WO2012029913A1 - Oral preparation - Google Patents
Oral preparation Download PDFInfo
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- WO2012029913A1 WO2012029913A1 PCT/JP2011/069919 JP2011069919W WO2012029913A1 WO 2012029913 A1 WO2012029913 A1 WO 2012029913A1 JP 2011069919 W JP2011069919 W JP 2011069919W WO 2012029913 A1 WO2012029913 A1 WO 2012029913A1
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- pitavastatin
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Classifications
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to an oral preparation with suppressed bitterness derived from pitavastatin or a salt thereof.
- Examples of such a bitterness suppressing technique include a gel form having a pH of 7 to 10 comprising an HMG-CoA reductase inhibitor containing pitavastatin, a gelling agent, a polymer compound, a buffering agent, a sweetener, a base, and water.
- An oral preparation has been reported (Patent Document 2).
- An object of the present invention is to provide an oral preparation in which bitterness derived from pitavastatin or a salt thereof is suppressed.
- one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide are effective in suppressing bitterness derived from pitavastatin or a salt thereof. As a result, the present invention was completed.
- the present invention is as follows. [1] An oral preparation containing pitavastatin or a salt thereof and one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide. [2] A bitterness inhibitor of pitavastatin or a salt thereof containing as an active ingredient one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide.
- the total content of the magnesium compound is preferably less than 30 parts by weight, more preferably 0.001 to 25 parts by weight, and still more preferably 0.005 to 1 part by weight of pitavastatin or its salt in terms of pitavastatin calcium.
- the total content of the magnesium compound is preferably 0.001 to 60% by mass, more preferably 0.01 to 40% by mass, and still more preferably 0.05 to 20% by mass with respect to the total mass of the agent.
- the corrigent is preferably a terpene, more preferably menthol, and still more preferably l-menthol.
- the content of the corrigent is preferably 0.005 to 20% by mass, more preferably 0.01 to 15% by mass, and still more preferably 0.02 to 10% by mass with respect to the total mass of the agent.
- a sweetener is at least one selected from aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, and saccharin sodium.
- the sweetener is sucralose.
- the sweetener content is preferably 0.1 to 30% by mass, more preferably 0.2 to 25% by mass, and still more preferably 0.5 to 20% by mass, based on the total mass of the agent.
- the orally disintegrating preparation is an orally disintegrating tablet or an orally disintegrating film agent.
- a drug that does not contain a corrigent on both sides of a drug-containing layer, wherein the orally disintegrating film preparation contains pitavastatin or a salt thereof, a magnesium compound, and optionally at least one selected from a corrigent and a sweetener The agent according to [16] above, which has a non-containing layer.
- the disintegration time in the oral cavity is preferably within 90 seconds, more preferably within 60 seconds, and even more preferably within 30 seconds.
- a method for suppressing the bitter taste of pitavastatin or a salt thereof, wherein pitavastatin or a salt thereof contains at least one magnesium compound selected from magnesium oxide and magnesium hydroxide [20] A method for suppressing bitterness of an oral preparation containing pitavastatin or a salt thereof, the method comprising the step of adding one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide to pitavastatin or a salt thereof. [21] A method for producing an oral preparation in which the bitter taste of pitavastatin or a salt thereof is suppressed, the method comprising a step of incorporating one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide into pitavastatin or a salt thereof .
- the total content of the magnesium compound is preferably less than 30 parts by weight, more preferably 0.001 to 25 parts by weight, and still more preferably 0.005 to 1 part by weight of pitavastatin or its salt in terms of pitavastatin calcium.
- [30] Use of one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide for suppressing the bitter taste of pitavastatin or a salt thereof.
- the total amount of magnesium compound used is preferably less than 30 parts by weight, more preferably 0.001 to 25 parts by weight, and still more preferably 0.005, per 1 part by weight of pitavastatin or its salt in terms of pitavastatin calcium.
- corrigent is preferably a terpene, more preferably menthol, and still more preferably l-menthol.
- the amount of the corrigent used is preferably 0.005 to 20% by mass, more preferably 0.01 to 15% by mass, still more preferably 0.02 to 10% by mass, based on the total mass of the agent.
- [35] The use according to any one of [30] to [34] above, further using a sweetener.
- the sweetener is at least one selected from aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin and saccharin sodium.
- the sweetener is sucralose.
- the amount of the sweetener used is preferably 0.1 to 30% by mass, more preferably 0.2 to 25% by mass, still more preferably 0.5 to 20% by mass, based on the total mass of the agent.
- the oral preparation of the present invention is useful as a medicine with high taking compliance.
- the oral preparation of the present invention is an orally disintegrating preparation, the bitter taste derived from pitavastatin or a salt thereof when the preparation is disintegrated in the oral cavity is sufficiently suppressed, and can be taken without water Therefore, it is extremely useful as a medicine with high compliance.
- the oral preparation of this invention can be easily manufactured by making pitavastatin or its salt contain 1 or more types of magnesium compounds chosen from magnesium oxide and magnesium hydroxide.
- pitavastatin or a salt thereof includes, in addition to pitavastatin itself, pharmaceutically acceptable salts of pitavastatin (alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; Organic amine salts such as phenethylamine salts; ammonium salts and the like, and solvates of pitavastatin or a pharmaceutically acceptable salt thereof with water, alcohol or the like. In the present invention, one or more of these can be used in combination.
- pitavastatin calcium (chemical name: (+)-monocalcium bis ⁇ (3R, 5S, 6E) -7- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] -3,5-dihydroxy -6-heptenoate ⁇ ) is preferred.
- Pitavastatin or a salt thereof is a known compound and can be produced, for example, by the method described in JP-A-1-279866, US Pat. No. 5,854,259, US Pat. No. 5,856,336, and the like. Note that the descriptions of these documents are all cited in the present specification.
- the content of pitavastatin or a salt thereof in the oral preparation of the present invention is not particularly limited and can be appropriately determined according to the sex, age, symptoms, etc. of the user.
- pitavastatin calcium 0.1 to 16 mg, more preferably 0.5 to 8 mg, and particularly 1 to 4 mg are preferable.
- a preparation containing 0.01 to 30% by mass of pitavastatin or a salt thereof in terms of pitavastatin calcium relative to the total mass of the oral preparation is preferable, and a preparation containing 0.05 to 20% by mass is more preferable.
- a formulation containing 0.1 to 15% by mass is particularly preferable.
- One feature of the oral preparation of the present invention is that it suppresses bitterness derived from pitavastatin or a salt thereof by containing one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide.
- magnesium oxide and magnesium hydroxide may be used alone or in combination.
- the particle diameter and specific volume of “magnesium oxide” are not particularly limited, and may be heavy magnesium oxide or light magnesium oxide.
- magnesium oxide described in the 15th revision Japanese Pharmacopoeia is preferable. Magnesium oxide may be produced by a known method or may be a commercially available product. Furthermore, as the said commercial item, you may use what is marketed as a mixture with another compound.
- magnesium oxide examples include magnesium oxide manufactured by Kyowa Chemical Industry, Alkamak manufactured by Kyowa Chemical Industry, and the like.
- particle diameter and specific volume of “magnesium hydroxide” are not particularly limited.
- magnesium hydroxide described in Japanese Pharmacopoeia Pharmaceutical Standard 2002 is preferable.
- Magnesium hydroxide may be produced by a known method or may be a commercially available product. Furthermore, as the said commercial item, you may use what is marketed as a mixture with another compound.
- Specific examples of the commercially available product include magnesium hydroxide manufactured by Kyowa Chemical Industry.
- the content of the magnesium compound in the oral preparation of the present invention is not particularly limited and can be appropriately determined according to the bitterness intensity. From the viewpoint of bitterness suppression, the total amount of magnesium compound is 0 with respect to the total mass of the oral preparation.
- the content is preferably 0.001 to 60% by mass, more preferably 0.01 to 40% by mass, and particularly preferably 0.05 to 20% by mass.
- the content mass ratio of pitavastatin or a salt thereof and a magnesium compound in the oral preparation of the present invention is not particularly limited and can be appropriately determined according to the bitterness intensity. From the viewpoint of bitterness suppression, pitavastatin converted to pitavastatin calcium or its
- the total amount of magnesium compound is less than 30 parts by weight, further 0.001 to 25 parts by weight, especially 0.005 to 20 parts by weight, especially 0.01 to 10 parts by weight, based on 1 part by weight of the total salt. preferable.
- the oral preparation of the present invention preferably further contains a corrigent. Thereby, the bitter taste derived from pitavastatin or its salt can be suppressed further.
- corrigent examples include terpenes such as limonene, pinene, camphene, cymen, cineole, citronellol, geraniol, nerol, linalool, menthol, terpineol, rosinol, borneol, isoborneol, menthone, camphor, eugenol, synzeanol, etc .; Contains terpenes such as oil, orange oil, peppermint oil, camphor white oil, eucalyptus oil, turpentine oil, lemon oil, pepper oil, clove oil, cinnamon oil, lavender oil, fennel oil, chamomile oil, perilla oil, spearmint oil Essential oils (hereinafter, terpenes and essential oils containing terpenes are collectively referred to as “terpenes”); acidulants such as ascorbic acid, tartaric acid, citric acid, malic acid and their salts.
- terpenes
- the content of the corrigent in the oral preparation of the present invention is not particularly limited, but from the viewpoint of bitterness suppression, 0.005 to 20 mass%, further 0.01 to 15 mass%, based on the total mass of the oral preparation, In particular, the content is preferably 0.02 to 10% by mass.
- the oral preparation of the present invention preferably further contains a sweetening agent.
- a sweetening agent preferably a maltitol, a maltitol, a maltitol, a maltitol, a maltitol, a maltitol, a maltitol, a maltitol, a maltitol, a maltitol, a maltame, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol,
- sweetening agent examples include aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, saccharin sodium and the like, and these can be used alone or in combination of two or more. Of these, sucralose is preferable.
- the content of the sweetener in the oral preparation of the present invention is not particularly limited, but from the viewpoint of bitterness suppression, 0.1 to 30% by mass, and further 0.2 to 25% by mass with respect to the total mass of the oral preparation, In particular, the content is preferably 0.5 to 20% by mass.
- a magnesium compound in the present invention, it is preferable to contain not only a magnesium compound but also a taste-masking agent, and it is particularly preferable to contain a taste-masking agent and a sweetening agent.
- a suitable combination of a corrigent and sweetener includes terpenes (particularly l-menthol) and sucralose.
- the oral preparation of the present invention may contain additives usually used in the technical field depending on the dosage form.
- additives include excipients, disintegrants, binders, lubricants, colorants, plasticizers, film forming agents, poorly water-soluble polymeric substances, antioxidants, pH adjusters, and surfactants. , Stabilizers, fragrances, fluidizing agents, liquid media and the like. These can be used alone or in combination of two or more.
- the usage-amount of each additive can be suitably determined within the range which does not interfere with the objective of this invention.
- the thing which does not contain fenofibrate, ubidecarenone, and glutathione is preferable.
- excipients include titanium oxide, aluminum silicate, silicon dioxide, anhydrous sodium sulfate, anhydrous calcium hydrogen phosphate, sodium chloride, hydrous amorphous silicon oxide, calcium silicate, light anhydrous silicic acid, and heavy anhydrous silica.
- Inorganic excipients such as acid, calcium sulfate, calcium monohydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, sodium dihydrogen phosphate; candy powder, starch (Wheat starch, rice starch, corn starch, etc.), fructose, caramel, agar, xylitol, paraffin, crystalline cellulose, sucrose, fructose, maltose, lactose, sucrose, glucose, pullulan, polyoxyethylene hydrogenated castor oil, maltitol, Reduced maltose water candy, powdered reduced maltose water candy, erythrito Le, xylitol, sorbitol, mannitol, lactitol, trehalose, reduced palatinose, maltose, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylamino acetate, organic ex
- disintegrant examples include super disintegrants such as sodium carboxymethyl starch, croscarmellose sodium, crospovidone, carmellose, carmellose calcium, starch, sucrose fatty acid ester, gelatin, sodium bicarbonate, dextrin, dehydroacetic acid and the like. Salt, povidone, polyoxyethylene hydrogenated castor oil 60 and the like.
- binder examples include methyl cellulose, hydroxypropyl cellulose, hypromellose, carmellose sodium, wheat starch, rice starch, corn starch, dextrin, partially pregelatinized starch, pullulan, gum arabic, agar, gelatin, tragacanth, sodium alginate, povidone , Polyvinyl alcohol, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylaminoacetate and the like.
- lubricant examples include calcium stearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, and the like.
- the colorant examples include yellow iron sesquioxide, brown iron oxide, caramel, black iron oxide, titanium oxide, iron sesquioxide, tar dye, aluminum lake dye, copper chlorophyllin sodium, and the like.
- the plasticizer examples include glycerin, sesame oil, sorbitol, castor oil, propylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate 80 (polyoxyethylene (20) sorbitan oleate), polyethylene glycol [for example, Macrogol 400 (The degree of polymerization n of the oxyethylene unit is 7 to 9, hereinafter “n” represents the degree of polymerization), macrogol 600 (n is 11 to 13), macrogol 1500 (n is 5 to 6, n is 28 ⁇ 36), macrogol 4000 (n is 59 to 84), macrogol 6000 (n is 165 to 210)] and the like.
- the plasticizer is preferably one or a combination of two or more selected from these, and more preferably one or more selected from the group consisting of
- the type of film forming agent is not particularly limited as long as it has film forming ability.
- alkyl cellulose such as methyl cellulose and ethyl cellulose; alginic acid such as sodium alginate or a salt thereof; carrageenan; carboxyalkyl cellulose such as sodium carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose potassium, carboxymethyl cellulose, carboxymethyl ethyl cellulose; xanthan gum; Hydroxyalkylcelluloses such as hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose); hydroxyalkylcellulose phthalates such as hydroxypropylmethylcellulose phthalate; pullulan; polyvinyl acetate; Over preparative; polyvinyl alcohol; polyvinyl pyrrolidone, and the like, one or more combinations are preferred selected from these.
- Examples of the poorly water-soluble polymer substance include carboxyvinyl polymer and aminoalkyl methacrylate copolymer.
- Examples of the antioxidant include ascorbic acid, sodium bisulfite, sodium sulfite, sodium edetate, erythorbic acid, tocopherol acetate, dibutylhydroxytoluene, natural vitamin E, tocopherol, butylhydroxyanisole and the like.
- oral preparation means a preparation to be administered orally, and its specific form (dosage form) is not particularly limited.
- any form of solid, semi-solid and liquid may be used, and a form normally used in pharmaceuticals can be used.
- solid preparations such as tablets (including chewable tablets, effervescent tablets, orally disintegrating tablets), films, troches, drops, granules, fine granules, powders, pills, and dry syrups;
- Semi-solid preparations such as lozenges, chewing gums, jelly preparations, jelly-like drops, whip preparations; liquid preparations such as syrups, drinks, suspensions, spirits, liquids, etc.
- Japanese Pharmacopoeia US Pharmacopoeia Or a dosage form described in the European Pharmacopoeia.
- the dosage form of the oral preparation of the present invention is preferably an orally disintegrating preparation, more preferably an orally disintegrating solid preparation, and particularly preferably an orally disintegrating tablet or an orally disintegrating film preparation.
- Orally disintegrating preparations are to be taken by disintegrating in the oral cavity in a short time, and pitavastatin or a salt thereof directly contacts the tongue by completely disintegrating the preparation in the oral cavity at the time of taking. Therefore, where the bad feeling due to bitterness is a particularly serious problem, as specifically disclosed in Test Example 1 below, according to the present invention, the oral dosage form is an orally disintegrating preparation. It was revealed that the effect of suppressing bitterness was effectively exhibited.
- the disintegration time in the oral cavity of the orally disintegrating preparation (the time until the preparation is completely disintegrated with saliva in the oral cavity of a healthy person) is not particularly limited, and the dosage form of the preparation, although it varies depending on the size, for example, it is preferably within 90 seconds, more preferably within 60 seconds, and particularly preferably within 30 seconds.
- the oral preparation of the present invention can be produced by a known method described in Japanese Pharmacopoeia, US Pharmacopoeia, European Pharmacopoeia or the like according to the above dosage form.
- OD tablet which is a preferred dosage form of the present invention, from pitavastatin or a salt thereof, a magnesium compound, and optionally a corrigent and a sweetener.
- a method of producing an OD tablet by filling a suspension or solution containing pitavastatin or a salt thereof and a magnesium compound into a mold such as a blister pocket, freeze-drying, and drying and solidifying.
- the suspension or solution may further contain gelatin, dextran, alginic acid, a salt of alginic acid, sugar alcohol (erythritol, xylitol, sorbitol, mannitol, etc.), glycine and the like.
- an OD tablet is produced by a method in which a mixture containing pitavastatin or a salt thereof, a magnesium compound, and a saccharide and / or a sugar alcohol is wetted with water or an aqueous alcohol solution and molded at low pressure, so-called wet compression.
- a method is mentioned.
- examples thereof include a method of producing an OD tablet by dry compression using a super disintegrant such as sodium starch, croscarmellose sodium, crospovidone and the like.
- lactose hydrate mannitol, glucose hydrate
- low moldability saccharides such as sucrose and xylitol
- high moldability saccharides such as maltose, maltitol, sorbitol and oligosaccharides such as lactose fructose.
- pitavastatin or a salt thereof and a magnesium compound may be contained in the granulated product, or may be mixed after the granulated product is produced, but contained in the granulated product. The caulked one is preferred.
- relative low melting point sugars such as xylitol, trehalose, maltose, sorbitol, erythritol, glucose, maltitol, mannitol, sucrose, lactose hydrate, etc.
- pitavastatin or a salt thereof may be contained in the melt-solidified product, or may be mixed after the melt-solidified product is produced, but is preferably contained in the melt-solidified product.
- the content of additives such as excipients and disintegrants used in the OD tablet of the present invention is not particularly limited, but the excipient is 20 to 95% by mass relative to the total mass of the OD tablet of the present invention. It is preferably contained in an amount of 30 to 90% by mass, particularly 35 to 85% by mass. Further, the disintegrant is preferably contained in an amount of 0.5 to 25% by mass, more preferably 1 to 20% by mass, particularly 2 to 15% by mass, based on the total mass of the OD tablet of the present invention.
