JP2012107049A - Tablet disintegrating in the oral cavity - Google Patents

Tablet disintegrating in the oral cavity Download PDF

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JP2012107049A
JP2012107049A JP2012037354A JP2012037354A JP2012107049A JP 2012107049 A JP2012107049 A JP 2012107049A JP 2012037354 A JP2012037354 A JP 2012037354A JP 2012037354 A JP2012037354 A JP 2012037354A JP 2012107049 A JP2012107049 A JP 2012107049A
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Kazuki Mimura
和樹 三村
Takeshi Kaneda
健 金田
Kiyohisa Ouchi
清久 大内
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Kissei Pharmaceutical Co Ltd
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Abstract

PROBLEM TO BE SOLVED: To provide a tablet disintegrating in the oral cavity, which has a rapid disintegrating property and appropriate hardness, and is suitable for industrial production, and a method of producing the same.SOLUTION: The tablet disintegrating in the oral cavity comprises: (I) a granulated material obtained by granulating a mixture containing (a) an active ingredient and (b) D-mannitol while spraying a water dispersant of partial alpha starch with 10-20 wt.% of a cold water-soluble content; and (II) at least one disintegrating agent selected from crospovidone and maize starch.

Description

本発明は、口腔内で速やかに崩壊する錠剤およびその製造方法に関する。   The present invention relates to a tablet that rapidly disintegrates in the oral cavity and a method for producing the same.

近年、高齢者、小児や嚥下困難な患者が服用しやすい剤形、あるいは水なしで服用できる剤形として、口腔内で速やかに崩壊もしくは溶解する固形製剤の開発が進められている。   In recent years, development of solid preparations that rapidly disintegrate or dissolve in the oral cavity has been promoted as dosage forms that can be easily taken by elderly people, children, and patients who have difficulty swallowing, or can be taken without water.

例えば、活性成分の懸濁液を鋳型に分注後、凍結乾燥して調製される口腔内崩壊錠が知られているが(例えば、特許文献1参照)、当該方法では凍結乾燥設備を必要とし、さらに得られる口腔内崩壊錠は、硬度が小さいため取り扱いが不便である。   For example, an orally disintegrating tablet prepared by dispensing a suspension of an active ingredient into a mold and then freeze-drying is known (see, for example, Patent Document 1), but this method requires freeze-drying equipment. Further, the orally disintegrating tablet obtained is inconvenient to handle because of its low hardness.

特開平8−291051には、活性成分、水溶性結合剤および水溶性賦形剤を含有する造粒物を圧縮成形後、加湿、乾燥して調製される口腔内崩壊錠の製造方法が開示されているが、当該方法では特殊な製造設備が必要とされている(例えば、特許文献2参照)。   Japanese Patent Application Laid-Open No. 8-291051 discloses a method for producing an orally disintegrating tablet prepared by compression-molding a granulated product containing an active ingredient, a water-soluble binder and a water-soluble excipient, followed by humidification and drying. However, this method requires special manufacturing equipment (see, for example, Patent Document 2).

WO95/20380には、成形性の低い糖類と成形性の高い糖類とを組み合わせて造粒、圧縮成形した後、硬度を高めるため加湿、乾燥して調製される口腔内崩壊製剤が開示されている(例えば、特許文献3参照)。   WO95 / 20380 discloses an orally disintegrating preparation prepared by granulating and compression-molding a combination of a low moldability saccharide and a high moldability saccharide, and then humidifying and drying to increase hardness. (For example, refer to Patent Document 3).

また、賦形剤として成形性の低い糖アルコールまたは糖類と、崩壊剤とを組み合わせてなる様々な口腔内崩壊錠が提案されている。   In addition, various orally disintegrating tablets have been proposed in which a sugar alcohol or saccharide having low moldability as an excipient and a disintegrant are combined.

例えば、WO97/47287には、平均粒子径30μm以下の糖アルコールまたは糖類と、活性成分および崩壊剤とを組み合わせてなり、適度な硬度と崩壊性を有する口腔内崩壊錠が開示されている(例えば、特許文献4参照)。しかしながら、ここに用いられているD−マンニトールは圧縮成形時に金属壁面との摩擦が大きく、バインディング、キャッピングなどの打錠障害を引き起こす問題があることから、圧縮成形時に、臼杵に滑沢剤を塗布して打錠するなどの特殊な製造設備が必要とされている。   For example, WO97 / 47287 discloses an orally disintegrating tablet comprising a combination of a sugar alcohol or saccharide having an average particle size of 30 μm or less, an active ingredient and a disintegrant, and having appropriate hardness and disintegration (for example, , See Patent Document 4). However, D-mannitol used here has a problem of causing a tableting trouble such as binding and capping due to large friction with the metal wall surface during compression molding, so a lubricant is applied to the mortar during compression molding. Therefore, special manufacturing equipment such as tableting is required.

WO2000/57857には、噴霧乾燥したD−マンニトールとクロスポビドンとを含有する混合物を直接打錠して調製される、適度な硬度と崩壊性を有する口腔内崩壊錠が開示されている(例えば、特許文献5参照)。また、特開2001−163770には、糖類および崩壊剤を含有する混合物の共粉砕物と、糖類の未粉砕物とを含有する打錠用末を直接圧縮してなる、適度な硬度と崩壊性を有する口腔内崩壊錠が開示されている(例えば、特許文献6参照)。しかしながら、賦形剤としてD−マンニトールを使用し、これらの方法に従って口腔内崩壊錠を調製した場合、圧縮成形時に、依然としてバインディングなどの打錠障害を生じやすいという課題を有している。
米国特許第4371516号明細書 特開2001−163770号公報 国際公開第95/20380号パンフレット 国際公開第97/47287号パンフレット 国際公開第2000/57857号パンフレット 特開2001−163770号公報
WO2000 / 57857 discloses an orally disintegrating tablet with moderate hardness and disintegration prepared by directly tableting a mixture containing spray-dried D-mannitol and crospovidone (for example, (See Patent Document 5). JP-A 2001-163770 discloses a moderate hardness and disintegration property obtained by directly compressing a tableting powder containing a co-ground product of a mixture containing a saccharide and a disintegrant and an unground product of the saccharide. An orally disintegrating tablet is disclosed (for example, see Patent Document 6). However, when orally disintegrating tablets are prepared according to these methods using D-mannitol as an excipient, there is still a problem that tableting troubles such as binding still tend to occur during compression molding.
U.S. Pat. No. 4,371,516 JP 2001-163770 A International Publication No. 95/20380 Pamphlet International Publication No. 97/47287 Pamphlet International Publication No. 2000/57857 Pamphlet JP 2001-163770 A

本発明の目的は、適度な硬度と速やかな崩壊性を有し、一般的な製造設備で工業的生産が可能である口腔内崩壊錠を提供することである。   An object of the present invention is to provide an orally disintegrating tablet that has moderate hardness and quick disintegration, and that can be industrially produced by general production equipment.

本発明者らは、上記課題を解決すべく鋭意研究を重ねた結果、活性成分、糖または糖アルコールおよび崩壊剤と、特定の範囲の冷水可溶分を有する部分アルファー化デンプンとを含有する口腔内崩壊錠が、適度な硬度と速やかな崩壊性を有すること、さらには当該口腔内崩壊錠が、予想外にも圧縮成形時における打錠障害を生じることなく一般的な製造設備で容易に生産できることを見出し、これらの知見に基づき、本発明を完成したものである。   As a result of intensive studies to solve the above problems, the present inventors have found that the oral cavity contains an active ingredient, sugar or sugar alcohol and a disintegrant, and partially pregelatinized starch having a specific range of cold water soluble content. The internally disintegrating tablet has moderate hardness and quick disintegration, and the orally disintegrating tablet is easily produced with ordinary manufacturing equipment without unexpectedly causing tableting troubles during compression molding. Based on these findings, the present invention has been completed.

