JP2015098470A - Tablet containing loxoprofen or salt thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a tablet containing loxoprofen or a salt thereof with improved hardness, disintegration time, and dissolution property of a tablet.SOLUTION: When 1) the weight ratio of carmellose and crospovidone is 20:1 to 5:1, 2) sucralose, aspartame, and/or acesulfame potassium are contained as a sweetening agent, and 3) a granulated material containing loxoprofen or a salt thereof is contained in an amount of 20-80% by weight of the entire formulation, a tablet containing loxoprofen or a salt thereof with improved hardness, disintegration time, and dissolution property of the tablet can be provided.

Description

  The present invention relates to a tablet containing loxoprofen or a salt thereof having a fast disintegration time and improved dissolution by containing carmellose and crospovidone.

Loxoprofen or its salt, especially loxoprofen sodium hydrate, is a non-steroidal anti-inflammatory agent of phenylpropionic acid type, and after absorption from the gastrointestinal tract, it is converted into an active metabolite that has anti-inflammatory, analgesic and antipyretic effects. The effect is fast. Until now, loxoprofen sodium hydrate has been marketed in tablets, tapes, etc. in addition to tablets called Loxonin ^R.

  Of these, commercially available loxoprofen sodium hydrate tablets are to be taken with water or hot water. However, in order to ensure immediate efficacy in anti-inflammatory action, analgesic action, and antipyretic action, it is desired to develop a tablet that is rapidly disintegrating and has improved dissolution properties.

In producing a tablet that is rapidly disintegrating and has improved dissolution properties, saccharides and / or disintegrants are generally used. Examples of documents disclosing tablets containing saccharides and disintegrants include the following documents.
Patent Document 1 discloses an oral solid preparation containing nateglinide as an active ingredient and a water-soluble polymer, and 0.3 to 6 parts by weight of the water-soluble polymer in terms of solid content with respect to 1 part by weight of nateglinide. An orally disintegrating tablet characterized in that it contains an active ingredient particle containing a drug exhibiting an unpleasant taste and having a coating layer covering the drug, and disintegration of the Wicking type An orally disintegrating tablet comprising an agent (carmellose) and a Swelling type disintegrant (crospovidone) is disclosed.
Patent Document 3 includes (1) D-mannitol, (2) active ingredient, (3) one or more disintegrants selected from the group consisting of crospovidone and carmellose, and (4) sodium stearyl fumarate and sucrose fatty acid. An orally disintegrating tablet containing one or more lubricants selected from the group consisting of esters is disclosed.
Patent Document 4 is a preparation having an outer layer covering the periphery of the inner core, and is selected from the group consisting of (a) crystalline cellulose, (b) inorganic excipient, and (c) crospovidone, carmellose and the like as outer layer components. A nucleated type orally disintegrating tablet selected from 1 or 2 or more is disclosed.
Patent Document 5 discloses a solid preparation for oral dissolution comprising an anti-inflammatory part for a throat and a part containing a medicine for treating colds with different disintegration or dissolution times.
Patent Document 6 discloses an orally disintegrating tablet containing a drug, crystalline cellulose, anhydrous calcium hydrogen phosphate, carmellose, and 0.8% by weight or less of a lubricant.
Patent Document 7 discloses an orally disintegrating tablet containing risperidone, crystalline cellulose, anhydrous calcium hydrogen phosphate, carmellose and 0.8% by weight or less of a lubricant.
Furthermore, Patent Document 8 discloses a tablet produced by mixing and tableting a granulated product containing loxoprofen sodium and carmellose and a granulated product containing butylscopolamine bromide.

WO2006 / 016602 JP2013-147470A WO2008 / 120548 WO2010 / 134540 JP 2006-124288 A WO2007 / 018192 WO2008 / 081774 WO2013 / 018766

Patent Documents 1 to 7 are formulation examples in which carmellose and / or crospovidone are blended as a disintegrating agent to shorten the disintegration time. However, tablets containing loxoprofen sodium and improved dissolution are not disclosed. Depending on the drug, the disintegration and hardness of the tablet may vary.
Patent Document 8 is a preparation containing loxoprofen sodium, but does not disclose a fast disintegrating tablet or a tablet with improved dissolution.

  Thus, there has been a demand for providing a tablet containing loxoprofen sodium hydrate having a fast disintegration time, an appropriate tablet hardness, and improved dissolution.

  As a result of intensive investigations to develop a tablet containing loxoprofen or a salt thereof having a fast disintegration time, an appropriate tablet hardness, and improved dissolution, an optimal formulation was found. The present invention has been completed. Specifically, by containing carmellose and crospovidone as disintegrants and sucralose, aspartame and / or acesulfame potassium as sweeteners, it has good disintegration, ensured tablet hardness, and improved dissolution. A tablet containing loxoprofen or a salt thereof could be obtained.