- film agent An orally disintegrating film agent (hereinafter simply referred to as “film agent”), which is another preferable dosage form of the present invention, can be appropriately produced by a known method. Specifically, a suspension in which one or more selected from pitavastatin or a salt thereof, a magnesium compound, and, optionally, a corrigent and a sweetener and an additive are applied on a holding substrate such as a plastic film or a mount. After spraying, it can be produced by drying. In addition, as a solvent in suspension, water, alcohol (ethanol etc.), those mixed liquids, etc. are mentioned.
- the film agent of the present invention may be a multi-layer film agent in which a plurality of layers are laminated, and contains pitavastatin or a salt thereof and a magnesium compound in at least one of the plurality of layers. It only has to be. Furthermore, although pitavastatin or a salt thereof and a magnesium compound may be contained in different layers, it is preferable that pitavastatin or a salt thereof and a magnesium compound are contained in the same layer from the viewpoint of bitterness suppression.
- each layer may be laminated by crimping or suspended. Lamination may be performed by sequentially repeating application, spraying, and drying of the liquid.
- the content of additives such as a film forming agent and a plasticizer used in the film agent of the present invention is not particularly limited, but the film forming agent is 25 to 95% by mass relative to the total mass of the film agent of the present invention, It is preferably contained in an amount of 30 to 80% by mass, particularly 35 to 65% by mass.
- the plasticizer is preferably contained in an amount of 1 to 25% by mass, more preferably 3 to 20% by mass, especially 5 to 15% by mass, based on the total mass of the film agent of the present invention.
- a drug-free layer containing no flavourant on both sides of a drug-containing layer containing pitavastatin or a salt thereof, a magnesium compound, and optionally at least one selected from a corrigent and a sweetener It is preferable that it is a film agent which has. As specifically disclosed in Test Example 2 below, it was found that a remarkable bitterness-inhibiting effect was observed by using a film agent having such a configuration.
- the oral preparation of the present invention contains pitavastatin or a salt thereof, it can be used as, for example, a therapeutic agent for hyperlipidemia, a therapeutic agent for hypercholesterolemia, a therapeutic agent for familial hypercholesterolemia, and the like.
- Example 1 12 g of water and 28 g of absolute ethanol were mixed, to which 2 g of sucralose, 0.15 g of 1-menthol and 1 g of pitavastatin calcium were dissolved, and 1 g of magnesium oxide was further dispersed. In this solution, 15.85 g of hypromellose was dissolved to obtain a film preparation solution. A film preparation solution was uniformly applied onto a PET (polyethylene terephthalate) film and then dried with warm air to form a layer having a mass of 10 mg per area of 2.8 cm 2 to obtain an intermediate product 1. Two intermediate products 1 were prepared, bonded and pressure-bonded so that the layers were opposed to each other, and the PET film on one side was peeled off to obtain intermediate product 2.
- PET polyethylene terephthalate
- Comparative Example 1 A film preparation of Comparative Example 1 was obtained in the same manner as in Example 1 except that hypromellose was added instead of magnesium oxide.
- Example 1 Bitterness inhibition test
- the film preparations of Example 1 and Comparative Example 1 were subjected to a sensory test by six panelists to evaluate the feeling of taking (bitterness).
- the bitterness evaluation is a visual analog scale method in which the film preparation is completely disintegrated with saliva in the oral cavity of the paneler with 10 points when no bitterness is felt and 0 when it is unbearable bitterness. It carried out by.
- the sensory test results (average score of evaluation by 6 panelists in each film agent) are shown in Table 1 together with the composition of each film agent (component amount (mg) per film agent).
- the magnesium compound has an action of suppressing the bitter taste of pitavastatin or a salt thereof.
- Example 2 480 g of water and 480 g of absolute ethanol were mixed, 30 g of macrogol, aminoalkyl methacrylate copolymer E120 g and 30 g of trehalose were dissolved therein, and 30 g of titanium oxide and 3 g of iron sesquioxide were dispersed. In this solution, 240 g of hypromellose was dissolved to obtain a drug-free layer preparation solution. 600 g of water and 600 g of absolute ethanol were mixed, to which 30 g of macrogol, 60 g of calcium chloride dihydrate, 30 g of sucralose and 15 g of 1-menthol were dissolved, and 60 g of pitavastatin calcium and 30 g of magnesium oxide were dispersed.
- hydroxypropylcellulose 300 g was dissolved to obtain a drug-containing layer preparation solution.
- a drug-free layer preparation solution was uniformly applied onto a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg.
- the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. Obtained.
- Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Product 2 was obtained.
- the intermediate product 2 was cut into an area of 2.8 cm 2 and the PET film was peeled off to obtain the film agent of Example 3.
- Example 2 Bitterness suppression test For the film preparation of Example 2, a sensory test was carried out by five panelists to evaluate the feeling of taking (bitterness). The bitterness was evaluated by scoring according to the following evaluation criteria for the feeling of ingestion when the film was completely disintegrated with saliva in the mouth of the panel. “Little bitterness is not worrisome”: 2 points “Bitterness is slightly worrisome”: 1 point “Bitterness is worrisome and unpleasant”: 0 points Sensory test results (evaluation by 5 panelists in film preparation) Table 2 shows the composition of each film agent (component amount per film agent (mg)).
- the film agent of the present invention in a form in which a drug-containing layer containing pitavastatin calcium having a bitter taste together with magnesium oxide and menthol is sandwiched between drug-free layers not containing menthol (Example 2) was confirmed to be an easy-to-use film agent in which the bitter taste of pitavastatin calcium was suppressed.
- a film agent having a drug-free layer containing no terpene on both sides of a drug-containing layer containing pitavastatin or a salt thereof having a bitter taste, a magnesium compound, and a terpene is pitavastatin or a salt thereof. Since the bitterness of the origin is suppressed, it became clear that the discomfort at the time of taking was relieved.
- a granulated product is sprayed with a coating solution of a 70% ethanol solution or dispersion containing 72 parts by mass of hypromellose, 36 parts by mass of yellow iron sesquioxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
- a granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
- 456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed.
- an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
- a granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
- 456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed.
- an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
- a granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
- 228 parts by weight of the coated granule, 370 parts by weight of D-mannitol, 28 parts by weight of xylitol, 440 parts by weight of crystalline cellulose, 105 parts by weight of crospovidone, 22 parts by weight of anhydrous calcium hydrogen phosphate and 1 part by weight of yogurt micron were further mixed.
- an orally disintegrating tablet having a diameter of 7 mm and a mass of 120 mg can be obtained.
- a granulated product is sprayed with a coating solution of 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow iron sesquioxide, 266.4 parts by mass of titanium oxide and 72 parts by mass of magnesium oxide, Get. 456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed.
- a coating solution of 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow iron sesquioxide, 266.4 parts by mass of titanium oxide and 72 parts by mass of magnesium oxide, Get. 456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550
- a granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
- 456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed.
- an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
- a granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
- 456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed.
- an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
- a granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
- 456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed.
- an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
- a granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
- 436 parts by weight of coated granules 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate, 20 parts by weight of magnesium oxide and 2 parts by weight of yogurt micron And 8 parts by mass of calcium stearate, and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
- 600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved.
- 60 parts by mass and 6 parts by mass of magnesium oxide are dispersed.
- 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
- a drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg.
- the drug-containing layer preparation solution After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 8.35 mg per area of 2.8 cm 2. obtain.
- Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
- the intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
- 600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved.
- 60 parts by mass and 150 parts by mass of magnesium oxide are dispersed.
- 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
- a drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg.
- the drug-containing layer preparation solution After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 10.75 mg per area of 2.8 cm 2. obtain.
- Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
- the intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
- 600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, 30 parts by weight of macrogol, 30 parts by weight of sucralose and 15 parts by weight of l-menthol are dissolved in this, and 60 parts by weight of pitavastatin calcium and 210 parts by weight of magnesium oxide are further added. scatter.
- 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
- a drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg.
- the drug-containing layer preparation solution After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 10.75 mg per area of 2.8 cm 2. obtain.
- Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
- the intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
- 600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved.
- 60 parts by mass and 30 parts by mass of magnesium hydroxide are dispersed.
- 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
- a drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg.
- the drug-containing layer preparation solution After the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. obtain.
- Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
- the intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
- 600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. Disperse 60 parts by weight.
- 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
- a drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 8.05 mg.
- the drug-containing layer preparation solution After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.25 mg. obtain.
- Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
- the intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
- 600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 30 parts by weight of sucralose and 15 parts by weight of l-menthol are dissolved therein, and further 60 parts by weight of pitavastatin calcium and 90 parts by weight of magnesium hydroxide To distribute.
- 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
- a drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg.
- the drug-containing layer preparation solution After the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. obtain.
- Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
- the intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled off to obtain an orally disintegrating film agent.
- an oral preparation having a satisfactory dosage feeling and high compliance, in which the bitterness derived from pitavastatin or a salt thereof is sufficiently suppressed, and can be used in the pharmaceutical industry and the like.
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Abstract
Provided is an oral preparation wherein the bitterness of pitavastatin or salt thereof has been suppressed. This oral preparation comprises pitavastatin or salt thereof and at least one magnesium compound selected from magnesium oxide and magnesium hydroxide.
Description
本発明は、ピタバスタチン又はその塩由来の苦味の抑制された経口剤に関する。
The present invention relates to an oral preparation with suppressed bitterness derived from pitavastatin or a salt thereof.
ピタバスタチンカルシウム(化学名:(+)-monocalcium bis{(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate})などのピタバスタチン又はその塩は優れたHMG-CoA還元酵素阻害活性を有し、高脂血症治療剤、高コレステロール血症治療剤等の有効成分として有用であることが知られている(特許文献1)。
Pitavastatin calcium (chemical name: (+)-monocalciumcalcbis {(3R, 5S, 6E) -7- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] -3,5-dihydroxy-6-heptenoate }) And other salts thereof have excellent HMG-CoA reductase inhibitory activity and are known to be useful as active ingredients such as therapeutic agents for hyperlipidemia and therapeutic agents for hypercholesterolemia ( Patent Document 1).
しかしながら、ピタバスタチン又はその塩は苦味を有するため、経口剤とした場合における服用感が損なわれやすかった。そのため、ピタバスタチン又はその塩を含有する経口剤における苦味の抑制技術が検討されてきた。
However, since pitavastatin or a salt thereof has a bitter taste, the feeling of administration in the case of an oral preparation was easily impaired. Therefore, techniques for suppressing bitterness in oral preparations containing pitavastatin or a salt thereof have been studied.
係る苦味の抑制技術としては、例えば、ピタバスタチンを含むHMG-CoA還元酵素阻害剤、ゲル化剤、高分子化合物、緩衝剤、甘味剤、基剤及び水からなりpHが7から10であるゲル状経口製剤が報告されている(特許文献2)。
Examples of such a bitterness suppressing technique include a gel form having a pH of 7 to 10 comprising an HMG-CoA reductase inhibitor containing pitavastatin, a gelling agent, a polymer compound, a buffering agent, a sweetener, a base, and water. An oral preparation has been reported (Patent Document 2).
しかしながら、係る技術はゲル状の製剤に限定され汎用性のあるものではなく、苦味の抑制技術として十分なものではなかった。
However, such technology is limited to gel-form preparations and is not versatile, and is not sufficient as a bitterness suppression technology.
本発明の課題は、ピタバスタチン又はその塩由来の苦味が抑制された経口剤を提供することにある。
An object of the present invention is to provide an oral preparation in which bitterness derived from pitavastatin or a salt thereof is suppressed.
本発明者は、上記課題を解決するため鋭意検討したところ、驚くべきことに、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物が、ピタバスタチン又はその塩由来の苦味の抑制に有効であることを見出し、本発明を完成した。
As a result of intensive studies to solve the above problems, the present inventors have surprisingly found that one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide are effective in suppressing bitterness derived from pitavastatin or a salt thereof. As a result, the present invention was completed.
本発明は、以下のとおりである。
〔1〕ピタバスタチン又はその塩と、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有する経口剤。
〔2〕酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を有効成分として含有する、ピタバスタチン又はその塩の苦味抑制剤。 The present invention is as follows.
[1] An oral preparation containing pitavastatin or a salt thereof and one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide.
[2] A bitterness inhibitor of pitavastatin or a salt thereof containing as an active ingredient one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide.
〔1〕ピタバスタチン又はその塩と、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有する経口剤。
〔2〕酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を有効成分として含有する、ピタバスタチン又はその塩の苦味抑制剤。 The present invention is as follows.
[1] An oral preparation containing pitavastatin or a salt thereof and one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide.
[2] A bitterness inhibitor of pitavastatin or a salt thereof containing as an active ingredient one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide.
〔3〕マグネシウム化合物の合計含有量が、ピタバスタチンカルシウム換算したピタバスタチン又はその塩1質量部に対して、好ましくは30質量部未満、より好ましくは0.001~25質量部、更に好ましくは0.005~20質量部、特に好ましくは0.01~10質量部である、上記〔1〕又は〔2〕記載の剤。
〔4〕マグネシウム化合物の合計含有量が、当該剤の全質量に対して、好ましくは0.001~60質量%、より好ましくは0.01~40質量%、更に好ましくは0.05~20質量%である、上記〔1〕~〔3〕のいずれか一に記載の剤。 [3] The total content of the magnesium compound is preferably less than 30 parts by weight, more preferably 0.001 to 25 parts by weight, and still more preferably 0.005 to 1 part by weight of pitavastatin or its salt in terms of pitavastatin calcium. The agent according to the above [1] or [2], which is ˜20 parts by mass, particularly preferably 0.01 to 10 parts by mass.
[4] The total content of the magnesium compound is preferably 0.001 to 60% by mass, more preferably 0.01 to 40% by mass, and still more preferably 0.05 to 20% by mass with respect to the total mass of the agent. The agent according to any one of [1] to [3] above, which is%.
〔4〕マグネシウム化合物の合計含有量が、当該剤の全質量に対して、好ましくは0.001~60質量%、より好ましくは0.01~40質量%、更に好ましくは0.05~20質量%である、上記〔1〕~〔3〕のいずれか一に記載の剤。 [3] The total content of the magnesium compound is preferably less than 30 parts by weight, more preferably 0.001 to 25 parts by weight, and still more preferably 0.005 to 1 part by weight of pitavastatin or its salt in terms of pitavastatin calcium. The agent according to the above [1] or [2], which is ˜20 parts by mass, particularly preferably 0.01 to 10 parts by mass.
[4] The total content of the magnesium compound is preferably 0.001 to 60% by mass, more preferably 0.01 to 40% by mass, and still more preferably 0.05 to 20% by mass with respect to the total mass of the agent. The agent according to any one of [1] to [3] above, which is%.
〔5〕更に、矯味剤を含有する、上記〔1〕~〔4〕のいずれか一に記載の剤。
〔6〕矯味剤が、好ましくはテルペン類、より好ましくはメントール、更に好ましくはl-メントールである、上記〔5〕記載の剤。
〔7〕矯味剤の含有量が、当該剤の全質量に対して、好ましくは0.005~20質量%、より好ましくは0.01~15質量%、更に好ましくは0.02~10質量%である、上記〔5〕又は〔6〕記載の剤。 [5] The agent according to any one of [1] to [4], further comprising a taste-masking agent.
[6] The agent according to [5] above, wherein the corrigent is preferably a terpene, more preferably menthol, and still more preferably l-menthol.
[7] The content of the corrigent is preferably 0.005 to 20% by mass, more preferably 0.01 to 15% by mass, and still more preferably 0.02 to 10% by mass with respect to the total mass of the agent. The agent according to [5] or [6] above.
〔6〕矯味剤が、好ましくはテルペン類、より好ましくはメントール、更に好ましくはl-メントールである、上記〔5〕記載の剤。
〔7〕矯味剤の含有量が、当該剤の全質量に対して、好ましくは0.005~20質量%、より好ましくは0.01~15質量%、更に好ましくは0.02~10質量%である、上記〔5〕又は〔6〕記載の剤。 [5] The agent according to any one of [1] to [4], further comprising a taste-masking agent.
[6] The agent according to [5] above, wherein the corrigent is preferably a terpene, more preferably menthol, and still more preferably l-menthol.
[7] The content of the corrigent is preferably 0.005 to 20% by mass, more preferably 0.01 to 15% by mass, and still more preferably 0.02 to 10% by mass with respect to the total mass of the agent. The agent according to [5] or [6] above.
〔8〕更に、甘味料を含有する、上記〔1〕~〔7〕のいずれか一に記載の剤。
〔9〕甘味料が、アスパルテーム、ステビア、スクラロース、グリチルリチン酸、ソーマチン、アセスルファムカリウム、サッカリン及びサッカリンナトリウムから選ばれる少なくとも1種である、上記〔8〕記載の剤。
〔10〕甘味料が、スクラロースである、上記〔8〕記載の剤。
〔11〕甘味剤の含有量が、当該剤の全質量に対して、好ましくは0.1~30質量%、より好ましくは0.2~25質量%、更に好ましくは0.5~20質量%である、上記〔8〕~〔10〕のいずれか一に記載の剤。 [8] The agent according to any one of [1] to [7], further comprising a sweetener.
[9] The agent according to [8] above, wherein the sweetener is at least one selected from aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, and saccharin sodium.
[10] The agent according to [8] above, wherein the sweetener is sucralose.
[11] The sweetener content is preferably 0.1 to 30% by mass, more preferably 0.2 to 25% by mass, and still more preferably 0.5 to 20% by mass, based on the total mass of the agent. The agent according to any one of [8] to [10] above.
〔9〕甘味料が、アスパルテーム、ステビア、スクラロース、グリチルリチン酸、ソーマチン、アセスルファムカリウム、サッカリン及びサッカリンナトリウムから選ばれる少なくとも1種である、上記〔8〕記載の剤。
〔10〕甘味料が、スクラロースである、上記〔8〕記載の剤。
〔11〕甘味剤の含有量が、当該剤の全質量に対して、好ましくは0.1~30質量%、より好ましくは0.2~25質量%、更に好ましくは0.5~20質量%である、上記〔8〕~〔10〕のいずれか一に記載の剤。 [8] The agent according to any one of [1] to [7], further comprising a sweetener.
