WO2010119851A1 - Comprimé à délitement oral - Google Patents

Comprimé à délitement oral Download PDF

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Publication number
WO2010119851A1
WO2010119851A1 PCT/JP2010/056555 JP2010056555W WO2010119851A1 WO 2010119851 A1 WO2010119851 A1 WO 2010119851A1 JP 2010056555 W JP2010056555 W JP 2010056555W WO 2010119851 A1 WO2010119851 A1 WO 2010119851A1
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WO
WIPO (PCT)
Prior art keywords
mass
particles
coating
orally disintegrating
tablet
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PCT/JP2010/056555
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English (en)
Japanese (ja)
Inventor
佑理子 石田
聖治 伊藤
美行 尾林
Original Assignee
ライオン株式会社
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Priority to JP2011509290A priority Critical patent/JPWO2010119851A1/ja
Publication of WO2010119851A1 publication Critical patent/WO2010119851A1/fr

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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
    • A61K9/48—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
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/60—Salicylic acid; 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Definitions

  • the present invention relates to an orally disintegrating tablet containing drug particles having an unpleasant taste, and in particular, an oral disintegration in which the texture is good, the disintegration is good, and the unpleasant taste of the drug is masked It relates to locks.
  • a masking method by adding a flavor, a sweetening agent, or the like, and a masking method by coating a drug particle with a polymer base or the like is known.
  • masking of unpleasant taste by that method alone is difficult, and it can be applied only to limited drugs. Therefore, in order to mask a drug having a low unpleasant taste threshold, it is necessary to suppress the release of the drug in the oral cavity by coating with a polymer base or the like.
  • the normal coating amount may cause fine cracks in the coating film due to tableting pressure during production, In some cases, it is not possible to sufficiently suppress unpleasant taste due to the effect of chewing or peeling due to friction.
  • a method of making the coating layer thicker than usual can be considered, but as a result, sufficient release of the drug in the gastrointestinal tract cannot be ensured, and bioavailability is reduced as compared with a normal preparation. There is a problem.
  • the present invention has been made in view of the above circumstances, and is an orally disintegrating tablet that can be applied to drugs having various unpleasant tastes, has a good texture, good disintegration, and masks the unpleasant taste of drugs.
  • the purpose is to provide.
  • the chewable tablet is a tablet containing the tablet in the oral cavity, which is taken by being disintegrated / dissolved in the oral cavity by chewing or by contact with saliva or shear (friction) between the tongue and upper jaw. is there.
  • An orally disintegrating tablet is a tablet that contains a tablet in the oral cavity and is disintegrated and dissolved mainly by contact with saliva and by shearing between the tongue and upper jaw (mastication is not denied).
  • chewable tablets and orally disintegrating tablets are usually tablets that disintegrate in the oral cavity by chewing, contact with saliva, and sharing between the upper jaw and tongue, and are more effective than tablets taken with water.
  • the present invention has a common problem in that it is easy to feel an unpleasant taste, and is not clearly distinguished.
  • chewable tablets and orally disintegrating tablets are collectively referred to as “orally disintegrating tablets” unless otherwise specified.
  • crospovidone having specific physical properties among crospovidones known as disintegrants that is, an average particle size of 50 ⁇ m or less and a swelling amount of 5 (g )
  • Crospovidone particles having a water / (g) product of 5% by weight and a 5% by weight aqueous suspension with a viscosity of 20 mPa ⁇ s or less not only improve the disintegration (speed) of the tablet but also chew in the oral cavity. Prevents drug particles from being broken or peeled off due to friction and masking, resulting in an unpleasant taste masking of the drug.
  • the tablet disintegrates in the mouth the texture of each particle that makes up the tablet is reduced to reduce the texture. It has been found that it has the effect of significantly improving the above, and has led to the present invention.
  • the present invention provides the following orally disintegrating tablets.