That is, the present invention
(1) A tablet comprising loxoprofen or a salt thereof, carmellose and crospovidone,
(2) The tablet according to (1) above, wherein the weight ratio of carmellose and crospovidone is 20: 1 to 5: 1.
(3) The tablet according to (2) above, wherein the weight ratio of carmellose and crospovidone is 10: 1 to 5: 1.
(4) The tablet according to any one of (1) to (3) above containing sucralose,
(5) The tablet according to any one of (1) to (4) above containing aspartame and / or acesulfame potassium,
(6) The tablet according to any one of (1) to (5) above, comprising a granulated product containing loxoprofen or a salt thereof,
(7) A tablet obtained by mixing carmellose and crospovidone into a granulated product containing loxoprofen or a salt thereof and compressing the mixture.
(8) The tablet according to the above (6) or (7), wherein the ratio of the granulated product containing loxoprofen or a salt thereof is 20 to 80% by weight relative to the whole tablet,
(9) The tablet according to (8) above, wherein the ratio of the granulated product containing loxoprofen or a salt thereof is 40 to 60% by weight relative to the whole tablet,
(10) The tablet according to any one of (1) to (9) above, which contains loxoprofen sodium hydrate as loxoprofen or a salt thereof,
(11) The tablet according to (10) above, comprising loxoprofen sodium hydrate, carmellose, crospovidone, sucralose, aspartame, and acesulfame potassium, wherein the weight ratio of carmellose to crospovidone is 10: 1 to 5: 1.
(12) Granules containing loxoprofen sodium hydrate, carmellose, crospovidone, sucralose, aspartame and acesulfame potassium, the weight ratio of carmellose and crospovidone is 10: 1 to 5: 1, and loxoprofen sodium The tablet according to the above (10) or (11), wherein the ratio of the granulated product containing 40 to 60% by weight with respect to the whole tablet,
(13) A granulated product containing loxoprofen sodium hydrate and carmellose, crospovidone, sucralose, aspartame and acesulfame potassium are mixed and tableted, and the weight ratio of carmellose to crospovidone is 10: 1 to 5 1 and the ratio of the granulated product containing loxoprofen sodium is 40 to 60% by weight based on the whole tablet,
(14) Granules containing loxoprofen sodium hydrate, carmellose, crospovidone, sucralose, aspartame and acesulfame potassium, the weight ratio of carmellose and crospovidone is 10: 1 to 5: 1, and loxoprofen sodium The above-mentioned (12), wherein the ratio of the granulated product containing 40 to 60% by weight with respect to the whole tablet and the dissolution rate for 30 minutes is 85% or more in the 16th revised Japanese Pharmacopoeia The tablet described.
(15) A granulated product containing loxoprofen sodium hydrate and carmellose, crospovidone, sucralose, aspartame and acesulfame potassium are mixed and tableted, and the weight ratio of carmellose to crospovidone is 10: 1 to 5 1 and the proportion of the granulated product containing loxoprofen sodium is 40 to 60% by weight with respect to the whole tablet. In the dissolution test method of the 16th revised Japanese Pharmacopoeia, the dissolution rate for 30 minutes is 85%. The tablet according to (14) above,
(16) In the disintegration test of the 16th revised Japanese Pharmacopeia, the tablet according to any one of (1) to (15), wherein the disintegration time is within 60 seconds,
(17) The tablet according to any one of claims 1 to 16, which is an orally disintegrating tablet,
About.

  A tablet containing loxoprofen or a salt thereof of the present invention (hereinafter referred to as “the present preparation”) has a disintegration time of 1 to 60 seconds or less, a tablet hardness of 10 to 200 N, and the 16th revised Japanese Pharmacopoeia. In the dissolution test method, the preparation has a dissolution rate of 85% or more for 30 minutes.

  In the present specification, loxoprofen or a salt thereof includes a solvate. As the salt, sodium salt, calcium salt, potassium salt, p-toluenesulfonic acid, benzenesulfonic acid, sulfuric acid, hydrochloric acid and hydrobromide can be used. In particular, a sodium salt is preferable. As the solvate, a hydrate or an alcohol solvate can be used. Particularly preferred are hydrates. For example, loxoprofen sodium hydrate listed in the 16th revision Japanese Pharmacopoeia and Japanese Pharmacopoeia Standards can be used. Loxoprofen sodium hydrate is equivalent to 60 mg, compared to 68.1 mg of loxoprofen sodium hydrate.

  The content of loxoprofen or a salt thereof in this preparation may be an amount that produces a medicinal effect. For example, it is 5 to 50% by weight, preferably 7.5 to 40% by weight, more preferably 10 to 30% by weight, based on the total amount of the preparation. If the amount is more than these, the bitterness may increase, and if it is less, the medicinal effect may not be sufficiently exerted.

  Loxoprofen or a salt thereof in this preparation may be used in combination with other active ingredients. The kind of other active ingredient is not particularly limited. For example, butyl scopolamine bromide, ibuprofen, acetaminophen, allylisopropylacetylurea, acetylsalicylic acid, caffeine anhydride, aspirin, aspirin aluminum, ethenamide, salicylamide, sodium salicylate, sazabiline, isopropylantipyrine, lactylphenetidine, ketoprofen, piroxicam, Acemetacin and indomethacin.

  In this specification, carmellose (carboxymethylcellulose, CMC) and crospovidone may be those listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Pharmaceuticals, the Standards for Pharmaceutical Additives, and the Official Food Additives. . Carmellose is a polyvalent carboxymethyl ether of cellulose, and crospovidone is a crosslinked polymer of 1-vinyl-2-pyrrolidone.

  The content of carmellose in this preparation can be selected within a wide range where the tablet can be disintegrated. For example, with respect to 100 parts by weight of loxoprofen sodium, it is usually 10 to 100 parts by weight, preferably 25 to 90 parts by weight, more preferably 40 to 80 parts by weight. Preferably it is 2.5 to 25 weight%, More preferably, it is 5 to 20 weight%. If the blending amount is larger than these, the hardness may be lowered, and if it is smaller, the disintegration time may be longer.

  The content of crospovidone in this preparation can be selected within a wide range where the tablet can be disintegrated. For example, with respect to 100 parts by weight of loxoprofen sodium, it is usually 1 to 30 parts by weight, preferably 2 to 20 parts by weight, more preferably 3 to 10 parts by weight. %, Preferably 0.025 to 15% by weight, more preferably 0.05 to 10% by weight. If the blending amount is larger than these, the hardness may be lowered, and if it is smaller, the disintegration time may be longer.

  The weight ratio of carmellose and crospovidone in this preparation can be selected within a wide range where the tablet can be disintegrated. For example, the weight ratio of carmellose and crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably 10: 1 to 5: 1. If the amount of carmellose is greater than the blending ratio, the disintegration time may be long.

  In this preparation, a disintegrant can be used in combination with carmellose and crospovidone. Examples of disintegrants that can be used in combination include croscarmellose sodium, carmellose calcium, sodium carboxymethyl starch, and low-substituted hydroxypropylcellulose.

  In the present specification, as sucralose, those listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Drugs, the Standards for Pharmaceutical Additives and the Official Food Additives can be used.

  The content of sucralose in this preparation can be selected within a wide range that can be tasted. For example, with respect to 100 parts by weight of loxoprofen sodium, it is usually 0.1 to 10 parts by weight, preferably 0.25 to 7.5 parts by weight, more preferably 0.5 to 5 parts by weight. For example, it is 0.01 to 5% by weight, preferably 0.025 to 2.5% by weight, and more preferably 0.05 to 1% by weight. If the amount is more than these, the degree of discoloration may increase, and if it is less, the taste-masking may not be sufficiently generated.

  In this specification, aspartame can be used aspartame listed in Japanese Pharmacopoeia, Japanese Pharmacopoeia Standards for Pharmaceuticals, Pharmaceutical Additives Standards and Food Additives Standards.

