JP7419057B2 - Tablets and coated tablets - Google Patents
Tablets and coated tablets Download PDFInfo
- Publication number
- JP7419057B2 JP7419057B2 JP2019237739A JP2019237739A JP7419057B2 JP 7419057 B2 JP7419057 B2 JP 7419057B2 JP 2019237739 A JP2019237739 A JP 2019237739A JP 2019237739 A JP2019237739 A JP 2019237739A JP 7419057 B2 JP7419057 B2 JP 7419057B2
- Authority
- JP
- Japan
- Prior art keywords
- component
- tablet
- mass
- disintegration
- tablets
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000011247 coating layer Substances 0.000 claims description 22
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 claims description 17
- 229960000514 ethenzamide Drugs 0.000 claims description 16
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000001023 inorganic pigment Substances 0.000 claims description 11
- 229940024546 aluminum hydroxide gel Drugs 0.000 claims description 9
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 claims description 9
- 239000011230 binding agent Substances 0.000 claims description 9
- 229960002373 loxoprofen Drugs 0.000 claims description 9
- 239000003826 tablet Substances 0.000 description 154
- 239000000843 powder Substances 0.000 description 29
- 229940079593 drug Drugs 0.000 description 28
- 239000003814 drug Substances 0.000 description 28
- 238000004519 manufacturing process Methods 0.000 description 26
- 239000010410 layer Substances 0.000 description 25
- 230000000694 effects Effects 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 239000011248 coating agent Substances 0.000 description 13
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- 239000004480 active ingredient Substances 0.000 description 11
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 11
- 229940069428 antacid Drugs 0.000 description 10
- 239000003159 antacid agent Substances 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 9
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- -1 magnesium aluminate Chemical class 0.000 description 9
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- 238000003860 storage Methods 0.000 description 8
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
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- 238000000576 coating method Methods 0.000 description 6
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- 230000000202 analgesic effect Effects 0.000 description 4
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
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- 229920002261 Corn starch Polymers 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- 229950008138 carmellose Drugs 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- PGZIKUPSQINGKT-UHFFFAOYSA-N dialuminum;dioxido(oxo)silane Chemical compound [Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O PGZIKUPSQINGKT-UHFFFAOYSA-N 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 229960004211 loxoprofen sodium dihydrate Drugs 0.000 description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 3
- 239000001095 magnesium carbonate Substances 0.000 description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 3
- 229960001708 magnesium carbonate Drugs 0.000 description 3
- 235000010449 maltitol Nutrition 0.000 description 3
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- 238000005550 wet granulation Methods 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
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- 206010053155 Epigastric discomfort Diseases 0.000 description 2
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、錠剤及びコーティング錠に関する。 The present invention relates to tablets and coated tablets.
エテンザミドは、解熱、鎮痛等に有効なサリチル酸系の非ステロイド系抗炎症薬(NSAIDs)として広く使用されている。しかし、エテンザミドを含む錠剤は、崩壊性及び硬度(耐摩損性)に課題がある。
前記課題に対し、結晶乳糖の粒子核にポリビニルピロリドンのエタノール水溶液を添加し、その上に、予め無水ケイ酸を添加、混合して粉末物性を改善したエテンザミドを粉末コーティングし、乾燥、整粒し、造粒乳糖、結晶セルロース、クロスポビドン及びマルチトールを混合し、さらにステアリン酸マグネシウムを混合し、打錠する方法が知られている(特許文献1)。
Ethenzamide is widely used as a salicylic acid-based nonsteroidal anti-inflammatory drug (NSAIDs) that is effective for antipyretic, analgesic, and the like. However, tablets containing ethenzamide have problems with disintegration and hardness (abrasion resistance).
To solve the above problem, an ethanol aqueous solution of polyvinylpyrrolidone was added to the particle cores of crystalline lactose, and ethenzamide, which had been improved in powder properties by adding and mixing silicic anhydride in advance, was powder-coated thereon, dried, and sized. A method is known in which granulated lactose, crystalline cellulose, crospovidone, and maltitol are mixed, and then magnesium stearate is mixed and tableted (Patent Document 1).
エテンザミドはイブプロフェン等と比較して胃障害が低いNSAIDsではあるが、胃障害をより低減するため、制酸剤を配合することがある。しかし、エテンザミドと制酸剤を配合した錠剤は、経時による崩壊性の低下(崩壊遅延)が生じやすい。
特許文献1では、エテンザミドと制酸剤を配合した場合の崩壊遅延の問題について検討されていない。また、特許文献1の方法は、錠剤の大型化や1回服用錠数が多くなることが懸念される。
錠剤の崩壊性や崩壊遅延を改善する一般的な方法として、崩壊剤を増量する方法も知られているが、この方法も、錠剤の大型化や1回服用錠数が多くなることが懸念される。
Although ethenzamide is an NSAID that causes less gastric irritation than ibuprofen and the like, antacids may be added to it to further reduce gastric irritation. However, tablets containing ethenzamide and antacids tend to have reduced disintegration properties (delayed disintegration) over time.
Patent Document 1 does not consider the problem of delayed disintegration when ethenzamide and an antacid are combined. Furthermore, there are concerns that the method of Patent Document 1 may result in larger tablets and an increase in the number of tablets to be taken at one time.
A common method for improving tablet disintegration and disintegration delay is to increase the amount of disintegrant, but there are concerns that this method also increases the size of the tablet and the number of tablets to be taken at a time. Ru.
本発明の一態様は、摩損が生じ難い硬度と速やかな崩壊性を有し、エテンザミド及び制酸剤の組み合わせによる崩壊遅延が抑制された錠剤及びコーティング錠の提供を目的とする。 One aspect of the present invention aims to provide tablets and coated tablets that have hardness that does not easily cause abrasion and rapid disintegration, and in which the delay in disintegration caused by the combination of ethenzamide and antacids is suppressed.
本発明者らは鋭意検討した結果、エテンザミド及び制酸剤を含む錠剤に、NSAIDsであるロキソプロフェン又はその塩を含有させることで、意外にも、摩損が生じ難い硬度と速やかな崩壊性を維持しつつ、崩壊遅延を抑制できることを知見し、本発明を完成させるに至った。 As a result of extensive studies, the present inventors have surprisingly found that by incorporating loxoprofen, an NSAID, or its salt into tablets containing ethenzamide and antacids, they maintain hardness that prevents wear and tear and rapid disintegration. At the same time, they found that the delay in disintegration can be suppressed, and have completed the present invention.
本発明は、以下の態様を有する。
〔1〕下記(A)成分、(B)成分及び(C)成分を含有する、錠剤。
(A)成分:エテンザミド。
(B)成分:アルミニウム原子及びマグネシウム原子から選ばれる1種以上を含有する制酸剤。
(C)成分:ロキソプロフェン及びその医薬的に許容可能な塩からなる群より選ばれる少なくとも一種。
〔2〕前記(B)成分が、乾燥水酸化アルミニウムゲル、メタケイ酸アルミン酸マグネシウム、ケイ酸アルミン酸マグネシウム、合成ヒドロタルサイト、合成ケイ酸アルミニウム、炭酸マグネシウム、ジヒドロキシアルミニウムアミノアセテート、水酸化アルミニウム、水酸化アルミニウム・炭酸水素ナトリウム共沈物、水酸化アルミニウム・炭酸水素マグネシウム混合乾燥物、酸化マグネシウム及びケイ酸マグネシウムからなる群より選ばれる少なくとも一種である、前記〔1〕の錠剤。
〔3〕前記(C)成分/(前記(A)成分+前記(B)成分)で表される質量比が0.01~1.5である、前記〔1〕又は〔2〕の錠剤。
〔4〕前記(A)成分/前記(B)成分で表される質量比が0.1~15である、前記〔1〕~〔3〕のいずれかの錠剤。
〔5〕前記(A)成分/前記(C)成分で表される質量比が0.2~25である、前記〔1〕~〔4〕のいずれかの錠剤。
〔6〕前記〔1〕~〔5〕のいずれかの錠剤を素錠とし、前記素錠の表面にコーティング層を有する、コーティング錠。
〔7〕前記コーティング層が無機顔料を含む、前記〔6〕のコーティング錠。
The present invention has the following aspects.
[1] A tablet containing the following components (A), (B) and (C).
(A) Component: ethenzamide.
Component (B): An antacid containing one or more selected from aluminum atoms and magnesium atoms.
Component (C): at least one member selected from the group consisting of loxoprofen and pharmaceutically acceptable salts thereof.
[2] Component (B) is dry aluminum hydroxide gel, magnesium aluminate metasilicate, magnesium aluminate silicate, synthetic hydrotalcite, synthetic aluminum silicate, magnesium carbonate, dihydroxyaluminum aminoacetate, aluminum hydroxide, The tablet of [1] above, which is at least one selected from the group consisting of aluminum hydroxide/sodium hydrogen carbonate coprecipitate, aluminum hydroxide/magnesium hydrogen carbonate mixed dry product, magnesium oxide, and magnesium silicate.
[3] The tablet of [1] or [2] above, wherein the mass ratio represented by the component (C)/(component (A) + component (B)) is 0.01 to 1.5.
[4] The tablet according to any one of [1] to [3] above, wherein the mass ratio represented by the component (A)/component (B) is 0.1 to 15.