すなわち、本発明は、
〔1〕 a)活性成分、b)糖または糖アルコール、c)冷水可溶分が10〜20重量%である部分アルファー化デンプン、およびd)崩壊剤を含有する口腔内崩壊錠;
〔2〕 糖または糖アルコールが、乳糖およびD−マンニトールから選択される少なくとも1種である、〔1〕記載の口腔内崩壊錠;
〔3〕 糖または糖アルコールが、D−マンニトールである、〔1〕記載の口腔内崩壊錠;
〔4〕 崩壊剤が、クロスポビドンおよびトウモロコシデンプンから選択される少なくとも1種である、〔1〕記載の口腔内崩壊錠;
〔5〕 崩壊剤が、クロスポビドンである、〔1〕記載の口腔内崩壊錠;
〔6〕 さらに冷水可溶分が10重量%未満である部分アルファー化デンプンを含有する、〔1〕記載の口腔内崩壊錠;
〔7〕 冷水可溶分が10〜20重量%である部分アルファー化デンプンの含有量が、製剤100重量部に対して0.5〜30重量部である、〔1〕記載の口腔内崩壊錠;
〔8〕 (I)a)活性成分、b)糖または糖アルコール、およびc)冷水可溶分が10〜20重量%である部分アルファー化デンプンを含有する造粒物と、(II)崩壊剤とを含有する口腔内崩壊錠;
〔9〕 糖または糖アルコールが、乳糖およびD−マンニトールから選択される少なくとも1種である、〔8〕記載の口腔内崩壊錠;
〔10〕 糖または糖アルコールが、D−マンニトールである、〔8〕記載の口腔内崩壊錠;
〔11〕 崩壊剤が、クロスポビドンおよびトウモロコシデンプンからなる群から選択される少なくとも1種である、〔8〕記載の口腔内崩壊錠;
〔12〕 崩壊剤が、クロスポビドンである、〔8〕記載の口腔内崩壊錠;
〔13〕 造粒物が、さらに冷水可溶分が10重量%未満である部分アルファー化デンプンを含有する、〔8〕記載の口腔内崩壊錠;
〔14〕 活性成分が、ミチグリニドカルシウム水和物である、〔1〕または〔8〕項記載の口腔内崩壊錠;
〔15〕 活性成分が、塩酸リトドリンである、〔1〕または〔8〕項記載の口腔内崩壊錠;
〔16〕 a)活性成分、b)糖または糖アルコール、およびc)冷水可溶分が10〜20重量%である部分アルファー化デンプンを含有する造粒物に崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法;
〔17〕 造粒物が、さらに冷水可溶分が10重量%未満である部分アルファー化デンプンを含有する、〔16〕記載の製造方法;
〔18〕 a)活性成分およびb)糖または糖アルコールを含有する混合物を、冷水可溶分が10〜20重量%である部分アルファー化デンプンを噴霧しながら造粒し、得られた造粒物に崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法;
〔19〕 混合物が、さらに冷水可溶分が10重量%未満である部分アルファー化デンプンを含有する、〔18〕記載の製造方法;
〔20〕 a)活性成分、b)糖または糖アルコール、およびc)冷水可溶分が10〜20重量%である部分アルファー化デンプンを含有する混合物を、水を添加しながら造粒し、得られた造粒物に崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法;および
〔21〕 a)活性成分、b)糖または糖アルコール、c)冷水可溶分が10〜20重量%である部分アルファー化デンプン、およびd)冷水可溶分が10重量%未満である部分アルファー化デンプンを含有する混合物を、水を添加しながら造粒し、得られた造粒物に崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法、に関する。
That is, the present invention
[1] An orally disintegrating tablet containing a) an active ingredient, b) a sugar or sugar alcohol, c) a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, and d) a disintegrant;
[2] The orally disintegrating tablet according to [1], wherein the sugar or sugar alcohol is at least one selected from lactose and D-mannitol;
[3] The orally disintegrating tablet according to [1], wherein the sugar or sugar alcohol is D-mannitol;
[4] The orally disintegrating tablet according to [1], wherein the disintegrant is at least one selected from crospovidone and corn starch;
[5] The orally disintegrating tablet according to [1], wherein the disintegrant is crospovidone;
[6] The orally disintegrating tablet according to [1], further comprising partially pregelatinized starch having a cold water soluble content of less than 10% by weight;
[7] The orally disintegrating tablet according to [1], wherein the content of partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is 0.5 to 30 parts by weight with respect to 100 parts by weight of the preparation ;
[8] Granulated product containing (I) a) active ingredient, b) sugar or sugar alcohol, and c) partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, and (II) a disintegrant. Orally disintegrating tablets containing:
[9] The orally disintegrating tablet according to [8], wherein the sugar or sugar alcohol is at least one selected from lactose and D-mannitol;
[10] The orally disintegrating tablet according to [8], wherein the sugar or sugar alcohol is D-mannitol;
[11] The orally disintegrating tablet according to [8], wherein the disintegrant is at least one selected from the group consisting of crospovidone and corn starch;
[12] The orally disintegrating tablet according to [8], wherein the disintegrant is crospovidone;
[13] The orally disintegrating tablet according to [8], wherein the granulated product further contains a partially pregelatinized starch having a cold water soluble content of less than 10% by weight;
[14] The orally disintegrating tablet according to [1] or [8], wherein the active ingredient is mitiglinide calcium hydrate;
[15] The orally disintegrating tablet according to [1] or [8], wherein the active ingredient is ritodrine hydrochloride;
[16] A disintegrant is mixed into a granulated product containing a) an active ingredient, b) sugar or sugar alcohol, and c) partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, followed by compression molding. A method for producing an orally disintegrating tablet, comprising:
[17] The production method according to [16], wherein the granulated product further contains partially pregelatinized starch having a cold water soluble content of less than 10% by weight;
[18] A granulated product obtained by granulating a mixture containing a) active ingredient and b) sugar or sugar alcohol while spraying partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight. A method for producing an orally disintegrating tablet, comprising mixing a disintegrant and compression molding;
[19] The production method according to [18], wherein the mixture further contains partially pregelatinized starch having a cold water soluble content of less than 10% by weight;
[20] A mixture containing a) an active ingredient, b) sugar or sugar alcohol, and c) partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is granulated while adding water. A method for producing an orally disintegrating tablet comprising mixing a disintegrant with the granulated product and compression molding; and [21] a) active ingredient, b) sugar or sugar alcohol, c) cold water acceptable A mixture containing partially pregelatinized starch having a soluble content of 10-20% by weight and d) partially pregelatinized starch having a cold water soluble content of less than 10% by weight is obtained by granulating with addition of water. The present invention relates to a method for producing an orally disintegrating tablet, wherein a disintegrant is mixed with a granulated product and compression molded.

本発明の口腔内崩壊錠に適用される活性成分としては、特に制限はなく、経口投与が可能であるいかなる活性成分を用いることができる。このような活性成分としては、例えば、抗パーキンソン病薬、抗高脂血症剤、抗糖尿病薬、気管支喘息治療剤、アレルギー性疾患治療剤、切迫流・早産治療薬、排尿障害治療薬などから選ばれる1種または2種以上の成分が用いられる。抗パーキンソン病薬としては、例えば、L−ドパ、カベルゴリンなどが挙げられる。抗高脂血症剤としては、例えば、ベザフィブラート、フェノフィブラート、シンフィブラートなどが挙げられる。抗糖尿病薬としては、例えば、ミチグリニドカルシウム水和物、ナテグリニドなどが挙げられる。気管支喘息治療剤としては、例えば、塩酸オザグレルなどが挙げられる。アレルギー性疾患治療剤としては、例えば、トラニラストなどが挙げられる。切迫流・早産治療薬としては、例えば、塩酸リトドリンなどが挙げられる。排尿障害治療薬としては、例えば、シロドシンなどが挙げられる。本発明の口腔内崩壊錠において、好適な活性成分は、ミチグリニドカルシウム水和物、塩酸リトドリン、シロドシンまたはカベルゴリンである。   The active ingredient applied to the orally disintegrating tablet of the present invention is not particularly limited, and any active ingredient that can be administered orally can be used. Examples of such active ingredients include antiparkinsonian drugs, antihyperlipidemic drugs, antidiabetic drugs, bronchial asthma drugs, allergic disease drugs, urgency / premature birth drugs, urination disorder drugs, etc. One or more selected components are used. Examples of the antiparkinsonian drug include L-dopa, cabergoline and the like. Examples of the antihyperlipidemic agent include bezafibrate, fenofibrate, simfibrate and the like. Examples of the antidiabetic drug include mitiglinide calcium hydrate, nateglinide and the like. Examples of the bronchial asthma therapeutic agent include ozagrel hydrochloride. Examples of the allergic disease therapeutic agent include tranilast. Examples of the treatment for urgency / premature birth include ritodrine hydrochloride and the like. Examples of the urination disorder therapeutic agent include silodosin. In the orally disintegrating tablet of the present invention, the preferred active ingredient is mitiglinide calcium hydrate, ritodrine hydrochloride, silodosin or cabergoline.

本発明の口腔内崩壊錠において、活性成分の含有量は、その種類によっても異なるが、通常、錠剤100重量部に対して約0.01〜約50重量部、好ましくは約0.01〜約20重量部である。活性成分としてミチグリニドカルシウム水和物を用いる場合、ミチグリニドカルシウム水和物の含有量は、錠剤100重量部に対して約1〜約20重量部、好ましくは約1〜約10重量部、さらに好ましくは約2〜約5重量部である。   In the orally disintegrating tablet of the present invention, the content of the active ingredient varies depending on the type, but is usually about 0.01 to about 50 parts by weight, preferably about 0.01 to about 50 parts by weight with respect to 100 parts by weight of the tablet. 20 parts by weight. When mitiglinide calcium hydrate is used as the active ingredient, the content of mitiglinide calcium hydrate is about 1 to about 20 parts by weight, preferably about 1 to about 10 parts by weight, more preferably 100 parts by weight of tablet. About 2 to about 5 parts by weight.

本発明の口腔内崩壊錠に用いられる、糖または糖アルコールとしては、水溶性が高く、成形性が低いものが好適に使用される。このような糖または糖アルコールとしては、例えば、乳糖、グルコース、蔗糖、果糖などの糖;およびD−マンニトール、キシリトール、マルチトール、ソルビトールなどの糖アルコールが挙げられ、乳糖またはD−マンニトールが、服用の際、良好な甘味を有するので好適であり、D−マンニトールが、清涼な服用感を有し、適度な硬度と速やかな崩壊性を得やすいので特に好適である。
これらの糖または糖アルコールは、必要に応じて、2種以上を組み合わせて用いることができる。また、糖と糖アルコールとを、組み合わせて用いることもできる。
As the sugar or sugar alcohol used in the orally disintegrating tablet of the present invention, those having high water solubility and low moldability are preferably used. Examples of such sugars or sugar alcohols include sugars such as lactose, glucose, sucrose, and fructose; and sugar alcohols such as D-mannitol, xylitol, maltitol, and sorbitol, and lactose or D-mannitol is taken. In this case, D-mannitol is preferable because it has a good sweetness, and D-mannitol is particularly preferable because it has a refreshing feeling and can easily obtain an appropriate hardness and quick disintegration.
These sugars or sugar alcohols can be used in combination of two or more as required. In addition, sugars and sugar alcohols can be used in combination.