  The content of aspartame in this preparation can be selected within a wide range that can be tasted. For example, with respect to 100 parts by weight of loxoprofen sodium, it is usually 0.3 to 30 parts by weight, preferably 0.75 to 25 parts by weight, more preferably 1.5 to 50 parts by weight. It is 0.03-30 weight%, Preferably it is 0.075-22.5 weight%, More preferably, it is 0.15-15 weight%. If the amount is more than these, the degree of discoloration may increase, and if it is less, the taste-masking may not be sufficiently generated.

  In the present specification, as acesulfame potassium, those listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Pharmaceutical Standards, the Pharmaceutical Additives Standard and the Food Additives Official Standard can be used.

  The content of acesulfame potassium in this preparation can be selected within a wide range that can be tasted. For example, with respect to 100 parts by weight of loxoprofen sodium, it is usually 0.1 to 10 parts by weight, preferably 0.25 to 7.5 parts by weight, more preferably 0.5 to 5 parts by weight. For example, it is 0.01 to 5% by weight, preferably 0.025 to 2.5% by weight, and more preferably 0.05 to 1% by weight. If the amount is more than these, the degree of discoloration may increase, and if it is less, the taste-masking may not be sufficiently generated.

  This preparation may contain excipients and uses the excipients listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Drugs, the Standards for Pharmaceutical Additives, and the Food Additives Standards can do. For example, powdered reduced maltose starch syrup, glucose, fructose, lactose, D-mannitol, erythritol, maltitol, trehalose, sorbitol, sucrose, sucrose, fructooligosaccharides, palatinose, maltose (maltose), reduced maltose, flour, starch syrup, fructose , Lactulose, reduced lactose lactitol, honey sugar, D-sorbitol, xylitol, corn starch, potato starch, wheat starch, rice starch, crystalline cellulose, anhydrous silicic acid, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate and the like. Preferably, it is powder reduced maltose starch syrup.

  The content of the excipient is usually 20 to 80% by weight, preferably 30 to 75% by weight, more preferably 40 to 70% by weight, based on the total amount of the preparation. If the content is higher than these, the preparation itself may be increased in size or a large amount of tablets may need to be taken.

  This preparation may contain a binder, and binders listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Drugs, the Standards for Pharmaceutical Additives, and the Official Food Additives can be used. For example, hydroxypropyl cellulose, corn starch, pregelatinized starch, partially pregelatinized starch, gum arabic, gum arabic powder, gelatin, agar, dextrin, pullulan, polyvinylpyrrolidone (Povidone), polyvinyl alcohol, crystalline cellulose, methylcellulose, ethylcellulose, carboxy Examples thereof include methyl ethyl cellulose, carmellose, carmellose sodium, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl cellulose, hypromellose, and preferably hydroxypropyl cellulose.

  The content of the binder is usually 0.01 to 5% by weight, preferably 0.05 to 4.5% by weight, more preferably 0.1 to 4% by weight, based on the total amount of the preparation. If the content is higher than these contents, the adhesiveness increases, the preparation may adhere to the production equipment and the yield of the preparation may decrease, and if it is less, the preparation may not be produced.

  This preparation may contain a lubricant, and the lubricants listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Drugs, the Standards for Pharmaceutical Additives, and the Official Food Additives can be used. Examples thereof include sucrose fatty acid ester, magnesium stearate (Taihei Chemical Industry, Nippon Oil & Fats, Sakai Chemical Industry), calcium stearate, talc, hydrous silicon dioxide, and the like, preferably sucrose fatty acid ester.

  The content of the lubricant is usually 0.05 to 10% by weight, preferably 0.075 to 7.5% by weight, more preferably 0.1 to 5% by weight, based on the total amount of the preparation. If it is more than these contents, tablet hardness and disintegration may be lowered, and if it is less, there is a possibility that tablets cannot be produced.

If necessary, this preparation may contain additives other than those mentioned above. Additives listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Pharmaceutical Standards, the Pharmaceutical Additives Standard, and the Food Additives Official Standard Can be used. Moreover, the content of these additives may be an arbitrary ratio. Examples of additives other than those described above include fragrances, fluidizing agents, coloring agents, coating agents, and the like.
The fragrance includes what is called a flavoring agent, such as banana flavor, sun fix banana, orange essence, orange oil, caramel, camphor, cinnamon oil, spearmint oil, strawberry essence, chocolate essence, cherry flavor, spruce oil, Examples include pine oil, peppermint oil, vanilla flavor, bitter essence, fruit flavor, peppermint essence, mixed flavor, mint flavor, menthol, lemon powder, lemon oil, and rose oil.
Examples of the fluidizing agent include hydrous silicon dioxide, light anhydrous silicic acid, crystalline cellulose, synthetic aluminum silicate, talc, and the like, and preferably hydrous silicon dioxide.
Examples of colorants include yellow sesquioxide, sesquioxide, edible red No. 3, edible yellow No. 5, edible blue No. 1 and the like, brown iron oxide, black iron oxide, copper chlorophyll, copper chlorophyllin sodium, riboflavin , Riboflavin butyrate, matcha powder, and the like.
As a coating agent, for example, polyvinyl alcohol, ethyl cellulose, carboxymethyl ethyl cellulose, carmellose, carmellose sodium, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, PVA copolymer, ethyl acrylate / methyl methacrylate copolymer dispersion, Aminoalkyl methacrylate copolymer, Opadry, carnauba wax, carboxyvinyl polymer, dry methacrylic acid copolymer, dimethylaminoethyl methacrylate / methyl methacrylate copolymer, stearyl alcohol, shellac, cetanol, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose Sufutareto, fumaric acid, stearic acid Polyvinyl acetal diethylamino acetate hydroxypropylmethylcellulose mixture, polyvinylacetal diethylamino acetate, polyvinyl alcohol, methacrylic acid copolymer, 2-methyl-5-vinylpyridine methylacrylate-methacrylic acid copolymer, and the like.

  Apart from aspartame and sucralose, other flavoring agents can be used in combination. For example, glycine, sodium chloride, magnesium chloride, hydrochloric acid, dilute hydrochloric acid, citric acid and its salt (sodium citrate), anhydrous citric acid, L-glutamic acid and its salt, succinic acid and its salt, acetic acid, tartaric acid and its salt, carbonic acid Examples include sodium hydrogen, fumaric acid and its salt, malic acid and its salt, glacial acetic acid, disodium inosinate, honey and the like.