[5] The tablet according to any one of [1] to [4] above, wherein the mass ratio represented by the component (A)/component (C) is 0.2 to 25.
[6] A coated tablet comprising the tablet of any one of [1] to [5] above as a plain tablet, and having a coating layer on the surface of the plain tablet.
[7] The coated tablet of [6] above, wherein the coating layer contains an inorganic pigment.
本発明の一態様によれば、摩損が生じ難い硬度と速やかな崩壊性を有し、エテンザミド及び制酸剤の組み合わせによる崩壊遅延が抑制された錠剤及びコーティング錠を提供できる。 According to one aspect of the present invention, it is possible to provide tablets and coated tablets that have hardness that does not easily cause abrasion and rapid disintegration, and in which the delay in disintegration caused by the combination of ethenzamide and antacids is suppressed.
〔錠剤〕
本発明の一態様に係る錠剤は、以下に示す(A)成分、(B)成分及び(C)成分を含有する。
〔tablet〕
The tablet according to one aspect of the present invention contains the following components (A), (B), and (C).
<(A)成分>
(A)成分はエテンザミドである。
エテンザミド(2-エトキシベンザミド)は、サリチル酸系の非ステロイド系抗炎症薬(NSAIDs)であり、解熱鎮痛成分として使用される。
<(A) component>
Component (A) is ethenzamide.
Ethenzamide (2-ethoxybenzamide) is a salicylic acid-based nonsteroidal anti-inflammatory drug (NSAIDs) and is used as an antipyretic and analgesic ingredient.
(A)成分の1回当たりの服用量は、30~1000mgが好ましく、50~500mgがより好ましく、70~300mgがさらに好ましい。(A)成分の1回当たりの服用量が上記下限値以上であれば、解熱鎮痛効果が十分に得られ、上記上限値以下であれば、1回当たりの服用錠剤数を低減できる。
錠剤1錠あたりの(A)成分の質量は、30~400mgが好ましい。1錠あたりの(A)成分の質量が上記下限値以上であれば、1回服用量あたりの錠剤数を低減でき、上記上限値以下であれば、錠剤硬度を良好に維持でき、また1錠中に他の有効成分を十分に配合できる。
錠剤1錠あたりの(A)成分の質量割合は、5~70質量%が好ましく、10~60質量%がより好ましく、13~40質量%がさらに好ましい。(A)成分の質量割合が上記下限以上であれば、1回服用量あたりの錠剤数を低減でき、上記上限値以下であれば、1錠中に他の有効成分を十分に配合できる。
The dose of component (A) per dose is preferably 30 to 1000 mg, more preferably 50 to 500 mg, even more preferably 70 to 300 mg. If the dose of component (A) per dose is at least the above lower limit, a sufficient antipyretic and analgesic effect can be obtained, and if it is below the above upper limit, the number of tablets to be taken per dose can be reduced.
The mass of component (A) per tablet is preferably 30 to 400 mg. If the mass of component (A) per tablet is greater than or equal to the above lower limit, the number of tablets per dose can be reduced, and if it is less than or equal to the above upper limit, good tablet hardness can be maintained, and the number of tablets per tablet can be reduced. Other active ingredients can be sufficiently incorporated therein.
The mass proportion of component (A) per tablet is preferably 5 to 70% by mass, more preferably 10 to 60% by mass, and even more preferably 13 to 40% by mass. If the mass ratio of component (A) is at least the above lower limit, the number of tablets per dose can be reduced, and if it is below the above upper limit, other active ingredients can be sufficiently blended into one tablet.
<(B)成分>
(B)成分はアルミニウム原子及びマグネシウム原子から選ばれる1種以上を含有する制酸剤である。
(A)成分と(B)成分とを併用することで、(A)成分による胃障害が緩和される。また、製造直後の崩壊性、強度等の錠剤物性が改善される。また、(A)成分を含む粉体の流動性が改善され、製造工程における製造機への付着が抑制される。
<(B) component>
Component (B) is an antacid containing one or more selected from aluminum atoms and magnesium atoms.
By using component (A) and component (B) together, gastric disorders caused by component (A) are alleviated. In addition, the physical properties of the tablet, such as disintegration and strength, immediately after production are improved. Furthermore, the fluidity of the powder containing component (A) is improved, and adhesion to manufacturing machines during the manufacturing process is suppressed.
(B)成分としては、アルミニウム原子及びマグネシウム原子から選ばれる1種以上を含有する制酸剤であれば特に限定されず、例えば、乾燥水酸化アルミニウムゲル、メタケイ酸アルミン酸マグネシウム、ケイ酸アルミン酸マグネシウム、合成ヒドロタルサイト、合成ケイ酸アルミニウム、炭酸マグネシウム、ジヒドロキシアルミニウムアミノアセテート、水酸化アルミニウム、水酸化アルミニウム・炭酸水素ナトリウム共沈物、水酸化アルミニウム・炭酸水素マグネシウム混合乾燥物、酸化マグネシウム、ケイ酸マグネシウムが挙げられる。
(B)成分としては、摩損が生じ難い硬度が確保しやすい点で、乾燥水酸化アルミニウムゲル、メタケイ酸アルミン酸マグネシウム、ケイ酸アルミン酸マグネシウム、合成ヒドロタルサイト、炭酸マグネシウム、水酸化アルミニウム、水酸化アルミニウム・炭酸水素ナトリウム共沈物、酸化マグネシウムが好ましく、乾燥水酸化アルミニウムゲル、メタケイ酸アルミン酸マグネシウム、合成ヒドロタルサイト、水酸化アルミニウム、酸化マグネシウムがさらに好ましく、乾燥水酸化アルミニウムゲル、メタケイ酸アルミン酸マグネシウム、合成ヒドロタルサイト、酸化マグネシウムがより好ましい。これらの中でも、保存後の錠剤の臭いの抑制効果が高い点で、乾燥水酸化アルミニウムゲル、メタケイ酸アルミン酸マグネシウムが好ましい。
乾燥水酸化アルミニウムゲルとしては、「第十七改正 日本薬局方」に所載の乾燥水酸化アルミニウムゲルが挙げられる。なお、乾燥水酸化アルミニウムゲルには、結合水等の水が保持されていてもよく、後述する(B)成分の服用量、および質量割合は、水和している水も含む量である。
(B)成分は1種単独で用いてもよいし、2種以上を適宜組み合わせて用いてもよい。
Component (B) is not particularly limited as long as it is an antacid containing one or more selected from aluminum atoms and magnesium atoms, and examples include dry aluminum hydroxide gel, magnesium aluminate metasilicate, and aluminate silicate. Magnesium, synthetic hydrotalcite, synthetic aluminum silicate, magnesium carbonate, dihydroxyaluminum aminoacetate, aluminum hydroxide, aluminum hydroxide/sodium hydrogen carbonate coprecipitate, dried aluminum hydroxide/magnesium hydrogen carbonate mixture, magnesium oxide, silica Examples include magnesium oxide.
Ingredients (B) are dry aluminum hydroxide gel, magnesium aluminate metasilicate, magnesium aluminate silicate, synthetic hydrotalcite, magnesium carbonate, aluminum hydroxide, water Aluminum oxide/sodium bicarbonate coprecipitate and magnesium oxide are preferred, dried aluminum hydroxide gel, magnesium aluminate metasilicate, synthetic hydrotalcite, aluminum hydroxide, and magnesium oxide are more preferred, and dried aluminum hydroxide gel and metasilicate More preferred are magnesium aluminate, synthetic hydrotalcite, and magnesium oxide. Among these, dry aluminum hydroxide gel and magnesium aluminate metasilicate are preferred because they are highly effective in suppressing the odor of tablets after storage.
Examples of the dry aluminum hydroxide gel include the dry aluminum hydroxide gel listed in the "17th Edition Japanese Pharmacopoeia". Note that the dry aluminum hydroxide gel may retain water such as bound water, and the dose and mass ratio of component (B) described below include hydrated water.
Component (B) may be used alone or in an appropriate combination of two or more.
(B)成分の1回あたりの服用量は、5~500mgが好ましく、30~300mgがより好ましく、50~200mgがさらに好ましい。(B)成分の1回当たりの服用量が上記下限値以上であれば、(A)成分による胃障害を十分に緩和でき、上記上限値以下であれば、他の有効成分を十分に配合できる。
錠剤1錠あたりの(B)成分の質量は、5~200mgが好ましい。1錠あたりの(B)成分の質量が上記下限値以上であれば、摩損が生じ難い硬度を確保しやすくなり、上記上限値以下であれば、崩壊遅延が生じ難くなり、また他の有効成分を十分に配合できるため1回当たりの服用量を低減できる。
錠剤1錠あたりの(B)成分の質量割合は、1~70質量%が好ましく、3~50質量%がより好ましく、5~40質量%がさらに好ましい。(B)成分の質量割合が上記下限以上であれば、摩損が生じ難い硬度を確保しやすくなり、上記上限値以下であれば、崩壊遅延が生じ難くなり、また他の有効成分を十分に配合できるため1回当たりの服用量を低減できる。
The dose of component (B) per dose is preferably 5 to 500 mg, more preferably 30 to 300 mg, even more preferably 50 to 200 mg. If the dose of component (B) is above the above lower limit, gastric disorders caused by component (A) can be sufficiently alleviated, and if it is below the above upper limit, other active ingredients can be sufficiently incorporated. .
