliptin-containing orally disintegrating tablet having a thickness of 3.4 mm and 210.0 mg per tablet was prepared in the same manner as in Comparative Example 3 except that the amount of crospopidone was changed to 20 g and the amount of anhydrous calcium hydrogen phosphate was reduced accordingly. Obtained.
  • Example 5 A linagliptin-containing orally disintegrating tablet having a thickness of 3.4 mm and 210.0 mg per tablet was obtained by the same method as in Example 3 except that anhydrous calcium hydrogen phosphate was increased by that amount without adding a disintegrant. rice field.
  • the amount of carmellose calcium added is preferably 0.9 parts by weight or more, more preferably 1.8 parts by weight or more with respect to 1 part by weight of linagliptin.
  • the amount of sodium croscarmellose added was preferably 0.5 part by weight or more, more preferably 0.9 part by weight or more with respect to 1 part by weight of linagliptin. 1.8 parts by weight or more is more preferable.
  • the amount of carmellose added is preferably 0.9 parts by weight or more, more preferably 2.0 parts by weight or more with respect to 1 part by weight of linagliptin.
  • the amount of sodium starch glycolate added is preferably 2.0 parts by weight or more with respect to 1 part by weight of linagliptin, and 4.0 parts by weight. The above is more preferable.
  • the linagliptin-containing orally disintegrating tablets according to Comparative Examples 3 and 4 containing crospopidone as a disintegrant had a good disintegration time, but could not suppress the bitterness.
  • the linagliptin-containing orally disintegrating tablet according to Comparative Example 5 containing no disintegrant delayed the disintegration time and could not suppress the bitterness.
  • Example 16 Per 5.0 g of linagliptin, D-mannitol (Mannit P: Mitsubishi Corporation Life Science) 135.7 g, crystalline cellulose (Theoras PH101: Asahi Kasei) 17.0 g, low substitution hydroxypropyl cellulose (NBD-022: Shin-Etsu Chemical) 8 .5 g, crospovidone (CL-F: BASF) 3.4 g, crospovidone (CL-M: BASF) 3.4 g, croscarmellose sodium (Kiccolate ND-2HS: Nichirin Chemical Industry) 20.0 g and aspartame (Ajinomoto) ) 15.0 g is mixed in a dairy pot, 50 g of purified water is added and kneaded, dried in a shelf-type dryer (MO-921: Toyama Sangyo), sieved with a No.
  • MO-921 Toyama Sangyo
  • Example 17 In the same method as in Example 16, linagliptin-containing oral disintegration of 210.0 mg and 4.0 mm in thickness, except that croscarmellose sodium was changed to carmellose calcium (ECG-505: Nichirin Chemical Industry). I got a lock.
  • Example 18 A linagliptin-containing orally disintegrating tablet having a thickness of 4.0 mm and 210.0 mg per tablet was prepared in the same manner as in Example 16 except that the sodium croscarmellose was changed to carmellose (NS-300: Nichirin Chemical Industry Co., Ltd.). Obtained.
  • Example 19 An orally disintegrating tablet containing linagliptin having a thickness of 4.1 mm and 210.0 mg per tablet in the same manner as in Example 16 except that croscarmellose sodium was changed to sodium starch glycolate (Primogel: DFE Pharma).
  • Example 6 A linagliptin-containing orally disintegrating tablet having a thickness of 4.1 mm and 210.0 mg per tablet was obtained by the same method as in Example 16 except that croscarmellose sodium was changed to crospovidone (CL-F: BASF). rice field.
  • CL-F crospovidone
  • Example 7 A linagliptin-containing orally disintegrating tablet having a thickness of 4.0 mm and 210.0 mg per tablet was obtained by the same method as in Example 16 except that D-mannitol was added in place of sodium croscarmellose.
  • Example 20 Per 10.0 g of linagliptin, D-mannitol (Mannit P: Mitsubishi Corporation Life Science) 271.4 g, crystalline cellulose (Theoras PH101: Asahi Kasei) 34.0 g, low substitution hydroxypropyl cellulose (NBD-022: Shin-Etsu Chemical) 17 0.0 g, crospovidone (CL-F: BASF) 6.8 g, crospovidone (CL-M: BASF) 6.8 g, croscarmellose sodium (Kiccolate ND-2HS: Nichirin Chemical Industry) 40.0 g, aspartame (Ajinomoto) ) 30.0 g is mixed with a fluidized layer granulator (MP-01: Paulec), then 300 g of purified water is sprayed to granulate, and after drying, it is sieved with a No.
  • MP-01 fluidized layer granulator
  • the linagliptin-containing orally disintegrating tablets according to Examples 16 to 20 to which croscarmellose sodium, carmellose calcium, carmellose, or sodium starch glycolate was added as a disintegrant were all in Example 5. Similar to 9, 12, and 15, the sensory evaluation was good. On the other hand, the linagliptin-containing orally disintegrating tablet according to Comparative Example 6 containing crospopidone as a disintegrant could not suppress the bitterness. Further, the linagliptin-containing orally disintegrating tablet according to Comparative Example 7 containing no disintegrant could not suppress the bitterness.
  • the method for producing the linagliptin-containing orally disintegrating tablet in the present embodiment can be obtained by the kneading method or the fluidized bed granulation method as well as the direct tableting method.
  • the disintegration time varied, but this is thought to be due to the fact that the amount of disintegrant used in the granulation method was larger than that of the disintegrant, and the formability was stronger than the disintegration property of the disintegrant.