  By taking orally disintegrating tablets containing loxoprofen sodium, headache, menstrual pain (menstrual pain), pain after tooth extraction, sore throat, back pain, joint pain, neuralgia, muscle pain, shoulder pain, ear pain, bruise It is effective for pain, fracture pain, brutal pain, pain relief, trauma, antipyretic during chills and fever.

  The daily dose of loxoprofen sodium hydrate is, for example, 10 to 300 mg, preferably 30 to 240 mg, more preferably 60 to 180 mg of loxoprofen sodium hydrate in terms of loxoprofen sodium anhydride. The daily dose may be divided into 1 to 4 times.

  The dosage form of this preparation is usually a tablet defined in the Japanese Pharmacopoeia General Rules for Preparation.

  As a method for producing a tablet containing loxoprofen or a salt thereof, 1) a method in which loxoprofen or a salt thereof and an additive are mixed, and the mixed powder is tableted (direct tableting method); 2) loxoprofen or a salt thereof There is a method in which a salt and an additive are mixed and granulated, and the granulated product is tableted (indirect tableting method). Preferably, loxoprofen or a salt thereof and an additive are mixed and granulated, and the granulated product is tableted and produced. In the case of 2), the granulated material may be a granulation method usually used pharmaceutically. For example, extrusion granulation method, stirring granulation method, fluidized bed granulation method, rolling granulation method and the like. The granulated product may be covered with a coating agent.

  When tableting is performed, compression molding is performed at a tableting pressure of 200 kgf to 1500 kgf using a device that performs external lubricant tableting, a single-punch tableting machine, a rotary tableting machine, or the like. If the pressure is lower than this, the tablet hardness is insufficient and sufficient hardness for handling cannot be secured, and if the pressure is high, disintegration is delayed, which is not preferable.

  Any shape can be adopted for the molding of this preparation, for example, a round shape, an oval shape, a spherical shape, a rod shape, a donut shape, a laminated tablet, a dry-coated tablet, etc. It can also be coated by coating. Further, marks for improving the identification, characters, etc., or dividing lines for division may be added.

  The diameter of the tablet of this preparation should just be a magnitude | size which can be taken | dosed. For example, it is 5 to 30 mm, preferably 6 to 25 mm, more preferably 7 to 20 mm.

  In the present invention, it is also possible to produce a tablet containing an active ingredient in advance and suppressing the bitterness (for example, powder / particles), and then mixing the above ingredients together with these preparations to produce a tablet. In this case, it is possible to produce a tablet with suppressed bitterness and improved dissolution.

  In the case of a tablet produced by mixing loxoprofen or a salt thereof and an additive and granulating the tablet, and then granulating the granulated product, the tablet may not be disintegrated to the end in the oral cavity and the core may remain. Therefore, the inventors have intensively studied and found that the core does not remain by optimizing the ratio of the granulated product in the whole tablet. That is, the ratio of the granulated product with respect to the whole tablet is 20 to 80% by weight, preferably 40 to 60% by weight, and more preferably 45 to 55% by weight. If the amount is less than this amount, the content of loxoprofen in the tablet is decreased, and the tablet may be enlarged. If the amount is higher, the core may remain at the time of taking.

  Loxoprofen or a salt thereof, and an additive can usually be used in any amount alone or in admixture as long as the disintegration time, dissolution property, hardness, sweetness and discomfort in the oral cavity do not occur. . Preferred loxoprofen or a salt thereof and a combination of additives are 1) loxoprofen or a salt thereof / carmellose / crospovidone, 2) loxoprofen or a salt thereof / carmellose / crospovidone / sucralose, 3) loxoprofen or a salt thereof / carmellose / crospovidone / Sucralose / aspartame, 4) loxoprofen or a salt thereof / carmellose / crospovidone / sucralose / aspartame cesulfame potassium.

  In the combination of loxoprofen or a salt thereof / carmellose / crospovidone, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably 10: 1. ~ 5: 1. The content of each of the preparations is, for example, 5-50% by weight of loxoprofen or a salt thereof, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, preferably loxoprofen or a salt thereof. 7.5 to 40% by weight, carmellose 2.5 to 25% by weight, crospovidone 0.025 to 15% by weight, more preferably loxoprofen or a salt thereof 10 to 30% by weight, carmellose 5 to 20% by weight Crospovidone is 0.05 to 10% by weight.

  In the combination of loxoprofen or a salt thereof / carmellose / crospovidone / sucralose, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably 10 : 1 to 5: 1. Moreover, each content with respect to the whole preparation amount is, for example, 5 to 50% by weight of loxoprofen or a salt thereof, 1 to 30% by weight of carmellose, 0.01 to 20% by weight of crospovidone, and 0.01 to 5 of sucralose. % By weight, preferably loxoprofen or a salt thereof 7.5 to 40% by weight, carmellose 2.5 to 25% by weight, crospovidone 0.025 to 15% by weight, sucralose 0.025 to 2.5% by weight More preferably, loxoprofen or a salt thereof is 10 to 30% by weight, carmellose is 5 to 20% by weight, crospovidone is 0.05 to 10% by weight, and sucralose is 0.05 to 1% by weight.

  In the combination of loxoprofen or a salt thereof / carmellose / crospovidone / sucralose / aspartame, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably. Is 10: 1 to 5: 1. Moreover, each content with respect to the whole preparation amount is, for example, 5-50% by weight of loxoprofen or a salt thereof, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, and 0.025-2 of sucralose. 0.5 wt%, aspartame 0.03-15 wt%, preferably 7.5-40 wt% loxoprofen or a salt thereof, carmellose 2.5-25 wt%, crospovidone 0.025-15 wt% 0.025 to 2.5% by weight of sucralose, 0.075 to 22.5% by weight of aspartame, more preferably 10 to 30% by weight of loxoprofen or a salt thereof, 5 to 20% by weight of carmellose, and crospovidone 0.05 to 10% by weight, sucralose is 0.05 to 1% by weight, and aspartame is 0.15 to 15% by weight.