  • A Drug particles in which a drug having an unpleasant taste is coated with a coating agent
  • B an average particle size of 50 ⁇ m or less, a swelling amount of 5 (g) water / (g) product or more, and 5 mass% water suspension
  • An orally disintegrating tablet comprising crospovidone particles having a viscosity (25 ° C.) of a turbid liquid of 20 mPa ⁇ s or less.
  • B The orally disintegrating tablet according to [1], wherein the content of the particles is 1 to 20% by mass.
  • A The orally disintegrating tablet according to [1] or [2], wherein the coating ratio of the coating agent to the drug in the particles is 1 to 60% by mass as a solid content.
  • an orally disintegrating tablet which can be applied to drugs having various unpleasant tastes, has a good texture, has good disintegration, and masks the unpleasant taste of drugs.
  • the orally disintegrating tablet of the present invention comprises (A) drug particles in which a drug having an unpleasant taste is coated with a coating agent, (B) an average particle size of 50 ⁇ m or less, and a swelling amount of 5 (g) water / (g)
  • the product contains crospovidone particles having a product of 5 mass% or more and a viscosity (25 ° C.) of a 5 mass% water suspension of 20 mPa ⁇ s or less.
  • Drug particles are obtained by coating a drug having an unpleasant taste with a coating agent.
  • Drugs with an unpleasant taste include acetaminophen, aspirin, ibuprofen, etenzamide, phenacetin, mefenamic acid, antipyrine, phenylbutazone, sulpyrine, sodium diclofenate, ketoprofen, naproxen, epilysole, thiaramide hydrochloride, indomethacin, pentazocine, chloride Acetylcholine, alimemazine tartrate, cyproheptadine hydrochloride, diphedramine hydrochloride, chlorpheniramine maleate, codeine phosphate, dihydrocodeine phosphate, dextromethorphan hydrobromide, pentoxyberine citrate, theophylline, aminophylline, ephedrine hydrochloride, epinephrine hydrochloride, sulfuric acid
  • the coating agent in the present invention refers to a component existing on the surface of a drug, and includes a coating base composed of a poorly water-soluble polymer compound and a plasticizer. By using this base, bitterness masking property and dissolution property are improved.
  • the “poorly water-soluble polymer compound” refers to a compound whose amount dissolved in 10,000 mL of water is 1 g or less than 1 mL.
  • Specific examples of the poorly water-soluble polymer compound include ethyl cellulose, aminoacryl methacrylate copolymer, and methacrylic acid copolymer. These can be used individually by 1 type or in combination of 2 or more types. Of these, ethyl cellulose is preferred from the viewpoint of usability and odor.
  • the content of the poorly water-soluble polymer compound is preferably 40 to 90% by mass, more preferably 40 to 80% by mass, based on the total solid content of the coating agent, in consideration of ease of coating, plasticity, elution, and the like. 50 to 70% by mass is particularly preferable.
  • the coating agent in the present invention preferably contains a plasticizer.
  • the plasticizer is presumed to have a function of imparting appropriate spreadability to the solution containing the coating agent and facilitating film formation.
  • the plasticizer include those described in official documents such as standards for pharmaceutical additives such as triacetin and triethyl citrate (Pharmaceutical Daily Inc.). These can be used individually by 1 type or in combination of 2 or more types. Considering film formability, triacetin and triethyl citrate are preferable, and triacetin is more preferable.
  • the content of the plasticizer is preferably 5 to 50% by mass, more preferably 10 to 40% by mass, based on the total solid content of the coating agent.
  • the total solid content (mass ratio) of the plasticizer: poorly water-soluble polymer compound is preferably 0.05: 1 to 0.5: 1, more preferably 0.1: 1 to 0.4: 1.
  • the coating agent may further contain an elution control agent from the viewpoint of improving the masking effect.
  • the elution control agent include sugars such as lactose, trehalose and sucrose, and sugar alcohols such as mannitol, erythritol, xylitol and sorbitol. These can be used alone or in combination of two or more.
  • the elution control agent may not be contained, and the content thereof is preferably 0 to 60% by mass, more preferably 0 to 50% by mass with respect to the total solid content of the coating agent.