[9] The agent according to [8] above, wherein the sweetener is at least one selected from aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, and saccharin sodium.
[10] The agent according to [8] above, wherein the sweetener is sucralose.
[11] The sweetener content is preferably 0.1 to 30% by mass, more preferably 0.2 to 25% by mass, and still more preferably 0.5 to 20% by mass, based on the total mass of the agent. The agent according to any one of [8] to [10] above.
〔12〕フェノフィブラート、ユビデカレノン及びグルタチオンを含有しないものである、上記〔1〕~〔11〕のいずれか一に記載の剤。
〔13〕ピタバスタチン又はその塩を、当該剤の全質量に対して、ピタバスタチンカルシウム換算で、好ましくは0.01~30質量%、より好ましくは0.05~20質量%、更に好ましくは0.1~15質量%含有する、上記〔1〕、〔3〕~〔12〕のいずれか一に記載の剤。
〔14〕ピタバスタチン又はその塩を、1日あたり、ピタバスタチンカルシウム換算で、好ましくは0.1~16mg、より好ましくは0.5~8mg、更に好ましくは1~4mg服用できるものである、上記〔1〕、〔3〕~〔13〕のいずれか一に記載の剤。 [12] The agent according to any one of [1] to [11] above, which does not contain fenofibrate, ubidecarenone and glutathione.
[13] Pitavastatin or a salt thereof is preferably 0.01 to 30% by mass, more preferably 0.05 to 20% by mass, and still more preferably 0.1% in terms of pitavastatin calcium with respect to the total mass of the agent. The agent according to any one of [1], [3] to [12], which is contained in an amount of 15% by mass.
[14] Pitavastatin or a salt thereof can be taken per day, preferably 0.1 to 16 mg, more preferably 0.5 to 8 mg, and still more preferably 1 to 4 mg in terms of pitavastatin calcium. ] The agent according to any one of [3] to [13].
〔13〕ピタバスタチン又はその塩を、当該剤の全質量に対して、ピタバスタチンカルシウム換算で、好ましくは0.01~30質量%、より好ましくは0.05~20質量%、更に好ましくは0.1~15質量%含有する、上記〔1〕、〔3〕~〔12〕のいずれか一に記載の剤。
〔14〕ピタバスタチン又はその塩を、1日あたり、ピタバスタチンカルシウム換算で、好ましくは0.1~16mg、より好ましくは0.5~8mg、更に好ましくは1~4mg服用できるものである、上記〔1〕、〔3〕~〔13〕のいずれか一に記載の剤。 [12] The agent according to any one of [1] to [11] above, which does not contain fenofibrate, ubidecarenone and glutathione.
[13] Pitavastatin or a salt thereof is preferably 0.01 to 30% by mass, more preferably 0.05 to 20% by mass, and still more preferably 0.1% in terms of pitavastatin calcium with respect to the total mass of the agent. The agent according to any one of [1], [3] to [12], which is contained in an amount of 15% by mass.
[14] Pitavastatin or a salt thereof can be taken per day, preferably 0.1 to 16 mg, more preferably 0.5 to 8 mg, and still more preferably 1 to 4 mg in terms of pitavastatin calcium. ] The agent according to any one of [3] to [13].
〔15〕口腔内崩壊型の製剤である、上記〔1〕、〔3〕~〔14〕のいずれか一に記載の剤。
〔16〕口腔内崩壊型の製剤が口腔内崩壊型錠剤又は口腔内崩壊型フィルム剤である、上記〔15〕記載の剤。
〔17〕口腔内崩壊型フィルム剤が、ピタバスタチン又はその塩と、マグネシウム化合物と、所望により矯味剤及び甘味剤から選ばれる少なくとも1種を含有する薬物含有層の両面に、矯味剤を含有しない薬物非含有層を有するものである、上記〔16〕記載の剤。
〔18〕口腔内での崩壊時間が、好ましくは90秒以内、より好ましくは60秒以内、更に好ましくは30秒以内である、上記〔15〕~〔17〕のいずれか一に記載の剤。 [15] The agent according to any one of [1], [3] to [14], which is an orally disintegrating preparation.
[16] The agent according to [15] above, wherein the orally disintegrating preparation is an orally disintegrating tablet or an orally disintegrating film agent.
[17] A drug that does not contain a corrigent on both sides of a drug-containing layer, wherein the orally disintegrating film preparation contains pitavastatin or a salt thereof, a magnesium compound, and optionally at least one selected from a corrigent and a sweetener The agent according to [16] above, which has a non-containing layer.
[18] The agent according to any one of [15] to [17] above, wherein the disintegration time in the oral cavity is preferably within 90 seconds, more preferably within 60 seconds, and even more preferably within 30 seconds.
〔16〕口腔内崩壊型の製剤が口腔内崩壊型錠剤又は口腔内崩壊型フィルム剤である、上記〔15〕記載の剤。
〔17〕口腔内崩壊型フィルム剤が、ピタバスタチン又はその塩と、マグネシウム化合物と、所望により矯味剤及び甘味剤から選ばれる少なくとも1種を含有する薬物含有層の両面に、矯味剤を含有しない薬物非含有層を有するものである、上記〔16〕記載の剤。
〔18〕口腔内での崩壊時間が、好ましくは90秒以内、より好ましくは60秒以内、更に好ましくは30秒以内である、上記〔15〕~〔17〕のいずれか一に記載の剤。 [15] The agent according to any one of [1], [3] to [14], which is an orally disintegrating preparation.
[16] The agent according to [15] above, wherein the orally disintegrating preparation is an orally disintegrating tablet or an orally disintegrating film agent.
[17] A drug that does not contain a corrigent on both sides of a drug-containing layer, wherein the orally disintegrating film preparation contains pitavastatin or a salt thereof, a magnesium compound, and optionally at least one selected from a corrigent and a sweetener The agent according to [16] above, which has a non-containing layer.
[18] The agent according to any one of [15] to [17] above, wherein the disintegration time in the oral cavity is preferably within 90 seconds, more preferably within 60 seconds, and even more preferably within 30 seconds.
〔19〕ピタバスタチン又はその塩に、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめる、ピタバスタチン又はその塩の苦味抑制方法。
〔20〕ピタバスタチン又はその塩を含有する経口剤の苦味抑制方法であって、ピタバスタチン又はその塩に酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめる工程を含む苦味抑制方法。
〔21〕ピタバスタチン又はその塩の苦味が抑制された経口剤の製造方法であって、ピタバスタチン又はその塩に酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめる工程を含む製造方法。 [19] A method for suppressing the bitter taste of pitavastatin or a salt thereof, wherein pitavastatin or a salt thereof contains at least one magnesium compound selected from magnesium oxide and magnesium hydroxide.
[20] A method for suppressing bitterness of an oral preparation containing pitavastatin or a salt thereof, the method comprising the step of adding one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide to pitavastatin or a salt thereof.
[21] A method for producing an oral preparation in which the bitter taste of pitavastatin or a salt thereof is suppressed, the method comprising a step of incorporating one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide into pitavastatin or a salt thereof .
〔20〕ピタバスタチン又はその塩を含有する経口剤の苦味抑制方法であって、ピタバスタチン又はその塩に酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめる工程を含む苦味抑制方法。
〔21〕ピタバスタチン又はその塩の苦味が抑制された経口剤の製造方法であって、ピタバスタチン又はその塩に酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめる工程を含む製造方法。 [19] A method for suppressing the bitter taste of pitavastatin or a salt thereof, wherein pitavastatin or a salt thereof contains at least one magnesium compound selected from magnesium oxide and magnesium hydroxide.
[20] A method for suppressing bitterness of an oral preparation containing pitavastatin or a salt thereof, the method comprising the step of adding one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide to pitavastatin or a salt thereof.
[21] A method for producing an oral preparation in which the bitter taste of pitavastatin or a salt thereof is suppressed, the method comprising a step of incorporating one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide into pitavastatin or a salt thereof .
〔22〕マグネシウム化合物の合計含有量が、ピタバスタチンカルシウム換算したピタバスタチン又はその塩1質量部に対して、好ましくは30質量部未満、より好ましくは0.001~25質量部、更に好ましくは0.005~20質量部、特に好ましくは0.01~10質量部である、上記〔19〕~〔21〕のいずれか一に記載の方法。
[22] The total content of the magnesium compound is preferably less than 30 parts by weight, more preferably 0.001 to 25 parts by weight, and still more preferably 0.005 to 1 part by weight of pitavastatin or its salt in terms of pitavastatin calcium. The method according to any one of [19] to [21], wherein the amount is from 20 to 20 parts by mass, particularly preferably from 0.01 to 10 parts by mass.
〔23〕更に、矯味剤を含有する、上記〔19〕~〔22〕のいずれか一に記載の方法。
〔24〕矯味剤が、好ましくはテルペン類、より好ましくはメントール、更に好ましくはl-メントールである、上記〔23〕記載の方法。
〔25〕矯味剤の含有量が、当該剤の全質量に対して、好ましくは0.005~20質量%、より好ましくは0.01~15質量%、更に好ましくは0.02~10質量%である、上記〔23〕又は〔24〕記載の方法。 [23] The method according to any one of [19] to [22] above, further comprising a corrigent.
[24] The method described in [23] above, wherein the corrigent is preferably a terpene, more preferably menthol, and still more preferably l-menthol.
[25] The content of the corrigent is preferably 0.005 to 20% by mass, more preferably 0.01 to 15% by mass, and still more preferably 0.02 to 10% by mass, based on the total mass of the agent. The method according to [23] or [24] above.
〔24〕矯味剤が、好ましくはテルペン類、より好ましくはメントール、更に好ましくはl-メントールである、上記〔23〕記載の方法。
〔25〕矯味剤の含有量が、当該剤の全質量に対して、好ましくは0.005~20質量%、より好ましくは0.01~15質量%、更に好ましくは0.02~10質量%である、上記〔23〕又は〔24〕記載の方法。 [23] The method according to any one of [19] to [22] above, further comprising a corrigent.
[24] The method described in [23] above, wherein the corrigent is preferably a terpene, more preferably menthol, and still more preferably l-menthol.
[25] The content of the corrigent is preferably 0.005 to 20% by mass, more preferably 0.01 to 15% by mass, and still more preferably 0.02 to 10% by mass, based on the total mass of the agent. The method according to [23] or [24] above.
〔26〕更に、甘味料を含有する、上記〔19〕~〔25〕のいずれか一に記載の方法。
〔27〕甘味料が、アスパルテーム、ステビア、スクラロース、グリチルリチン酸、ソーマチン、アセスルファムカリウム、サッカリン及びサッカリンナトリウムから選ばれる少なくとも1種である、上記〔26〕記載の方法。
〔28〕甘味料が、スクラロースである、上記〔26〕記載の方法。
〔29〕甘味剤の含有量が、当該剤の全質量に対して、好ましくは0.1~30質量%、より好ましくは0.2~25質量%、更に好ましくは0.5~20質量%である、上記〔26〕~〔28〕のいずれか一に記載の方法。 [26] The method according to any one of [19] to [25] above, further comprising a sweetener.
[27] The method described in [26] above, wherein the sweetener is at least one selected from aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, and saccharin sodium.
[28] The method described in [26] above, wherein the sweetener is sucralose.
[29] The content of the sweetener is preferably 0.1 to 30% by mass, more preferably 0.2 to 25% by mass, and still more preferably 0.5 to 20% by mass relative to the total mass of the agent. The method according to any one of [26] to [28] above.
〔27〕甘味料が、アスパルテーム、ステビア、スクラロース、グリチルリチン酸、ソーマチン、アセスルファムカリウム、サッカリン及びサッカリンナトリウムから選ばれる少なくとも1種である、上記〔26〕記載の方法。
〔28〕甘味料が、スクラロースである、上記〔26〕記載の方法。
〔29〕甘味剤の含有量が、当該剤の全質量に対して、好ましくは0.1~30質量%、より好ましくは0.2~25質量%、更に好ましくは0.5~20質量%である、上記〔26〕~〔28〕のいずれか一に記載の方法。 [26] The method according to any one of [19] to [25] above, further comprising a sweetener.
[27] The method described in [26] above, wherein the sweetener is at least one selected from aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, and saccharin sodium.
[28] The method described in [26] above, wherein the sweetener is sucralose.
[29] The content of the sweetener is preferably 0.1 to 30% by mass, more preferably 0.2 to 25% by mass, and still more preferably 0.5 to 20% by mass relative to the total mass of the agent. The method according to any one of [26] to [28] above.
〔30〕ピタバスタチン又はその塩の苦味を抑制するための、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物の使用。
〔31〕マグネシウム化合物の合計使用量が、ピタバスタチンカルシウム換算したピタバスタチン又はその塩1質量部に対して、好ましくは30質量部未満、より好ましくは0.001~25質量部、更に好ましくは0.005~20質量部、特に好ましくは0.01~10質量部である、上記〔30〕記載の使用。 [30] Use of one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide for suppressing the bitter taste of pitavastatin or a salt thereof.
[31] The total amount of magnesium compound used is preferably less than 30 parts by weight, more preferably 0.001 to 25 parts by weight, and still more preferably 0.005, per 1 part by weight of pitavastatin or its salt in terms of pitavastatin calcium. Use according to the above [30], which is 20 to 20 parts by mass, particularly preferably 0.01 to 10 parts by mass.
〔31〕マグネシウム化合物の合計使用量が、ピタバスタチンカルシウム換算したピタバスタチン又はその塩1質量部に対して、好ましくは30質量部未満、より好ましくは0.001~25質量部、更に好ましくは0.005~20質量部、特に好ましくは0.01~10質量部である、上記〔30〕記載の使用。 [30] Use of one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide for suppressing the bitter taste of pitavastatin or a salt thereof.
[31] The total amount of magnesium compound used is preferably less than 30 parts by weight, more preferably 0.001 to 25 parts by weight, and still more preferably 0.005, per 1 part by weight of pitavastatin or its salt in terms of pitavastatin calcium. Use according to the above [30], which is 20 to 20 parts by mass, particularly preferably 0.01 to 10 parts by mass.
〔32〕更に、矯味剤を使用する、上記〔30〕又は〔31〕記載の使用。
〔33〕矯味剤が、好ましくはテルペン類、より好ましくはメントール、更に好ましくはl-メントールである、上記〔32〕記載の使用。
〔34〕矯味剤の使用量が、当該剤の全質量に対して、好ましくは0.005~20質量%、より好ましくは0.01~15質量%、更に好ましくは0.02~10質量%である、上記〔32〕又は〔33〕記載の使用。 [32] The use according to [30] or [31] above, further using a corrigent.
[33] The use according to [32] above, wherein the corrigent is preferably a terpene, more preferably menthol, and still more preferably l-menthol.
[34] The amount of the corrigent used is preferably 0.005 to 20% by mass, more preferably 0.01 to 15% by mass, still more preferably 0.02 to 10% by mass, based on the total mass of the agent. The use according to [32] or [33] above.
〔33〕矯味剤が、好ましくはテルペン類、より好ましくはメントール、更に好ましくはl-メントールである、上記〔32〕記載の使用。
〔34〕矯味剤の使用量が、当該剤の全質量に対して、好ましくは0.005~20質量%、より好ましくは0.01~15質量%、更に好ましくは0.02~10質量%である、上記〔32〕又は〔33〕記載の使用。 [32] The use according to [30] or [31] above, further using a corrigent.
[33] The use according to [32] above, wherein the corrigent is preferably a terpene, more preferably menthol, and still more preferably l-menthol.
[34] The amount of the corrigent used is preferably 0.005 to 20% by mass, more preferably 0.01 to 15% by mass, still more preferably 0.02 to 10% by mass, based on the total mass of the agent. The use according to [32] or [33] above.
〔35〕更に、甘味料を使用する、上記〔30〕~〔34〕のいずれか一に記載の使用。
〔36〕甘味料が、アスパルテーム、ステビア、スクラロース、グリチルリチン酸、ソーマチン、アセスルファムカリウム、サッカリン及びサッカリンナトリウムから選ばれる少なくとも1種である、上記〔35〕記載の使用。
〔37〕甘味料が、スクラロースである、上記〔35〕記載の使用。
〔38〕甘味剤の使用量が、当該剤の全質量に対して、好ましくは0.1~30質量%、より好ましくは0.2~25質量%、更に好ましくは0.5~20質量%である、上記〔35〕~〔37〕のいずれか一に記載の使用。 [35] The use according to any one of [30] to [34] above, further using a sweetener.
[36] The use according to [35] above, wherein the sweetener is at least one selected from aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin and saccharin sodium.
[37] Use of the above-mentioned [35], wherein the sweetener is sucralose.
[38] The amount of the sweetener used is preferably 0.1 to 30% by mass, more preferably 0.2 to 25% by mass, still more preferably 0.5 to 20% by mass, based on the total mass of the agent. The use according to any one of [35] to [37] above.
〔36〕甘味料が、アスパルテーム、ステビア、スクラロース、グリチルリチン酸、ソーマチン、アセスルファムカリウム、サッカリン及びサッカリンナトリウムから選ばれる少なくとも1種である、上記〔35〕記載の使用。
〔37〕甘味料が、スクラロースである、上記〔35〕記載の使用。
〔38〕甘味剤の使用量が、当該剤の全質量に対して、好ましくは0.1~30質量%、より好ましくは0.2~25質量%、更に好ましくは0.5~20質量%である、上記〔35〕~〔37〕のいずれか一に記載の使用。 [35] The use according to any one of [30] to [34] above, further using a sweetener.
[36] The use according to [35] above, wherein the sweetener is at least one selected from aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin and saccharin sodium.
[37] Use of the above-mentioned [35], wherein the sweetener is sucralose.
[38] The amount of the sweetener used is preferably 0.1 to 30% by mass, more preferably 0.2 to 25% by mass, still more preferably 0.5 to 20% by mass, based on the total mass of the agent. The use according to any one of [35] to [37] above.