  In the combination of loxoprofen or a salt thereof / carmellose / crospovidone / sucralose / aspartame / acesulfame potassium, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1. More preferably, it is 10: 1 to 5: 1. Moreover, each content with respect to the whole preparation amount is, for example, 5-50% by weight of loxoprofen or a salt thereof, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, and 0.025-2 of sucralose. 0.5 wt%, aspartame 0.03-15 wt%, acesulfame potassium 0.01-5 wt%, preferably loxoprofen or a salt thereof 7.5-40 wt%, carmellose 2.5-25 wt% Crospovidone 0.025-15%, sucralose 0.025-2.5% by weight, aspartame 0.075-22.5% by weight, acesulfame potassium 0.025-2.5% by weight, and more Preferably, loxoprofen or a salt thereof is 10 to 30% by weight, carmellose is 5 to 20% by weight, crospovidone is 0.05 to 0 wt%, sucralose 0.05 wt%, aspartame 0.15 to 15 wt%, acesulfame potassium is 0.05 wt%.

  Loxoprofen sodium hydrate and additives can be used alone or in admixture in any amount as long as they do not cause disintegration time, hardness, sweetness and discomfort in the oral cavity. Preferred loxoprofen sodium hydrate and additive combinations are: 1) loxoprofen sodium / carmellose / crospovidone, 2) loxoprofen sodium hydrate / carmellose / crospovidone / sucralose, 3) loxoprofen sodium hydrate / carmellose / crospovidone / Sucralose / aspartame, 4) loxoprofen sodium hydrate / carmellose / crospovidone / sucralose / aspartame / acesulfame potassium.

  In the loxoprofen sodium hydrate / carmellose / crospovidone combination, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably 10: 1-5: 1. Moreover, each content with respect to the total amount of the preparation is, for example, 5-50% by weight of loxoprofen sodium hydrate, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, preferably loxoprofen sodium hydrate. 7.5 to 40% by weight, carmellose 2.5 to 25% by weight, crospovidone 0.025 to 15% by weight, more preferably loxoprofen sodium hydrate 10 to 30% by weight, carmellose 5 to 5% 20% by weight, crospovidone is 0.05 to 10% by weight.

  In the combination of loxoprofen sodium hydrate / carmellose / crospovidone / sucralose, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably 10: 1 to 5: 1. Moreover, each content with respect to the total amount of the preparation is, for example, 5 to 50% by weight of loxoprofen sodium hydrate, 1 to 30% by weight of carmellose, 0.01 to 20% by weight of crospovidone, and 0.01 to 20% of sucralose. 5% by weight, preferably loxoprofen sodium hydrate 7.5-40% by weight, carmellose 2.5-25% by weight, crospovidone 0.025-15% by weight, sucralose 0.025-2.5 More preferably, loxoprofen sodium hydrate is 10 to 30% by weight, carmellose is 5 to 20% by weight, crospovidone is 0.05 to 10% by weight, and sucralose is 0.05 to 1% by weight.

  In the combination of loxoprofen sodium hydrate / carmellose / crospovidone / sucralose / aspartame, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1 Preferably it is 10: 1-5: 1. Moreover, each content with respect to the whole preparation amount is, for example, 5 to 50% by weight of loxoprofen sodium hydrate, 1 to 30% by weight of carmellose, 0.01 to 20% by weight of crospovidone, and 0.025 to sucralose. 2.5 wt%, aspartame 0.03-15 wt%, preferably 7.5-40 wt% loxoprofen sodium hydrate, 2.5-25 wt% carmellose, 0.025-15 crospovidone % By weight, 0.025 to 2.5% by weight of sucralose, 0.075 to 22.5% by weight of aspartame, more preferably 10 to 30% by weight of sodium loxoprofen hydrate, 5 to 20% by weight of carmellose, 0.05 to 10% by weight of crospovidone, 0.05 to 1% by weight of sucralose, 0.15 to 15 of aspartame It is the amount%.

  In the combination of loxoprofen sodium hydrate / carmellose / crospovidone / sucralose / aspartame / acesulfame potassium, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably 10: 1 to 5: 1. Moreover, each content with respect to the whole preparation amount is, for example, 5 to 50% by weight of loxoprofen sodium hydrate, 1 to 30% by weight of carmellose, 0.01 to 20% by weight of crospovidone, and 0.025 to sucralose. 2.5 wt%, aspartame 0.03-15 wt%, acesulfame potassium 0.01-5 wt%, preferably loxoprofen sodium hydrate 7.5-40 wt%, carmellose 2.5-25 Wt%, crospovidone 0.025-15 wt%, sucralose 0.025-2.5 wt%, aspartame 0.075-22.5 wt%, acesulfame potassium 0.025-2.5 wt% More preferably, loxoprofen sodium hydrate is 10 to 30% by weight, carmellose is 5 to 20% by weight, Don 0.05 to 10% by weight, sucralose 0.05 wt%, aspartame 0.15 to 15 wt%, acesulfame potassium is 0.05 wt%.

  The granulated product containing loxoprofen or a salt thereof and the additive are usually used in any amount alone or in admixture as long as the tablet disintegration time, hardness, sweetness, and oral discomfort do not occur. be able to. Preferred combinations of granulated product and additive containing loxoprofen or a salt thereof are: 1) granulated product containing loxoprofen or a salt thereof / carmellose / crospovidone, 2) granulated product containing loxoprofen or a salt thereof / carmellose / Crospovidone / sucralose, 3) granulated product containing loxoprofen or a salt thereof / carmellose / crospovidone / sucralose / aspartame, 4) granulated product containing loxoprofen or a salt thereof / carmellose / crospovidone / sucralose / aspartame / Acesulfame potassium.

  In the combination of granulated product / carmellose / crospovidone containing loxoprofen or a salt thereof, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1. More preferably, the ratio is 10: 1 to 5: 1, and the ratio of the granulated product to the whole tablet is 20 to 80% by weight, preferably 40 to 60% by weight, and more preferably 45 to 55% by weight. The content of each of the preparations is, for example, 5-50% by weight of loxoprofen or a salt thereof, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, preferably loxoprofen or a salt thereof. 7.5 to 40% by weight, carmellose 2.5 to 25% by weight, crospovidone 0.025 to 15% by weight, more preferably loxoprofen or a salt thereof 10 to 30% by weight, carmellose 5 to 20% by weight Crospovidone is 0.05 to 10% by weight.