The mass of component (B) per tablet is preferably 5 to 200 mg. If the mass of component (B) per tablet is greater than or equal to the above lower limit, it will be easier to ensure hardness that does not cause wear and tear, and if it is less than the above upper limit, it will be difficult to cause delayed disintegration, and other active ingredients Since the drug can be sufficiently blended, the amount per dose can be reduced.
The mass proportion of component (B) per tablet is preferably 1 to 70% by mass, more preferably 3 to 50% by mass, and even more preferably 5 to 40% by mass. If the mass ratio of component (B) is above the above lower limit, it will be easier to ensure hardness that does not cause wear and tear, and if it is below the above upper limit, it will be difficult to cause delayed disintegration, and other active ingredients will be sufficiently blended. This makes it possible to reduce the dose per dose.
<(C)成分>
(C)成分は、ロキソプロフェン及びその医薬的に許容可能な塩からなる群より選ばれる少なくとも一種である。
(A)成分と(B)成分との組み合わせにおいて(C)成分を併用することで、摩損が生じ難い硬度と製造直後の速やかな崩壊性を有し、且つ崩壊遅延が抑制される。
<(C) component>
Component (C) is at least one member selected from the group consisting of loxoprofen and pharmaceutically acceptable salts thereof.
By using component (C) in combination with component (A) and component (B), the product has hardness that does not easily cause abrasion and rapid disintegration immediately after production, and the delay in disintegration is suppressed.
ロキソプロフェンの医薬的に許容可能な塩としては、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩、カルシウム塩等のアルカリ土類金属塩が挙げられる。
ロキソプロフェン及びその医薬的に許容可能な塩はそれぞれ水和物の状態で存在していてもよい。水和物の例としては、ロキソプロフェンナトリウム二水和物(水分量として原薬末中約12%に相当する)が挙げられる。ロキソプロフェン及びその医薬的に許容可能な塩が水和物である場合、後述する(C)成分の服用量、および質量割合は、水和している水も含む量である。
(C)成分としては、ロキソプロフェンのアルカリ金属塩が好ましく、ロキソプロフェンナトリウムがより好ましい。
(C)成分は1種単独で用いてもよいし、2種以上を適宜組み合わせて用いてもよい。
Pharmaceutically acceptable salts of loxoprofen include, for example, alkali metal salts such as sodium salts and potassium salts, and alkaline earth metal salts such as calcium salts.
Loxoprofen and its pharmaceutically acceptable salts may each exist in the form of a hydrate. An example of a hydrate is loxoprofen sodium dihydrate (corresponding to about 12% water content in the bulk drug powder). When loxoprofen and its pharmaceutically acceptable salt are hydrates, the dose and mass proportion of component (C) described below include hydrated water.
As component (C), an alkali metal salt of loxoprofen is preferable, and loxoprofen sodium is more preferable.
Component (C) may be used alone or in an appropriate combination of two or more.
(C)成分の1回あたりの服用量は、11~170mgが好ましく、20~113mgがより好ましく、27~70mgがさらに好ましい。(C)成分の1回当たりの服用量が上記下限値以上であれば、解熱鎮痛効果の増強が期待でき、上記上限値以下であれば、(C)成分による胃傷害を抑制できる。
錠剤1錠あたりの(C)成分の質量は、10~100mgが好ましい。1錠あたりの(C)成分の質量が上記下限値以上であれば、崩壊遅延抑制効果が十分に得られるほか、摩損が生じ難くなり、上記上限値以下であれば、製造工程における製造機への付着を抑制でき、また他の有効成分を十分に配合できる。
錠剤1錠あたり(C)成分の質量割合は、1~70質量%が好ましく、2~50質量%がより好ましく、2~20質量%がさらに好ましい。(C)成分の質量割合が上記下限以上であれば、崩壊遅延抑制効果が十分に得られるほか、摩損が生じ難くなり、上記上限値以下であれば、製造工程における製造機への付着を抑制でき、また他の有効成分を十分に配合できるため1回当たりの服用量を低減できる。
The dose of component (C) per dose is preferably 11 to 170 mg, more preferably 20 to 113 mg, and even more preferably 27 to 70 mg. If the dose of component (C) per dose is equal to or higher than the above lower limit, enhancement of the antipyretic and analgesic effect can be expected, and if it is equal to or lower than the above upper limit, gastric injury caused by component (C) can be suppressed.
The mass of component (C) per tablet is preferably 10 to 100 mg. If the mass of component (C) per tablet is equal to or greater than the above lower limit, the effect of suppressing disintegration delay will be sufficiently obtained, and wear and tear will be less likely to occur. adhesion can be suppressed, and other active ingredients can be sufficiently incorporated.
The mass proportion of component (C) per tablet is preferably 1 to 70% by mass, more preferably 2 to 50% by mass, and even more preferably 2 to 20% by mass. If the mass ratio of component (C) is at least the above lower limit, the effect of suppressing disintegration delay will be sufficiently obtained, and wear and tear will be less likely to occur, and if it is below the above upper limit, adhesion to the manufacturing machine during the manufacturing process will be suppressed. In addition, since other active ingredients can be sufficiently incorporated, the amount per dose can be reduced.
<C/(A+B)比>
(C)成分/((A)成分+(B)成分)で表される質量比(以下、「C/(A+B)比」ともいう。)、すなわち(A)成分及び(B)成分の合計質量に対する(C)成分の質量の割合は、0.01~1.5が好ましく、0.02~1がより好ましく、0.03~0.5がさらに好ましく、0.2~0.5が特に好ましく、0.2~0.3が最も好ましい。C/(A+B)比が上記下限値以上であれば、崩壊遅延抑制効果がより得られやすく、また摩損が生じ難くなり、上記上限値以下であれば、製造直後の崩壊性がより優れ、また他の有効成分を十分に配合できるため1回当たりの服用量を低減できる。
<C/(A+B) ratio>
Mass ratio expressed as (C) component/((A) component + (B) component) (hereinafter also referred to as "C/(A+B) ratio"), that is, the sum of (A) component and (B) component The ratio of the mass of component (C) to the mass is preferably 0.01 to 1.5, more preferably 0.02 to 1, even more preferably 0.03 to 0.5, and 0.2 to 0.5. Particularly preferred, and most preferably 0.2 to 0.3. If the C/(A+B) ratio is at least the above lower limit, the effect of suppressing the delay in disintegration is more likely to be obtained and wear and tear is less likely to occur, and when it is at or below the above upper limit, the disintegration properties immediately after production are better, and Since other active ingredients can be sufficiently incorporated, the dosage per dose can be reduced.
<A/B比>
(A)成分/(B)成分で表される質量比(以下、「A/B比」ともいう。)、すなわち(B)成分の質量に対する(A)成分の質量の割合は、0.1~15が好ましく、0.15~10がより好ましく、0.2~8がさらに好ましく、0.35~4.5が特に好ましく、1~4.5が最も好ましい。A/B比が上記下限値以上であれば、崩壊遅延抑制効果がより得られやすく、上記上限値以下であれば、摩損が生じ難くなり、また製造直後の崩壊性がより優れる。
<A/B ratio>
The mass ratio expressed by component (A)/component (B) (hereinafter also referred to as "A/B ratio"), that is, the ratio of the mass of component (A) to the mass of component (B) is 0.1 -15 is preferred, 0.15-10 is more preferred, 0.2-8 is even more preferred, 0.35-4.5 is particularly preferred, and 1-4.5 is most preferred. If the A/B ratio is at least the above lower limit, the effect of suppressing the delay in disintegration can be more easily obtained, and if it is at most the above upper limit, wear and tear will be less likely to occur, and the disintegration properties immediately after production will be better.
<A/C比>
(A)成分/(C)成分で表される質量比(以下、「A/C比」ともいう。)、すなわち(C)成分の質量に対する(A)成分の質量の割合は、0.2~25が好ましく、0.2~20がより好ましく、0.4~10がさらに好ましく、0.5~7が特に好ましく、1~4.5が最も好ましい。A/C比が上記下限値以上であれば、製造工程における製造機への付着が抑制され、上記上限値以下であれば、保存後の崩壊遅延抑制効果がより優れる。
<A/C ratio>
The mass ratio expressed by component (A)/component (C) (hereinafter also referred to as "A/C ratio"), that is, the ratio of the mass of component (A) to the mass of component (C) is 0.2 -25 is preferred, 0.2-20 is more preferred, 0.4-10 is even more preferred, 0.5-7 is particularly preferred, and 1-4.5 is most preferred. When the A/C ratio is at least the above lower limit, adhesion to the manufacturing machine during the manufacturing process is suppressed, and when it is at most the above upper limit, the effect of suppressing the delay in disintegration after storage is more excellent.