本発明の経口剤は、ピタバスタチン又はその塩由来の苦味が十分に抑制されており、服用感が良好であるため、服用コンプライアンスの高い医薬品として有用である。特に、本発明の経口剤が口腔内崩壊型の製剤である場合、当該製剤を口腔内にて崩壊させた場合のピタバスタチン又はその塩由来の苦味が十分に抑制されており、しかも水無しで服用が可能なため、服用コンプライアンスの高い医薬品として極めて有用である。
また、本発明の経口剤は、ピタバスタチン又はその塩に、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめることによって容易に製造することができる。 Since the bitterness derived from pitavastatin or a salt thereof is sufficiently suppressed and the feeling of taking is good, the oral preparation of the present invention is useful as a medicine with high taking compliance. In particular, when the oral preparation of the present invention is an orally disintegrating preparation, the bitter taste derived from pitavastatin or a salt thereof when the preparation is disintegrated in the oral cavity is sufficiently suppressed, and can be taken without water Therefore, it is extremely useful as a medicine with high compliance.
Moreover, the oral preparation of this invention can be easily manufactured by making pitavastatin or its salt contain 1 or more types of magnesium compounds chosen from magnesium oxide and magnesium hydroxide.
また、本発明の経口剤は、ピタバスタチン又はその塩に、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめることによって容易に製造することができる。 Since the bitterness derived from pitavastatin or a salt thereof is sufficiently suppressed and the feeling of taking is good, the oral preparation of the present invention is useful as a medicine with high taking compliance. In particular, when the oral preparation of the present invention is an orally disintegrating preparation, the bitter taste derived from pitavastatin or a salt thereof when the preparation is disintegrated in the oral cavity is sufficiently suppressed, and can be taken without water Therefore, it is extremely useful as a medicine with high compliance.
Moreover, the oral preparation of this invention can be easily manufactured by making pitavastatin or its salt contain 1 or more types of magnesium compounds chosen from magnesium oxide and magnesium hydroxide.
本発明において「ピタバスタチン又はその塩」には、ピタバスタチンそのもののほか、ピタバスタチンの薬学上許容される塩(ナトリウム塩、カリウム塩等のアルカリ金属塩;カルシウム塩、マグネシウム塩等のアルカリ土類金属塩;フェネチルアミン塩等の有機アミン塩;アンモニウム塩等)、更にはピタバスタチン又はその薬学上許容される塩と、水又はアルコール等との溶媒和物も含まれる。本発明においては、これらの1種又は2種以上を組み合わせて使用できる。
これらの中でも、ピタバスタチンカルシウム(化学名:(+)-monocalcium bis{(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate})が好ましい。
ピタバスタチン又はその塩は公知の化合物であり、例えば、特開平1-279866号公報、米国特許第5854259号明細書、米国特許第5856336号明細書等に記載の方法により製造することができる。なお、これらの文献の記載は、全て本明細書に引用するものとする。 In the present invention, “pitavastatin or a salt thereof” includes, in addition to pitavastatin itself, pharmaceutically acceptable salts of pitavastatin (alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; Organic amine salts such as phenethylamine salts; ammonium salts and the like, and solvates of pitavastatin or a pharmaceutically acceptable salt thereof with water, alcohol or the like. In the present invention, one or more of these can be used in combination.
Among these, pitavastatin calcium (chemical name: (+)-monocalcium bis {(3R, 5S, 6E) -7- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] -3,5-dihydroxy -6-heptenoate}) is preferred.
Pitavastatin or a salt thereof is a known compound and can be produced, for example, by the method described in JP-A-1-279866, US Pat. No. 5,854,259, US Pat. No. 5,856,336, and the like. Note that the descriptions of these documents are all cited in the present specification.
これらの中でも、ピタバスタチンカルシウム(化学名:(+)-monocalcium bis{(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate})が好ましい。
ピタバスタチン又はその塩は公知の化合物であり、例えば、特開平1-279866号公報、米国特許第5854259号明細書、米国特許第5856336号明細書等に記載の方法により製造することができる。なお、これらの文献の記載は、全て本明細書に引用するものとする。 In the present invention, “pitavastatin or a salt thereof” includes, in addition to pitavastatin itself, pharmaceutically acceptable salts of pitavastatin (alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; Organic amine salts such as phenethylamine salts; ammonium salts and the like, and solvates of pitavastatin or a pharmaceutically acceptable salt thereof with water, alcohol or the like. In the present invention, one or more of these can be used in combination.
Among these, pitavastatin calcium (chemical name: (+)-monocalcium bis {(3R, 5S, 6E) -7- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] -3,5-dihydroxy -6-heptenoate}) is preferred.
Pitavastatin or a salt thereof is a known compound and can be produced, for example, by the method described in JP-A-1-279866, US Pat. No. 5,854,259, US Pat. No. 5,856,336, and the like. Note that the descriptions of these documents are all cited in the present specification.
本発明の経口剤におけるピタバスタチン又はその塩の含有量は特に限定されず、服用者の性別、年齢、症状等に応じて、適宜決定することができるが、例えば、ピタバスタチン又はその塩を、1日あたり、ピタバスタチンカルシウム換算で0.1~16mg、更に0.5~8mg、特に1~4mg服用できるものが好ましい。
本発明においては、ピタバスタチン又はその塩を、経口剤の全質量に対して、ピタバスタチンカルシウム換算で0.01~30質量%含有する製剤が好ましく、0.05~20質量%含有する製剤がより好ましく、0.1~15質量%含有する製剤が特に好ましい。 The content of pitavastatin or a salt thereof in the oral preparation of the present invention is not particularly limited and can be appropriately determined according to the sex, age, symptoms, etc. of the user. In terms of pitavastatin calcium, 0.1 to 16 mg, more preferably 0.5 to 8 mg, and particularly 1 to 4 mg are preferable.
In the present invention, a preparation containing 0.01 to 30% by mass of pitavastatin or a salt thereof in terms of pitavastatin calcium relative to the total mass of the oral preparation is preferable, and a preparation containing 0.05 to 20% by mass is more preferable. A formulation containing 0.1 to 15% by mass is particularly preferable.
本発明においては、ピタバスタチン又はその塩を、経口剤の全質量に対して、ピタバスタチンカルシウム換算で0.01~30質量%含有する製剤が好ましく、0.05~20質量%含有する製剤がより好ましく、0.1~15質量%含有する製剤が特に好ましい。 The content of pitavastatin or a salt thereof in the oral preparation of the present invention is not particularly limited and can be appropriately determined according to the sex, age, symptoms, etc. of the user. In terms of pitavastatin calcium, 0.1 to 16 mg, more preferably 0.5 to 8 mg, and particularly 1 to 4 mg are preferable.
In the present invention, a preparation containing 0.01 to 30% by mass of pitavastatin or a salt thereof in terms of pitavastatin calcium relative to the total mass of the oral preparation is preferable, and a preparation containing 0.05 to 20% by mass is more preferable. A formulation containing 0.1 to 15% by mass is particularly preferable.
本発明の経口剤は、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめることにより、ピタバスタチン又はその塩由来の苦味を抑制することを一つの特徴とする。本発明においては、酸化マグネシウム及び水酸化マグネシウムを単独で用いてもよく、両者を組み合わせて用いてもよい。
本発明において「酸化マグネシウム」の粒子径や比容等は特に限定されず、重質酸化マグネシウムであっても軽質酸化マグネシウムであってもよい。本発明においては、第十五改正 日本薬局方に記載の酸化マグネシウムが好ましい。酸化マグネシウムは、公知の方法により製造したものを用いても、市販品を用いてもよい。更に、当該市販品としては、他の化合物との混合物として市販されているものを用いてもよい。酸化マグネシウムの市販品として、具体的には、協和化学工業製の酸化マグネシウム、協和化学工業製のアルカマックなどが挙げられる。
本発明において「水酸化マグネシウム」の粒子径や比容等は特に限定されない。本発明においては、日本薬局方外医薬品規格2002に記載の水酸化マグネシウムが好ましい。水酸化マグネシウムは、公知の方法により製造したものを用いても、市販品を用いてもよい。更に、当該市販品としては、他の化合物との混合物として市販されているものを用いてもよい。当該市販品として、具体的には、協和化学工業製の水酸化マグネシウムなどが挙げられる。 One feature of the oral preparation of the present invention is that it suppresses bitterness derived from pitavastatin or a salt thereof by containing one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide. In the present invention, magnesium oxide and magnesium hydroxide may be used alone or in combination.
In the present invention, the particle diameter and specific volume of “magnesium oxide” are not particularly limited, and may be heavy magnesium oxide or light magnesium oxide. In the present invention, magnesium oxide described in the 15th revision Japanese Pharmacopoeia is preferable. Magnesium oxide may be produced by a known method or may be a commercially available product. Furthermore, as the said commercial item, you may use what is marketed as a mixture with another compound. Specific examples of commercially available magnesium oxide include magnesium oxide manufactured by Kyowa Chemical Industry, Alkamak manufactured by Kyowa Chemical Industry, and the like.
In the present invention, the particle diameter and specific volume of “magnesium hydroxide” are not particularly limited. In the present invention, magnesium hydroxide described in Japanese Pharmacopoeia Pharmaceutical Standard 2002 is preferable. Magnesium hydroxide may be produced by a known method or may be a commercially available product. Furthermore, as the said commercial item, you may use what is marketed as a mixture with another compound. Specific examples of the commercially available product include magnesium hydroxide manufactured by Kyowa Chemical Industry.
本発明において「酸化マグネシウム」の粒子径や比容等は特に限定されず、重質酸化マグネシウムであっても軽質酸化マグネシウムであってもよい。本発明においては、第十五改正 日本薬局方に記載の酸化マグネシウムが好ましい。酸化マグネシウムは、公知の方法により製造したものを用いても、市販品を用いてもよい。更に、当該市販品としては、他の化合物との混合物として市販されているものを用いてもよい。酸化マグネシウムの市販品として、具体的には、協和化学工業製の酸化マグネシウム、協和化学工業製のアルカマックなどが挙げられる。
本発明において「水酸化マグネシウム」の粒子径や比容等は特に限定されない。本発明においては、日本薬局方外医薬品規格2002に記載の水酸化マグネシウムが好ましい。水酸化マグネシウムは、公知の方法により製造したものを用いても、市販品を用いてもよい。更に、当該市販品としては、他の化合物との混合物として市販されているものを用いてもよい。当該市販品として、具体的には、協和化学工業製の水酸化マグネシウムなどが挙げられる。 One feature of the oral preparation of the present invention is that it suppresses bitterness derived from pitavastatin or a salt thereof by containing one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide. In the present invention, magnesium oxide and magnesium hydroxide may be used alone or in combination.
In the present invention, the particle diameter and specific volume of “magnesium oxide” are not particularly limited, and may be heavy magnesium oxide or light magnesium oxide. In the present invention, magnesium oxide described in the 15th revision Japanese Pharmacopoeia is preferable. Magnesium oxide may be produced by a known method or may be a commercially available product. Furthermore, as the said commercial item, you may use what is marketed as a mixture with another compound. Specific examples of commercially available magnesium oxide include magnesium oxide manufactured by Kyowa Chemical Industry, Alkamak manufactured by Kyowa Chemical Industry, and the like.
In the present invention, the particle diameter and specific volume of “magnesium hydroxide” are not particularly limited. In the present invention, magnesium hydroxide described in Japanese Pharmacopoeia Pharmaceutical Standard 2002 is preferable. Magnesium hydroxide may be produced by a known method or may be a commercially available product. Furthermore, as the said commercial item, you may use what is marketed as a mixture with another compound. Specific examples of the commercially available product include magnesium hydroxide manufactured by Kyowa Chemical Industry.
本発明の経口剤におけるマグネシウム化合物の含有量は特に限定されず、苦味強度に応じて適宜決定することができるが、苦味抑制の観点から、経口剤の全質量に対してマグネシウム化合物を合計で0.001~60質量%含有することが好ましく、0.01~40質量%含有することがより好ましく、0.05~20質量%含有することが特に好ましい。
The content of the magnesium compound in the oral preparation of the present invention is not particularly limited and can be appropriately determined according to the bitterness intensity. From the viewpoint of bitterness suppression, the total amount of magnesium compound is 0 with respect to the total mass of the oral preparation. The content is preferably 0.001 to 60% by mass, more preferably 0.01 to 40% by mass, and particularly preferably 0.05 to 20% by mass.
本発明の経口剤におけるピタバスタチン又はその塩と、マグネシウム化合物の含有質量比率は特に限定されず、苦味強度に応じて適宜決定することができるが、苦味抑制の観点から、ピタバスタチンカルシウム換算したピタバスタチン又はその塩の合計1質量部に対して、マグネシウム化合物を合計で30質量部未満、更に0.001~25質量部、殊更0.005~20質量部、特に0.01~10質量部含有することが好ましい。
The content mass ratio of pitavastatin or a salt thereof and a magnesium compound in the oral preparation of the present invention is not particularly limited and can be appropriately determined according to the bitterness intensity. From the viewpoint of bitterness suppression, pitavastatin converted to pitavastatin calcium or its The total amount of magnesium compound is less than 30 parts by weight, further 0.001 to 25 parts by weight, especially 0.005 to 20 parts by weight, especially 0.01 to 10 parts by weight, based on 1 part by weight of the total salt. preferable.
本発明の経口剤は、更に矯味剤を含有することが好ましい。これにより、ピタバスタチン又はその塩由来の苦味をより一層抑制することができる。
The oral preparation of the present invention preferably further contains a corrigent. Thereby, the bitter taste derived from pitavastatin or its salt can be suppressed further.
矯味剤としては、例えば、リモネン、ピネン、カンフェン、サイメン、シネオール、シトロネロール、ゲラニオール、ネロール、リナロール、メントール、テルピネオール、ロジノール、ボルネオール、イソボルネオール、メントン、カンフル、オイゲノール、シンゼイラノールなどのテルペン;トウヒ油、オレンジ油、ハッカ油、樟脳白油、ユーカリ油、テレピン油、レモン油、ショウキョウ油、チョウジ油、ケイヒ油、ラベンダー油、ウイキョウ油、カミツレ油、シソ油、スペアミント油などのテルペンを含有する精油(以下、テルペン及びテルペンを含有する精油をまとめて「テルペン類」と称する。);アスコルビン酸、酒石酸、クエン酸、リンゴ酸及びこれらの塩などの酸味剤などが挙げられる。これらは1種又は2種以上を組み合わせて使用することができる。中でも、テルペン類が好ましく、メントールがより好ましく、l-メントールが特に好ましい。なお、本発明の経口剤における矯味剤の含有量は特に限定されないが、苦味抑制の観点から、経口剤の全質量に対して0.005~20質量%、更に0.01~15質量%、特に0.02~10質量%であることが好ましい。
Examples of the corrigent include terpenes such as limonene, pinene, camphene, cymen, cineole, citronellol, geraniol, nerol, linalool, menthol, terpineol, rosinol, borneol, isoborneol, menthone, camphor, eugenol, synzeanol, etc .; Contains terpenes such as oil, orange oil, peppermint oil, camphor white oil, eucalyptus oil, turpentine oil, lemon oil, pepper oil, clove oil, cinnamon oil, lavender oil, fennel oil, chamomile oil, perilla oil, spearmint oil Essential oils (hereinafter, terpenes and essential oils containing terpenes are collectively referred to as “terpenes”); acidulants such as ascorbic acid, tartaric acid, citric acid, malic acid and their salts. These can be used alone or in combination of two or more. Among them, terpenes are preferable, menthol is more preferable, and l-menthol is particularly preferable. Incidentally, the content of the corrigent in the oral preparation of the present invention is not particularly limited, but from the viewpoint of bitterness suppression, 0.005 to 20 mass%, further 0.01 to 15 mass%, based on the total mass of the oral preparation, In particular, the content is preferably 0.02 to 10% by mass.
本発明の経口剤は、更に甘味剤を含有することが好ましい。これにより、ピタバスタチン又はその塩由来の苦味をより一層抑制することができる。
The oral preparation of the present invention preferably further contains a sweetening agent. Thereby, the bitter taste derived from pitavastatin or its salt can be suppressed further.
甘味剤としては、例えば、アスパルテーム、ステビア、スクラロース、グリチルリチン酸、ソーマチン、アセスルファムカリウム、サッカリン、サッカリンナトリウムなどが挙げられ、これらは1種又は2種以上を組み合わせて使用することができる。中でも、スクラロースが好ましい。なお、本発明の経口剤における甘味剤の含有量は特に限定されないが、苦味抑制の観点から、経口剤の全質量に対して0.1~30質量%、更に0.2~25質量%、特に0.5~20質量%であることが好ましい。
Examples of the sweetening agent include aspartame, stevia, sucralose, glycyrrhizic acid, thaumatin, acesulfame potassium, saccharin, saccharin sodium and the like, and these can be used alone or in combination of two or more. Of these, sucralose is preferable. The content of the sweetener in the oral preparation of the present invention is not particularly limited, but from the viewpoint of bitterness suppression, 0.1 to 30% by mass, and further 0.2 to 25% by mass with respect to the total mass of the oral preparation, In particular, the content is preferably 0.5 to 20% by mass.
本発明においては、マグネシウム化合物のみならず、矯味剤を少なくとも含有することが好ましく、矯味剤及び甘味剤を含有することが特に好ましい。矯味剤及び甘味剤の好適な組み合わせとしては、テルペン類(とりわけl-メントール)と、スクラロースが挙げられる。
In the present invention, it is preferable to contain not only a magnesium compound but also a taste-masking agent, and it is particularly preferable to contain a taste-masking agent and a sweetening agent. A suitable combination of a corrigent and sweetener includes terpenes (particularly l-menthol) and sucralose.