  In the combination of granulated product / carmellose / crospovidone / sucralose containing loxoprofen or a salt thereof, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, More preferably, it is 10: 1-5: 1, The ratio of the granulated material with respect to the whole tablet is 20-80 weight%, Preferably it is 40-60 weight%, More preferably, it is 45-55 weight%. Moreover, each content with respect to the whole preparation amount is, for example, 5-50% by weight of loxoprofen or a salt thereof, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, and 0.025-2 of sucralose. 0.5% by weight, preferably 7.5-40% by weight of loxoprofen or a salt thereof, 2.5-25% by weight of carmellose, 0.025-15% by weight of crospovidone, 0.025-2.5 of sucralose More preferably, loxoprofen or a salt thereof is 10 to 30% by weight, carmellose is 5 to 20% by weight, crospovidone is 0.05 to 10% by weight, and sucralose is 0.05 to 1% by weight.

  In the combination of granulated product / carmellose / crospovidone / sucralose / aspartame containing loxoprofen or a salt thereof, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably 10: 1 to 5: 1, and the ratio of the granulated product to the whole tablet is 20 to 80% by weight, preferably 40 to 60% by weight, more preferably 45 to 55% by weight. is there. Moreover, each content with respect to the whole preparation amount is, for example, 5-50% by weight of loxoprofen or a salt thereof, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, and 0.025-2 of sucralose. 0.5 wt%, aspartame 0.03-15 wt%, preferably 7.5-40 wt% loxoprofen or a salt thereof, carmellose 2.5-25 wt%, crospovidone 0.025-15 wt% 0.025 to 2.5% by weight of sucralose, 0.075 to 22.5% by weight of aspartame, more preferably 10 to 30% by weight of loxoprofen or a salt thereof, 5 to 20% by weight of carmellose, and crospovidone 0.05 to 10% by weight, sucralose is 0.05 to 1% by weight, and aspartame is 0.15 to 15% by weight.

  In the combination of granulated material containing loxoprofen or a salt thereof / carmellose / crospovidone / sucralose / aspartame / acesulfame potassium, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20 : 1 to 5: 1, more preferably 10: 1 to 5: 1. The ratio of the granulated product to the whole tablet is 20 to 80% by weight, preferably 40 to 60% by weight, more preferably 45 to 55%. % By weight. Moreover, each content with respect to the whole preparation amount is, for example, 5-50% by weight of loxoprofen or a salt thereof, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, and 0.025-2 of sucralose. 0.5 wt%, aspartame 0.03-15 wt%, acesulfame potassium 0.01-5 wt%, preferably loxoprofen or a salt thereof 7.5-40 wt%, carmellose 2.5-25 wt% Crospovidone 0.025-15%, sucralose 0.025-2.5% by weight, aspartame 0.075-22.5% by weight, acesulfame potassium 0.025-2.5% by weight, and more Preferably, loxoprofen or a salt thereof is 10 to 30% by weight, carmellose is 5 to 20% by weight, crospovidone is 0.05 to 0 wt%, sucralose 0.05 wt%, aspartame 0.15 to 15 wt%, acesulfame potassium is 0.05 wt%.

  Granulated products containing loxoprofen sodium hydrate and additives are usually used alone or in admixture, as long as the tablet disintegration time, hardness, sweetness, and oral discomfort do not occur. can do. Preferred combinations of granulates and additives containing loxoprofen or a salt thereof are: 1) granule containing loxoprofen sodium hydrate / carmellose / crospovidone, 2) granulation containing loxoprofen sodium hydrate / Carmellose / crospovidone / sucralose, 3) granulated product containing loxoprofen sodium hydrate / carmellose / crospovidone / sucralose / aspartame, 4) granulated product containing loxoprofen sodium hydrate / carmellose / crospovidone / Sucralose / aspartame / acesulfame potassium.

  In the combination of granulate / carmellose / crospovidone containing loxoprofen sodium hydrate, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1. More preferably, the ratio is 10: 1 to 5: 1, and the ratio of the granulated product to the whole tablet is 20 to 80% by weight, preferably 40 to 60% by weight, and more preferably 45 to 55% by weight. Moreover, each content with respect to the total amount of the preparation is, for example, 5-50% by weight of loxoprofen sodium hydrate, 1-30% by weight of carmellose, 0.01-20% by weight of crospovidone, preferably loxoprofen sodium hydrate. 7.5 to 40% by weight, carmellose 2.5 to 25% by weight, crospovidone 0.025 to 15% by weight, more preferably loxoprofen sodium hydrate 10 to 30% by weight, carmellose 5 to 5% 20% by weight, crospovidone is 0.05 to 10% by weight.

  In the combination of granulated product / carmellose / crospovidone / sucralose containing loxoprofen sodium hydrate, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1. : 1, more preferably 10: 1 to 5: 1, and the ratio of the granulated product to the whole tablet is 20 to 80% by weight, preferably 40 to 60% by weight, more preferably 45 to 55% by weight. . Moreover, each content with respect to the whole preparation amount is, for example, 5 to 50% by weight of loxoprofen sodium hydrate, 1 to 30% by weight of carmellose, 0.01 to 20% by weight of crospovidone, and 0.025 to sucralose. 2.5 wt%, preferably 7.5-40 wt% loxoprofen sodium hydrate, 2.5-25 wt% carmellose, 0.025-15 wt% crospovidone, 0.025-2 sucralose 0.5% by weight, more preferably loxoprofen sodium hydrate is 10-30% by weight, carmellose is 5-20% by weight, crospovidone is 0.05-10% by weight, and sucralose is 0.05-1% by weight. .

  In the combination of granulate / carmellose / crospovidone / sucralose / aspartame containing loxoprofen sodium hydrate, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1. To 5: 1, more preferably 10: 1 to 5: 1, and the ratio of the granulated product to the whole tablet is 20 to 80% by weight, preferably 40 to 60% by weight, more preferably 45 to 55% by weight. It is. Moreover, each content with respect to the whole preparation amount is, for example, 5 to 50% by weight of loxoprofen sodium hydrate, 1 to 30% by weight of carmellose, 0.01 to 20% by weight of crospovidone, and 0.025 to sucralose. 2.5 wt%, aspartame 0.03-15 wt%, preferably 7.5-40 wt% loxoprofen sodium hydrate, 2.5-25 wt% carmellose, 0.025-15 crospovidone % By weight, 0.025 to 2.5% by weight of sucralose, 0.075 to 22.5% by weight of aspartame, more preferably 10 to 30% by weight of sodium loxoprofen hydrate, 5 to 20% by weight of carmellose, 0.05 to 10% by weight of crospovidone, 0.05 to 1% by weight of sucralose, 0.15 to 15 of aspartame It is the amount%.