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PCT/JP2021/040258 2020-11-10 2021-11-01 リナグリプチン含有口腔内崩壊錠 WO2022102457A1 (ja)

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Cited By (3)

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JP2022135317A (ja) * 2021-03-05 2022-09-15 日医工株式会社 リナグリプチン製剤
JP2022192036A (ja) * 2021-06-16 2022-12-28 日本ジェネリック株式会社 リナグリプチン含有製剤及びリナグリプチン含有口腔内崩壊性錠剤
JPWO2024128031A1 (enrdf_load_stackoverflow) * 2022-12-14 2024-06-20

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013161823A1 (ja) * 2012-04-24 2013-10-31 第一三共株式会社 口腔内崩壊錠及びその製造方法
EP2848242A1 (en) * 2013-09-12 2015-03-18 Sanovel Ilac Sanayi ve Ticaret A.S. Orally disintegrating formulations of Linagliptin
CN105853382A (zh) * 2016-05-19 2016-08-17 广州迈达康医药科技有限公司 一种利格列汀口崩片及其制备方法
JP2018530566A (ja) * 2015-10-09 2018-10-18 ヘクサル・アクチェンゲゼルシャフトＨｅｘａｌ ＡＧ ８−［（３ｒ）−３−アミノ−１−ピペリジニル］−７−（２−ブチン−１−イル）−３，７−ジヒドロ−３−メチル−１−［４−メチル−２−キナゾリニル）メチル］−１ｈ−プリン−２，６−ジオンまたは薬学上許容できるその塩を含有する医薬組成物
JP2020158435A (ja) * 2019-03-26 2020-10-01 エルメッド株式会社 リナグリプチン含有医薬組成物及びその製造方法、並びにリナグリプチン含有医薬組成物の品質の向上方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013161823A1 (ja) * 2012-04-24 2013-10-31 第一三共株式会社 口腔内崩壊錠及びその製造方法
EP2848242A1 (en) * 2013-09-12 2015-03-18 Sanovel Ilac Sanayi ve Ticaret A.S. Orally disintegrating formulations of Linagliptin
JP2018530566A (ja) * 2015-10-09 2018-10-18 ヘクサル・アクチェンゲゼルシャフトＨｅｘａｌ ＡＧ ８−［（３ｒ）−３−アミノ−１−ピペリジニル］−７−（２−ブチン−１−イル）−３，７−ジヒドロ−３−メチル−１−［４−メチル−２−キナゾリニル）メチル］−１ｈ−プリン−２，６−ジオンまたは薬学上許容できるその塩を含有する医薬組成物
CN105853382A (zh) * 2016-05-19 2016-08-17 广州迈达康医药科技有限公司 一种利格列汀口崩片及其制备方法
JP2020158435A (ja) * 2019-03-26 2020-10-01 エルメッド株式会社 リナグリプチン含有医薬組成物及びその製造方法、並びにリナグリプチン含有医薬組成物の品質の向上方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NAKAGAWA, TOMOYA ET AL.: "Drug Development Research with Taste Sensor, Part 2: Taste Masking and Formulation Development of Donepezil Hydrochloride OD Tablets", PHARM TECH JAPAN, vol. 28, no. 3, 1 January 2012 (2012-01-01), JP , pages 511 - 517, XP009536655, ISSN: 0910-4739 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2022135317A (ja) * 2021-03-05 2022-09-15 日医工株式会社 リナグリプチン製剤
JP2022192036A (ja) * 2021-06-16 2022-12-28 日本ジェネリック株式会社 リナグリプチン含有製剤及びリナグリプチン含有口腔内崩壊性錠剤
JP7210794B2 (ja) 2021-06-16 2023-01-23 日本ジェネリック株式会社 リナグリプチン含有製剤及びリナグリプチン含有口腔内崩壊性錠剤
JPWO2024128031A1 (enrdf_load_stackoverflow) * 2022-12-14 2024-06-20
JP7675977B2 (ja) 2022-12-14 2025-05-14 株式会社シクロケム コラーゲン・シクロデキストリン混合食品組成物を製造する方法

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