<A+B>
錠剤1錠あたりの(A)成分及び(B)成分の合計質量(以下、「A+B合計質量」ともいう。)は、製造上問題ない範囲内であれば、特に限定されないが、35~600mgが好ましい。(C)成分を含まない場合は1錠あたりのA+B合計質量が上記下限値以上になると崩壊遅延の発生が顕著になる傾向がある。1錠あたりのA+B合計質量が上記下限値以上であれば、本発明の有用性が高い。1錠あたりのA+B合計質量が上記上限値以下であれば、錠剤の大きさを服用性に適した大きさにしやすい。
錠剤1錠あたりのA+B合計質量の割合(以下、「A+B割合」ともいう。)は、6~97質量%が好ましく、13~90質量%がより好ましく、18~80質量%がさらに好ましい。A+B割合が上記下限値以上であれば、本発明の有用性が高く、上記上限値以下であれば、他の有効成分を十分に配合できるため1回当たりの服用量を低減できる。
<A+B>
The total mass of component (A) and component (B) per tablet (hereinafter also referred to as "A+B total mass") is not particularly limited as long as it is within a range that does not cause any problems in manufacturing, but 35 to 600 mg is acceptable. preferable. When component (C) is not included, when the total mass of A+B per tablet exceeds the above lower limit, there is a tendency for the occurrence of delayed disintegration to become noticeable. If the total mass of A+B per tablet is at least the above lower limit, the present invention is highly useful. If the total mass of A+B per tablet is below the above upper limit, the size of the tablet can be easily adjusted to suit ease of administration.
The ratio of the total mass of A + B per tablet (hereinafter also referred to as "A + B ratio") is preferably 6 to 97% by mass, more preferably 13 to 90% by mass, and even more preferably 18 to 80% by mass. If the A+B ratio is at least the above lower limit value, the usefulness of the present invention is high, and if it is below the above upper limit value, other active ingredients can be sufficiently blended, so that the dosage per dose can be reduced.
<任意成分>
本態様の錠剤は、錠剤物性や保存安定性を損なわない範囲で任意に、(A)成分、(B)成分及び(C)成分以外の成分(以下、「任意成分」とも記す。)を含有していてもよい。
任意成分としては、(A)成分、(B)成分及び(C)成分以外の生理活性成分、添加剤等が挙げられる。
<Optional ingredients>
The tablet of this embodiment optionally contains components other than component (A), component (B), and component (C) (hereinafter also referred to as "optional component") within a range that does not impair the physical properties or storage stability of the tablet. You may do so.
Optional components include physiologically active components other than component (A), component (B), and component (C), additives, and the like.
生理活性成分としては、例えば、(A)成分及び(C)成分以外の解熱鎮痛成分(例えばピロキシカム、メロキシカム、アンピロキシカム、セロコキシブ、ロフェコキシブ、チアラミド、アセトアミノフェン、スルピリン等)、鎮静催眠成分(例えば、アリルイソプロピルアセチル尿素、ブロムワレリル尿素等)、抗ヒスタミン成分(例えば、塩酸イソチペンジル、塩酸ジフェニルピラリン、塩酸ジフェンヒドラミン、塩酸ジフェテロール、塩酸トリプロリジン、塩酸トリペレナミン、塩酸トンジルアミン、塩酸フェネタジン、塩酸メトジラジン、サリチル酸ジフェンヒドラミン、ジフェニルジスルホン酸カルビノキサミン、酒石酸アリメマジン、タンニン酸ジフェンヒドラミン、テオクル酸ジフェニルピラリン、ナパジシル酸メブヒドロリン、プロメタジンメチレン二サリチル酸塩、マレイン酸カルビノキサミン、dl-マレイン酸クロルフェニラミン、d-マレイン酸クロルフェニラミン、リン酸ジフェテロール等)、中枢興奮成分(例えば、安息香酸ナトリウムカフェイン、カフェイン、無水カフェイン等)、鎮咳去痰成分(コデインリン酸塩、デキストロメトルファン臭化水素酸塩、ジメモルファンリン酸塩、チペピジンヒベンズ酸塩、メトキシフェナミン塩酸塩、トリメトキノール塩酸塩、カルボシステイン、アセチルシステイン、エチルシステイン、dl-メチルエフェドリン、ブロムヘキシン塩酸塩、セラペプターゼ、塩化リゾチーム、アンブロキソール、テオフィリン、アミノフィリン)、ビタミン成分(例えば、ビタミンB1及びその誘導体並びにそれらの塩類、ビタミンB2及びその誘導体並びにそれらの塩類、ビタミンC及びその誘導体並びにそれらの塩類、ヘスペリジン及びその誘導体並びにそれらの塩類等)、生薬(例えば、ジリュウ、カノコソウ、ケイヒ、ボタンピ、サンショウ、ショウキョウ及びチンピ等)等が挙げられる。これらの生理活性成分は、1種単独で又は2種以上を適宜組み合わせて用いることができる。 Examples of physiologically active ingredients include antipyretic analgesic ingredients other than component (A) and component (C) (e.g. piroxicam, meloxicam, ampiroxicam, cerocoxib, rofecoxib, tialamide, acetaminophen, sulpirin, etc.), sedative-hypnotic ingredients (e.g. , allylisopropylacetylurea, bromovalerylurea, etc.), antihistamine components (e.g., isothipendyl hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, difeterol hydrochloride, triprolidine hydrochloride, tripelenamine hydrochloride, tonzylamine hydrochloride, phenethazine hydrochloride, methdilazine hydrochloride, diphenhydramine salicylate, diphenyl Carbinoxamine disulfonate, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline theoculate, mebhydroline napadisylate, promethazine methylene disalicylate, carbinoxamine maleate, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, difeterol phosphate, etc. ), central stimulant ingredients (e.g. sodium benzoate caffeine, caffeine, anhydrous caffeine, etc.), antitussive expectorant ingredients (codeine phosphate, dextromethorphan hydrobromide, dimemorphan phosphate, tipepidine hibenzate) salt, methoxyphenamine hydrochloride, trimethoquinol hydrochloride, carbocysteine, acetylcysteine, ethylcysteine, dl-methylephedrine, bromhexine hydrochloride, serrapeptase, lysozyme chloride, ambroxol, theophylline, aminophylline), vitamin components (e.g. , vitamin B1 and its derivatives and their salts, vitamin B2 and its derivatives and their salts, vitamin C and its derivatives and their salts, hesperidin and its derivatives and their salts, etc.), herbal medicines (for example, valerian root, valerian root, Keihi, Botanpi, Sansho, Shokyo, Chinpi, etc.). These physiologically active ingredients can be used alone or in an appropriate combination of two or more.
本態様の錠剤が生薬を含む場合、錠剤1錠あたりの生薬の質量割合は50質量%以下であることが好ましく、10質量%以下であることがより好ましい。生薬の質量割合が上記上限値以下であれば、崩壊遅延の抑制効果の増強が期待できる。
本態様の錠剤は生薬を含まないことが好ましい。
When the tablet of this embodiment contains a crude drug, the mass proportion of the crude drug per tablet is preferably 50% by mass or less, more preferably 10% by mass or less. If the mass proportion of the crude drug is below the above upper limit, it can be expected that the effect of suppressing the delay in disintegration will be enhanced.
Preferably, the tablet of this embodiment does not contain any crude drug.
添加剤としては、例えば、結合剤、賦形剤、崩壊剤、滑沢剤、香料、甘味剤、酸味料等が挙げられる。
結合剤としては、デンプン(トウモロコシデンプン、コムギデンプン、バレイショデンプン等)、α化デンプン、結晶セルロース、ゼラチン、アラビアゴム末、ポリビニルピロリドン、プルラン、デキストリン等が挙げられる。
賦形剤としては、乳糖、マンニトール、エリスリトール、キシリトール、ラクチトール、トレハロース、マルチトール、カルボキシメチルセルロース、カルボキシメチルセルロースカルシウム、カルボキシメチルスターチ、カルボキシメチルスターチナトリウム、リン酸水素ナトリウム、リン酸水素カルシウム等が挙げられる。
崩壊剤としては、低置換度ヒドロキシプロピルセルロース、カルメロース、カルメロースナトリウム、カルメロースカルシウム、クロスポビドン、クロスカルメロースナトリウム、部分α化デンプン等が挙げられる。
滑沢剤としては、ステアリン酸マグネシウム、ステアリン酸カルシウム、フマル酸ステアリルナトリウム、ショ糖脂肪酸エステル、軽質無水ケイ酸、タルク等が挙げられる。
香料としては、メントール、リモネン、植物精油(ハッカ油、ミント油、ライチ油、オレンジ油、レモン油等)等が挙げられる。
甘味料としては、サッカリンナトリウム、アスパルテーム、ステビア、スクラロース、グリチルリチン酸二カリウム、アセスルファムカリウム等が挙げられる。
酸味料としては、クエン酸、酒石酸、リンゴ酸、コハク酸、フマル酸、乳酸又はそれらの塩等が挙げられる。
これらの添加剤は、1種単独で又は2種以上を適宜組み合わせて用いることができる。
Examples of additives include binders, excipients, disintegrants, lubricants, fragrances, sweeteners, and acidulants.
Examples of the binder include starch (corn starch, wheat starch, potato starch, etc.), pregelatinized starch, crystalline cellulose, gelatin, gum arabic powder, polyvinylpyrrolidone, pullulan, dextrin, and the like.
Excipients include lactose, mannitol, erythritol, xylitol, lactitol, trehalose, maltitol, carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl starch, sodium carboxymethyl starch, sodium hydrogen phosphate, calcium hydrogen phosphate, etc. .