  In the combination of granulate / carmellose / crospovidone / sucralose / aspartame / acesulfame potassium containing loxoprofen sodium hydrate, for example, the weight ratio of carmellose to crospovidone is 30: 1 to 5: 1, preferably 20: 1 to 5: 1, more preferably 10: 1 to 5: 1, and the ratio of the granulated product to the whole tablet is 20 to 80% by weight, preferably 40 to 60% by weight, more preferably 45 to 45%. 55% by weight. Moreover, each content with respect to the whole preparation amount is, for example, 5 to 50% by weight of loxoprofen sodium hydrate, 1 to 30% by weight of carmellose, 0.01 to 20% by weight of crospovidone, and 0.025 to sucralose. 2.5 wt%, aspartame 0.03-15 wt%, acesulfame potassium 0.01-5 wt%, preferably loxoprofen sodium hydrate 7.5-40 wt%, carmellose 2.5-25 Wt%, crospovidone 0.025-15 wt%, sucralose 0.025-2.5 wt%, aspartame 0.075-22.5 wt%, acesulfame potassium 0.025-2.5 wt% More preferably, loxoprofen sodium hydrate is 10 to 30% by weight, carmellose is 5 to 20% by weight, Don 0.05 to 10% by weight, sucralose 0.05 wt%, aspartame 0.15 to 15 wt%, acesulfame potassium is 0.05 wt%.

  The tablet of the present invention has a disintegration time of usually 1 to 30 seconds, preferably 1 to 20 seconds, more preferably about 1 to 10 seconds in the 16th revised Japanese Pharmacopoeia disintegration test.

  The tablet of the present invention is also useful as an orally disintegrating tablet, and is rapidly disintegrated in the oral cavity by saliva and can be taken smoothly without leaving roughness. The dissolution of the orally disintegrating tablet of the present invention is usually 1 to 60 seconds, preferably 1 to 40 seconds, and more preferably about 1 to 30 seconds.

  The hardness (measured with a tablet hardness meter) is usually known to be a value that is not problematic if it is about 30 to 70 N, but the tablet of the present invention is about 10 to 200 N, preferably about 30 to 150 N. is there.

  In addition, this formulation can also be normally taken with water.

EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated in detail, this invention is not restrict | limited by these. The tablets of Examples and Comparative Examples were produced by the following method. The tablet hardness and oral disintegration time were measured and a sensory test was performed.
(1) Influence of disintegrant In order to investigate the influence of a disintegrant, the tablet of Table 1 was manufactured and those hardness and oral disintegration time were measured.

Tablet production method Table 1 shows the formulation of tablets per tablet. Loxoprofen sodium hydrate (Daiwa Pharmaceutical Co., Ltd.), crystalline cellulose (UF-702, Asahi Kasei Chemicals Co., Ltd.), stevia extract (Maruzen Pharmaceutical Co., Ltd.), sodium citrate (Merck Co., Ltd.), polyvinyl Pyrrolidone (Povidone 90F, manufactured by BASF JAPAN) and hydrous silicon dioxide (manufactured by EVONIK JAPAN) were mixed and granulated by a stirring granulation method. The granulated material was covered with Eudragit (EVONIK JAPAN) to complete the granulated material (hereinafter, this may be referred to as “main drug granulated material”).
Completed agglomerated active ingredient, crystalline cellulose (UF-711, manufactured by Asahi Kasei Chemicals Corporation), anhydrous calcium hydrogen phosphate (manufactured by Kyowa Chemical Co., Ltd.), carmellose (manufactured by Nichirin Chemical Industry Co., Ltd.), sucralose (San-Eigen F. F Eye Co., Ltd.), Magnesium Stearate (Taihei Chemical Industry Co., Ltd.), Hydrous Silicon Dioxide (Evonik Japan Ltd.), Banana Flavor (Ogawa Fragrance Co., Ltd.) and Sunfix Banana (San-Eigen F.F. In some cases, Crospopidone (BASF JAPN) was mixed to obtain a mixed powder. This mixed powder was tableted by a single tableting machine. The tablet diameter was 10 mm and the tableting pressure was 550 kgf. In addition, the content of sodium loxoprofen as the main drug was 68.1 mg.

Hardness test Measured using a dedicated hardness measurement machine (ERWEKA International AG). The test is performed with 10 tablets, and the average value is shown.

Oral disintegration test Six healthy adults included tablets, and the disintegration time of the oral tablets was measured. The maximum value of the decay time is shown in the table.

表１に示す通り、崩壊剤としてカルメロースのみを含有する製剤では、口腔内崩壊時間が１２０秒と長かった（比較例１、２）が、カルメロースおよびクロスポビドンを含有する製剤とすることで、口腔内崩壊時間は短くなった（実施例１）。
result

As shown in Table 1, in the preparation containing only carmellose as the disintegrant, the disintegration time in the oral cavity was long as 120 seconds (Comparative Examples 1 and 2), but by making the preparation containing carmellose and crospovidone, The internal disintegration time was shortened (Example 1).

(2) Influence of blending ratio of carmellose and crospovidone In order to examine the influence of the blending ratio of carmellose and crospovidone, tablets shown in Table 2 were produced, and their hardness and disintegration time in the oral cavity were measured. The tablet production method is the same as in Comparative Examples 1 and 2 and Example 1. The tablet diameter was about 10 mm and the tableting pressure was 550 kgf. In addition, the content of loxoprofen sodium hydrate as the main drug was 68.1 mg.
In the sensory test, six healthy adults include orally disintegrating tablets, and the oral feeling during oral administration is evaluated. Moreover, the tablet contained in the oral cavity is discharged after the test, and the oral cavity is washed with water.

実施例１の製剤は、口腔内全体で甘味を感じず、もさもさ感が生じた。そこで、カルメロースとクロスポビドンの配合量を検討した。その結果、カルメロースとクロスポビドンの重量比を変化させることで、もさもさ感を軽減または消失させることができた。最適化した結果、カルメロース：クロスポビドンの配合比を４０ｍｇ：５ｍｇ（＝８：１）とすることにより、口腔内全体で甘味を感じ、もさもさ感が生じなかった。 result

The preparation of Example 1 did not feel sweetness in the entire oral cavity, and a sense of irritability occurred. Then, the compounding quantity of carmellose and crospovidone was examined. As a result, by changing the weight ratio of carmellose and crospovidone, it was possible to reduce or eliminate the irritating feeling. As a result of optimization, when the blending ratio of carmellose: crospovidone was 40 mg: 5 mg (= 8: 1), sweet taste was felt in the entire oral cavity, and no irritating feeling was generated.