本発明の口腔内崩壊錠において、糖または糖アルコールの含有量は、錠剤100重量部に対して約10〜約95重量部、好ましくは約30〜約90重量部、さらに好ましくは約50〜約90重量部である。   In the orally disintegrating tablet of the present invention, the sugar or sugar alcohol content is about 10 to about 95 parts by weight, preferably about 30 to about 90 parts by weight, more preferably about 50 to about 90 parts by weight per 100 parts by weight of the tablet. 90 parts by weight.

本発明の口腔内崩壊錠において、糖と糖アルコールとを組み合わせて使用する場合、糖と糖アルコールの含有量は任意の比率で用いることができるが、好ましくは、糖:糖アルコールが、0:1〜約9:約1の範囲で用いられる。   In the orally disintegrating tablet of the present invention, when sugar and sugar alcohol are used in combination, the content of sugar and sugar alcohol can be used in any ratio, but preferably sugar: sugar alcohol is 0: It is used in the range of 1 to about 9: about 1.

本発明において「冷水可溶分(重量%)」は、次のようにして測定することができる。
試料3g(無水換算)を精秤し、25℃の精製水297mLを加え、1500rpmで2分間高速撹拌する。得られた懸濁液を丸底遠心管に移し、2000rpmで15分間遠心分離する。秤量瓶に上澄み液30mLをとり、105℃で重量が一定になるまで乾燥する。秤量瓶中の乾燥物重量を1000倍し、最初の試料の乾燥物重量で割った値を冷水可溶分(重量%)とする。
In the present invention, “cold water soluble content (% by weight)” can be measured as follows.
3 g (anhydrous conversion) of the sample is precisely weighed, 297 mL of 25 ° C. purified water is added, and the mixture is stirred at 1500 rpm for 2 minutes at high speed. The resulting suspension is transferred to a round bottom centrifuge tube and centrifuged at 2000 rpm for 15 minutes. Take 30 mL of the supernatant in a weighing bottle and dry at 105 ° C. until the weight is constant. The dry matter weight in the weighing bottle is multiplied by 1000, and the value divided by the dry matter weight of the first sample is taken as the cold water soluble content (% by weight).

本発明において、「冷水可溶分が10〜20重量%である部分アルファー化デンプン」とは、上記測定法に従って冷水可溶分を測定したときに、上澄み液中に含まれる部分、すなわち、水に溶解する部分が10〜20重量%である部分アルファー化デンプンを意味する。また本発明において、「冷水可溶分が10重量%未満である部分アルファー化デンプン」とは、上記測定法に従って冷水可溶分を測定したときに、水に溶解する部分が10重量%未満の部分アルファー化デンプンを意味する。   In the present invention, “partially pregelatinized starch having a cold water-soluble content of 10 to 20% by weight” means a portion contained in a supernatant liquid, that is, water when the cold water-soluble content is measured according to the above-described measurement method. This means a partially pregelatinized starch having a portion dissolved in 10 to 20% by weight. In the present invention, “partially pregelatinized starch having a cold water-soluble content of less than 10% by weight” means that the portion dissolved in water is less than 10% by weight when the cold water-soluble content is measured according to the above-described measurement method. It means partially pregelatinized starch.

本発明の口腔内崩壊錠に用いられる部分アルファー化デンプンは、トウモロコシ、コムギ、コメなどの穀物デンプンを物理的に変性させることによって得られるものであり、その種類は特に限定されないが、トウモロコシデンプンを原料として調製された部分アルファー化デンプンが好適である。   The partially pregelatinized starch used in the orally disintegrating tablet of the present invention is obtained by physically modifying cereal starches such as corn, wheat, rice and the like, and the type thereof is not particularly limited. Partially pregelatinized starch prepared as a raw material is preferred.

本発明者ら、アルファー化の度合いや加工の異なるデンプン類について種々、検討した結果、部分アルファー化デンプンの中でも「冷水可溶分が10〜20重量%である部分アルファー化デンプン」を配合する場合に、予想外にも圧縮成形時における打錠障害が改善されるということを見出した。この部分アルファー化デンプンの冷水可溶分は、後述する試験例に示すように、冷水可溶分が10重量%未満である部分アルファー化デンプンや未加工デンプンでは、打錠障害改善効果は認められず、また、アルファー化デンプンのように水に可溶性のデンプン類でも打錠障害改善効果は認められなかった。また、水に易溶性のデキストリンでは、後述するように速やかな崩壊性が得られなかった。   As a result of various studies on starches having different degrees of alphalation and processing, the present inventors have formulated "partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight" among the partially pregelatinized starches. In addition, it has been unexpectedly found that the tableting trouble at the time of compression molding is improved. The cold water soluble content of this partially pregelatinized starch, as shown in the test examples to be described later, is confirmed to have a tableting disorder improving effect with partially pregelatinized starch and raw starch whose cold water soluble content is less than 10% by weight. In addition, even in starches that are soluble in water, such as pregelatinized starch, the effect of improving tableting trouble was not observed. Also, dextrins that are readily soluble in water did not provide rapid disintegration as described later.

本発明の口腔内崩壊錠に用いられる、「冷水可溶分が10〜20重量%である部分アルファー化デンプン」は、市販されている部分アルファー化デンプン、例えば、Starch1500(日本カラコン製、冷水可溶分:10〜20重量%)を用いることができる。
また、「冷水可溶分が10〜20重量%である部分アルファー化デンプン」と組み合わせて使用される「冷水可溶分が10重量%未満である部分アルファー化デンプン」としては、例えば、PCS(旭化成工業製、冷水可溶分:10重量%未満)、LYCATAB C(ロケット製)などを用いることができる。
また、「冷水可溶分が10〜20重量%である部分アルファー化デンプン」および「冷水可溶分が10重量%未満である部分アルファー化デンプン」は、公知の方法、例えば、特公昭59−47600、特開平4−318001などに記載された方法に従って製造することもできる。
The “partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight” used for the orally disintegrating tablet of the present invention is a commercially available partially pregelatinized starch such as Starch 1500 (manufactured by Nippon Colorcon, cold water is acceptable). Solute: 10 to 20% by weight) can be used.
Examples of the “partially pregelatinized starch having a cold water soluble content of less than 10% by weight” used in combination with the “partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight” include, for example, PCS ( Asahi Kasei Kogyo Co., Ltd., cold water soluble content: less than 10% by weight), LYCATAB C (manufactured by rocket), etc. can be used.
Further, “partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight” and “partially pregelatinized starch having a cold water soluble content of less than 10% by weight” are known methods, for example, JP-B-59- 47600, JP-A-4-31801 and the like.

本発明の口腔内崩壊錠に用いられる、「冷水可溶分が10〜20重量%である部分アルファー化デンプン」の冷水可溶分は、好ましくは約12〜約18重量%であり、さらに好ましくは約14〜約16重量%である。また、本発明の口腔内崩壊錠に用いられる、「冷水可溶分が10重量%未満である部分アルファー化デンプン」の冷水可溶分は、好ましくは約1〜約8重量%であり、さらに好ましくは約1〜約6重量%であり、なおさらに好ましくは約1〜約3重量%である。   The cold water soluble content of the “partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight” used in the orally disintegrating tablet of the present invention is preferably about 12 to about 18% by weight, and more preferably Is from about 14 to about 16 weight percent. In addition, the cold water soluble content of the “partially pregelatinized starch having a cold water soluble content of less than 10% by weight” used in the orally disintegrating tablet of the present invention is preferably about 1 to about 8% by weight, Preferably from about 1 to about 6 weight percent, and even more preferably from about 1 to about 3 weight percent.

本発明の口腔内崩壊錠において、冷水可溶分が10〜20重量%である部分アルファー化デンプンの含有量は、錠剤100重量部に対し、通常、約0.5〜約30重量部であり、錠剤100重量部に対して0.5重量部未満であると十分な打錠障害改善効果は得られず、30重量部を超えると速やかな崩壊性が得られない。冷水可溶分が10〜20重量%である部分アルファー化デンプンの好ましい含有量は、錠剤100重量部に対して、約1〜約20重量部であり、さらに好ましくは約2〜約15重量部である。   In the orally disintegrating tablet of the present invention, the content of partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is usually about 0.5 to about 30 parts by weight with respect to 100 parts by weight of the tablet. When the amount is less than 0.5 part by weight relative to 100 parts by weight of the tablet, a sufficient tableting trouble improving effect cannot be obtained, and when it exceeds 30 parts by weight, quick disintegration cannot be obtained. The content of partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is about 1 to about 20 parts by weight, more preferably about 2 to about 15 parts by weight, based on 100 parts by weight of the tablet. It is.

また、本発明の口腔内崩壊錠において、冷水可溶分が10〜20重量%である部分アルファー化デンプンと、冷水可溶分が10重量%未満である部分アルファー化デンプンとを組み合わせて使用する場合、冷水可溶分が10〜20重量%である部分アルファー化デンプンと、冷水可溶分が10重量%未満である部分アルファー化デンプンとの比率は、1:0〜約1:約9、好ましくは約2:約1〜約1:約9の範囲で用いられる。   In the orally disintegrating tablet of the present invention, a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight and a partially pregelatinized starch having a cold water soluble content of less than 10% by weight are used in combination. The ratio of partially pregelatinized starch having a cold water soluble content of 10-20% by weight to partially pregelatinized starch having a cold water soluble content of less than 10% by weight is 1: 0 to about 1: about 9, Preferably it is used in the range of about 2: about 1 to about 1: about 9.