  • a sweetener may be added to the coating agent.
  • the sweetener include aspartame, sucralose, erythritol, acesulfame potassium, saccharin sodium, stevia extract, thaumatin, sugar cane extract, heated palatinose, licorice, etc. Can do. Of these, aspartame and sucralose are preferable.
  • the content of the sweetening agent is preferably 0 to 50% by mass with respect to the total solid content of the coating agent.
  • the coating rate is preferably set in the range of 1 to 60% by mass as the solid content with respect to the drug (coating material).
  • a coating rate means the mass% of a coating agent when a drug (coating object) is 100 mass%.
  • the coating rate is 1% by mass or more, a sufficient masking effect is obtained, and when it exceeds 60% by mass, the effect is saturated and the drug release property may be deteriorated.
  • the lower limit of the coating rate is more preferably 3% by mass or more, further preferably 5% by mass or more, and particularly preferably 8% by mass or more. Further, from the viewpoint of drug release, it is preferable to set the coating rate low.
  • the upper limit is preferably 50% by mass or less, 40% by mass or less, 30% by mass or less, 25% by mass or less, It is preferable to set it as 15 mass% or less and 10 mass% or less.
  • coating deterioration due to external force such as impact or friction during manufacture (especially tableting) or taking is suppressed, so a low coating rate
  • a good taste masking effect can be obtained.
  • the average particle size of the particles is preferably 75 to 500 ⁇ m, more preferably 150 to 300 ⁇ m.
  • the average particle size is 1000 ⁇ m, 850 ⁇ m, 500 ⁇ m, 355 ⁇ m, 250 ⁇ m, 150 ⁇ m, and 75 ⁇ m sieves with an inner diameter of 75 mm. Based on the test and measurement, the cumulative particle size is 50%.
  • the content of the drug particles (A) is preferably 80% by mass or less, more preferably 70% by mass or less with respect to the orally disintegrating tablet from the viewpoint of ingestion and tablet physical properties (hardness, friability, disintegration, etc.). 65 mass% or less is particularly preferable.
  • the lower limit is not particularly limited, and can be a set content considering the effectiveness of each drug within the range below the upper limit.
  • Crospovidone particles (crospovidone particles (B)) of the present invention have (1) an average particle size of 50 ⁇ m or less, (2) a swelling amount of 5 (g) water / (g) product or more, and (3) The viscosity of the 5% by mass aqueous suspension is 20 mPa ⁇ s or less.
  • Crospovidone is a cross-linked polyvinyl pyrrolidone, which is a cross-linked polymer having the chemical name 1-ethenyl-2-pyrrolidinone homopolymer.
  • Orally disintegrating tablets disintegrate or bite in the oral cavity (especially between the tongue and upper jaw), causing the drug coating to peel off and unpleasant taste due to the share and impact at that time
  • tablets containing crospovidone particles (B) with the above physical properties collapse into creamy when applied in the oral cavity, and the influence on the coating layer due to friction and impact is suppressed, and the coating does not deteriorate. It can disintegrate and, as a result, has a good texture, good disintegration, and can enhance the masking effect of the unpleasant taste of the drug.
  • the average particle size of the crospovidone particles (B) used in the present invention is 50 ⁇ m or less, preferably 10 to 50 ⁇ m, more preferably 30 ⁇ m or less. If the average particle size exceeds 50 ⁇ m, the friction between the coating particles at the time of tablet disintegration is reduced and the cushioning role for suppressing the roughness is not achieved, and the roughness of the crospovidone particles themselves is also felt, resulting in poor texture. On the other hand, when the thickness is less than 10 ⁇ m, the uniformity of mixing may be deteriorated due to the deterioration of fluidity.
  • the average particle size is measured by a laser scattering diffraction particle size distribution analyzer (LS 13 320, manufactured by Beckman Coulter, Inc.).