(3) Influence of sweetener In order to investigate the influence of a sweetener, the tablet of Table 3 was manufactured, and those hardness and oral disintegration time were measured. The tablet production method is the same as in Comparative Examples 1 and 2 and Example 1. In addition to sucralose as a sweetener, aspartame (manufactured by Ajinomoto Healthy Supply Co., Ltd.), acesulfame potassium (manufactured by Nutriva Japan Co., Ltd.) It was used. The tablet diameter was about 10 mm and the tableting pressure was 550 kgf. In addition, the content of sodium loxoprofen as the main drug was 68.1 mg.

表３に示す通り、甘味剤をスクラロースのみの製剤（実施例２）と、甘味剤をスクラロース、アスパルテームおよびアセスルファムカリウムとした製剤（実施例３）の錠剤硬度および口腔内崩壊時間を比較した。その結果、錠剤の硬度はほとんど変わらなかったが、実施例２よりも実施例３の口腔内崩壊時間は短くなった。
result

As shown in Table 3, the tablet hardness and oral disintegration time of a preparation containing only sucralose as a sweetener (Example 2) and a preparation containing sucralose, aspartame and acesulfame potassium as sweeteners (Example 3) were compared. As a result, the hardness of the tablet hardly changed, but the oral disintegration time of Example 3 was shorter than that of Example 2.

(4) Effect of the ratio of the active ingredient granule in the tablet In order to examine the effect of the ratio of the active ingredient granule in the tablet, the tablets shown in Table 4 were produced, and the dissolution rate after 15 minutes and 30 minutes of dissolution test. Was measured. The tablet production method is the same as in Comparative Examples 1 and 2 and Example 1. The tablet diameter was about 9 to 10.5 mm in accordance with the tablet weight, and the tableting pressure was 350 kgf. In addition, the content of loxoprofen sodium hydrate as the main drug was 68.1 mg.

Dissolution test method The dissolution test of loxoprofen sodium tablets listed in the 16th revision Japanese Pharmacopoeia Second Supplement was followed.

Disintegration test method The disintegration time of tablets was measured based on the 16th revised Japanese Pharmacopoeia disintegration test method.

表４に示す通り、主薬造粒物の割合を３７．２重量％（比較例３）から５９．５重量％（実施例６）とすると、溶出率が高くなった。特に、実施例５は、崩壊試験法による崩壊時間が１０秒であり、３０分間の溶出率も８５％以上であった。
result

As shown in Table 4, when the proportion of the active ingredient granule was changed from 37.2 wt% (Comparative Example 3) to 59.5 wt% (Example 6), the elution rate increased. In particular, in Example 5, the disintegration time by the disintegration test method was 10 seconds, and the elution rate for 30 minutes was 85% or more.

  About a tablet containing loxoprofen or a salt thereof, it is possible to provide a tablet having a practical level of hardness, disintegration and dissolution. Furthermore, a tablet comprising a combination of loxoprofen or a salt thereof and another pharmaceutical product can be produced.

Claims (17)

A tablet comprising loxoprofen or a salt thereof, carmellose and crospovidone. The tablet according to claim 1, wherein the weight ratio of carmellose to crospovidone is 20: 1 to 5: 1. The tablet according to claim 2, wherein the weight ratio of carmellose to crospovidone is 10: 1 to 5: 1. The tablet according to any one of claims 1 to 3, comprising sucralose. The tablet according to any one of claims 1 to 4, comprising aspartame and / or acesulfame potassium. The tablet according to any one of claims 1 to 5, comprising a granulated product containing loxoprofen or a salt thereof. A tablet comprising a granulated product containing loxoprofen or a salt thereof mixed with carmellose and crospovidone and tableted. The tablet according to claim 6 or 7, wherein the ratio of the granulated product containing loxoprofen or a salt thereof is 20 to 80% by weight based on the whole tablet. The tablet according to claim 8, wherein the ratio of the granulated product containing loxoprofen or a salt thereof is 40 to 60% by weight based on the whole tablet. The tablet according to any one of claims 1 to 9, comprising loxoprofen sodium hydrate as loxoprofen or a salt thereof. The tablet according to claim 10, comprising loxoprofen sodium hydrate, carmellose, crospovidone, sucralose, aspartame and acesulfame potassium, wherein the weight ratio of carmellose to crospovidone is 10: 1 to 5: 1. Granules containing loxoprofen sodium hydrate, containing carmellose, crospovidone, sucralose, aspartame and acesulfame potassium, the weight ratio of carmellose to crospovidone is 10: 1 to 5: 1 and contains loxoprofen sodium The tablet according to claim 10 or 11, wherein a ratio of the granulated product is 40 to 60% by weight based on the whole tablet. A granulated product containing loxoprofen sodium hydrate and carmellose, crospovidone, sucralose, aspartame and acesulfame potassium are mixed and tableted, and the weight ratio of carmellose to crospovidone is 10: 1 to 5: 1. The tablet of Claim 12 whose ratio of the granulated material containing a loxoprofen sodium is 40 to 60 weight% with respect to the whole tablet. Granules containing loxoprofen sodium hydrate, containing carmellose, crospovidone, sucralose, aspartame and acesulfame potassium, the weight ratio of carmellose to crospovidone is 10: 1 to 5: 1 and contains loxoprofen sodium The tablet according to claim 12, wherein the ratio of the granulated product is 40 to 60% by weight with respect to the whole tablet, and the dissolution rate for 30 minutes is 85% or more in the 16th revised Japanese Pharmacopoeia dissolution test method. A granulated product containing loxoprofen sodium hydrate and carmellose, crospovidone, sucralose, aspartame and acesulfame potassium are mixed and tableted, and the weight ratio of carmellose to crospovidone is 10: 1 to 5: 1. Yes, the proportion of the granulated product containing loxoprofen sodium is 40-60% by weight with respect to the whole tablet, and the dissolution rate for 30 minutes is 85% or more in the dissolution test method of the 16th revised Japanese Pharmacopoeia The tablet according to claim 14. The tablet according to any one of claims 1 to 15, wherein the disintegration time is 30 seconds or less in the disintegration test of the 16th revised Japanese Pharmacopoeia. It is an orally disintegrating tablet, The tablet in any one of Claims 1-16.