Examples of the disintegrant include low-substituted hydroxypropylcellulose, carmellose, carmellose sodium, carmellose calcium, crospovidone, croscarmellose sodium, partially pregelatinized starch, and the like.
Examples of the lubricant include magnesium stearate, calcium stearate, sodium stearyl fumarate, sucrose fatty acid ester, light silicic anhydride, and talc.
Examples of fragrances include menthol, limonene, vegetable essential oils (mentha oil, mint oil, lychee oil, orange oil, lemon oil, etc.).
Examples of sweeteners include sodium saccharin, aspartame, stevia, sucralose, dipotassium glycyrrhizinate, potassium acesulfame, and the like.
Examples of the acidulant include citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid, or salts thereof.
These additives can be used alone or in an appropriate combination of two or more.
本態様の錠剤は、摩損が生じ難い硬度を確保しやすくする点で、結合剤を含有することが好ましい。
錠剤1錠あたりの結合剤の質量は、0.1~300mgが好ましく、1~100mgがより好ましい。結合剤の質量が上記下限値以上であれば、摩損がより生じ難く、上記上限値以下であれば、崩壊性がより優れる。
錠剤1錠あたりの結合剤の質量割合は、0.1~50質量%が好ましく、1~30質量%がより好ましい。結合剤の質量割合が上記下限値以上であれば、摩損がより生じ難く、上記上限値以下であれば、崩壊性がより優れる。
The tablet of this embodiment preferably contains a binder from the viewpoint of easily ensuring hardness that does not easily cause wear and tear.
The mass of the binder per tablet is preferably 0.1 to 300 mg, more preferably 1 to 100 mg. When the mass of the binder is at least the above lower limit, wear and tear is less likely to occur, and when it is at most the above upper limit, the disintegration properties are more excellent.
The mass proportion of the binder per tablet is preferably 0.1 to 50% by mass, more preferably 1 to 30% by mass. If the mass proportion of the binder is at least the above lower limit, wear and tear will be less likely to occur, and if it is below the above upper limit, the disintegration properties will be better.
本態様の錠剤は、硬度、崩壊性及び製造性の点で、滑沢剤を含有することが好ましい。
錠剤1錠あたりの滑沢剤の質量は、0.1~20mgが好ましく、1~10mgがより好ましい。滑沢剤の質量が上記下限値以上であれば、製造性がより優れ、上記上限値以下であれば、硬度及び崩壊性がより優れる。
錠剤1錠あたりの滑沢剤の質量割合は、0.01~5質量%が好ましく、0.1~3質量%がより好ましい。滑沢剤の質量割合が上記下限値以上であれば、製造性がより優れ、上記上限値以下であれば、硬度及び崩壊性がより優れる。
The tablet of this embodiment preferably contains a lubricant in terms of hardness, disintegration, and manufacturability.
The mass of the lubricant per tablet is preferably 0.1 to 20 mg, more preferably 1 to 10 mg. If the mass of the lubricant is greater than or equal to the above lower limit, the manufacturability will be better, and if it is less than or equal to the above upper limit, the hardness and disintegrability will be better.
The mass proportion of the lubricant per tablet is preferably 0.01 to 5% by mass, more preferably 0.1 to 3% by mass. If the mass proportion of the lubricant is at least the above lower limit, the manufacturability will be better, and if it is less than the above upper limit, the hardness and disintegrability will be better.
<錠剤の形態>
錠剤の寸法は特に限定されないが、錠剤の取り扱いやすさと嚥下性の観点から、錠剤の径として5~14mmφが好ましく、6~13mmφがより好ましく、7~12mmφがさらに好ましい。
1錠あたりの錠剤質量は、150mg~750mg程度が適切である。
錠剤の形状は特に限定されないが、スミ角平錠、スミ丸平錠、丸みを帯びたR錠、又は2段R錠が好ましい。
<Tablet form>
The size of the tablet is not particularly limited, but from the viewpoint of ease of handling and swallowing of the tablet, the diameter of the tablet is preferably 5 to 14 mmφ, more preferably 6 to 13 mmφ, and even more preferably 7 to 12 mmφ.
The appropriate mass of each tablet is about 150 mg to 750 mg.
The shape of the tablet is not particularly limited, but preferably a square square tablet, a round flat tablet, a rounded R tablet, or a two-stage R tablet.
錠剤は、単層錠でも良いし、他の任意の層を加え積層錠としてもよい。
錠剤が単層錠の場合、錠剤は、上述した(A)成分、(B)成分及び(C)成分を含む錠剤で構成される。
錠剤が積層錠の場合、上述した(A)成分、(B)成分及び(C)成分は同一の層に含まれても異なる層に含まれてもよい。例えば、積層錠は、(A)成分、(B)成分及び(C)成分を含む薬物層と、この薬物層以外の層(任意層)とで構成されてもよい。また、(B)成分及び(C)成分を含む薬物層と、(A)成分を含む薬物層とで構成されてもよく、(A)成分及び(C)成分を含む薬物層と、(B)成分を含む薬物層とで構成されていてもよく、(A)成分及び(C)成分を含む薬物層と、(B)成分及び(C)成分を含む薬物層とで構成されてもよく、それぞれの形態においてさらに任意層を有してもよい。本態様では、(C)成分による効果が効果的に得られる点から、上述した(A)成分、(B)成分及び(C)成分を含む薬物層を有することが好ましい。
なお、任意層は、(A)成分、(B)成分及び(C)成分のいずれか1以上を含んでいても、いずれも含まなくてもよい。任意層におけるこれらの成分の含有の有無及び含有量は、錠剤1錠あたりのこれらの成分の服用量等を勘案して適宜、選択することができる。また、上述した任意成分は、薬物層のみに含まれていてもよいし、任意層のみに含まれていてもよいし、薬物層及び任意層の両方に含まれていてもよい。錠剤が単層錠の場合、任意成分は薬物層に含まれる。
The tablet may be a single-layer tablet, or may be a laminated tablet by adding any other layer.
When the tablet is a single-layer tablet, the tablet is composed of a tablet containing the above-mentioned component (A), component (B), and component (C).
When the tablet is a layered tablet, the above-mentioned components (A), (B) and (C) may be contained in the same layer or in different layers. For example, a laminated tablet may be composed of a drug layer containing component (A), component (B), and component (C), and a layer (optional layer) other than the drug layer. Further, it may be composed of a drug layer containing the component (B) and the component (C), and a drug layer containing the component (A), and a drug layer containing the component (A) and the component (C), and a drug layer containing the component (A). ) may be composed of a drug layer containing the component (A) and the component (C), and a drug layer containing the component (B) and the component (C). , each form may further have an optional layer. In this embodiment, it is preferable to have a drug layer containing the above-described components (A), (B), and (C), since the effect of component (C) can be effectively obtained.
Note that the optional layer may contain one or more of component (A), component (B), and component (C), or may contain none of them. The presence or absence and content of these components in the arbitrary layer can be appropriately selected in consideration of the dosage of these components per tablet, etc. Further, the above-mentioned optional components may be contained only in the drug layer, only in the arbitrary layer, or in both the drug layer and the arbitrary layer. If the tablet is a single-layer tablet, the optional ingredients are included in the drug layer.
錠剤中の水分量は、錠剤の総質量に対し、1~10質量%が好ましい。水分量が上記下限値以上であれば、経時による圧縮時の成形性の低下が生じ難く、上記上限値以下であれば、崩壊遅延抑制効果がより優れる。
錠剤中の水分量は、電子水分計(例えば島津製作所製のMOISTURE BALANCE MOC-120H)で、錠剤の粉砕物を120℃10分間熱したときの乾燥減量から算出できる。
なお、(C)成分としてロキソプロフェンナトリウム二水和物等の水和物を用いる場合、錠剤中の水分には、この水和物より持ち込まれる水分も含まれる。
The amount of water in the tablet is preferably 1 to 10% by mass based on the total mass of the tablet. When the moisture content is at least the above lower limit, the moldability during compression is less likely to deteriorate over time, and when it is at most the above upper limit, the effect of suppressing disintegration delay is more excellent.
The amount of water in the tablet can be calculated from the loss on drying when the crushed tablet is heated at 120° C. for 10 minutes using an electronic moisture meter (for example, MOISTURE BALANCE MOC-120H manufactured by Shimadzu Corporation).
Note that when a hydrate such as loxoprofen sodium dihydrate is used as component (C), the water in the tablet also includes water brought in from this hydrate.
<錠剤の製造方法>
本態様の錠剤は、錠剤を構成する粉体(以下、「薬物含有粉体」という。)を打錠成形することで得られる。以下、本態様の錠剤の製造方法の一実施形態について説明する。
本実施形態の錠剤の製造方法は、臼と杵とを有する打錠機を用いて、薬物含有粉体を打錠成形する工程(打錠工程)を有する。
<Tablet manufacturing method>
The tablet of this embodiment is obtained by compressing the powder (hereinafter referred to as "drug-containing powder") constituting the tablet. An embodiment of the tablet manufacturing method of this aspect will be described below.
The method for manufacturing a tablet of this embodiment includes a step of compressing a drug-containing powder into a tablet using a tableting machine having a mortar and a punch (tableting step).