  • the swelling amount is 5 (g) water / (g) product or more
  • the swelling amount of the crospovidone particles (B) used in the present invention is 5 (g) water / (g) product or more, and 5 to 20 (G) water / (g) product is preferable, and 5.5 to 8.5 (g) water / (g) product is more preferable.
  • the swelling amount is less than 5 (g) water / (g) product, the absorption of moisture is small, the function as a disintegrant is not sufficient in the tablet, and the disintegration property is deteriorated.
  • the swelling amount of the present invention can be determined as follows. (I) Add 1 g (M0) sample and 50 mL of distilled water at 20 ° C. to a centrifuge tube, shake and let stand for 15 minutes, then centrifuge (relative centrifugal acceleration 850 [ ⁇ g]; 15 minutes) and remove the supernatant. The mass (M1g) of the swollen sample is measured, and an approximate swelling amount M1 (M1 / M0) is calculated.
  • the viscosity (25 ° C.) of the 5% by mass aqueous suspension is 20 mPa ⁇ s or less
  • the viscosity (25 ° C.) of the 5% by mass aqueous suspension of crospovidone particles (B) used in the present invention is 20 mPa ⁇ s. s or less. Although a minimum is not specifically limited, It is about 10 mPa * s.
  • the viscosity of the aqueous suspension exceeds 20 mPa ⁇ s, it absorbs moisture at the time of tablet disintegration and changes into a gel, which prevents water from entering the tablet and deteriorates disintegration.
  • the viscosity is measured using a B-type viscometer (Toki Sangyo Co., Ltd., RB-80L) under the following conditions (rotor No. H-1, measuring rotation speed 30 rpm, measuring time 1 minute).
  • the content of the crospovidone particles (B) of the present invention is preferably 1 to 20% by mass with respect to the orally disintegrating tablet, the lower limit is more preferably 2% by mass or more, and particularly preferably 5% by mass.
  • the upper limit is more preferably 15% by mass or less, and particularly preferably 10% by mass. If the crospovidone particles (B) are added in an amount exceeding 20% by mass, the hardness and friability may be deteriorated, and if it is less than 1% by mass, the disintegration property may be deteriorated.
  • optional components can be blended within a range that does not impair the effects of the present invention.
  • other active ingredients, excipients, disintegrants other than the crosspolydon particles (B) of the present invention, sweeteners, sour agents, fragrances, lubricants, pigments and the like can be blended. These may be used alone or in appropriate combination of two or more, and an appropriate amount may be blended.
  • antacids such as magnesium aluminate metasilicate and magnesium aluminate silicate can be suitably blended.
  • commercially available products can be used, and Neusilin US2, Neusilin UFL2 (manufactured by Fuji Chemical Industry Co., Ltd.) and the like can be used (content: 5 to 20% by mass with respect to the orally disintegrating tablet).
  • excipients examples include cellulose powders, sugar powders, starches, powders such as silicon dioxide (content: usually 5 to 60% by mass with respect to orally disintegrating tablets).
  • cellulose powders include crystalline cellulose, powdered cellulose, carmellose, hydroxypropylcellulose, hydroxypropylmethylcellulose, low-substituted hydroxypropylcellulose, hydroxymethylcellulose, methylcellulose, and ethylcellulose.
  • saccharide powder examples include monosaccharides, disaccharides or higher polysaccharides (sugar (granulated sugar, etc.), lactose, maltose, xylose, isomerized lactose, etc.), sugar alcohols (palatinite, sorbitol, lactitol, erythritol, Xylitol, reduced starch saccharified product, maltitol, mannitol, etc.), starch syrup, isomerized sugar, oligosaccharide, sucrose, trehalose, reduced starch saccharified product (reduced starch decomposed product) and the like are preferable.
  • sugar alcohols palatinite, sorbitol, lactitol, erythritol, Xylitol, reduced starch saccharified product, maltitol, mannitol, etc.