本発明の口腔内崩壊錠に用いられる崩壊剤としては、例えば、クロスポビドン、トウモロコシデンプンなどが挙げられ、好適にはクロスポビドンである。   Examples of the disintegrant used in the orally disintegrating tablet of the present invention include crospovidone and corn starch, and crospovidone is preferred.

本発明の口腔内崩壊錠において、崩壊剤の含有量は、崩壊錠の種類によっても異なるが、錠剤100重量部に対し、通常、約0.5〜約30重量部である。より具体的には、クロスポビドンの含有量は、錠剤100重量部に対して約0.5〜約10重量部であり、好ましくは約1〜約7重量部である。トウモロコシデンプンの含有量は、錠剤100重量部に対して約3〜約20重量部であり、好ましくは約5〜約20重量部である。   In the orally disintegrating tablet of the present invention, the content of the disintegrant varies depending on the type of disintegrating tablet, but is usually about 0.5 to about 30 parts by weight with respect to 100 parts by weight of the tablet. More specifically, the content of crospovidone is about 0.5 to about 10 parts by weight, preferably about 1 to about 7 parts by weight, based on 100 parts by weight of the tablet. The content of corn starch is about 3 to about 20 parts by weight, preferably about 5 to about 20 parts by weight, based on 100 parts by weight of the tablet.

また、本発明の口腔内崩壊錠は、発明の効果に支障のない限り、製剤の製造に用いられる種々の添加剤、例えば、賦形剤、結合剤、滑沢剤、甘味料、酸味料、発泡剤、香料、着色剤などを適量含有することができる。   In addition, the orally disintegrating tablet of the present invention has various additives used in the preparation of the preparation, for example, excipients, binders, lubricants, sweeteners, acidulants, as long as the effects of the invention are not hindered. An appropriate amount of a foaming agent, a fragrance, a colorant, and the like can be contained.

このような賦形剤としては、例えば、コメデンプン、結晶セルロース、無水リン酸カルシウム、沈降炭酸カルシウム、ケイ酸カルシウム、乳酸カルシウム、エチルセルロースなどが挙げられる。結合剤としては、例えば、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、ポリビニルピロリドン、メチルセルロース、ポリビニルアルコール、アルギン酸ナトリウム、アミノアルキルメタクリレートコポリマー、ポリエチレングリコールなどが挙げられる。滑沢剤としては、例えば、ステアリン酸マグネシウム、ステアリン酸カルシウム、タルク、軽質無水ケイ酸、蔗糖脂肪酸エステル、フマル酸ステアリルナトリウムなどが挙げられる。甘味料としては、例えば、アスパルテーム(登録商標)、サッカリンナトリウム、グリチルリチン二カリウム、ステビア、ソーマチン、アセサルファムKなどが挙げられる。酸味料としては、例えば、クエン酸、酒石酸、リンゴ酸、アスコルビン酸などが挙げられる。発泡剤としては、例えば、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カルシウムなどが挙げられる。矯味剤としては、例えば、L-アスパラギン酸、塩化ナトリウム、塩化マグネシウム、クエン酸ナトリウム、クエン酸カルシウム、L-グルタミン酸ナトリウム、炭酸水素ナトリウムなどが挙げられる。香料としては、例えば、オレンジ油、レモン油、メントール、および各種香料粉末などが挙げられる。着色剤としては、例えば、食用黄色5号、食用赤色2号、食用青色2号などの食用色素、黄色三二酸化鉄、三二酸化鉄、カラメル色素などが挙げられる。   Examples of such excipients include rice starch, crystalline cellulose, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, calcium lactate, and ethyl cellulose. Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, methylcellulose, polyvinyl alcohol, sodium alginate, aminoalkyl methacrylate copolymer, polyethylene glycol and the like. Examples of the lubricant include magnesium stearate, calcium stearate, talc, light anhydrous silicic acid, sucrose fatty acid ester, sodium stearyl fumarate and the like. Examples of the sweetener include aspartame (registered trademark), saccharin sodium, dipotassium glycyrrhizin, stevia, thaumatin, and acesulfame K. Examples of the sour agent include citric acid, tartaric acid, malic acid, ascorbic acid and the like. Examples of the foaming agent include sodium hydrogen carbonate, sodium carbonate, calcium carbonate and the like. Examples of the corrigent include L-aspartic acid, sodium chloride, magnesium chloride, sodium citrate, calcium citrate, sodium L-glutamate, sodium bicarbonate and the like. Examples of the fragrances include orange oil, lemon oil, menthol, and various fragrance powders. Examples of the colorant include edible pigments such as edible yellow No. 5, edible red No. 2, and edible blue No. 2, yellow ferric oxide, ferric oxide, and caramel pigment.

次に本発明の口腔内崩壊錠の製造方法について説明する。   Next, the manufacturing method of the orally disintegrating tablet of this invention is demonstrated.

本発明の口腔内崩壊錠は、a)活性成分、b)糖または糖アルコール、およびc)冷水可溶分が10〜20重量%である部分アルファー化デンプンを含有する造粒物に、崩壊剤を添加、混合し、圧縮成形することにより、製造することができる。このように本発明の口腔内崩壊錠の製造方法では、造粒物中に冷水可溶分が10〜20重量%である部分アルファー化デンプンが含まれるのが特徴であり、造粒物中に糖または糖アルコールとともに冷水可溶分が10〜20重量%である部分アルファー化デンプンを共存させることにより、圧縮成形時の打錠障害を改善することができる。   The orally disintegrating tablet of the present invention comprises a granulated material containing a) an active ingredient, b) a sugar or sugar alcohol, and c) a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight. Can be produced by adding, mixing, and compression molding. Thus, in the method for producing an orally disintegrating tablet of the present invention, the granulated product is characterized in that partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is contained in the granulated product. By coexisting sugar or sugar alcohol with partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, it is possible to improve tableting troubles during compression molding.

また、本発明の口腔内崩壊錠において、造粒物中の活性成分は任意の量を含有させることが可能であり、発明の効果に支障のない限り、糖または糖アルコールおよび部分アルファー化デンプンからなる造粒物に、活性成分および崩壊剤を添加、混合し、圧縮成形して製造することも可能である。   Moreover, in the orally disintegrating tablet of the present invention, the active ingredient in the granulated product can be contained in any amount, and from sugar or sugar alcohol and partially pregelatinized starch as long as the effect of the invention is not hindered. It is also possible to add an active ingredient and a disintegrant to the resulting granulated product, mix, and compression-mold.

また、上記造粒物中に、さらに冷水可溶分が10重量%未満である部分アルファー化デンプンを添加することによって崩壊性を増強することができ、冷水可溶分が10〜20重量%である部分アルファー化デンプンと、冷水可溶分が10重量%未満である部分アルファー化デンプンの添加量を適宜増減することにより、口腔内における崩壊時間を好ましい時間に調節することができる。   Moreover, disintegration can be enhanced by adding a partially pregelatinized starch having a cold water soluble content of less than 10% by weight to the granulated product, and the cold water soluble content is 10 to 20% by weight. The disintegration time in the oral cavity can be adjusted to a preferred time by appropriately increasing or decreasing the addition amount of a certain partially pregelatinized starch and a partially pregelatinized starch having a cold water soluble content of less than 10% by weight.

本発明の口腔内崩壊錠に用いられる造粒方法としては、例えば、流動層造粒法、高速撹拌造粒法、押し出し造粒法、転動造粒法、転動流動造粒法などが挙げられ、好適には流動層造粒法、高速撹拌造粒法が用いられる。   Examples of the granulation method used for the orally disintegrating tablet of the present invention include a fluidized bed granulation method, a high speed stirring granulation method, an extrusion granulation method, a rolling granulation method, and a rolling fluid granulation method. Preferably, a fluidized bed granulation method or a high speed stirring granulation method is used.

本発明の口腔内崩壊錠は、例えば、以下のようにして製造することができる。   The orally disintegrating tablet of the present invention can be produced, for example, as follows.

製法1
本発明の口腔内崩壊錠は、a)活性成分およびb)糖または糖アルコールを含有する混合物を、冷水可溶分が10〜20重量%である部分アルファー化デンプンを噴霧しながら造粒し、当該造粒物に崩壊剤を添加、混合し、圧縮成形することにより製造することができる。また、上記の造粒工程において、冷水可溶分が10〜20重量%である部分アルファー化デンプンの一部を、活性成分および糖または糖アルコールと混合し、残りの部分アルファー化デンプンを噴霧しながら造粒することもできる。
Manufacturing method 1
The orally disintegrating tablet of the present invention is a granulated mixture containing a) active ingredient and b) sugar or sugar alcohol while spraying partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, It can manufacture by adding a disintegrating agent to the said granulated material, mixing, and compression-molding. In the granulation step, a part of the partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight is mixed with the active ingredient and sugar or sugar alcohol, and the remaining partially pregelatinized starch is sprayed. It can also be granulated.