薬物含有粉体は、(A)成分、(B)成分及び(C)成分を含有する粉体であればよく、必要に応じて任意成分を含有してもよい。
薬物含有粉体は、例えば、粉体の(A)成分と、粉体の(B)成分と、粉体の(C)成分との粉体混合物でもよいし、(A)成分、(B)成分及び(C)成分を含む造粒物でもよい。
薬物含有粉体は、予め混合されたものでもよく、新たに調製されたものでもよい。すなわち、本実施形態の錠剤の製造方法は、粉体の各成分を混合して薬物含有粉体を調製する工程(粉体調製工程)を有してもよい。
The drug-containing powder may be any powder containing component (A), component (B), and component (C), and may contain arbitrary components as necessary.
The drug-containing powder may be, for example, a powder mixture of component (A), component (B), and component (C), or component (A), component (B). It may also be a granulated product containing the component and component (C).
The drug-containing powder may be premixed or freshly prepared. That is, the method for manufacturing a tablet of the present embodiment may include a step of preparing a drug-containing powder by mixing each component of the powder (powder preparation step).
粉体調製工程は、粉体の(A)成分と、粉体の(B)成分と、粉体の(C)成分と、必要に応じて粉体の任意成分とを混合して薬物含有粉体を得る。
粉体調製工程における混合方法としては特に限定されず、従来公知の粉体混合方法が挙げられる。
粉体調製工程に用いられる各成分は、公知の製造方法により得られたものを用いてもよく、市販のものを用いてもよい。各成分は、原末がそのまま用いられてもよく、造粒されたもの(造粒物)が用いられてもよい。二種以上の造粒物が併用されてもよい。造粒物は(A)成分、(B)成分及び(C)成分より選ばれる少なくとも一種を含んでいてもよく、さらに任意成分を含んでもよい。製造性及び保存後の崩壊遅延抑制効果が優れる点から、(C)成分は、(A)成分および(B)成分の少なくとも一種と同一造粒物中に含まれることが好ましく、(A)成分と同一造粒物中に含まれることがより好ましい。
造粒物の造粒方法としては公知の造粒方法を採用でき、湿式造粒法、乾式造粒法もしくは溶融造粒法などにより製造できるが、製造機器への付着性が低く安定性の観点から、湿式造粒法が好ましく、湿式造粒法の中でも攪拌造粒又は流動層造粒が特に好ましい。
In the powder preparation step, component (A) of the powder, component (B) of the powder, component (C) of the powder, and optional components of the powder are mixed to form a drug-containing powder. Get a body.
The mixing method in the powder preparation step is not particularly limited, and conventionally known powder mixing methods can be used.
Each component used in the powder preparation step may be obtained by a known manufacturing method, or may be commercially available. Each component may be used as a raw powder or in a granulated form (granulated product). Two or more types of granules may be used in combination. The granules may contain at least one selected from component (A), component (B), and component (C), and may further contain an optional component. From the viewpoint of excellent manufacturability and the effect of suppressing the delay in disintegration after storage, component (C) is preferably contained in the same granule as at least one of component (A) and component (B), and component (A) It is more preferable that the granules are contained in the same granulate.
Known granulation methods can be used to granulate the granules, such as wet granulation, dry granulation, or melt granulation. Therefore, a wet granulation method is preferred, and among the wet granulation methods, stirring granulation or fluidized bed granulation is particularly preferred.
打錠工程で用いられる打錠機としては、例えば、ロータリー式打錠機(株式会社菊水製作所製:リブラ3L)等が挙げられる。
打錠圧、回転盤の回転速度等の打錠条件は適宜設定される。
なお、錠剤が積層錠である場合、薬物含有粉体は、臼に最初に充填されてもよく、任意層を構成する成分よりも後に充填されてもよい。
Examples of the tableting machine used in the tableting process include a rotary tabletting machine (Libra 3L, manufactured by Kikusui Seisakusho Co., Ltd.).
Tableting conditions such as tableting pressure and rotating speed of the rotary disk are appropriately set.
In addition, when the tablet is a laminated tablet, the drug-containing powder may be filled into the mortar first, or may be filled after the components constituting the arbitrary layers.
〔コーティング錠〕
本発明の一態様に係るコーティング錠は、上記した錠剤を素錠とし、この素錠の表面にコーティング層を有する。すなわち、(A)成分、(B)成分及び(C)成分を含有する錠剤である素錠と、この素錠の表面に設けられたコーティング層とを有する。
[Coated tablets]
The coated tablet according to one aspect of the present invention uses the above-mentioned tablet as an uncoated tablet, and has a coating layer on the surface of the uncoated tablet. That is, it has a plain tablet that is a tablet containing component (A), component (B), and component (C), and a coating layer provided on the surface of this plain tablet.
<コーティング層>
コーティング層は、コーティング剤を含む構成素材より形成されている層である。
素錠の表面にコーティング層を有することで、素錠の吸湿が抑制され、崩壊遅延抑制効果が向上する。
<Coating layer>
The coating layer is a layer formed from a constituent material containing a coating agent.
By having a coating layer on the surface of the uncoated tablet, moisture absorption of the uncoated tablet is suppressed, and the effect of suppressing disintegration delay is improved.
コーティング剤としては、崩壊性を著しく損なわないものを選択することが好ましく、例えば皮膜形成剤、可塑剤が好ましい。
皮膜形成剤としては、例えばカルメロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース(ヒプロメロース)、ヒドロキシメチルセルロース、メチルセルロース等のセルロース類;アラビアゴム、カルボキシビニルポリマー、ポビドン、ポリビニルアルコール、ポリアクリル酸、単糖類、二糖類以上の多糖類(砂糖(グラニュー糖等)、乳糖、麦芽糖、キシロース、異性化乳糖等)、糖アルコール(パラチニット、ソルビトール、ラクチトール、エリスリトール、キシリトール、還元澱粉糖化物、マルチトール、マンニトール等)、水飴、異性化糖類、オリゴ糖、スクロース、トレハロース、還元澱粉糖化物(還元澱粉分解物等)等が挙げられる。特に、製造性及び防湿性に優れる点から、ヒドロキシプロピルメチルセルロース、ポリビニルアルコールが好ましい。
可塑剤としては、例えばクエン酸トリエチル、トリアセチン、カルナウバロウ、グリセリン、マクロゴール、プロピレングリコール、ポリソルベート等の、日本薬局方(広川書店)及び医薬品添加物規格(株式会社薬事日報社)等の公定書に記載されているものが挙げられる。
コーティング剤は1種単独で用いてもよく、2種以上を組み合わせて用いてもよい。
As the coating agent, it is preferable to select one that does not significantly impair the disintegrability, such as film forming agents and plasticizers.
Examples of film-forming agents include celluloses such as carmellose, hydroxypropylcellulose, hydroxypropylmethylcellulose (hypromellose), hydroxymethylcellulose, and methylcellulose; gum arabic, carboxyvinyl polymer, povidone, polyvinyl alcohol, polyacrylic acid, monosaccharides, and disaccharides. The above polysaccharides (sugar (granulated sugar, etc.), lactose, maltose, xylose, isomerized lactose, etc.), sugar alcohols (palatinit, sorbitol, lactitol, erythritol, xylitol, reduced starch saccharide, maltitol, mannitol, etc.), starch syrup , isomerized sugars, oligosaccharides, sucrose, trehalose, reduced starch saccharides (reduced starch decomposition products, etc.), and the like. In particular, hydroxypropyl methylcellulose and polyvinyl alcohol are preferred from the viewpoint of excellent manufacturability and moisture resistance.
Examples of plasticizers include triethyl citrate, triacetin, carnauba wax, glycerin, macrogol, propylene glycol, and polysorbate, which are listed in the Japanese Pharmacopoeia (Hirokawa Shoten) and Pharmaceutical Excipient Standards (Yakuji Nippo Co., Ltd.). These include those listed.
One type of coating agent may be used alone, or two or more types may be used in combination.
コーティング層は、無機顔料を含むことが好ましい。コーティング層が無機顔料を含んでいれば、崩壊遅延抑制効果がより優れる。
無機顔料としては、製造上問題ないものであれば特に限定されないが、例えば酸化チタン、三二酸化鉄、黄色三二酸化鉄、黒酸化鉄、褐色酸化鉄、酸化亜鉛、軽質無水ケイ酸、含水二酸化ケイ素等が挙げられる。これらの中でも、崩壊遅延抑制効果が高い点で、酸化チタン、三二酸化鉄、黄色三二酸化鉄、酸化亜鉛、軽質無水ケイ酸が好ましく、酸化チタン、三二酸化鉄が特に好ましい。
無機顔料は1種単独で用いてもよく、2種以上を組み合わせて用いてもよい。
Preferably, the coating layer contains an inorganic pigment. If the coating layer contains an inorganic pigment, the effect of suppressing the delay in disintegration will be more excellent.
Inorganic pigments are not particularly limited as long as they do not cause manufacturing problems, but examples include titanium oxide, iron sesquioxide, yellow iron sesquioxide, black iron oxide, brown iron oxide, zinc oxide, light anhydrous silicic acid, and hydrated silicon dioxide. etc. Among these, titanium oxide, iron sesquioxide, yellow iron sesquioxide, zinc oxide, and light anhydrous silicic acid are preferable, and titanium oxide and iron sesquioxide are particularly preferable, since they have a high effect of suppressing the delay in disintegration.