  • starch syrup isomerized sugar, oligosaccharide, sucrose
  • starch powder examples include corn starch (corn starch), potato starch (potato starch), starch such as wheat starch and rice starch, and starch derivatives such as hydroxypropyl starch and partially pregelatinized starch.
  • corn starch corn starch
  • potato starch potato starch
  • starch such as wheat starch and rice starch
  • starch derivatives such as hydroxypropyl starch and partially pregelatinized starch.
  • Starch corn starch (corn starch) is more preferred.
  • the disintegrant for example, croscarmellose or the like can be used.
  • the sweetening agent for example, saccharin sodium, aspartame, stevia, dipotassium glycyrrhizinate, acesulfame potassium, thaumatin, sucralose and the like can be used (content: usually 0.05 to 10% by mass based on orally disintegrating tablet).
  • the sour agent for example, citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid or a salt thereof can be used (content: usually 0.2 to 3 mass based on orally disintegrating tablet) %).
  • flavor, menthol, limonene, vegetable essential oils (mint oil, mint oil, lychee oil, orange oil, lemon oil etc.) etc. can be used, for example.
  • Examples of the lubricant include magnesium stearate and calcium stearate (content: usually 0.5% by mass or less, preferably 0.05 to 0.2% by mass with respect to the orally disintegrating tablet).
  • the particles (A) can be obtained, for example, by coating drug particles having a primary average particle size of 150 to 300 ⁇ m with a coating agent containing a poorly water-soluble polymer compound and a plasticizer. Specifically, it can be obtained by spraying a coating agent dispersion or solution containing a poorly water-soluble polymer compound and a plasticizer onto drug particles.
  • the dispersion medium or solvent include water and ethanol.
  • Coating is performed by a coating apparatus having a fluidized bed, and an apparatus by the Wurster method is particularly preferable.
  • the Wurster method is a method in which the raw material particles and the spray liquid flow in the same direction from the bottom of the fluidized bed toward the top, and includes tangential bottom spray and bottom spray.
  • the coating apparatus using the Wurster method is suitable for suppressing coarse powder because it is easy to suppress aggregation of particles.
  • the conditions for coating are not particularly limited, and commonly used conditions can be used.
  • the exhaust temperature of the coating apparatus is preferably 20 to 70 ° C.
  • the supply air temperature is preferably 60 to 90 ° C.
  • the orally disintegrating tablet of the present invention can be obtained by mixing the above (A) particles, (B) particles and optional components, and tableting. Molding conditions such as tableting pressure vary depending on the tableting machine, the type and content of ingredients, the diameter of the tablet, etc., but are adjusted as appropriate in consideration of tablet physical properties and the like.
  • the size of the orally disintegrating tablet of the present invention is not particularly limited, but is preferably about 6 to 25 mm in diameter, and the tablet hardness is preferably 3 to 20 kgf, more preferably 5 to 15 kgf.
  • the tablet hardness represents the force required for the tablet to break up by standing the tablet vertically on the anvil and applying a static pressure to the tablet with a moving plunger.
  • the tablet hardness meter (Toyama Sangyo Co., Ltd.) )).
  • the oral disintegration rate is preferably less than 60 seconds, and more preferably less than 30 seconds.
  • the oral disintegration rate refers to the time from when the tablet is put into the oral cavity until the tablet is disintegrated by applying shear with the tongue and upper jaw.
  • Preparation Example 1 Acetaminophen coated particles 1 (coating rate 8.8%)] A 30% by weight aqueous dispersion of ethyl cellulose (trade name: Serios Coat: Asahi Kasei Chemicals), sugars and a plasticizer were added to JP purified water, and stirred well to obtain a coating agent solution having the composition described in the table below.
  • ethyl cellulose trade name: Serios Coat: Asahi Kasei Chemicals
  • ⁇ Coating agent solution composition Ethylcellulose 30 mass% aqueous dispersion 178.3 g Mannitol 26.7g Triacetin 13.4g JP purified water 249.6g Total 468.0g Solid content (20%) Ethylcellulose concentration based on solid content: 57.1% Mannitol concentration based on solid content: 28.6% Triacetin concentration based on solid content: 14.3%
  • acetaminophen particles are added, and the air volume is 65 ° C. and the exhaust temperature is 28 to 32 ° C.