製法2
また、本発明の口腔内崩壊錠は、a)活性成分、b)糖または糖アルコール、およびc)冷水可溶分が10重量%未満である部分アルファー化デンプンを含有する混合物を、冷水可溶分が10〜20重量%である部分アルファー化デンプンを噴霧しながら造粒し、当該造粒物に崩壊剤を添加、混合し、圧縮成形することにより製造することができる。
Manufacturing method 2
In addition, the orally disintegrating tablet of the present invention comprises a mixture containing a) active ingredient, b) sugar or sugar alcohol, and c) partially pregelatinized starch having a cold water soluble content of less than 10% by weight, which is soluble in cold water. It can be produced by granulating a partially pregelatinized starch having a content of 10 to 20% by weight while spraying, adding a disintegrant to the granulated product, mixing, and compression molding.

製法3
また、本発明の口腔内崩壊錠は、a)活性成分、b)糖または糖アルコール、およびc)冷水可溶分が10〜20重量%である部分アルファー化デンプンを含有する混合物を、水を添加しながら造粒し、当該造粒物に崩壊剤を添加、混合し、圧縮成形することにより製造することができる。
Manufacturing method 3
Moreover, the orally disintegrating tablet of the present invention comprises a mixture containing a) an active ingredient, b) a sugar or sugar alcohol, and c) a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight. It can be manufactured by granulating while adding, adding a disintegrant to the granulated product, mixing, and compression molding.

製法4
また、本発明の口腔内崩壊錠は、a)活性成分、b)糖または糖アルコール、c)冷水可溶分が10〜20重量%である部分アルファー化デンプン、およびd)10重量%未満の冷水可溶分を有する部分アルファー化デンプンを含有する混合物を、水を添加しながら造粒し、当該造粒物に崩壊剤を添加、混合し、圧縮成形することにより製造することができる。
Manufacturing method 4
Also, the orally disintegrating tablet of the present invention comprises: a) an active ingredient, b) a sugar or sugar alcohol, c) a partially pregelatinized starch having a cold water soluble content of 10 to 20% by weight, and d) less than 10% by weight A mixture containing partially pregelatinized starch having a cold water soluble content can be produced by granulating while adding water, adding a disintegrant to the granulated product, mixing, and compression molding.

上記の製法1〜4において、糖と糖アルコールとを組み合わせて使用する場合、糖および糖アルコールの双方を活性成分と混合、造粒してもよいが、いずれか一方を造粒物中に含有させ、他方を造粒後に添加、混合してもよい。好ましくは、活性成分と糖アルコールとを含有する混合物を造粒し、得られた造粒物に、糖および崩壊剤を添加、混合することにより、圧縮成形時の打錠障害を生じることなく、本発明の口腔内崩壊錠を調製することができる。   In the above production methods 1 to 4, when sugar and sugar alcohol are used in combination, both the sugar and sugar alcohol may be mixed with the active ingredient and granulated, but either one is contained in the granulated product. The other may be added and mixed after granulation. Preferably, a mixture containing an active ingredient and a sugar alcohol is granulated, and a sugar and a disintegrant are added to and mixed with the obtained granulated product, without causing a tableting trouble during compression molding. The orally disintegrating tablet of the present invention can be prepared.

また、上記の製法1〜4において、造粒後、必要に応じて、滑沢剤、甘味料、発泡剤、酸味料、矯味剤、香料などを適量、混合してもよい。   Moreover, in said manufacturing methods 1-4, after granulation, you may mix a lubricant, a sweetener, a foaming agent, a sour agent, a corrigent, a fragrance | flavor, etc. in a proper quantity as needed.

本発明の口腔内崩壊錠において、圧縮成形は、単発打錠機、ロータリー打錠機などを用いて行うことができる。打錠する際の圧力は、通常、2〜60kN/cmであり、好適には6〜30kN/cmである。 In the orally disintegrating tablet of the present invention, compression molding can be performed using a single tableting machine, a rotary tableting machine or the like. The pressure at the time of tableting is usually 2 to 60 kN / cm 2 , and preferably 6 to 30 kN / cm 2 .

このようにして得られる本発明の口腔内崩壊錠は、適度な硬度と、口腔内での速やかな崩壊性または溶解性を示す。本発明の口腔内崩壊錠の口腔内崩壊時間は、錠剤の大きさや厚みによっても異なるが、通常、60秒以内であり、好適には40秒以内である。また、本発明の口腔内崩壊錠の硬度は、通常、30N以上であり、好適には50N以上である。   The orally disintegrating tablet of the present invention thus obtained exhibits moderate hardness and rapid disintegration or solubility in the oral cavity. The oral disintegration time of the orally disintegrating tablet of the present invention varies depending on the size and thickness of the tablet, but is usually within 60 seconds, and preferably within 40 seconds. Moreover, the hardness of the orally disintegrating tablet of the present invention is usually 30 N or more, and preferably 50 N or more.

本発明の口腔内崩壊錠は、口腔内において速やかに崩壊もしくは溶解するので、高齢者、小児や嚥下困難な患者が服用しやすい。また、本発明の口腔内崩壊錠は、流通過程で損傷しない十分な硬度を有するので取り扱いが容易である。さらに、本発明の口腔内崩壊錠は、製造過程において打錠障害等の問題を生じることなく容易に製造することができるので、工業的生産に適している。   Since the orally disintegrating tablet of the present invention rapidly disintegrates or dissolves in the oral cavity, it is easy for the elderly, children, and patients who have difficulty swallowing. In addition, the orally disintegrating tablet of the present invention is easy to handle because it has sufficient hardness so as not to be damaged in the distribution process. Furthermore, since the orally disintegrating tablet of the present invention can be easily produced without causing problems such as tableting troubles in the production process, it is suitable for industrial production.

本発明の内容を以下の実施例、比較例および試験例によりさらに詳細に説明するが、本発明の内容はこれらに限定されるものではない。   The content of the present invention will be described in more detail with reference to the following examples, comparative examples and test examples, but the content of the present invention is not limited to these.

試験例1
冷水可溶分の測定
デンプン類として、トウモロコシデンプン、部分アルファー化デンプンおよびアルファー化デンプン、並びにデキストリンの冷水可溶分を、以下の方法に従って測定した。
Test example 1
Measurement of cold water soluble content As starches, corn starch, partially pregelatinized starch and pregelatinized starch, and cold water soluble content of dextrin were measured according to the following method.

試料3g(無水換算)を精秤し、25℃の精製水297mLを加え、1500rpmで2分間高速撹拌した。得られた懸濁液を丸底遠心管に移し、2000rpmで15分間遠心分離した。秤量瓶に上澄み液30mLをとり、105℃で重量が一定になるまで乾燥した。秤量瓶中の乾燥物重量を1000倍し、最初の試料の乾燥物重量で割った値を冷水可溶分(重量%)とした。結果を表1に示した。   3 g (anhydrous conversion) of the sample was precisely weighed, 297 mL of purified water at 25 ° C. was added, and the mixture was stirred at 1500 rpm for 2 minutes at high speed. The resulting suspension was transferred to a round bottom centrifuge tube and centrifuged at 2000 rpm for 15 minutes. 30 mL of the supernatant was placed in a weighing bottle and dried at 105 ° C. until the weight was constant. The value obtained by multiplying the dry matter weight in the weighing bottle by 1000 and dividing by the dry matter weight of the first sample was taken as the cold water soluble content (% by weight). The results are shown in Table 1.

Figure 2012107049
Figure 2012107049

試験例2
硬度試験
実施例1〜11および比較例1〜8で製造した錠剤の硬度を、硬度計(TS-75N,岡田精工製)を用いて測定した。なお、試験は3錠で行い、平均値を求めた。結果を表2および表3に示した。
Test example 2
Hardness Test The hardness of the tablets produced in Examples 1 to 11 and Comparative Examples 1 to 8 was measured using a hardness meter (TS-75N, manufactured by Okada Seiko). The test was performed with 3 tablets, and the average value was obtained. The results are shown in Tables 2 and 3.

試験例3
口腔内崩壊試験
健常人男性3名において、実施例1〜11および比較例1〜8で製造した錠剤1錠を口腔内に含み、舌で軽く転がしながら錠剤が崩壊した時間を測定し、その平均値を求めた。結果を表2および表3に示した。
Test example 3
Oral disintegration test In 3 healthy males, one tablet produced in Examples 1 to 11 and Comparative Examples 1 to 8 was included in the oral cavity, and the time when the tablet disintegrated was measured while gently rolling with the tongue. The value was determined. The results are shown in Tables 2 and 3.

試験例4
打錠障害性
実施例1〜11および比較例1〜8の打錠工程において、錠剤の上下表面の外観からスティッキングの有無、錠剤側面の外観からバインディングの有無、錠剤の層状剥離の発生からキャッピングの有無を観察した。また、臼壁への粉の付着あるいは摩擦状況(異音の発生)がひどい場合は、打錠不可とした。結果を表2および表3に示した。
Test example 4
Tabletting obstacle In the tableting process of Examples 1 to 11 and Comparative Examples 1 to 8, capping from the appearance of the upper and lower surfaces of the tablet, the presence or absence of sticking from the appearance of the side of the tablet, the occurrence of delamination of the tablet The presence or absence was observed. In addition, when powder adheres to the mortar wall or the frictional state (occurrence of abnormal noise) is severe, tableting is not possible. The results are shown in Tables 2 and 3.

実施例1
D−マンニトール 181.0 mg
部分アルファー化デンプン(Starch1500) 6.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間解砕したD−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)633.5gを流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧7.8、11.7および15.6kN/cmの条件で錠剤を製した。
Example 1
D-mannitol 181.0 mg
Partially pregelatinized starch (Starch1500) 6.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

Fluidized bed granulation drying of 633.5g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45μm) pulverized for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek) Into the machine (LAB-1, Paulek), and 21 g of partially pregelatinized starch (Starch 1500, Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water, and this dispersion is sprayed with a spray nozzle. Granulation was performed while spraying. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 7.8, 11.7 and 15.6 kN / cm 2 Tablets were made.