本発明の経口剤は、剤形に応じて、当該技術分野において通常用いられている添加剤を含有していてもよい。当該添加剤としては、例えば、賦形剤、崩壊剤、結合剤、滑沢剤、着色剤、可塑剤、フィルム形成剤、難水溶性高分子物質、抗酸化剤、pH調整剤、界面活性剤、安定化剤、香料、流動化剤、液状媒体などが挙げられる。これらは1種又は2種以上を適宜組み合わせて使用することが可能である。なお、各添加剤の使用量は本発明の目的を妨げない範囲内で適宜決定することができる。なお、本発明の経口剤としては、フェノフィブラート、ユビデカレノン及びグルタチオンを含有しないものが好ましい。
The oral preparation of the present invention may contain additives usually used in the technical field depending on the dosage form. Examples of such additives include excipients, disintegrants, binders, lubricants, colorants, plasticizers, film forming agents, poorly water-soluble polymeric substances, antioxidants, pH adjusters, and surfactants. , Stabilizers, fragrances, fluidizing agents, liquid media and the like. These can be used alone or in combination of two or more. In addition, the usage-amount of each additive can be suitably determined within the range which does not interfere with the objective of this invention. In addition, as an oral preparation of this invention, the thing which does not contain fenofibrate, ubidecarenone, and glutathione is preferable.
賦形剤としては、例えば、酸化チタン、ケイ酸アルミニウム、二酸化ケイ素、無水硫酸ナトリウム、無水リン酸水素カルシウム、塩化ナトリウム、含水無晶形酸化ケイ素、ケイ酸カルシウム、軽質無水ケイ酸、重質無水ケイ酸、硫酸カルシウム、リン酸一水素カルシウム、リン酸水素カルシウム、リン酸水素ナトリウム、リン酸二水素カリウム、リン酸二水素カルシウム、リン酸二水素ナトリウム等の無機系賦形剤;アメ粉、デンプン(コムギデンプン、コメデンプン、トウモロコシデンプン等)、果糖、カラメル、カンテン、キシリトール、パラフィン、結晶セルロース、ショ糖、果糖、麦芽糖、乳糖、白糖、ブドウ糖、プルラン、ポリオキシエチレン硬化ヒマシ油、マルチトール、還元麦芽糖水アメ、粉末還元麦芽糖水アメ、エリスリトール、キシリトール、ソルビトール、マンニトール、ラクチトール、トレハロース、還元パラチノース、マルトース、アミノアルキルメタクリレートコポリマーE、ポリビニルアセタールジエチルアミノアセテート、クエン酸カルシウム等の有機系賦形剤等が挙げられる。
崩壊剤としては、例えば、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウム、クロスポビドン等のスーパー崩壊剤やカルメロース、カルメロースカルシウム、デンプン、ショ糖脂肪酸エステル、ゼラチン、炭酸水素ナトリウム、デキストリン、デヒドロ酢酸及びその塩、ポビドン、ポリオキシエチレン硬化ヒマシ油60等が挙げられる。 Examples of excipients include titanium oxide, aluminum silicate, silicon dioxide, anhydrous sodium sulfate, anhydrous calcium hydrogen phosphate, sodium chloride, hydrous amorphous silicon oxide, calcium silicate, light anhydrous silicic acid, and heavy anhydrous silica. Inorganic excipients such as acid, calcium sulfate, calcium monohydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, sodium dihydrogen phosphate; candy powder, starch (Wheat starch, rice starch, corn starch, etc.), fructose, caramel, agar, xylitol, paraffin, crystalline cellulose, sucrose, fructose, maltose, lactose, sucrose, glucose, pullulan, polyoxyethylene hydrogenated castor oil, maltitol, Reduced maltose water candy, powdered reduced maltose water candy, erythrito Le, xylitol, sorbitol, mannitol, lactitol, trehalose, reduced palatinose, maltose, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylamino acetate, organic excipients such as calcium citrate and the like.
Examples of the disintegrant include super disintegrants such as sodium carboxymethyl starch, croscarmellose sodium, crospovidone, carmellose, carmellose calcium, starch, sucrose fatty acid ester, gelatin, sodium bicarbonate, dextrin, dehydroacetic acid and the like. Salt, povidone, polyoxyethylene hydrogenated castor oil 60 and the like.
崩壊剤としては、例えば、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウム、クロスポビドン等のスーパー崩壊剤やカルメロース、カルメロースカルシウム、デンプン、ショ糖脂肪酸エステル、ゼラチン、炭酸水素ナトリウム、デキストリン、デヒドロ酢酸及びその塩、ポビドン、ポリオキシエチレン硬化ヒマシ油60等が挙げられる。 Examples of excipients include titanium oxide, aluminum silicate, silicon dioxide, anhydrous sodium sulfate, anhydrous calcium hydrogen phosphate, sodium chloride, hydrous amorphous silicon oxide, calcium silicate, light anhydrous silicic acid, and heavy anhydrous silica. Inorganic excipients such as acid, calcium sulfate, calcium monohydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, sodium dihydrogen phosphate; candy powder, starch (Wheat starch, rice starch, corn starch, etc.), fructose, caramel, agar, xylitol, paraffin, crystalline cellulose, sucrose, fructose, maltose, lactose, sucrose, glucose, pullulan, polyoxyethylene hydrogenated castor oil, maltitol, Reduced maltose water candy, powdered reduced maltose water candy, erythrito Le, xylitol, sorbitol, mannitol, lactitol, trehalose, reduced palatinose, maltose, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylamino acetate, organic excipients such as calcium citrate and the like.
Examples of the disintegrant include super disintegrants such as sodium carboxymethyl starch, croscarmellose sodium, crospovidone, carmellose, carmellose calcium, starch, sucrose fatty acid ester, gelatin, sodium bicarbonate, dextrin, dehydroacetic acid and the like. Salt, povidone, polyoxyethylene hydrogenated castor oil 60 and the like.
結合剤としては、例えば、メチルセルロース、ヒドロキシプロピルセルロース、ヒプロメロース、カルメロースナトリウム、コムギデンプン、コメデンプン、トウモロコシデンプン、デキストリン、部分アルファー化デンプン、プルラン、アラビアゴム、カンテン、ゼラチン、トラガント、アルギン酸ナトリウム、ポビドン、ポリビニルアルコール、アミノアルキルメタクリレートコポリマーE、ポリビニルアセタールジエチルアミノアセテート等が挙げられる。
滑沢剤としては、例えば、ステアリン酸カルシウム、ステアリン酸マグネシウム、フマル酸ステアリルナトリウム、ショ糖脂肪酸エステル等が挙げられる。 Examples of the binder include methyl cellulose, hydroxypropyl cellulose, hypromellose, carmellose sodium, wheat starch, rice starch, corn starch, dextrin, partially pregelatinized starch, pullulan, gum arabic, agar, gelatin, tragacanth, sodium alginate, povidone , Polyvinyl alcohol, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylaminoacetate and the like.
Examples of the lubricant include calcium stearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, and the like.
滑沢剤としては、例えば、ステアリン酸カルシウム、ステアリン酸マグネシウム、フマル酸ステアリルナトリウム、ショ糖脂肪酸エステル等が挙げられる。 Examples of the binder include methyl cellulose, hydroxypropyl cellulose, hypromellose, carmellose sodium, wheat starch, rice starch, corn starch, dextrin, partially pregelatinized starch, pullulan, gum arabic, agar, gelatin, tragacanth, sodium alginate, povidone , Polyvinyl alcohol, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylaminoacetate and the like.
Examples of the lubricant include calcium stearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, and the like.
着色剤としては、例えば、黄色三二酸化鉄、褐色酸化鉄、カラメル、黒酸化鉄、酸化チタン、三二酸化鉄、タール色素、アルミニウムレーキ色素、銅クロロフィリンナトリウム等が挙げられる。
可塑剤としては、例えば、グリセリン、ゴマ油、ソルビトール、ヒマシ油、プロピレングリコール、ポリオキシエチレンポリオキシプロピレングリコール、ポリソルベート80(ポリオキシエチレン(20)ソルビタンオレイン酸エステル)、ポリエチレングリコール[例えば、マクロゴール400(オキシエチレン単位の重合度nが7~9、以下、「n」は重合度を示す)、マクロゴール600(nが11~13)、マクロゴール1500(nが5~6と、nが28~36との等量混合物)、マクロゴール4000(nが59~84)、マクロゴール6000(nが165~210)]等が挙げられる。可塑剤としては、これらから選ばれる1種又は2種以上の組み合わせが好ましく、グリセリン、プロピレングリコール及びマクロゴール400からなる群より選ばれる1種以上がより好ましい。 Examples of the colorant include yellow iron sesquioxide, brown iron oxide, caramel, black iron oxide, titanium oxide, iron sesquioxide, tar dye, aluminum lake dye, copper chlorophyllin sodium, and the like.
Examples of the plasticizer include glycerin, sesame oil, sorbitol, castor oil, propylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate 80 (polyoxyethylene (20) sorbitan oleate), polyethylene glycol [for example, Macrogol 400 (The degree of polymerization n of the oxyethylene unit is 7 to 9, hereinafter “n” represents the degree of polymerization), macrogol 600 (n is 11 to 13), macrogol 1500 (n is 5 to 6, n is 28 ˜36), macrogol 4000 (n is 59 to 84), macrogol 6000 (n is 165 to 210)] and the like. The plasticizer is preferably one or a combination of two or more selected from these, and more preferably one or more selected from the group consisting of glycerin, propylene glycol and macrogol 400.
可塑剤としては、例えば、グリセリン、ゴマ油、ソルビトール、ヒマシ油、プロピレングリコール、ポリオキシエチレンポリオキシプロピレングリコール、ポリソルベート80(ポリオキシエチレン(20)ソルビタンオレイン酸エステル)、ポリエチレングリコール[例えば、マクロゴール400(オキシエチレン単位の重合度nが7~9、以下、「n」は重合度を示す)、マクロゴール600(nが11~13)、マクロゴール1500(nが5~6と、nが28~36との等量混合物)、マクロゴール4000(nが59~84)、マクロゴール6000(nが165~210)]等が挙げられる。可塑剤としては、これらから選ばれる1種又は2種以上の組み合わせが好ましく、グリセリン、プロピレングリコール及びマクロゴール400からなる群より選ばれる1種以上がより好ましい。 Examples of the colorant include yellow iron sesquioxide, brown iron oxide, caramel, black iron oxide, titanium oxide, iron sesquioxide, tar dye, aluminum lake dye, copper chlorophyllin sodium, and the like.
Examples of the plasticizer include glycerin, sesame oil, sorbitol, castor oil, propylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate 80 (polyoxyethylene (20) sorbitan oleate), polyethylene glycol [for example, Macrogol 400 (The degree of polymerization n of the oxyethylene unit is 7 to 9, hereinafter “n” represents the degree of polymerization), macrogol 600 (n is 11 to 13), macrogol 1500 (n is 5 to 6, n is 28 ˜36), macrogol 4000 (n is 59 to 84), macrogol 6000 (n is 165 to 210)] and the like. The plasticizer is preferably one or a combination of two or more selected from these, and more preferably one or more selected from the group consisting of glycerin, propylene glycol and macrogol 400.
フィルム形成剤としては、フィルム形成能を有する限り、その種類は特に限定されるものではない。具体的には、メチルセルロース、エチルセルロースなどのアルキルセルロース;アルギン酸ナトリウムなどのアルギン酸又はその塩;カラギーナン;カルボキシメチルセルロースナトリウム、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロースカリウム、カルボキシメチルセルロース、カルボキシメチルエチルセルロースなどのカルボキシアルキルセルロース;キサンタンガム;ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒプロメロース(ヒドロキシプロピルメチルセルロース)などのヒドロキシアルキルセルロース;ヒドロキシプロピルメチルセルロースフタレートなどのヒドロキシアルキルセルロースフタレート;プルラン;ポリ酢酸ビニル;ポリ酢酸ビニルフタレート;ポリビニルアルコール;ポリビニルピロリドン等が挙げられ、これらから選ばれる1種又は2種以上の組み合せが好ましい。
The type of film forming agent is not particularly limited as long as it has film forming ability. Specifically, alkyl cellulose such as methyl cellulose and ethyl cellulose; alginic acid such as sodium alginate or a salt thereof; carrageenan; carboxyalkyl cellulose such as sodium carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose potassium, carboxymethyl cellulose, carboxymethyl ethyl cellulose; xanthan gum; Hydroxyalkylcelluloses such as hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose); hydroxyalkylcellulose phthalates such as hydroxypropylmethylcellulose phthalate; pullulan; polyvinyl acetate; Over preparative; polyvinyl alcohol; polyvinyl pyrrolidone, and the like, one or more combinations are preferred selected from these.
難水溶性高分子物質としては、例えば、カルボキシビニルポリマー、アミノアルキルメタクリレートコポリマー等が挙げられる。
抗酸化剤としては、例えば、アスコルビン酸、亜硫酸水素ナトリウム、亜硫酸ナトリウム、エデト酸ナトリウム、エリソルビン酸、酢酸トコフェロール、ジブチルヒドロキシトルエン、天然ビタミンE、トコフェロール、ブチルヒドロキシアニソール等が挙げられる。 Examples of the poorly water-soluble polymer substance include carboxyvinyl polymer and aminoalkyl methacrylate copolymer.
Examples of the antioxidant include ascorbic acid, sodium bisulfite, sodium sulfite, sodium edetate, erythorbic acid, tocopherol acetate, dibutylhydroxytoluene, natural vitamin E, tocopherol, butylhydroxyanisole and the like.
抗酸化剤としては、例えば、アスコルビン酸、亜硫酸水素ナトリウム、亜硫酸ナトリウム、エデト酸ナトリウム、エリソルビン酸、酢酸トコフェロール、ジブチルヒドロキシトルエン、天然ビタミンE、トコフェロール、ブチルヒドロキシアニソール等が挙げられる。 Examples of the poorly water-soluble polymer substance include carboxyvinyl polymer and aminoalkyl methacrylate copolymer.
Examples of the antioxidant include ascorbic acid, sodium bisulfite, sodium sulfite, sodium edetate, erythorbic acid, tocopherol acetate, dibutylhydroxytoluene, natural vitamin E, tocopherol, butylhydroxyanisole and the like.
本発明において「経口剤」とは、経口投与される製剤を意味し、その具体的な形態(剤形)は特に限定されるものではない。例えば、固形状、半固形状及び液状のいずれの形態であってもよく、医薬品において通常利用される形態とすることができる。具体的には、錠剤(チュアブル錠、発泡錠、口腔内崩壊錠などを含む)、フィルム剤、トローチ剤、ドロップ剤、顆粒剤、細粒剤、散剤、丸剤、ドライシロップ剤などの固形製剤;舐剤、チューインガム剤、ゼリー剤、ゼリー状ドロップ剤、ホイップ剤などの半固形製剤;シロップ剤、ドリンク剤、懸濁剤、酒精剤、液剤などの液状製剤などの、日本薬局方、米国薬局方、欧州薬局方等に記載の剤形とすることができる。
In the present invention, “oral preparation” means a preparation to be administered orally, and its specific form (dosage form) is not particularly limited. For example, any form of solid, semi-solid and liquid may be used, and a form normally used in pharmaceuticals can be used. Specifically, solid preparations such as tablets (including chewable tablets, effervescent tablets, orally disintegrating tablets), films, troches, drops, granules, fine granules, powders, pills, and dry syrups; Semi-solid preparations such as lozenges, chewing gums, jelly preparations, jelly-like drops, whip preparations; liquid preparations such as syrups, drinks, suspensions, spirits, liquids, etc. Japanese Pharmacopoeia, US Pharmacopoeia Or a dosage form described in the European Pharmacopoeia.
本発明の経口剤の剤形としては、口腔内崩壊型の製剤が好ましく、口腔内崩壊型の固形製剤がより好ましく、口腔内崩壊型錠剤又は口腔内崩壊型フィルム剤が特に好ましい。口腔内崩壊型の製剤は、口腔内で短時間に崩壊させることによって服用するものであり、服用時に製剤を口腔内で完全に崩壊させることによりピタバスタチン又はその塩が直接舌に接触することとなるため苦味による服用感の悪さが特に大きな問題となるところ、後記試験例1に具体的に開示されているとおり、本発明によれば、経口剤の剤形が口腔内崩壊型の製剤である場合において、苦味の抑制作用が有効に発揮されることが明らかとなった。
なお、本発明において、口腔内崩壊型の製剤の、口腔内での崩壊時間(健常人の口腔内の唾液で製剤が完全に崩壊するまでの時間)は特に限定されず、製剤の剤形、大きさなどによって異なるが、例えば、好ましくは90秒以内、より好ましくは60秒以内、特に好ましくは30秒以内である。 The dosage form of the oral preparation of the present invention is preferably an orally disintegrating preparation, more preferably an orally disintegrating solid preparation, and particularly preferably an orally disintegrating tablet or an orally disintegrating film preparation. Orally disintegrating preparations are to be taken by disintegrating in the oral cavity in a short time, and pitavastatin or a salt thereof directly contacts the tongue by completely disintegrating the preparation in the oral cavity at the time of taking. Therefore, where the bad feeling due to bitterness is a particularly serious problem, as specifically disclosed in Test Example 1 below, according to the present invention, the oral dosage form is an orally disintegrating preparation. It was revealed that the effect of suppressing bitterness was effectively exhibited.
In the present invention, the disintegration time in the oral cavity of the orally disintegrating preparation (the time until the preparation is completely disintegrated with saliva in the oral cavity of a healthy person) is not particularly limited, and the dosage form of the preparation, Although it varies depending on the size, for example, it is preferably within 90 seconds, more preferably within 60 seconds, and particularly preferably within 30 seconds.
なお、本発明において、口腔内崩壊型の製剤の、口腔内での崩壊時間(健常人の口腔内の唾液で製剤が完全に崩壊するまでの時間)は特に限定されず、製剤の剤形、大きさなどによって異なるが、例えば、好ましくは90秒以内、より好ましくは60秒以内、特に好ましくは30秒以内である。 The dosage form of the oral preparation of the present invention is preferably an orally disintegrating preparation, more preferably an orally disintegrating solid preparation, and particularly preferably an orally disintegrating tablet or an orally disintegrating film preparation. Orally disintegrating preparations are to be taken by disintegrating in the oral cavity in a short time, and pitavastatin or a salt thereof directly contacts the tongue by completely disintegrating the preparation in the oral cavity at the time of taking. Therefore, where the bad feeling due to bitterness is a particularly serious problem, as specifically disclosed in Test Example 1 below, according to the present invention, the oral dosage form is an orally disintegrating preparation. It was revealed that the effect of suppressing bitterness was effectively exhibited.