Inorganic pigments may be used alone or in combination of two or more.
コーティング層が無機顔料を含む場合、無機顔料の含有量は、製造上問題ない範囲であれば特に限定されないが、コーティング層の総質量に対し、0.01~5質量%が好ましく、0.05~1質量%がより好ましく、0.1~0.7質量%が特に好ましい。無機顔料の含有量が上記下限値以上であれば、無機顔料による崩壊遅延抑制効果を得やすくなり、上記上限値以下であれば、コーティング層の成形性が良好となる。 When the coating layer contains an inorganic pigment, the content of the inorganic pigment is not particularly limited as long as it does not cause any problems in production, but it is preferably 0.01 to 5% by mass, and 0.05% by mass based on the total mass of the coating layer. It is more preferably 1% by mass, and particularly preferably 0.1% by mass to 0.7% by mass. If the content of the inorganic pigment is at least the above lower limit, it will be easier to obtain the effect of suppressing the delay in disintegration by the inorganic pigment, and if it is below the above upper limit, the moldability of the coating layer will be good.
素錠の質量に対するコーティング層の質量割合は、0.1~10質量%が好ましく、0.5~5質量%がより好ましく、1~3質量%がさらに好ましい。コーティング層の質量割合が上記下限値以上であれば、崩壊遅延抑制効果がより優れ、上記上限値以下であれば、製造直後の崩壊性がより優れる。 The mass ratio of the coating layer to the mass of the uncoated tablet is preferably 0.1 to 10% by mass, more preferably 0.5 to 5% by mass, and even more preferably 1 to 3% by mass. If the mass ratio of the coating layer is at least the above lower limit, the disintegration delay suppressing effect will be better, and if it is below the above upper limit, the disintegration properties immediately after production will be better.
<コーティング錠の製造方法>
本態様のコーティング錠は、上記した錠剤の製造方法により錠剤を製造し、得られた錠剤を素錠とし、この素錠の表面に上述したコーティング層を設けることで製造することができる。
素錠の表面にコーティング層を設ける方法は、従来知られた方法を用いることができる。例えば、まず、コーティング剤を水等の媒体に分散させてコーティング剤の分散液であるコーティング液を得る。このとき、必要に応じて、コーティング剤とともに無機顔料を媒体に分散させる。その後、前記コーティング液を噴霧等によって素錠を被覆するように設ける。その後、コーティング液の前記媒体を乾燥させる。これにより、コーティング層が形成され、コーティング錠が得られる。
<Method for manufacturing coated tablets>
The coated tablet of this embodiment can be manufactured by manufacturing a tablet by the above-described tablet manufacturing method, making the obtained tablet into a plain tablet, and providing the above-mentioned coating layer on the surface of the plain tablet.
A conventionally known method can be used to provide a coating layer on the surface of the uncoated tablet. For example, first, a coating agent is dispersed in a medium such as water to obtain a coating liquid that is a dispersion of the coating agent. At this time, the inorganic pigment is dispersed in the medium together with the coating agent, if necessary. Thereafter, the coating liquid is applied to cover the uncoated tablet by spraying or the like. Thereafter, the medium of coating liquid is dried. Thereby, a coating layer is formed and a coated tablet is obtained.
以下、実施例を示して本発明を詳細に説明するが、本発明は以下の記載によって限定されるものではない。 EXAMPLES Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited to the following description.
[使用原料]
(A)成分として、以下に示す化合物を用いた。
・エテンザミド:岩城製薬株式会社製、「エテンザミド」日本薬局方規格。
[Raw materials used]
The following compounds were used as component (A).
・Ethenzamide: Manufactured by Iwaki Pharmaceutical Co., Ltd., "Ethenzamide" Japanese Pharmacopoeia Standards.
(B)成分として、以下に示す化合物を用いた。
・乾燥水酸化アルミニウムゲル:協和化学工業株式会社製、「乾燥水酸化アルミニウムゲルSN」。
・メタケイ酸アルミン酸マグネシウム(メタケイ酸アルミン酸Mg):富士化学工業株式会社製、「ノイシリン」(登録商標)。
・合成ヒドロタルサイト:協和化学工業株式会社製、「アルカマック SN」(登録商標)。
・酸化マグネシウム:富田製薬株式会社製、「酸化マグネシウム」。
As component (B), the following compounds were used.
- Dry aluminum hydroxide gel: "Dried aluminum hydroxide gel SN" manufactured by Kyowa Chemical Industry Co., Ltd.
- Magnesium metasilicate aluminate (Mg metasilicate aluminate): "Neusilin" (registered trademark) manufactured by Fuji Chemical Industry Co., Ltd.
-Synthetic hydrotalcite: "Alcamac SN" (registered trademark) manufactured by Kyowa Chemical Industry Co., Ltd.
・Magnesium oxide: "Magnesium oxide" manufactured by Tomita Pharmaceutical Co., Ltd.
(C)成分として、以下に示す化合物を用いた。
・ロキソプロフェンナトリウム二水和物:大和薬品工業株式会社製、日本薬局方規格。
As component (C), the following compounds were used.
・Loxoprofen sodium dihydrate: Manufactured by Daiwa Pharmaceutical Co., Ltd., Japanese Pharmacopoeia standards.
任意成分として、以下に示す化合物を用いた。
・低置換度ヒドロキシプロピルセルロース:信越化学工業株式会社製、「LH-31」。
・トウモロコシデンプン:松谷化学工業株式会社製、「局方松谷コーンスターチ」。
・結晶セルロース:旭化成株式会社製、「UF-702」。
The following compounds were used as optional components.
- Low-substituted hydroxypropyl cellulose: "LH-31" manufactured by Shin-Etsu Chemical Co., Ltd.
・Corn starch: "Koppo Matsutani Corn Starch" manufactured by Matsutani Chemical Industry Co., Ltd.
- Crystalline cellulose: "UF-702" manufactured by Asahi Kasei Corporation.
コーティング層を形成する材料として、以下に示す化合物を用いた。
・コーティング剤:日本カラコン合同会社製、「オパドライ(ポリマーとしてヒドロキシプロピルメチルセルロースを使用)」(商標)。
・酸化チタン:堺化学工業株式会社製、「酸化チタン」。
・三二酸化鉄:癸巳化成株式会社製、「三二酸化鉄」。
The following compounds were used as materials for forming the coating layer.
・Coating agent: “Opadry (uses hydroxypropyl methylcellulose as polymer)” (trademark) manufactured by Nippon Colorcon LLC.
・Titanium oxide: "Titanium oxide" manufactured by Sakai Chemical Industry Co., Ltd.
・Iron sesquioxide: "Iron sesquioxide" manufactured by Hijimi Kasei Co., Ltd.
[評価方法]
<錠剤強度の評価>
錠剤硬度が70Nとなるように本圧を調整し製造した錠剤について、第十七改日本薬局方に収載された錠剤の摩損度試験法に準じ、摩損度(初期質量に対する減少質量の質量百分率)を求め、以下の基準で評価した。評点2点以上を合格とした。なお、日本薬局方では、摩損度は1.0%以下が望ましいとされている。
(評価基準)
4:摩損度が0.1%以下。
3:摩損度が0.1%を超え、0.5%以下。
2:摩損度が0.5%を超え~1.0%以下。
1:摩損度が1.0%を超える。
[Evaluation method]
<Evaluation of tablet strength>
For tablets manufactured by adjusting the main pressure so that the tablet hardness is 70N, the friability (mass percentage of the reduced mass relative to the initial mass) was determined according to the tablet friability test method listed in the 17th revised Japanese Pharmacopoeia. was determined and evaluated using the following criteria. A score of 2 points or more was considered a pass. Note that, according to the Japanese Pharmacopoeia, the degree of friability is desirably 1.0% or less.
(Evaluation criteria)
4: Friability is 0.1% or less.
3: Friability is more than 0.1% and less than 0.5%.
2: Friability of more than 0.5% to less than 1.0%.
1: Friability exceeds 1.0%.
<製造直後の崩壊性の評価>
錠剤硬度が70Nとなるように本圧を調整し製造した錠剤について、第十七改日本薬局方に収載された錠剤の崩壊試験法に準じ、崩壊試験液として水を用い、6錠の崩壊時間(分および秒)を測定し、その平均値を求めた。求めた平均値を分に換算し、小数点以下第1位を四捨五入した値を「製造直後崩壊時間」とした。例えば、平均値が0.5分以上1.5分未満(30秒以上1分30秒未満)の場合の製造直後崩壊時間は1分である。なお、0.5分未満の場合は0分とする。
<Evaluation of disintegration immediately after production>
For tablets manufactured by adjusting the main pressure so that the tablet hardness is 70N, the disintegration time of 6 tablets was determined using water as the disintegration test liquid according to the tablet disintegration test method listed in the 17th revised Japanese Pharmacopoeia. (minutes and seconds) and calculated the average value. The obtained average value was converted into minutes, and the value rounded to the first decimal place was defined as the "disintegration time immediately after production." For example, when the average value is 0.5 minutes or more and less than 1.5 minutes (30 seconds or more and less than 1 minute 30 seconds), the immediate disintegration time is 1 minute. Note that if it is less than 0.5 minutes, it is considered 0 minutes.