実施例2
D−マンニトール 177.0 mg
部分アルファー化デンプン(Starch1500) 10.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)619.5gと部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)14gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧7.8、11.7および15.6kN/cmの条件で錠剤を製した。
Example 2
D-mannitol 177.0 mg
Partially pregelatinized starch (Starch1500) 10.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 619.5g and partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8% by weight) 14g Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 7.8, 11.7 and 15.6 kN / cm 2 Tablets were made.

実施例3
D−マンニトール 161.0 mg
部分アルファー化デンプン(Starch1500) 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)563.5gと部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)70gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7、15.6および19.5kN/cmの条件で錠剤を製した。
Example 3
D-mannitol 161.0 mg
Partially pregelatinized starch (Starch1500) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon Co., Ltd., cold water soluble content: 15.8% by weight) 70 g with high-speed mixing and granulation Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7, 15.6 and 19.5 kN / cm 2 Tablets were made.

実施例4
D−マンニトール 147.0 mg
部分アルファー化デンプン(Starch1500) 40.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)514.5gと部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)119gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7および15.6kN/cmの条件で錠剤を製した。
Example 4
D-mannitol 147.0 mg
Partially pregelatinized starch (Starch1500) 40.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 514.5 g and partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8% by weight) 119 g are mixed at high speed with stirring. Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablets were weighed under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 and 15.6 kN / cm 2. Made.

実施例5
D−マンニトール 152.0 mg
部分アルファー化デンプン(Starch1500) 5.0 mg
トウモロコシデンプン 40.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間解砕したD−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)633.5gを流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物219.8g、トウモロコシデンプン(日本食品化工製)56g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)1.4gおよびステアリン酸マグネシウム(太平化学産業製)2.8gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧7.8、11.7および15.6kN/cmの条件で錠剤を製した。
Example 5
D-mannitol 152.0 mg
Partially pregelatinized starch (Starch1500) 5.0 mg
Corn starch 40.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

Fluidized bed granulation drying of 633.5g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45μm) pulverized for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek) Into the machine (LAB-1, Paulek), and 21 g of partially pregelatinized starch (Starch 1500, Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water, and this dispersion is sprayed with a spray nozzle. Granulation was performed while spraying. 219.8g of granulated material sieved by No. 18 sieve, 56g of corn starch (manufactured by Nippon Shokuhin Kako), 1.4g of light anhydrous silicic acid (Adsolidar 101, manufactured by Freund Industries) and 2.8g of magnesium stearate (manufactured by Taihei Chemical Industries) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 7.8, 11.7 and 15.6 kN / cm 2 Tablets were made.

実施例6
D−マンニトール 161.0 mg
部分アルファー化デンプン(Starch1500) 6.0 mg
部分アルファー化デンプン(PCS) 20.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)563.5gと部分アルファー化デンプン(PCS,旭化成工業製,冷水可溶分:1.2重量%)70gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,冷水可溶分:15.8重量%,日本カラコン製)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g,軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cmの条件で錠剤を製した。
Example 6
D-mannitol 161.0 mg
Partially pregelatinized starch (Starch1500) 6.0 mg
Partially pregelatinized starch (PCS) 20.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) 70 g with high-speed mixing and granulation Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and 21 g of partially pregelatinized starch (Starch 1500, soluble in cold water: 15.8% by weight, manufactured by Nippon Colorcon) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved by No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this rotary tableting machine, a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Tablets were made.

比較例1
D−マンニトール 161.0 mg
部分アルファー化デンプン(PCS) 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)563.5gと部分アルファー化デンプン(PCS,旭化成工業製,冷水可溶分:1.2重量%)70gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(PCS,旭化成工業製,冷水可溶分:1.2重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm2の条件で錠剤を製した。
Comparative Example 1
D-mannitol 161.0 mg
Partially pregelatinized starch (PCS) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) 70 g with high-speed mixing and granulation Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and 21 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2% by weight) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Tablets were made.

比較例2
D−マンニトール 161.0 mg
部分アルファー化デンプン(LYCATAB C) 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)563.5gと部分アルファー化デンプン(LYCATAB C,ロケット製,冷水可溶分:5.1重量%)70gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(LYCATAB C,ロケット製,冷水可溶分:5.1重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm2の条件で錠剤を製した。
Comparative Example 2
D-mannitol 161.0 mg
Partially pregelatinized starch (LYCATAB C) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5g and partially pregelatinized starch (LYCATAB C, manufactured by Rocket, cold water soluble content: 5.1 wt%) 70g Mix for 2 minutes using a machine (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and 21 g of partially pregelatinized starch (LYCATAB C, manufactured by Rocket, soluble in cold water: 5.1% by weight) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Tablets were made.

比較例3
D−マンニトール 187.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)654.5gを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間解砕した。この解砕物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、精製水をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm2の条件で錠剤を製した。
Comparative Example 3
D-mannitol 187.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

654.5 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) was pulverized for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). This pulverized product was put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and granulated while spraying purified water with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). This tableting mixture is tableted using a rotary tableting machine (Correct 12HUK, Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Made.

比較例4
D−マンニトール 161.0 mg
トウモロコシデンプン 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)563.5gとトウモロコシデンプン(日本食品化工製,冷水可溶分:0.1重量%)91gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、精製水をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7kN/cm2の条件で錠剤を製した。
Comparative Example 4
D-mannitol 161.0 mg
Corn starch 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and corn starch (manufactured by Nippon Shokuhin Kako Co., Ltd., cold water soluble content: 0.1 wt%) 91 g are mixed at high speed with agitation granulator (FM -VG-10, manufactured by Paulek) and mixed for 2 minutes. This mixture was put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and granulated while spraying purified water with a spray nozzle. 374g of granulated material sieved by No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, manufactured by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, manufactured by Freund Corporation) and 4g of magnesium stearate (Taipei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, tablets were produced using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 kN / cm 2 . .

比較例5
D−マンニトール 161.0 mg
アルファー化デンプン(UNI-PURE) 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)563.5gとアルファー化デンプン(UNI-PURE,National Starch&Chemical製)70gを高速混合撹拌造粒機(FM-VG-10,パウレック製)とを用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別にアルファー化デンプン(UNI-PURE,National Starch&Chemical製)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7および15.6kN/cm2の条件で錠剤を製した。
Comparative Example 5
D-mannitol 161.0 mg
Alpha-modified starch (UNI-PURE) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and pregelatinized starch (UNI-PURE, manufactured by National Starch & Chemical) 70 g are mixed at high speed with agitation granulator (FM-VG-10, manufactured by POWREC) ) For 2 minutes. This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of pregelatinized starch (UNI-PURE, manufactured by National Starch & Chemical) is dispersed in 180 g of purified water, and this dispersion is sprayed with a spray nozzle. Granulation was performed while spraying. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablets were weighed under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 and 15.6 kN / cm 2. Made.

比較例6
D−マンニトール 161.0 mg
アルファー化デンプン(アミコールC) 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)563.5gとアルファー化デンプン(アミコールC,日澱化学製)80gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別にアルファー化デンプン(アミコールC,日澱化学)11gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,IS製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧15.6、19.5および23.4kN/cm2の条件で錠剤を製した。
Comparative Example 6
D-mannitol 161.0 mg
Alphalated starch (Amicol C) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and pregelatinized starch (Amicol C, manufactured by Nissho Chemical Co., Ltd.) 80 g were mixed at high speed with agitation granulator (FM-VG-10, For 2 minutes. This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC). Separately, 11 g of pregelatinized starch (Amicol C, Nissho Chemical) is dispersed in 180 g of purified water, and this dispersion is sprayed with a spray nozzle. While granulating. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, manufactured by IS), 2g of light anhydrous silicic acid (Adsolidar 101, manufactured by Freund Corporation) and 4g of magnesium stearate (produced by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 15.6, 19.5 and 23.4 kN / cm 2 Tablets were made.

比較例7
D−マンニトール 161.0 mg
デキストリン 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)563.5gとデキストリン(アミコール10,日澱化学製,冷水可溶分:100.0重量%)71gとを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別にデキストリン(アミコール10,日澱化学製,冷水可溶分:96.1%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7および15.6kN/cm2の条件で錠剤を製した。
Comparative Example 7
D-mannitol 161.0 mg
Dextrin 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) 563.5 g and dextrin (Amicol 10, manufactured by Nissho Chemical Co., Ltd., cold water soluble content: 100.0% by weight) 71 g are mixed at high speed with agitation. (FM-VG-10, manufactured by Paulek) was mixed for 2 minutes. This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC). Separately, 21 g of dextrin (Amicol 10, manufactured by Nissho Chemical Co., Ltd., cold water soluble component: 96.1%) is dispersed in 180 g of purified water. Granulation was performed while spraying the dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablets were weighed under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 and 15.6 kN / cm 2. Made.