In the present invention, the disintegration time in the oral cavity of the orally disintegrating preparation (the time until the preparation is completely disintegrated with saliva in the oral cavity of a healthy person) is not particularly limited, and the dosage form of the preparation, Although it varies depending on the size, for example, it is preferably within 90 seconds, more preferably within 60 seconds, and particularly preferably within 30 seconds.
本発明の経口剤は、上記剤形に応じて、日本薬局方、米国薬局方、欧州薬局方等に記載の公知の方法により、製造することができる。
例えば、本発明の好適な一剤形である口腔内崩壊型錠剤(以下、「OD錠」と称する。)の場合、ピタバスタチン又はその塩と、マグネシウム化合物と、所望により、矯味剤及び甘味剤から選ばれる1以上と添加剤等を用いて、直接圧縮成形する方法;ピタバスタチン又はその塩と、マグネシウム化合物とを混合し、板状圧縮成形又はスラッグ錠に圧縮成形した後、粉砕し、所望により、矯味剤及び甘味剤から選ばれる1以上と添加剤等を混合し、乾燥状態の混合物を圧縮成形する方法;ピタバスタチン又はその塩と、マグネシウム化合物と、所望により、矯味剤及び甘味剤から選ばれる1以上と添加剤等を混合後、適当な方法で造粒し、乾燥状態の混合物を圧縮成形する方法等が挙げられる。 The oral preparation of the present invention can be produced by a known method described in Japanese Pharmacopoeia, US Pharmacopoeia, European Pharmacopoeia or the like according to the above dosage form.
For example, in the case of an orally disintegrating tablet (hereinafter referred to as “OD tablet”) which is a preferred dosage form of the present invention, from pitavastatin or a salt thereof, a magnesium compound, and optionally a corrigent and a sweetener. A method of directly compression molding using one or more selected additives and the like; pitavastatin or a salt thereof and a magnesium compound are mixed, compressed into a plate-like compression molding or slug tablet, pulverized, and if desired, A method of mixing one or more selected from a corrigent and a sweetener and an additive, and compression-molding a mixture in a dry state; pitavastatin or a salt thereof, a magnesium compound, and optionally a corrigent and a sweetener 1 Examples thereof include a method in which the above and the additives are mixed and then granulated by an appropriate method, and a dry mixture is compression molded.
例えば、本発明の好適な一剤形である口腔内崩壊型錠剤(以下、「OD錠」と称する。)の場合、ピタバスタチン又はその塩と、マグネシウム化合物と、所望により、矯味剤及び甘味剤から選ばれる1以上と添加剤等を用いて、直接圧縮成形する方法;ピタバスタチン又はその塩と、マグネシウム化合物とを混合し、板状圧縮成形又はスラッグ錠に圧縮成形した後、粉砕し、所望により、矯味剤及び甘味剤から選ばれる1以上と添加剤等を混合し、乾燥状態の混合物を圧縮成形する方法;ピタバスタチン又はその塩と、マグネシウム化合物と、所望により、矯味剤及び甘味剤から選ばれる1以上と添加剤等を混合後、適当な方法で造粒し、乾燥状態の混合物を圧縮成形する方法等が挙げられる。 The oral preparation of the present invention can be produced by a known method described in Japanese Pharmacopoeia, US Pharmacopoeia, European Pharmacopoeia or the like according to the above dosage form.
For example, in the case of an orally disintegrating tablet (hereinafter referred to as “OD tablet”) which is a preferred dosage form of the present invention, from pitavastatin or a salt thereof, a magnesium compound, and optionally a corrigent and a sweetener. A method of directly compression molding using one or more selected additives and the like; pitavastatin or a salt thereof and a magnesium compound are mixed, compressed into a plate-like compression molding or slug tablet, pulverized, and if desired, A method of mixing one or more selected from a corrigent and a sweetener and an additive, and compression-molding a mixture in a dry state; pitavastatin or a salt thereof, a magnesium compound, and optionally a corrigent and a sweetener 1 Examples thereof include a method in which the above and the additives are mixed and then granulated by an appropriate method, and a dry mixture is compression molded.
また、ピタバスタチン又はその塩と、マグネシウム化合物を含有する懸濁液や溶液をブリスターポケット等の鋳型に充填し、凍結乾燥し、乾燥凝固してOD錠を製造する方法が挙げられる。前記懸濁液や溶液には、更にゼラチン、デキストラン、アルギン酸やアルギン酸の塩、糖アルコール(エリスリトール、キシリトール、ソルビトール、マンニトール等)、グリシン等を含有せしめることができる。
In addition, a method of producing an OD tablet by filling a suspension or solution containing pitavastatin or a salt thereof and a magnesium compound into a mold such as a blister pocket, freeze-drying, and drying and solidifying. The suspension or solution may further contain gelatin, dextran, alginic acid, a salt of alginic acid, sugar alcohol (erythritol, xylitol, sorbitol, mannitol, etc.), glycine and the like.
更に、ピタバスタチン又はその塩と、マグネシウム化合物と、糖類及び/又は糖アルコールを含有する混合物を水やアルコール水溶液等で湿潤して低圧で成形する方法、いわゆる湿式打錠することによりOD錠を製造する方法が挙げられる。
また更に、ピタバスタチン又はその塩と、マグネシウム化合物と、結晶セルロース等のセルロース系化合物と、アクリル酸系化合物やゼラチン等の易成形性の添加剤や微細化した添加剤等と、所望により、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウム、クロスポビドン等のスーパー崩壊剤を用いて、乾式打錠することによりOD錠を製造する方法が挙げられる。 Furthermore, an OD tablet is produced by a method in which a mixture containing pitavastatin or a salt thereof, a magnesium compound, and a saccharide and / or a sugar alcohol is wetted with water or an aqueous alcohol solution and molded at low pressure, so-called wet compression. A method is mentioned.
Furthermore, pitavastatin or a salt thereof, a magnesium compound, a cellulose compound such as crystalline cellulose, an easily moldable additive such as an acrylic acid compound or gelatin, a refined additive, and the like, and optionally carboxymethyl Examples thereof include a method of producing an OD tablet by dry compression using a super disintegrant such as sodium starch, croscarmellose sodium, crospovidone and the like.
また更に、ピタバスタチン又はその塩と、マグネシウム化合物と、結晶セルロース等のセルロース系化合物と、アクリル酸系化合物やゼラチン等の易成形性の添加剤や微細化した添加剤等と、所望により、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウム、クロスポビドン等のスーパー崩壊剤を用いて、乾式打錠することによりOD錠を製造する方法が挙げられる。 Furthermore, an OD tablet is produced by a method in which a mixture containing pitavastatin or a salt thereof, a magnesium compound, and a saccharide and / or a sugar alcohol is wetted with water or an aqueous alcohol solution and molded at low pressure, so-called wet compression. A method is mentioned.
Furthermore, pitavastatin or a salt thereof, a magnesium compound, a cellulose compound such as crystalline cellulose, an easily moldable additive such as an acrylic acid compound or gelatin, a refined additive, and the like, and optionally carboxymethyl Examples thereof include a method of producing an OD tablet by dry compression using a super disintegrant such as sodium starch, croscarmellose sodium, crospovidone and the like.
また、乳糖水和物、マンニトール、ブドウ糖水和物、白糖やキシリトール等の成形性の低い糖類及びマルトース、マルチトール、ソルビトールや、乳糖果糖等のオリゴ糖等の成形性の高い糖類を用いて造粒物を製し、次いで造粒物を打錠する方法が挙げられる。なお、当該方法においては、ピタバスタチン又はその塩と、マグネシウム化合物は前記造粒物中に含有せしめてもよいし、造粒物を製した後に混合してもよいが、前記造粒物中に含有せしめたものが好ましい。
It is also made using lactose hydrate, mannitol, glucose hydrate, low moldability saccharides such as sucrose and xylitol and high moldability saccharides such as maltose, maltitol, sorbitol and oligosaccharides such as lactose fructose. The method of making a granule and then tableting the granulated product is mentioned. In this method, pitavastatin or a salt thereof and a magnesium compound may be contained in the granulated product, or may be mixed after the granulated product is produced, but contained in the granulated product. The caulked one is preferred.
さらに、ピタバスタチン又はその塩や他の添加剤の融点や分解点よりも低い、キシリトール、トレハロース、マルトース、ソルビトール、エリスリトール、グルコース、マルチトール、マンニトール、白糖、乳糖水和物等の相対的低融点糖類を用いて、ピタバスタチン又はその塩や他の添加剤との溶融固化物を製造し、次いで溶融固化物を打錠してOD錠を製造する方法が挙げられる。当該方法においては、ピタバスタチン又はその塩は前記溶融固化物中に含有せしめてもよいし、溶融固化物を製した後に混合してもよいが、溶融固化物中に含有せしめたものが好ましい。
Furthermore, relative low melting point sugars such as xylitol, trehalose, maltose, sorbitol, erythritol, glucose, maltitol, mannitol, sucrose, lactose hydrate, etc., which are lower than the melting point and decomposition point of pitavastatin or its salts and other additives Is used to produce a melt-solidified product of pitavastatin or a salt thereof and other additives, and then tableting the melt-solidified product to produce an OD tablet. In this method, pitavastatin or a salt thereof may be contained in the melt-solidified product, or may be mixed after the melt-solidified product is produced, but is preferably contained in the melt-solidified product.
本発明のOD錠において用いられる賦形剤や崩壊剤等の添加剤の含有量は特に限定されないが、本発明のOD錠の全質量に対して、賦形剤は20~95質量%、更に30~90質量%、特に35~85質量%含有することが好ましい。また、崩壊剤は、本発明のOD錠の全質量に対して、0.5~25質量%、更に1~20質量%、特に2~15質量%含有することが好ましい。
The content of additives such as excipients and disintegrants used in the OD tablet of the present invention is not particularly limited, but the excipient is 20 to 95% by mass relative to the total mass of the OD tablet of the present invention. It is preferably contained in an amount of 30 to 90% by mass, particularly 35 to 85% by mass. Further, the disintegrant is preferably contained in an amount of 0.5 to 25% by mass, more preferably 1 to 20% by mass, particularly 2 to 15% by mass, based on the total mass of the OD tablet of the present invention.
本発明の好適な他の剤形である口腔内崩壊型フィルム剤(以下、単に「フィルム剤」と称する。)は、公知の方法により適宜製造できる。
具体的には、プラスチックフィルム、台紙等の保持基材の上に、ピタバスタチン又はその塩、マグネシウム化合物、所望により、矯味剤及び甘味剤から選ばれる1以上と添加剤を配合した懸濁液を塗布、噴霧等した後、これを乾燥させることにより製造することができる。なお、懸濁液における溶媒としては、水、アルコール(エタノール等)及びそれらの混液などが挙げられる。
また、本発明のフィルム剤は、複数の層を積層した多層型のフィルム(multi-layer film)剤であってもよく、複数の層のうち少なくとも一層にピタバスタチン又はその塩とマグネシウム化合物を含有していればよい。さらに、ピタバスタチン又はその塩とマグネシウム化合物はそれぞれ異なる層に含有していてもよいが、苦味抑制の観点から、ピタバスタチン又はその塩とマグネシウム化合物は同一の層に含有することが好ましい。なお、多層型のフィルム剤を製造する場合においては、例えば、保持基材の上に複数の層を別々に形成した後、各層を圧着することにより積層して製造してもよいし、懸濁液の塗布・噴霧、乾燥を順次繰り返すことにより積層して製造してもよい。 An orally disintegrating film agent (hereinafter simply referred to as “film agent”), which is another preferable dosage form of the present invention, can be appropriately produced by a known method.
Specifically, a suspension in which one or more selected from pitavastatin or a salt thereof, a magnesium compound, and, optionally, a corrigent and a sweetener and an additive are applied on a holding substrate such as a plastic film or a mount. After spraying, it can be produced by drying. In addition, as a solvent in suspension, water, alcohol (ethanol etc.), those mixed liquids, etc. are mentioned.
The film agent of the present invention may be a multi-layer film agent in which a plurality of layers are laminated, and contains pitavastatin or a salt thereof and a magnesium compound in at least one of the plurality of layers. It only has to be. Furthermore, although pitavastatin or a salt thereof and a magnesium compound may be contained in different layers, it is preferable that pitavastatin or a salt thereof and a magnesium compound are contained in the same layer from the viewpoint of bitterness suppression. In the case of producing a multilayer type film agent, for example, after forming a plurality of layers separately on a holding substrate, each layer may be laminated by crimping or suspended. Lamination may be performed by sequentially repeating application, spraying, and drying of the liquid.
具体的には、プラスチックフィルム、台紙等の保持基材の上に、ピタバスタチン又はその塩、マグネシウム化合物、所望により、矯味剤及び甘味剤から選ばれる1以上と添加剤を配合した懸濁液を塗布、噴霧等した後、これを乾燥させることにより製造することができる。なお、懸濁液における溶媒としては、水、アルコール(エタノール等)及びそれらの混液などが挙げられる。
また、本発明のフィルム剤は、複数の層を積層した多層型のフィルム(multi-layer film)剤であってもよく、複数の層のうち少なくとも一層にピタバスタチン又はその塩とマグネシウム化合物を含有していればよい。さらに、ピタバスタチン又はその塩とマグネシウム化合物はそれぞれ異なる層に含有していてもよいが、苦味抑制の観点から、ピタバスタチン又はその塩とマグネシウム化合物は同一の層に含有することが好ましい。なお、多層型のフィルム剤を製造する場合においては、例えば、保持基材の上に複数の層を別々に形成した後、各層を圧着することにより積層して製造してもよいし、懸濁液の塗布・噴霧、乾燥を順次繰り返すことにより積層して製造してもよい。 An orally disintegrating film agent (hereinafter simply referred to as “film agent”), which is another preferable dosage form of the present invention, can be appropriately produced by a known method.
Specifically, a suspension in which one or more selected from pitavastatin or a salt thereof, a magnesium compound, and, optionally, a corrigent and a sweetener and an additive are applied on a holding substrate such as a plastic film or a mount. After spraying, it can be produced by drying. In addition, as a solvent in suspension, water, alcohol (ethanol etc.), those mixed liquids, etc. are mentioned.
The film agent of the present invention may be a multi-layer film agent in which a plurality of layers are laminated, and contains pitavastatin or a salt thereof and a magnesium compound in at least one of the plurality of layers. It only has to be. Furthermore, although pitavastatin or a salt thereof and a magnesium compound may be contained in different layers, it is preferable that pitavastatin or a salt thereof and a magnesium compound are contained in the same layer from the viewpoint of bitterness suppression. In the case of producing a multilayer type film agent, for example, after forming a plurality of layers separately on a holding substrate, each layer may be laminated by crimping or suspended. Lamination may be performed by sequentially repeating application, spraying, and drying of the liquid.
本発明のフィルム剤において用いられるフィルム形成剤や可塑剤等の添加剤の含有量は特に限定されないが、本発明のフィルム剤の全質量に対して、フィルム形成剤は25~95質量%、更に30~80質量%、特に35~65質量%含有することが好ましい。また、可塑剤は、本発明のフィルム剤の全質量に対して、1~25質量%、更に3~20質量%、特に5~15質量%含有することが好ましい。
The content of additives such as a film forming agent and a plasticizer used in the film agent of the present invention is not particularly limited, but the film forming agent is 25 to 95% by mass relative to the total mass of the film agent of the present invention, It is preferably contained in an amount of 30 to 80% by mass, particularly 35 to 65% by mass. The plasticizer is preferably contained in an amount of 1 to 25% by mass, more preferably 3 to 20% by mass, especially 5 to 15% by mass, based on the total mass of the film agent of the present invention.
本発明のフィルム剤としては、ピタバスタチン又はその塩と、マグネシウム化合物と、所望により矯味剤及び甘味料から選ばれる少なくとも1種を含有する薬物含有層の両面に、矯味剤を含有しない薬物非含有層を有するフィルム剤であることが好ましい。後記試験例2に具体的に開示されているとおり、このような構成を有するフィルム剤とすることにより、顕著な苦味の抑制効果が認められることが見出された。
As the film agent of the present invention, a drug-free layer containing no flavourant on both sides of a drug-containing layer containing pitavastatin or a salt thereof, a magnesium compound, and optionally at least one selected from a corrigent and a sweetener It is preferable that it is a film agent which has. As specifically disclosed in Test Example 2 below, it was found that a remarkable bitterness-inhibiting effect was observed by using a film agent having such a configuration.
本発明の経口剤は、ピタバスタチン又はその塩を含有することから、例えば、高脂血症治療剤、高コレステロール血症治療剤、家族性高コレステロール血症治療剤などとして利用できる。
Since the oral preparation of the present invention contains pitavastatin or a salt thereof, it can be used as, for example, a therapeutic agent for hyperlipidemia, a therapeutic agent for hypercholesterolemia, a therapeutic agent for familial hypercholesterolemia, and the like.
以下に、実施例等により本発明をさらに具体的に説明するが、本発明は下記の実施例等に何ら限定されるものではない。
Hereinafter, the present invention will be described more specifically with reference to examples and the like, but the present invention is not limited to the following examples.
〔実施例1〕
水12gと無水エタノール28gを混合し、これにスクラロース2g、l-メントール0.15g及びピタバスタチンカルシウム1gを溶解し、更に酸化マグネシウム1gを分散した。この液にヒプロメロース15.85gを溶解し、フィルム調製液を得た。
PET(ポリエチレンテレフタラート)フィルム上にフィルム調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が10mgの層を形成し、中間製品1を得た。
中間製品1を2式準備し、層同士が対向するように貼り合わせ圧着し、片側のPETフィルムを剥離し、中間製品2とした。中間製品2を2式準備し、層同士が対向するように貼り合わせ圧着し、中間製品3を得た。
中間製品3を面積2.8cm2に裁断し、PETフィルムを剥離して、実施例1のフィルム剤を得た。 [Example 1]
12 g of water and 28 g of absolute ethanol were mixed, to which 2 g of sucralose, 0.15 g of 1-menthol and 1 g of pitavastatin calcium were dissolved, and 1 g of magnesium oxide was further dispersed. In this solution, 15.85 g of hypromellose was dissolved to obtain a film preparation solution.