  • the coating agent solution prepared in (1) was sprayed at a rate of 10 g / min so that the coating rate with respect to acetaminophen particles was 8.8%. This was cured at an air supply of 80 ° C. for 30 minutes to obtain acetaminophen coated particles 1 (average particle size 300 ⁇ m). The coating rate was 8.8%.
  • Preparation Example 2 Caffeine coated particles 1 (coating rate 30.0%)] A 30% by weight aqueous dispersion of ethyl cellulose (trade name: Serios Coat: Asahi Kasei Chemicals), sugars and a plasticizer were added to JP purified water, and stirred well to obtain a coating agent solution having the composition described in the table below.
  • ethyl cellulose trade name: Serios Coat: Asahi Kasei Chemicals
  • ⁇ Coating agent solution composition Ethylcellulose 30 mass% aqueous dispersion 742.9 g Mannitol 111.4g Triacetin 55.7g JP purified water 1040.0g Total 1950.0g Solid content (20%) Ethylcellulose concentration based on solid content: 57.1% Mannitol concentration based on solid content: 28.6% Triacetin concentration based on solid content: 14.3%
  • HPC-L hydroxypropylcellulose
  • Preparation Example 4 Preparation of granulated mannitol
  • 900 g of D-mannitol (manufactured by Rocket Japan Co., Ltd.) is placed in a fluidized bed granulator multiplex MP-01 (manufactured by POWREC Co., Ltd.), and at an air supply temperature of 80 ° C. and an exhaust temperature of 40-50 ° C., hydroxypropylcellulose 600 g of 12 mass% aqueous solution (HPC-SSL, manufactured by Nippon Soda Co., Ltd.) was sprayed and granulated.
  • HPC-SSL hydroxypropylcellulose 600 g of 12 mass% aqueous solution
  • Preparation Example 5 Preparation of l-menthol / corn starch co-ground product
  • 1000 g of l-menthol and 1000 g of corn starch were put into a polyethylene bag (0.6 m ⁇ 0.4 m) and shaken well by hand.
  • the mixture was put into a pulverizer equipped with a screen of ⁇ 1.0 mm (manufactured by Tokuju Kogakusho Co., Ltd., Fiore F-0 type) and pulverized at a rotation speed of 20 Hz.
  • the pulverized product is sieved with a sieve having an aperture of 850 ⁇ m, and the particles that have not passed through the sieve with an aperture of 850 ⁇ m are again pulverized under the same conditions and combined with the particles that have passed through the sieve with an aperture of 850 ⁇ m.
  • Corn starch co-ground product
  • Examples 1 to 22, Comparative Examples 1 to 7 Using the acetaminophen coated particles 1 and caffeine coated particles 1 obtained in Preparation Examples 1 and 2, each powder was weighed in the amounts shown in Tables 2 to 4, mixed, and then mixed with a rotary tableting machine (manufactured by Kikusui Seisakusho). To obtain tablets with a diameter of 14.7 mm. In tableting, the tableting pressure was adjusted so that the tablet hardness was about 8 kgf (8-9 kgf). The following evaluation was performed about the obtained tablet. The results are also shown in the table.
  • Preparation Example 6 Acetaminophen coated particles 2 (coating rate: 3.0%)] A 30% by weight aqueous dispersion of ethyl cellulose (trade name: Serios Coat: Asahi Kasei Chemicals), sugars and a plasticizer were added to JP purified water, and stirred well to obtain a coating agent solution having the composition described in the table below.