Figure 2012107049
Figure 2012107049
Figure 2012107049
Figure 2012107049

実施例8
塩酸リトドリン 5.0 mg
D−マンニトール 156.0 mg
部分アルファー化デンプン(Starch1500) 6.0 mg
部分アルファー化デンプン(PCS) 20.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 2.0 mg
(合計200.0 mg/1錠)

塩酸リトドリン17.5g、D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)546gおよび部分アルファー化デンプン(PCS,旭化成工業製,冷水可溶分:1.2重量%)70gを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物374g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)4gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7、15.6および19.5kN/cm2の条件で錠剤を製した。
Example 8
Ritodrine hydrochloride 5.0 mg
D-mannitol 156.0 mg
Partially pregelatinized starch (Starch1500) 6.0 mg
Partially pregelatinized starch (PCS) 20.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 2.0 mg
(Total 200.0 mg / tablet)

High-speed mixing of 17.5 g of ritodrine hydrochloride, 546 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) and 70 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) The mixture was mixed for 2 minutes using a stirring granulator (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 374g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 4g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7, 15.6 and 19.5 kN / cm 2 . Tablets were made.

実施例9
ミチグリニドカルシウム水和物 5.0 mg
D−マンニトール 155.0 mg
部分アルファー化デンプン(Starch1500) 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 3.0 mg
(合計200.0 mg/1錠)

ミチグリニドカルシウム水和物17.5g、D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)542.5gおよび部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)70gを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物372g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)6gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7、15.6および19.5kN/cm2の条件で錠剤を製した。
Example 9
Mitiglinide calcium hydrate 5.0 mg
D-mannitol 155.0 mg
Partially pregelatinized starch (Starch1500) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 3.0 mg
(Total 200.0 mg / tablet)

17.5 g of mitiglinide calcium hydrate, 542.5 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) and 70 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) Was mixed for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 372g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 6g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), this tableting mixture was used under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7, 15.6 and 19.5 kN / cm 2 . Tablets were made.

実施例10
ミチグリニドカルシウム水和物 5.0 mg
D−マンニトール 155.0 mg
部分アルファー化デンプン(Starch1500) 6.0 mg
部分アルファー化デンプン(PCS) 20.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 3.0 mg
(合計200.0 mg/1錠)

ミチグリニドカルシウム水和物17.5g、D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)542.5gおよび部分アルファー化デンプン(PCS,旭化成工業製,冷水可溶分:1.2重量%)70gを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物372g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)6gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7および15.6kN/cm2の条件で錠剤を製した。
Example 10
Mitiglinide calcium hydrate 5.0 mg
D-mannitol 155.0 mg
Partially pregelatinized starch (Starch1500) 6.0 mg
Partially pregelatinized starch (PCS) 20.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 3.0 mg
(Total 200.0 mg / tablet)

17.5 g of mitiglinide calcium hydrate, 542.5 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) and 70 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) Was mixed for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by POWREC), and 21 g of partially pregelatinized starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8 wt%) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 372g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 6g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho), tablets were weighed under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 and 15.6 kN / cm 2. Made.

実施例11
ミチグリニドカルシウム水和物 10.0 mg
D−マンニトール 50.0 mg
乳糖 114.2 mg
部分アルファー化デンプン(Starch1500) 3.75 mg
部分アルファー化デンプン(PCS) 11.25 mg
クロスポビドン 6.0 mg
アスパルテーム 0.8 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 3.0 mg
(合計200.0 mg/1錠)

ミチグリニドカルシウム水和物200g、D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)1000g、部分アルファー化デンプン(PCS,旭化成工業製,冷水可溶分:1.2重量%)225gおよび部分アルファー化デンプン(Starch1500,日本カラコン製,冷水可溶分:15.8重量%)75gを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて3分間混合した。このまま高速混合撹拌造粒機(FM-VG-10,パウレック製)中で、混合物に精製水465gを添加し造粒を行った後、湿潤した造粒物を流動層造粒乾燥機(LAB-1,パウレック)に投入し、入口温度80℃の条件で乾燥した。乾燥した造粒物を、パワーミル(P-02S、ダルトン製)を用いて整粒した。整粒した造粒物150g、乳糖(Tablettose80、メグレ製, 平均粒子径145μm)228.4g、クロスポビドン(Polyplasdone XL-10,ISP製)12gおよびアスパルテーム1.6gを、V型混合機(DV-1,ダルトン製)を用いて3分間混合した。さらに、ここへ軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gとステアリン酸マグネシウム(太平化学産業製)6gとを投入し、2分間混合した。この打錠用混合物をロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧19.5kN/cm2の条件で錠剤を製した。
Example 11
Mitiglinide calcium hydrate 10.0 mg
D-mannitol 50.0 mg
Lactose 114.2 mg
Partially pregelatinized starch (Starch1500) 3.75 mg
Partially pregelatinized starch (PCS) 11.25 mg
Crospovidone 6.0 mg
Aspartame 0.8 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 3.0 mg
(Total 200.0 mg / tablet)

200 g of mitiglinide calcium hydrate, 1000 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm), 225 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2% by weight) and parts Alpha starch (Starch 1500, manufactured by Nippon Colorcon, cold water soluble content: 15.8% by weight) 75 g was mixed for 3 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). In this state, after adding 465 g of purified water to the mixture and granulating in a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek), the wet granulated product is mixed with a fluidized bed granulator / dryer (LAB-). 1), and dried at an inlet temperature of 80 ° C. The dried granulated product was sized using a power mill (P-02S, manufactured by Dalton). The granulated product 150g, lactose (Tablettose80, made by Megre, average particle size 145μm) 228.4g, crospovidone (Polyplasdone XL-10, made by ISP) 12g and aspartame 1.6g are mixed into a V-type mixer (DV-1, For 3 minutes. Further, 2 g of light anhydrous silicic acid (Adsolidar 101, manufactured by Freund Corporation) and 6 g of magnesium stearate (produced by Taihei Chemical Industry) were added and mixed for 2 minutes. Tablets were produced from this tableting mixture using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho Co., Ltd.) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 19.5 kN / cm 2 .

比較例8
ミチグリニドカルシウム水和物 5.0 mg
D−マンニトール 155.0 mg

部分アルファー化デンプン(PCS) 26.0 mg
クロスポビドン 10.0 mg
軽質無水ケイ酸 1.0 mg
ステアリン酸マグネシウム 3.0 mg
(合計200.0 mg/1錠)

ミチグリニドカルシウム水和物17.5g、D−マンニトール(マンニットP,東和化成工業製, 平均粒子径45μm)542.5gおよび部分アルファー化デンプン(PCS,旭化成工業製,冷水可溶分:1.2重量%)70gを、高速混合撹拌造粒機(FM-VG-10,パウレック製)を用いて2分間混合した。この混合物を流動層造粒乾燥機(LAB-1,パウレック製)に投入し、別に部分アルファー化デンプン(PCS,旭化成工業製,冷水可溶分:1.2重量%)21gを精製水180gに分散させ、この分散液をスプレーノズルで噴霧しながら造粒を行った。18号篩で篩過した造粒物372g、クロスポビドン(Polyplasdone XL-10,ISP製)20g、軽質無水ケイ酸(Adsolidar 101,フロイント産業製)2gおよびステアリン酸マグネシウム(太平化学産業製)6gを、V型混合機(DV-1,ダルトン製)を用いて2分間混合した。この打錠用混合物を、ロータリー打錠機(Correct 12HUK,菊水製作所製)を用いて、錠剤重量200mg、8φmm円形、テーブル回転数30rpm、打錠圧11.7kN/cm2の条件で錠剤を製した。
Comparative Example 8
Mitiglinide calcium hydrate 5.0 mg
D-mannitol 155.0 mg

Partially pregelatinized starch (PCS) 26.0 mg
Crospovidone 10.0 mg
Light anhydrous silicic acid 1.0 mg
Magnesium stearate 3.0 mg
(Total 200.0 mg / tablet)

17.5 g of mitiglinide calcium hydrate, 542.5 g of D-mannitol (Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd., average particle size 45 μm) and 70 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2 wt%) Was mixed for 2 minutes using a high-speed mixing and agitation granulator (FM-VG-10, manufactured by Paulek). This mixture is put into a fluidized bed granulator / dryer (LAB-1, manufactured by Paulek), and 21 g of partially pregelatinized starch (PCS, manufactured by Asahi Kasei Kogyo Co., Ltd., cold water soluble content: 1.2% by weight) is dispersed in 180 g of purified water. Then, granulation was performed while spraying this dispersion with a spray nozzle. 372g of granulated material sieved with No. 18 sieve, 20g of crospovidone (Polyplasdone XL-10, made by ISP), 2g of light anhydrous silicic acid (Adsolidar 101, made by Freund Corporation) and 6g of magnesium stearate (made by Taihei Chemical Industry) The mixture was mixed for 2 minutes using a V-type mixer (DV-1, manufactured by Dalton). Using this tableting mixture, tablets were produced using a rotary tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) under the conditions of tablet weight 200 mg, 8φ mm circle, table rotation speed 30 rpm, tableting pressure 11.7 kN / cm 2 . .

Figure 2012107049
Figure 2012107049

本発明の口腔内崩壊錠は、流通過程で損傷しない十分な硬度を有し、かつ口腔内で速やかに崩壊もしくは溶解するので、高齢者、小児や嚥下困難な患者が服用しやすい剤形として有用である。   The orally disintegrating tablet of the present invention has sufficient hardness not to be damaged in the distribution process, and rapidly disintegrates or dissolves in the oral cavity, so it is useful as a dosage form that is easy to be taken by elderly people, children, and patients who have difficulty swallowing. It is.