A film preparation solution was uniformly applied onto a PET (polyethylene terephthalate) film and then dried with warm air to form a layer having a mass of 10 mg per area of 2.8 cm 2 to obtain an intermediate product 1.
Two intermediate products 1 were prepared, bonded and pressure-bonded so that the layers were opposed to each other, and the PET film on one side was peeled off to obtain intermediate product 2. Two sets of intermediate products 2 were prepared, and bonded and pressure-bonded so that the layers were opposed to each other, whereby an intermediate product 3 was obtained.
The intermediate product 3 was cut into an area of 2.8 cm 2 and the PET film was peeled off to obtain the film agent of Example 1.
水12gと無水エタノール28gを混合し、これにスクラロース2g、l-メントール0.15g及びピタバスタチンカルシウム1gを溶解し、更に酸化マグネシウム1gを分散した。この液にヒプロメロース15.85gを溶解し、フィルム調製液を得た。
PET(ポリエチレンテレフタラート)フィルム上にフィルム調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が10mgの層を形成し、中間製品1を得た。
中間製品1を2式準備し、層同士が対向するように貼り合わせ圧着し、片側のPETフィルムを剥離し、中間製品2とした。中間製品2を2式準備し、層同士が対向するように貼り合わせ圧着し、中間製品3を得た。
中間製品3を面積2.8cm2に裁断し、PETフィルムを剥離して、実施例1のフィルム剤を得た。 [Example 1]
12 g of water and 28 g of absolute ethanol were mixed, to which 2 g of sucralose, 0.15 g of 1-menthol and 1 g of pitavastatin calcium were dissolved, and 1 g of magnesium oxide was further dispersed. In this solution, 15.85 g of hypromellose was dissolved to obtain a film preparation solution.
A film preparation solution was uniformly applied onto a PET (polyethylene terephthalate) film and then dried with warm air to form a layer having a mass of 10 mg per area of 2.8 cm 2 to obtain an intermediate product 1.
Two intermediate products 1 were prepared, bonded and pressure-bonded so that the layers were opposed to each other, and the PET film on one side was peeled off to obtain intermediate product 2. Two sets of intermediate products 2 were prepared, and bonded and pressure-bonded so that the layers were opposed to each other, whereby an intermediate product 3 was obtained.
The intermediate product 3 was cut into an area of 2.8 cm 2 and the PET film was peeled off to obtain the film agent of Example 1.
〔比較例1〕
酸化マグネシウムの代わりにヒプロメロースを配合したほかは実施例1と同様の方法により、比較例1のフィルム剤を得た。 [Comparative Example 1]
A film preparation of Comparative Example 1 was obtained in the same manner as in Example 1 except that hypromellose was added instead of magnesium oxide.
酸化マグネシウムの代わりにヒプロメロースを配合したほかは実施例1と同様の方法により、比較例1のフィルム剤を得た。 [Comparative Example 1]
A film preparation of Comparative Example 1 was obtained in the same manner as in Example 1 except that hypromellose was added instead of magnesium oxide.
[試験例1]苦味抑制試験
実施例1及び比較例1のフィルム剤について、6名のパネラーにより官能試験を実施し、服用感(苦味)を評価した。
苦味の評価は、フィルム剤をパネラーの口腔内において唾液により完全に崩壊させた際の服用感につき、全く苦味を感じない場合を10点、耐え難い苦味を感じる場合を0点とするビジュアルアナログスケール法により実施した。
官能試験結果(各フィルム剤における6名のパネラーによる評価の平均点数)を、各フィルム剤の組成(フィルム剤1枚当りの成分量(mg))とともに表1に示す。 [Test Example 1] Bitterness inhibition test The film preparations of Example 1 and Comparative Example 1 were subjected to a sensory test by six panelists to evaluate the feeling of taking (bitterness).
The bitterness evaluation is a visual analog scale method in which the film preparation is completely disintegrated with saliva in the oral cavity of the paneler with 10 points when no bitterness is felt and 0 when it is unbearable bitterness. It carried out by.
The sensory test results (average score of evaluation by 6 panelists in each film agent) are shown in Table 1 together with the composition of each film agent (component amount (mg) per film agent).
実施例1及び比較例1のフィルム剤について、6名のパネラーにより官能試験を実施し、服用感(苦味)を評価した。
苦味の評価は、フィルム剤をパネラーの口腔内において唾液により完全に崩壊させた際の服用感につき、全く苦味を感じない場合を10点、耐え難い苦味を感じる場合を0点とするビジュアルアナログスケール法により実施した。
官能試験結果(各フィルム剤における6名のパネラーによる評価の平均点数)を、各フィルム剤の組成(フィルム剤1枚当りの成分量(mg))とともに表1に示す。 [Test Example 1] Bitterness inhibition test The film preparations of Example 1 and Comparative Example 1 were subjected to a sensory test by six panelists to evaluate the feeling of taking (bitterness).
The bitterness evaluation is a visual analog scale method in which the film preparation is completely disintegrated with saliva in the oral cavity of the paneler with 10 points when no bitterness is felt and 0 when it is unbearable bitterness. It carried out by.
The sensory test results (average score of evaluation by 6 panelists in each film agent) are shown in Table 1 together with the composition of each film agent (component amount (mg) per film agent).
表1に示す試験結果より、苦味を有するピタバスタチンカルシウムに加えて更に酸化マグネシウムを含有する実施例1のフィルム剤においては、酸化マグネシウムを含有しない比較例1のフィルム剤と比較して、口腔内で崩壊させた際の苦味が顕著に抑制されていることが明らかとなった。
From the test results shown in Table 1, in the film agent of Example 1 further containing magnesium oxide in addition to pitavastatin calcium having a bitter taste, compared with the film agent of Comparative Example 1 not containing magnesium oxide, in the oral cavity It was revealed that the bitterness when disintegrated was remarkably suppressed.
以上の試験結果より、マグネシウム化合物が、ピタバスタチン又はその塩の苦味を抑制する作用を有することが明らかとなった。
From the above test results, it was revealed that the magnesium compound has an action of suppressing the bitter taste of pitavastatin or a salt thereof.
〔実施例2〕
水480gと無水エタノール480gを混合し、これにマクロゴール30g、アミノアルキルメタクリレートコポリマーE120g及びトレハロース30gを溶解し、更に酸化チタン30g及び三二酸化鉄3gを分散した。この液にヒプロメロース240gを溶解し、薬物非含有層調製液を得た。
水600gと無水エタノール600gを混合し、これにマクロゴール30g、塩化カルシウム 二水和物60g、スクラロース30g及びl-メントール15gを溶解し、更にピタバスタチンカルシウム60g及び酸化マグネシウム30gを分散した。この液にヒドロキシプロピルセルロース300gを溶解し、薬物含有層調製液を得た。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成した。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.75mgの薬物含有層を形成し、中間製品1を得た。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得た。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、実施例3のフィルム剤を得た。 [Example 2]
480 g of water and 480 g of absolute ethanol were mixed, 30 g of macrogol, aminoalkyl methacrylate copolymer E120 g and 30 g of trehalose were dissolved therein, and 30 g of titanium oxide and 3 g of iron sesquioxide were dispersed. In this solution, 240 g of hypromellose was dissolved to obtain a drug-free layer preparation solution.
600 g of water and 600 g of absolute ethanol were mixed, to which 30 g of macrogol, 60 g of calcium chloride dihydrate, 30 g of sucralose and 15 g of 1-menthol were dissolved, and 60 g of pitavastatin calcium and 30 g of magnesium oxide were dispersed. In this solution, 300 g of hydroxypropylcellulose was dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution was uniformly applied onto a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. Obtained.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Product 2 was obtained.
The intermediate product 2 was cut into an area of 2.8 cm 2 and the PET film was peeled off to obtain the film agent of Example 3.
水480gと無水エタノール480gを混合し、これにマクロゴール30g、アミノアルキルメタクリレートコポリマーE120g及びトレハロース30gを溶解し、更に酸化チタン30g及び三二酸化鉄3gを分散した。この液にヒプロメロース240gを溶解し、薬物非含有層調製液を得た。
水600gと無水エタノール600gを混合し、これにマクロゴール30g、塩化カルシウム 二水和物60g、スクラロース30g及びl-メントール15gを溶解し、更にピタバスタチンカルシウム60g及び酸化マグネシウム30gを分散した。この液にヒドロキシプロピルセルロース300gを溶解し、薬物含有層調製液を得た。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成した。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.75mgの薬物含有層を形成し、中間製品1を得た。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得た。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、実施例3のフィルム剤を得た。 [Example 2]
480 g of water and 480 g of absolute ethanol were mixed, 30 g of macrogol, aminoalkyl methacrylate copolymer E120 g and 30 g of trehalose were dissolved therein, and 30 g of titanium oxide and 3 g of iron sesquioxide were dispersed. In this solution, 240 g of hypromellose was dissolved to obtain a drug-free layer preparation solution.
600 g of water and 600 g of absolute ethanol were mixed, to which 30 g of macrogol, 60 g of calcium chloride dihydrate, 30 g of sucralose and 15 g of 1-menthol were dissolved, and 60 g of pitavastatin calcium and 30 g of magnesium oxide were dispersed. In this solution, 300 g of hydroxypropylcellulose was dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution was uniformly applied onto a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. Obtained.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Product 2 was obtained.
The intermediate product 2 was cut into an area of 2.8 cm 2 and the PET film was peeled off to obtain the film agent of Example 3.
[試験例2]苦味抑制試験
実施例2のフィルム剤について、5名のパネラーにより官能試験を実施し、服用感(苦味)を評価した。
苦味の評価は、フィルム剤をパネラーの口腔内において唾液により完全に崩壊させた際の服用感につき、以下の評価基準に従いスコア化することにより実施した。
「苦味がほとんど気にならない」:2点
「苦味がやや気になる」:1点
「苦味が気になり、不味である」:0点
官能試験結果(フィルム剤における5名のパネラーによる評価の合計点数)を、各フィルム剤の組成(フィルム剤1枚当りの成分量(mg))とともに表2に示す。 [Test Example 2] Bitterness suppression test For the film preparation of Example 2, a sensory test was carried out by five panelists to evaluate the feeling of taking (bitterness).
The bitterness was evaluated by scoring according to the following evaluation criteria for the feeling of ingestion when the film was completely disintegrated with saliva in the mouth of the panel.
“Little bitterness is not worrisome”: 2 points “Bitterness is slightly worrisome”: 1 point “Bitterness is worrisome and unpleasant”: 0 points Sensory test results (evaluation by 5 panelists in film preparation) Table 2 shows the composition of each film agent (component amount per film agent (mg)).
実施例2のフィルム剤について、5名のパネラーにより官能試験を実施し、服用感(苦味)を評価した。
苦味の評価は、フィルム剤をパネラーの口腔内において唾液により完全に崩壊させた際の服用感につき、以下の評価基準に従いスコア化することにより実施した。
「苦味がほとんど気にならない」:2点
「苦味がやや気になる」:1点
「苦味が気になり、不味である」:0点
官能試験結果(フィルム剤における5名のパネラーによる評価の合計点数)を、各フィルム剤の組成(フィルム剤1枚当りの成分量(mg))とともに表2に示す。 [Test Example 2] Bitterness suppression test For the film preparation of Example 2, a sensory test was carried out by five panelists to evaluate the feeling of taking (bitterness).
The bitterness was evaluated by scoring according to the following evaluation criteria for the feeling of ingestion when the film was completely disintegrated with saliva in the mouth of the panel.
“Little bitterness is not worrisome”: 2 points “Bitterness is slightly worrisome”: 1 point “Bitterness is worrisome and unpleasant”: 0 points Sensory test results (evaluation by 5 panelists in film preparation) Table 2 shows the composition of each film agent (component amount per film agent (mg)).
表2に示す試験結果より、苦味を有するピタバスタチンカルシウムを酸化マグネシウム、メントールとともに含有させた薬物含有層を、メントールを含有しない薬物非含有層で挟み込んだ形態の本発明のフィルム剤(実施例2)は、ピタバスタチンカルシウムの苦味が抑制された、服用し易いフィルム剤であることが確認された。
From the test results shown in Table 2, the film agent of the present invention in a form in which a drug-containing layer containing pitavastatin calcium having a bitter taste together with magnesium oxide and menthol is sandwiched between drug-free layers not containing menthol (Example 2) Was confirmed to be an easy-to-use film agent in which the bitter taste of pitavastatin calcium was suppressed.
以上の試験結果から、苦味を有するピタバスタチン又はその塩と、マグネシウム化合物と、テルペン類を含有する薬物含有層の両面に、テルペン類を含有しない薬物非含有層を有するフィルム剤は、ピタバスタチン又はその塩由来の苦味が抑制されているため、服用時における不快感が緩和されることが明らかとなった。
From the above test results, a film agent having a drug-free layer containing no terpene on both sides of a drug-containing layer containing pitavastatin or a salt thereof having a bitter taste, a magnesium compound, and a terpene is pitavastatin or a salt thereof. Since the bitterness of the origin is suppressed, it became clear that the discomfort at the time of taking was relieved.
[製造例1]
D-マンニトール525.6質量部と結晶セルロース201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース74質量部、アミノアルキルメタクリレートコポリマーE 108質量部、アスパルテーム70質量部、塩化カルシウム 二水和物72質量部及び酸化マグネシウム144質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧してコーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスカルメロースナトリウム129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 1]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crystalline cellulose, 72 parts by mass of pitavastatin calcium, 74 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 70 parts by mass of aspartame, calcium chloride dihydrate A 70% ethanol solution or dispersion containing 72 parts by mass of the product and 144 parts by mass of magnesium oxide is sprayed and granulated to obtain a granulated product.
A granulated product is sprayed with a coating solution of a 70% ethanol solution or dispersion containing 72 parts by mass of hypromellose, 36 parts by mass of yellow iron sesquioxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of coated granules, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of croscarmellose sodium, 25 parts by weight of anhydrous calcium hydrogen phosphate, and 2 parts by weight of yogurt micron were mixed, Furthermore, by mixing 8 parts by mass of calcium stearate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
D-マンニトール525.6質量部と結晶セルロース201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース74質量部、アミノアルキルメタクリレートコポリマーE 108質量部、アスパルテーム70質量部、塩化カルシウム 二水和物72質量部及び酸化マグネシウム144質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧してコーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスカルメロースナトリウム129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 1]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crystalline cellulose, 72 parts by mass of pitavastatin calcium, 74 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 70 parts by mass of aspartame, calcium chloride dihydrate A 70% ethanol solution or dispersion containing 72 parts by mass of the product and 144 parts by mass of magnesium oxide is sprayed and granulated to obtain a granulated product.
A granulated product is sprayed with a coating solution of a 70% ethanol solution or dispersion containing 72 parts by mass of hypromellose, 36 parts by mass of yellow iron sesquioxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of coated granules, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of croscarmellose sodium, 25 parts by weight of anhydrous calcium hydrogen phosphate, and 2 parts by weight of yogurt micron were mixed, Furthermore, by mixing 8 parts by mass of calcium stearate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
[製造例2]
D-マンニトール525.6質量部、結晶セルロース201.6質量部及びピタバスタチンカルシウム72質量部の混合物に、ヒプロメロース59.6質量部、アミノアルキルメタクリレートコポリマーE 108質量部、アスパルテーム70質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及び酸化マグネシウム144質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 2]
In a mixture of 525.6 parts by weight of D-mannitol, 201.6 parts by weight of crystalline cellulose and 72 parts by weight of pitavastatin calcium, 59.6 parts by weight of hypromellose, 108 parts by weight of aminoalkyl methacrylate copolymer E, 70 parts by weight of aspartame, l-menthol A granulated product is obtained by spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by weight, 72 parts by weight of calcium chloride dihydrate and 144 parts by weight of magnesium oxide.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
D-マンニトール525.6質量部、結晶セルロース201.6質量部及びピタバスタチンカルシウム72質量部の混合物に、ヒプロメロース59.6質量部、アミノアルキルメタクリレートコポリマーE 108質量部、アスパルテーム70質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及び酸化マグネシウム144質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 2]
In a mixture of 525.6 parts by weight of D-mannitol, 201.6 parts by weight of crystalline cellulose and 72 parts by weight of pitavastatin calcium, 59.6 parts by weight of hypromellose, 108 parts by weight of aminoalkyl methacrylate copolymer E, 70 parts by weight of aspartame, l-menthol A granulated product is obtained by spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by weight, 72 parts by weight of calcium chloride dihydrate and 144 parts by weight of magnesium oxide.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
[製造例3]
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部、メタケイ酸アルミン酸マグネシウム43.2質量部及び酸化マグネシウム72質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 3]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol Spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by weight, calcium chloride dihydrate 72 parts by weight, magnesium metasilicate aluminate 43.2 parts by weight and magnesium oxide 72 parts by weight, Get a granulate.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部、メタケイ酸アルミン酸マグネシウム43.2質量部及び酸化マグネシウム72質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 3]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol Spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by weight, calcium chloride dihydrate 72 parts by weight, magnesium metasilicate aluminate 43.2 parts by weight and magnesium oxide 72 parts by weight, Get a granulate.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
[製造例4]
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及び酸化マグネシウム115.2質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒228質量部、D-マンニトール370質量部、キシリトール28質量部、結晶セルロース440質量部、クロスポビドン105質量部、無水リン酸水素カルシウム22質量部及びヨーグルトミクロン1質量部を混合し、さらにステアリン酸カルシウム6質量部を混合し、ロータリー式打錠機にて打錠することにより、直径7mm、質量120mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 4]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol A 70% ethanol solution or dispersion containing 14.4 parts by mass, calcium chloride dihydrate 72 parts by mass and magnesium oxide 115.2 parts by mass is sprayed and granulated to obtain a granulated product.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
228 parts by weight of the coated granule, 370 parts by weight of D-mannitol, 28 parts by weight of xylitol, 440 parts by weight of crystalline cellulose, 105 parts by weight of crospovidone, 22 parts by weight of anhydrous calcium hydrogen phosphate and 1 part by weight of yogurt micron were further mixed. By mixing 6 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 7 mm and a mass of 120 mg can be obtained.