  • ethyl cellulose trade name: Serios Coat: Asahi Kasei Chemicals
  • ⁇ Coating agent solution composition Ethylcellulose 30 mass% aqueous dispersion 178.3 g Mannitol 26.7g Triacetin 13.4g JP purified water 249.6g Total 468.0g Solid content (20%) Ethylcellulose concentration based on solid content: 57.1% Mannitol concentration based on solid content: 28.6% Triacetin concentration based on solid content: 14.3%
  • acetaminophen particles are added, and the air volume is 65 ° C. and the exhaust temperature is 28 to 32 ° C.
  • Coating was performed by spraying the coating agent solution prepared in step 1 at a rate of 10 g / min so that the coating rate with respect to acetaminophen particles was 3.0%. This was cured at an air supply of 80 ° C. for 30 minutes to obtain acetaminophen coated particles 2 (average particle size of 290 ⁇ m). The coating rate was 3.0%.
  • Preparation Example 7 Caffeine coating particle 2 (coating rate 50.0%)] A 30% by weight aqueous dispersion of ethyl cellulose (trade name: Serios Coat: Asahi Kasei Chemicals), sugars and a plasticizer were added to JP purified water, and stirred well to obtain a coating agent solution having the composition described in the table below.
  • ethyl cellulose trade name: Serios Coat: Asahi Kasei Chemicals
  • ⁇ Coating agent solution composition Ethylcellulose 30% by weight aqueous dispersion 1142.0 g Mannitol 171.6g Triacetin 85.8g JP0.6 Purified Water 1600.6g Total 3000.0g Solid content (20%) Ethylcellulose concentration based on solid content: 57.1% Mannitol concentration based on solid content: 28.6% Triacetin concentration based on solid content: 14.3%
  • Examples 23 to 31 Using the acetaminophen coated particles 1 and 2 and caffeine coated particles 2 obtained in Preparation Examples 1, 6 and 7, each powder was weighed in the amounts shown in Table 5 and mixed, and then a rotary tableting machine (Kikusui Seisakusho) was used. Manufactured) to obtain a tablet having a diameter of 14.7 mm. In tableting, the tableting pressure was adjusted so that the tablet hardness was about 8 kgf (8-9 kgf). The following evaluation was performed about the obtained tablet. The results are also shown in the table.

Abstract

La présente invention concerne un comprimé à délitement oral qui est applicable à divers agents médicamenteux désagréables au goût, présente une bonne sensation après ingestion et possède de bonnes propriétés de délitement, et dans lequel le goût désagréable d'un agent médicamenteux contenu à l'intérieur est masqué. Le comprimé à délitement oral renferme : (A) des particules d'un agent médicamenteux de goût désagréable qui ont été enrobées d'un agent d'enrobage ; et (B) des particules de crospovidone qui présentent un diamètre de particule moyen de 50 µm ou inférieur et un degré de gonflement de 5 (g) d'eau/(g) de produit ou plus et dont une suspension aqueuse à 5 % en masse présente une viscosité (25° C) de 20 mPa·s ou inférieure.
PCT/JP2010/056555 2009-04-14 2010-04-13 Comprimé à délitement oral WO2010119851A1 (fr)

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JPWO2018021265A1 (ja) * 2016-07-27 2019-01-17 沢井製薬株式会社 口腔内崩壊錠添加用組成物
JP2019182818A (ja) * 2018-04-17 2019-10-24 ライオン株式会社 舌苔除去用の口腔内崩壊錠及び舌苔除去方法
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JP2013136537A (ja) * 2011-12-28 2013-07-11 Lion Corp 錠剤及びその製造方法
JPWO2018021265A1 (ja) * 2016-07-27 2019-01-17 沢井製薬株式会社 口腔内崩壊錠添加用組成物
US11173122B2 (en) 2016-07-27 2021-11-16 Sawai Pharmaceutical Co., Ltd. Additive composition for orally disintegrating tablet
US11167031B2 (en) 2016-09-06 2021-11-09 Sawai Pharmaceutical Co., Ltd. Additive composition for orally disintegrating tablet
JP2019182818A (ja) * 2018-04-17 2019-10-24 ライオン株式会社 舌苔除去用の口腔内崩壊錠及び舌苔除去方法

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