<保存後の崩壊性の評価>
予め錠剤を収容する複数のポケットを成形した樹脂シート(大成化工製、「TAS-230」)の各ポケットに、製造した錠剤を入れ、樹脂シートのポケット開口側にアルミ箔を貼り合わせてPTP(プレススルー包装体)を得た。このPTPを50℃75%RHで8週間保存した。その後、PTPから錠剤を取出し、上記と同様に6錠の崩壊時間(分および秒)を測定し、その平均値を求めた。求めた平均値を分に換算し、小数点以下第1位を四捨五入した値を「保存後崩壊時間」とした。
<Evaluation of disintegration after storage>
The manufactured tablets are placed in each pocket of a resin sheet (TAS-230, manufactured by Taisei Kako) that has been pre-molded with multiple pockets for accommodating tablets, aluminum foil is pasted on the pocket opening side of the resin sheet, and PTP ( A press-through package) was obtained. This PTP was stored at 50° C. and 75% RH for 8 weeks. Thereafter, the tablets were taken out from the PTP, and the disintegration times (minutes and seconds) of the six tablets were measured in the same manner as above, and the average value was determined. The obtained average value was converted into minutes, and the value rounded to the first decimal place was defined as the "post-storage disintegration time."
<崩壊遅延の評価>
製造直後の崩壊性の評価で求めた「製造直後崩壊時間」T1(分)と、保存後の崩壊性の評価で求めた「保存後崩壊時間」T2(分)との差(T2-T1)を算出した。その値を崩壊遅延とし、以下の基準で評価した。評点2点以上を合格とした。なお、崩壊遅延が生じない錠剤において、測定のばらつきや四捨五入の影響により、上記の差が0分未満になる場合があるが、その場合は評点を5とした。
(評価基準)
5:崩壊遅延が10分未満。
4:崩壊遅延が10分以上~20分未満。
3:崩壊遅延が20分以上~30分未満。
2:崩壊遅延が30分以上~40分未満。
1:崩壊遅延が40分以上。
<Evaluation of decay delay>
The difference ( T 2 -T 1 ) was calculated. The value was defined as the decay delay and evaluated based on the following criteria. A score of 2 points or more was considered a pass. In addition, in tablets that do not cause disintegration delay, the above-mentioned difference may be less than 0 minutes due to measurement variations or rounding, and in that case, the score was set as 5.
(Evaluation criteria)
5: Disintegration delay is less than 10 minutes.
4: Disintegration delay is 10 minutes or more and less than 20 minutes.
3: Disintegration delay is 20 minutes or more and less than 30 minutes.
2: Disintegration delay is 30 minutes or more and less than 40 minutes.
1: Collapse delay is 40 minutes or more.
[実施例1~16、比較例1~4]
表1、2又は4に示す(A)成分、(B)成分、(C)成分及び任意成分を、錠剤1錠当たりの各成分の含有量が表1、2又は4に示す値となるように秤取し、混合して薬物含有粉体を調製した。得られた薬物含有粉体を以下に示す打錠条件で打錠成形して錠剤(単層錠)を得た。得られた錠剤の評価結果を表1、2、4に示す。
[Examples 1 to 16, Comparative Examples 1 to 4]
Component (A), component (B), component (C) and optional ingredients shown in Table 1, 2 or 4 are mixed so that the content of each component per tablet is the value shown in Table 1, 2 or 4. were weighed and mixed to prepare a drug-containing powder. The obtained drug-containing powder was compressed under the tableting conditions shown below to obtain a tablet (single-layer tablet). The evaluation results of the obtained tablets are shown in Tables 1, 2, and 4.
(打錠条件)
打錠機:ロータリー式打錠機 リブラ3L(菊水製作所製)。
盤回転速度:20rpm。
臼杵:φ8.5mm(2段R)×12本立て、刻印無し(キャップ高さ0.1mm、R1=3.4、R2=10)。
予圧:2kN(約20MPa、約200kg/cm2)。
本圧:錠剤ごとに調整(錠剤硬度が70Nとなるように調整)。
(Tableting conditions)
Tablet press: Rotary tablet press Libra 3L (manufactured by Kikusui Seisakusho).
Plate rotation speed: 20 rpm.
Mortar: φ8.5mm (2 steps R) x 12 pieces, no markings (cap height 0.1mm, R1 = 3.4, R2 = 10).
Preload: 2kN (about 20MPa, about 200kg/cm 2 ).
Main pressure: Adjusted for each tablet (adjusted so that the tablet hardness was 70N).
[実施例17~23]
実施例1と同様にして錠剤を製造し、この錠剤を素錠とした。
表3に示すコーティング層の欄に示す材料を、錠剤1錠当たりの各材料の含有量が表3に示す値となるように秤取し、水を加えてコーティング液を調製した。コーティング液の固形分濃度は15質量%とした。得られたコーティング液を、アクアコーター48型(フロイント産業株式会社製)を用いて、給気温度60℃、給気風量2.3m3/分、排気温度42±2℃の条件下で、素錠に噴霧した。その後、給気温度60℃、給気風量2.3m3/分で20分間乾燥させて、素錠の表面にコーティング層が設けられたコーティング錠を得た。得られたコーティング錠の評価結果を表3に示す。
[Examples 17 to 23]
Tablets were manufactured in the same manner as in Example 1, and the tablets were made into uncoated tablets.
The materials shown in the column of coating layer shown in Table 3 were weighed out so that the content of each material per tablet became the value shown in Table 3, and water was added to prepare a coating liquid. The solid content concentration of the coating liquid was 15% by mass. The obtained coating liquid was coated using an Aqua Coater Model 48 (manufactured by Freund Sangyo Co., Ltd.) under conditions of an air supply temperature of 60°C, a supply air flow rate of 2.3 m 3 /min, and an exhaust temperature of 42 ± 2°C. Sprayed onto tablets. Thereafter, the tablets were dried for 20 minutes at a supply air temperature of 60° C. and a supply air flow rate of 2.3 m 3 /min to obtain coated tablets in which a coating layer was provided on the surface of the plain tablet. Table 3 shows the evaluation results of the obtained coated tablets.
(A)成分を含み、(B)成分及び(C)成分を含まない比較例1の錠剤は、製造直後において、摩損度が大きく、崩壊性が悪かった。
(A)成分及び(B)成分を含み、(C)成分を含まない比較例2~4の錠剤は、保存により顕著な崩壊遅延が発生した。
これに対し、(A)成分、(B)成分及び(C)成分を同一層に含む実施例1~23の錠剤又はコーティング錠は、製造直後において、摩損度が小さく、崩壊性が良好であった。また、保存による崩壊遅延が抑制されていた。
The tablet of Comparative Example 1 containing component (A) but not containing components (B) and (C) had high friability and poor disintegration immediately after production.
Tablets of Comparative Examples 2 to 4 containing component (A) and component (B) but not containing component (C) experienced significant disintegration delay during storage.
In contrast, the tablets or coated tablets of Examples 1 to 23 containing component (A), component (B), and component (C) in the same layer had low friability and good disintegration immediately after production. Ta. In addition, the delay in disintegration due to storage was suppressed.
本発明の錠剤及びコーティング錠は、摩損が生じ難い硬度と速やかな崩壊性を有する。また、エテンザミド及び制酸剤の組み合わせによる崩壊遅延が抑制されている。 The tablets and coated tablets of the present invention have hardness that prevents wear and tear and rapid disintegration. Furthermore, the delay in disintegration caused by the combination of ethenzamide and antacids is suppressed.
Claims (5)
前記(C)成分/(前記(A)成分+前記(B)成分)で表される質量比が0.08~0.30であり、
前記(A)成分/前記(B)成分で表される質量比が0.35~15であり、
錠剤1錠あたりの前記(A)成分及び前記(B)成分の合計質量の割合が、39.22~80質量%である、錠剤。
(A)成分:エテンザミド。
(B)成分:乾燥水酸化アルミニウムゲル。
(C)成分:ロキソプロフェン及びその医薬的に許容可能な塩からなる群より選ばれる少なくとも一種。 Contains the following (A) component, (B) component and (C) component,
The mass ratio represented by the component (C)/(component (A) + component (B)) is 0.08 to 0.30,
The mass ratio represented by the component (A)/component (B) is 0.35 to 15,
A tablet, wherein the ratio of the total mass of the component (A) and the component (B) per tablet is 39.22 to 80% by mass .
(A) Component: ethenzamide.
(B) Component: Dry aluminum hydroxide gel .
Component (C): at least one member selected from the group consisting of loxoprofen and pharmaceutically acceptable salts thereof.
錠剤1錠あたりの前記結合剤の質量割合が、0.1~50質量%である、請求項1又は2に記載の錠剤。The tablet according to claim 1 or 2, wherein the mass proportion of the binder per tablet is 0.1 to 50% by mass.
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JP2018090577A (en) | 2016-12-06 | 2018-06-14 | 大正製薬株式会社 | Ibuprofen-containing solid formulation excellent in disintegration properties |
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WO1995015751A1 (en) | 1993-12-10 | 1995-06-15 | Fujisawa Pharmaceutical Co., Ltd. | Combined antipyretic analgesic drug |
JP2012097002A (en) | 2010-10-29 | 2012-05-24 | Kowa Co | Pharmaceutical preparation containing loxoprofen |
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