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及び酸化マグネシウム115.2質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒228質量部、D-マンニトール370質量部、キシリトール28質量部、結晶セルロース440質量部、クロスポビドン105質量部、無水リン酸水素カルシウム22質量部及びヨーグルトミクロン1質量部を混合し、さらにステアリン酸カルシウム6質量部を混合し、ロータリー式打錠機にて打錠することにより、直径7mm、質量120mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 4]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol A 70% ethanol solution or dispersion containing 14.4 parts by mass, calcium chloride dihydrate 72 parts by mass and magnesium oxide 115.2 parts by mass is sprayed and granulated to obtain a granulated product.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
228 parts by weight of the coated granule, 370 parts by weight of D-mannitol, 28 parts by weight of xylitol, 440 parts by weight of crystalline cellulose, 105 parts by weight of crospovidone, 22 parts by weight of anhydrous calcium hydrogen phosphate and 1 part by weight of yogurt micron were further mixed. By mixing 6 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 7 mm and a mass of 120 mg can be obtained.
[製造例5]
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及びメタケイ酸アルミン酸マグネシウム43.2質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部、酸化チタン266.4質量部及び酸化マグネシウム72質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 5]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol A granulated product is obtained by spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by mass, 72 parts by mass of calcium chloride dihydrate and 43.2 parts by mass of magnesium aluminate metasilicate.
A granulated product is sprayed with a coating solution of 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow iron sesquioxide, 266.4 parts by mass of titanium oxide and 72 parts by mass of magnesium oxide, Get.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及びメタケイ酸アルミン酸マグネシウム43.2質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部、酸化チタン266.4質量部及び酸化マグネシウム72質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 5]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol A granulated product is obtained by spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by mass, 72 parts by mass of calcium chloride dihydrate and 43.2 parts by mass of magnesium aluminate metasilicate.
A granulated product is sprayed with a coating solution of 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow iron sesquioxide, 266.4 parts by mass of titanium oxide and 72 parts by mass of magnesium oxide, Get.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
[製造例6]
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及びメタケイ酸アルミン酸マグネシウム115.2質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 6]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol A granulated product is obtained by spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by mass, 72 parts by mass of calcium chloride dihydrate and 115.2 parts by mass of magnesium aluminate metasilicate.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及びメタケイ酸アルミン酸マグネシウム115.2質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 6]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol A granulated product is obtained by spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by mass, 72 parts by mass of calcium chloride dihydrate and 115.2 parts by mass of magnesium aluminate metasilicate.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
[製造例7]
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部、メタケイ酸アルミン酸マグネシウム43.2質量部及び水酸化マグネシウム72質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 7]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol Spray and granulate a 70% ethanol solution or dispersion containing 14.4 parts by weight, calcium chloride dihydrate 72 parts by weight, magnesium metasilicate aluminate 43.2 parts by weight and magnesium hydroxide 72 parts by weight. Get a granulated product.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部、メタケイ酸アルミン酸マグネシウム43.2質量部及び水酸化マグネシウム72質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 7]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol Spray and granulate a 70% ethanol solution or dispersion containing 14.4 parts by weight, calcium chloride dihydrate 72 parts by weight, magnesium metasilicate aluminate 43.2 parts by weight and magnesium hydroxide 72 parts by weight. Get a granulated product.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
[製造例8]
D-マンニトール525.6質量部、クロスポビドン201.6質量部とピタバスタチンカルシウム72質量部の混合物に、ヒプロメロース59.6質量部、アミノアルキルメタクリレートコポリマーE 108質量部、アスパルテーム70質量部、l-メントール14.4質量部及び酸化マグネシウム216質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 8]
In a mixture of 525.6 parts by mass of D-mannitol, 201.6 parts by mass of crospovidone and 72 parts by mass of calcium pitavastatin, 59.6 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 70 parts by mass of aspartame, l-menthol A 70% ethanol solution or dispersion containing 14.4 parts by mass and 216 parts by mass of magnesium oxide is sprayed and granulated to obtain a granulated product.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
D-マンニトール525.6質量部、クロスポビドン201.6質量部とピタバスタチンカルシウム72質量部の混合物に、ヒプロメロース59.6質量部、アミノアルキルメタクリレートコポリマーE 108質量部、アスパルテーム70質量部、l-メントール14.4質量部及び酸化マグネシウム216質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒456質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 8]
In a mixture of 525.6 parts by mass of D-mannitol, 201.6 parts by mass of crospovidone and 72 parts by mass of calcium pitavastatin, 59.6 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 70 parts by mass of aspartame, l-menthol A 70% ethanol solution or dispersion containing 14.4 parts by mass and 216 parts by mass of magnesium oxide is sprayed and granulated to obtain a granulated product.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
456 parts by weight of the coated granule, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate and 2 parts by weight of yogurt micron are further mixed. By mixing 8 parts by mass of calcium phosphate and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
[製造例9]
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及びメタケイ酸アルミン酸マグネシウム43.2質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒436質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部、酸化マグネシウム20質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 9]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol A granulated product is obtained by spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by mass, 72 parts by mass of calcium chloride dihydrate and 43.2 parts by mass of magnesium aluminate metasilicate.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
436 parts by weight of coated granules, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate, 20 parts by weight of magnesium oxide and 2 parts by weight of yogurt micron And 8 parts by mass of calcium stearate, and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
D-マンニトール525.6質量部とクロスポビドン201.6質量部の混合物に、ピタバスタチンカルシウム72質量部、ヒプロメロース86.4質量部、アミノアルキルメタクリレートコポリマーE 108質量部、スクラロース72質量部、l-メントール14.4質量部、塩化カルシウム 二水和物72質量部及びメタケイ酸アルミン酸マグネシウム43.2質量部を含む70%エタノール溶液又は分散液を噴霧し、造粒して、造粒物を得る。
造粒物に、ヒプロメロース72質量部、黄色三二酸化鉄36質量部及び酸化チタン266.4質量部を含む70%エタノール溶液又は分散液のコーティング液を噴霧して、コーティング顆粒を得る。
コーティング顆粒436質量部、D-マンニトール400質量部、キシリトール30質量部、結晶セルロース550質量部、クロスポビドン129質量部、無水リン酸水素カルシウム25質量部、酸化マグネシウム20質量部及びヨーグルトミクロン2質量部を混合し、さらにステアリン酸カルシウム8質量部を混合し、ロータリー式打錠機にて打錠することにより、直径8mm、質量160mgの口腔内崩壊型の錠剤を得ることができる。 [Production Example 9]
In a mixture of 525.6 parts by mass of D-mannitol and 201.6 parts by mass of crospovidone, 72 parts by mass of pitavastatin calcium, 86.4 parts by mass of hypromellose, 108 parts by mass of aminoalkyl methacrylate copolymer E, 72 parts by mass of sucralose, l-menthol A granulated product is obtained by spraying and granulating a 70% ethanol solution or dispersion containing 14.4 parts by mass, 72 parts by mass of calcium chloride dihydrate and 43.2 parts by mass of magnesium aluminate metasilicate.
A granulated product is sprayed with a 70% ethanol solution or dispersion liquid containing 72 parts by mass of hypromellose, 36 parts by mass of yellow ferric oxide and 266.4 parts by mass of titanium oxide to obtain coated granules.
436 parts by weight of coated granules, 400 parts by weight of D-mannitol, 30 parts by weight of xylitol, 550 parts by weight of crystalline cellulose, 129 parts by weight of crospovidone, 25 parts by weight of anhydrous calcium hydrogen phosphate, 20 parts by weight of magnesium oxide and 2 parts by weight of yogurt micron And 8 parts by mass of calcium stearate, and tableting with a rotary tableting machine, an orally disintegrating tablet having a diameter of 8 mm and a mass of 160 mg can be obtained.
[製造例10]
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、塩化カルシウム 二水和物60質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び酸化マグネシウム6質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.35mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 10]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. 60 parts by mass and 6 parts by mass of magnesium oxide are dispersed. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 8.35 mg per area of 2.8 cm 2. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、塩化カルシウム 二水和物60質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び酸化マグネシウム6質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.35mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 10]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. 60 parts by mass and 6 parts by mass of magnesium oxide are dispersed. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 8.35 mg per area of 2.8 cm 2. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
[製造例11]
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、塩化カルシウム 二水和物60質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び酸化マグネシウム150質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が10.75mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 11]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. 60 parts by mass and 150 parts by mass of magnesium oxide are dispersed. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 10.75 mg per area of 2.8 cm 2. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、塩化カルシウム 二水和物60質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び酸化マグネシウム150質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が10.75mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 11]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. 60 parts by mass and 150 parts by mass of magnesium oxide are dispersed. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 10.75 mg per area of 2.8 cm 2. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
[製造例12]
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び酸化マグネシウム210質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が10.75mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 12]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, 30 parts by weight of macrogol, 30 parts by weight of sucralose and 15 parts by weight of l-menthol are dissolved in this, and 60 parts by weight of pitavastatin calcium and 210 parts by weight of magnesium oxide are further added. scatter. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 10.75 mg per area of 2.8 cm 2. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び酸化マグネシウム210質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が10.75mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 12]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, 30 parts by weight of macrogol, 30 parts by weight of sucralose and 15 parts by weight of l-menthol are dissolved in this, and 60 parts by weight of pitavastatin calcium and 210 parts by weight of magnesium oxide are further added. scatter. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass of 10.75 mg per area of 2.8 cm 2. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
[製造例13]
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、塩化カルシウム 二水和物60質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び水酸化マグネシウム30質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.75mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 13]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. 60 parts by mass and 30 parts by mass of magnesium hydroxide are dispersed. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、塩化カルシウム 二水和物60質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び水酸化マグネシウム30質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.75mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 13]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. 60 parts by mass and 30 parts by mass of magnesium hydroxide are dispersed. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
[製造例14]
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部、黄色三二酸化鉄3質量部及び酸化マグネシウム30質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、塩化カルシウム 二水和物60質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.05mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.25mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 14]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide, yellow iron sesquioxide 3 parts by mass and 30 parts by mass of magnesium oxide are dispersed. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. Disperse 60 parts by weight. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 8.05 mg. After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.25 mg. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部、黄色三二酸化鉄3質量部及び酸化マグネシウム30質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、塩化カルシウム 二水和物60質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.05mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.25mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 14]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide, yellow iron sesquioxide 3 parts by mass and 30 parts by mass of magnesium oxide are dispersed. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 60 parts by weight of calcium chloride dihydrate, 30 parts by weight of sucralose and 15 parts by weight of 1-menthol are dissolved in this, and pitavastatin calcium is further dissolved. Disperse 60 parts by weight. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 8.05 mg. After the drug-containing layer preparation solution is uniformly applied above the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.25 mg. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled to obtain an orally disintegrating film agent.
[製造例15]
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び水酸化マグネシウム90質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.75mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 15]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 30 parts by weight of sucralose and 15 parts by weight of l-menthol are dissolved therein, and further 60 parts by weight of pitavastatin calcium and 90 parts by weight of magnesium hydroxide To distribute. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled off to obtain an orally disintegrating film agent.
水480質量部と無水エタノール480質量部を混合し、これにマクロゴール30質量部、アミノアルキルメタクリレートコポリマーE 120質量部及びトレハロース30質量部を溶解し、更に酸化チタン30質量部及び黄色三二酸化鉄3質量部を分散する。この液にヒプロメロース240質量部を溶解し、薬物非含有層調製液を得る。
水600質量部と無水エタノール600質量部を混合し、これにマクロゴール30質量部、スクラロース30質量部及びl-メントール15質量部を溶解し、更にピタバスタチンカルシウム60質量部及び水酸化マグネシウム90質量部を分散する。この液にヒドロキシプロピルセルロース300質量部を溶解し、薬物含有層調製液を得る。
PET(ポリエチレンテレフタラート)フィルム上に薬物非含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が7.55mgの薬物非含有層を形成する。薬物非含有層の上方に薬物含有層調製液を均一に塗布した後、温風にて乾燥し、面積2.8cm2あたりの質量が8.75mgの薬物含有層を形成し、中間製品1を得る。
中間製品1を2式作成し、薬物含有層同士が対向するように貼り合わせ圧着し、2つのPETフィルムの間に、薬物非含有層、薬物含有層、薬物非含有層が順次積層された中間製品2を得る。
中間製品2を面積2.8cm2に裁断し、PETフィルムを剥離して、口腔内崩壊型のフィルム剤を得ることができる。 [Production Example 15]
480 parts by mass of water and 480 parts by mass of absolute ethanol are mixed, and 30 parts by mass of macrogol, 120 parts by mass of aminoalkyl methacrylate copolymer E and 30 parts by mass of trehalose are dissolved therein, and further 30 parts by mass of titanium oxide and yellow ferric oxide. Disperse 3 parts by weight. In this solution, 240 parts by mass of hypromellose is dissolved to obtain a drug-free layer preparation solution.
600 parts by weight of water and 600 parts by weight of absolute ethanol are mixed, and 30 parts by weight of macrogol, 30 parts by weight of sucralose and 15 parts by weight of l-menthol are dissolved therein, and further 60 parts by weight of pitavastatin calcium and 90 parts by weight of magnesium hydroxide To distribute. In this solution, 300 parts by mass of hydroxypropylcellulose is dissolved to obtain a drug-containing layer preparation solution.
A drug-free layer preparation solution is uniformly applied on a PET (polyethylene terephthalate) film, and then dried with warm air to form a drug-free layer having a mass per area of 2.8 cm 2 of 7.55 mg. After the drug-containing layer preparation solution is uniformly applied over the drug-free layer, it is dried with warm air to form a drug-containing layer having a mass per area of 2.8 cm 2 of 8.75 mg. obtain.
Two intermediate products 1 are prepared, bonded and pressure-bonded so that the drug-containing layers face each other, and a drug-free layer, a drug-containing layer, and a drug-free layer are sequentially laminated between two PET films Obtain product 2.
The intermediate product 2 can be cut into an area of 2.8 cm 2 and the PET film can be peeled off to obtain an orally disintegrating film agent.
本発明によれば、ピタバスタチン又はその塩由来の苦味が十分に抑制された、服用感が良好で服用コンプライアンスの高い経口剤を提供することができ、医薬品産業等において利用できる。
According to the present invention, it is possible to provide an oral preparation having a satisfactory dosage feeling and high compliance, in which the bitterness derived from pitavastatin or a salt thereof is sufficiently suppressed, and can be used in the pharmaceutical industry and the like.
Claims (9)
- ピタバスタチン又はその塩と、
酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有する経口剤。 Pitavastatin or a salt thereof,
An oral preparation containing one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide. - マグネシウム化合物の合計含有量がピタバスタチンカルシウム換算したピタバスタチン又はその塩1質量部に対して30質量部未満である、請求項1記載の経口剤。 The oral preparation according to claim 1, wherein the total content of the magnesium compound is less than 30 parts by mass with respect to 1 part by mass of pitavastatin or a salt thereof in terms of pitavastatin calcium.
- 更に、矯味剤を含有する、請求項1又は2記載の経口剤。 Furthermore, the oral preparation of Claim 1 or 2 containing a corrigent.
- 更に、甘味料を含有する、請求項1~3のいずれか1項に記載の経口剤。 The oral preparation according to any one of claims 1 to 3, further comprising a sweetener.
- 口腔内崩壊型の製剤である、請求項1~4のいずれか1項に記載の経口剤。 The oral preparation according to any one of claims 1 to 4, which is an orally disintegrating preparation.
- 口腔内崩壊型の製剤が口腔内崩壊型錠剤又は口腔内崩壊型フィルム剤である、請求項5記載の経口剤。 The oral preparation according to claim 5, wherein the orally disintegrating preparation is an orally disintegrating tablet or an orally disintegrating film preparation.
- 酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を有効成分として含有する、ピタバスタチン又はその塩の苦味抑制剤。 A bitter taste inhibitor of pitavastatin or a salt thereof containing, as an active ingredient, one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide.
- ピタバスタチン又はその塩の苦味を抑制するための、酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物の使用。 Use of one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide for suppressing the bitter taste of pitavastatin or a salt thereof.
- ピタバスタチン又はその塩の苦味が抑制された経口剤の製造方法であって、ピタバスタチン又はその塩に酸化マグネシウム及び水酸化マグネシウムから選ばれる1種以上のマグネシウム化合物を含有せしめる工程を含む製造方法。 A method for producing an oral preparation in which the bitter taste of pitavastatin or a salt thereof is suppressed, the method comprising a step of incorporating one or more magnesium compounds selected from magnesium oxide and magnesium hydroxide into pitavastatin or a salt thereof.
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JP2013221029A (en) * | 2012-04-18 | 2013-10-28 | Orient Pharma Co Ltd | Stabilized pitavastatin preparation |
JP2013224285A (en) * | 2012-06-27 | 2013-10-31 | Kowa Co | Pharmaceutical |
JP2014090676A (en) * | 2012-10-31 | 2014-05-19 | Kirin Beverage Corp | Taste improver for triterpene and glycoside thereof |
CN107126423A (en) * | 2017-05-02 | 2017-09-05 | 华润双鹤药业股份有限公司 | Pitavastatin Calcium tablet pharmaceutical composition and its dry type or wet type preparation method |
JP2018193360A (en) * | 2017-05-18 | 2018-12-06 | エルメッド エーザイ株式会社 | Production method of molded tablet, and method for improving quality of molded tablet |
US20200281889A1 (en) * | 2019-03-07 | 2020-09-10 | Terpene Therapeutics Inc. | Edible Film Comprising Adjacent Conjoined Strips |
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JP2015040206A (en) * | 2013-08-23 | 2015-03-02 | 高田製薬株式会社 | Oral fast-disintegrating tablet containing irritative (astringency, acidity, bitterness) drug and method for producing the same |
JP6272730B2 (en) * | 2014-05-21 | 2018-01-31 | 救急薬品工業株式会社 | Fast dissolving film agent |
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WO2010098482A1 (en) * | 2009-02-27 | 2010-09-02 | 興和株式会社 | Stable capsule preparation and method for producing same |
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Also Published As
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JPWO2012029913A1 (en) | 2013-10-31 |
JP2013144717A (en) | 2013-07-25 |
JP5259880B2 (en) | 2013-08-07 |
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