Claims (8)

(I)活性成分およびD−マンニトールを含有する混合物を、冷水可溶分が10〜20重量%である部分アルファー化デンプンの水分散液を噴霧しながら造粒してなる造粒物と、該造粒物以外の成分として(II)クロスポビドンおよびトウモロコシデンプンから選択される少なくとも1種の崩壊剤とを含有する口腔内崩壊錠。 The mixture containing (I) active ingredient and D- mannitol, and granulated product obtained by granulating with spraying an aqueous dispersion of partially pregelatinized starch is a cold water soluble content from 10 to 20 wt%, the An orally disintegrating tablet containing (II) at least one disintegrating agent selected from crospovidone and corn starch as a component other than the granulated product . 崩壊剤が、クロスポビドンである、請求項1記載の口腔内崩壊錠。   The orally disintegrating tablet according to claim 1, wherein the disintegrant is crospovidone. 冷水可溶分が10〜20重量%である部分アルファー化デンプンの含有量が、錠剤100重量部に対して0.5〜30重量部である、請求項1記載の口腔内崩壊錠。 The content of partially pregelatinized starch is a cold water soluble content from 10 to 20% by weight, 0.5 to 30 parts by weight per 100 parts by weight of the tablet, according to claim 1 orally disintegrating tablet according. D−マンニトールの含有量が、錠剤100重量部に対して30〜90重量部である、請求項1記載の口腔内崩壊錠。The orally disintegrating tablet according to claim 1, wherein the content of D-mannitol is 30 to 90 parts by weight with respect to 100 parts by weight of the tablet. 崩壊剤の含有量が、錠剤100重量部に対して0.5〜30重量部である、請求項1記載の口腔内崩壊錠。The orally disintegrating tablet according to claim 1, wherein the content of the disintegrant is 0.5 to 30 parts by weight with respect to 100 parts by weight of the tablet. 活性成分が、ミチグリニドカルシウム水和物である、請求項1記載の口腔内崩壊錠。   The orally disintegrating tablet according to claim 1, wherein the active ingredient is mitiglinide calcium hydrate. 活性成分が、塩酸リトドリンである、請求項1記載の口腔内崩壊錠。   The orally disintegrating tablet according to claim 1, wherein the active ingredient is ritodrine hydrochloride. 活性成分およびD−マンニトールを含有する混合物を、冷水可溶分が10〜20重量%である部分アルファー化デンプンの水分散液を噴霧しながら造粒してなる造粒物に、クロスポビドンおよびトウモロコシデンプンから選択される少なくとも1種の崩壊剤を混合し、圧縮成形してなることを特徴とする口腔内崩壊錠の製造方法。 The mixtures containing the active ingredient and D- mannitol, the granules cold water solubles is then granulated while spraying an aqueous dispersion of partially pregelatinized starch is 10 to 20 wt%, crospovidone and corn A method for producing an orally disintegrating tablet, comprising mixing at least one disintegrant selected from starch and compression molding.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017178823A (en) * 2016-03-29 2017-10-05 小林製薬株式会社 Granule
JP2017178822A (en) * 2016-03-29 2017-10-05 小林製薬株式会社 tablet
WO2021095779A1 (en) * 2019-11-11 2021-05-20 大塚製薬株式会社 Orally disintegrating tablet

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5332615B2 (en) * 2006-09-14 2013-11-06 アステラス製薬株式会社 Orally disintegrating tablet and method for producing the same
FR2933299B1 (en) * 2008-07-04 2012-02-03 Roquette Freres MANNITOL ORODISPERSIBLE
MX365568B (en) * 2010-12-02 2019-06-07 Adare Pharmaceuticals Inc Rapidly dispersing granules, orally disintegrating tablets and methods.
JPWO2016051782A1 (en) * 2014-09-30 2017-07-13 キッセイ薬品工業株式会社 Orally administered preparations masking the bitterness of drugs with bitterness
JP6128160B2 (en) * 2015-05-07 2017-05-17 ニプロ株式会社 Method for producing orally disintegrating tablets
MA45972B1 (en) * 2015-06-18 2020-06-30 Estetra Sprl Orodispersible dosage unit containing an estetrol component
JP2019031491A (en) * 2017-08-08 2019-02-28 日本ケミファ株式会社 Diabetes therapeutic agent

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6011414A (en) * 1983-06-07 1985-01-21 マリンクロツド・インコ−ポレイテツド Granular n-acetyl-p-aminophenol composition and manufacture
JPH06502194A (en) * 1991-07-22 1994-03-10 ラボラトワール プログラファルム Rapidly disintegrating multiparticulate tablet
JP2001513545A (en) * 1997-08-22 2001-09-04 スミスクライン・ビーチャム・コーポレイション Rapidly disintegrating methylcellulose tablets
JP2002524410A (en) * 1998-09-08 2002-08-06 スミスクライン・ビーチャム・コーポレイション Lipstatin derivative-soluble fiber tablet
JP2005015477A (en) * 2003-06-06 2005-01-20 Takeda Chem Ind Ltd Solid formulation

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5047246A (en) * 1988-09-09 1991-09-10 Bristol-Myers Company Direct compression cyclophosphamide tablet
EP1022025A3 (en) * 1991-06-26 2002-06-05 Sepracor, Inc. Method and compositions for treating emesis nausea and other disorders using optically pure R(+) ondansetron
EP0591395A1 (en) * 1991-06-26 1994-04-13 Sepracor, Inc. Methods and compositions for treating emesis, nausea and other disorders using optically pure s(-) ondansetron
WO1995020380A1 (en) * 1994-01-31 1995-08-03 Yamanouchi Pharmaceutical Co., Ltd. Intraorally soluble compressed molding and process for producing the same
DE19637082A1 (en) * 1996-09-12 1998-03-19 Boehringer Mannheim Gmbh Rapidly disintegrating pellets
GB9802201D0 (en) * 1998-02-03 1998-04-01 Cerestar Holding Bv Free-flowable directly compressible starch as binder,disintegrant and filler for compresion tablets and hard gelatine capsules
NZ507271A (en) * 1998-03-06 2003-03-28 Eurand Internat S Fast disintegrating tablets
JP2000273039A (en) * 1999-01-20 2000-10-03 Taisho Pharmaceut Co Ltd Composition disintegrable in oral cavity
KR20100008007A (en) * 1999-02-15 2010-01-22 다이닛본 스미토모 세이야꾸 가부시끼가이샤 Tablets quickly disintegrated in the oral cavity
WO2000057857A1 (en) * 1999-03-25 2000-10-05 Yuhan Corporation Rapidly disintegrable tablet for oral administration
GB9914936D0 (en) * 1999-06-26 1999-08-25 Cerestar Holding Bv Directly compressible starch as enhancer of properties of excipients when used as binder and disintegrant for compression tablets
JP3435664B2 (en) * 1999-12-08 2003-08-11 ヤンセンファーマ株式会社 Oral fast disintegrating tablet and method for producing the same
JP2003055197A (en) * 2001-06-07 2003-02-26 Tanabe Seiyaku Co Ltd Functional particle-containing intraoral disintegrative preparation
CA2405918A1 (en) * 2001-10-01 2003-04-01 Ind-Swift Limited Controlled release macrolide pharmaceutical formulations
US6827946B2 (en) * 2001-12-05 2004-12-07 Collegium Pharmaceutical, Inc. Compositions containing both sedative and non-sedative antihistamines
JP2005519924A (en) * 2002-02-07 2005-07-07 ファルマシア・コーポレーション Pharmaceutical dosage forms for mucosal delivery
WO2003074029A1 (en) * 2002-03-07 2003-09-12 Vectura Limited Fast melt multiparticulate formulations for oral delivery
JP4408340B2 (en) * 2002-03-22 2010-02-03 武田薬品工業株式会社 Fast disintegrating solid preparation
WO2004064810A1 (en) * 2003-01-21 2004-08-05 Nippon Shinyaku Co., Ltd. Tablet quickly melting in oral cavity
JP4551627B2 (en) * 2003-02-28 2010-09-29 東和薬品株式会社 Method for producing orally disintegrating tablets
US8545881B2 (en) * 2004-04-19 2013-10-01 Eurand Pharmaceuticals, Ltd. Orally disintegrating tablets and methods of manufacture
NZ555470A (en) * 2004-11-24 2011-02-25 Teva Pharma Rasagiline orally disintegrating compositions

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6011414A (en) * 1983-06-07 1985-01-21 マリンクロツド・インコ−ポレイテツド Granular n-acetyl-p-aminophenol composition and manufacture
JPH06502194A (en) * 1991-07-22 1994-03-10 ラボラトワール プログラファルム Rapidly disintegrating multiparticulate tablet
JP2001513545A (en) * 1997-08-22 2001-09-04 スミスクライン・ビーチャム・コーポレイション Rapidly disintegrating methylcellulose tablets
JP2002524410A (en) * 1998-09-08 2002-08-06 スミスクライン・ビーチャム・コーポレイション Lipstatin derivative-soluble fiber tablet
JP2005015477A (en) * 2003-06-06 2005-01-20 Takeda Chem Ind Ltd Solid formulation

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017178823A (en) * 2016-03-29 2017-10-05 小林製薬株式会社 Granule
JP2017178822A (en) * 2016-03-29 2017-10-05 小林製薬株式会社 tablet
JP7001332B2 (en) 2016-03-29 2022-01-19 小林製薬株式会社 Granulation
WO2021095779A1 (en) * 2019-11-11 2021-05-20 大塚製薬株式会社 Orally disintegrating tablet
JPWO2021095779A1 (en) * 2019-11-11 2021-05-20
WO2021095092A1 (en) * 2019-11-11 2021-05-20 大塚製薬株式会社 Orally disintegrating tablet
JP7395607B2 (en) 2019-11-11 2023-12-11 大塚製薬株式会社 Orally disintegrating tablet

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