JP2004315483A - Orally disintegrating tablets - Google Patents

Orally disintegrating tablets Download PDF

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JP2004315483A
JP2004315483A JP2003119154A JP2003119154A JP2004315483A JP 2004315483 A JP2004315483 A JP 2004315483A JP 2003119154 A JP2003119154 A JP 2003119154A JP 2003119154 A JP2003119154 A JP 2003119154A JP 2004315483 A JP2004315483 A JP 2004315483A
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orally disintegrating
tablet
water
granulated
tablets
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JP2003119154A
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JP4551627B2 (en )
Inventor
Michio Mamiya
Akiko Masaoki
Yutaka Okuda
Naomi Suda
豊 奥田
彰子 正置
美知雄 間宮
尚美 須田
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Towa Yakuhin Kk
東和薬品株式会社
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Abstract

<P>PROBLEM TO BE SOLVED: To provide an orally disintegrating tablet that has appropriate balance between oral disintegration and tablet hardness. <P>SOLUTION: This orally disintegrating tablet is produced by using a sugar or a sugar alcohol used as an excipient in tablet formation, and is a compression-molded product using a granulating component that is insoluble in water but is hydrophilic. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【0001】 [0001]
【技術分野】 【Technical field】
本発明は、水の服用なしで口腔内で速やかに崩壊する口腔内崩壊錠剤に関する。 The present invention relates to orally disintegrating tablets that disintegrate quickly in the oral cavity without taking water.
【0002】 [0002]
経口投与のための固形製剤の剤形としては錠剤やカプセル剤が一般的である。 Dosage forms of the solid preparation for oral administration is tablets and capsules are common.
これらは投与後そのままの形で食道を通って消化管に達し、消化管内で崩壊して薬物を放出するように設計されている。 They are designed to emit through the esophagus reaches the gastrointestinal tract intact and disintegrated in the gastrointestinal tract the drug after administration. しかしながら老齢者や小児にとってはその嚥下が困難な場合があり、そのような患者に適した剤形として口腔内崩壊錠剤がある。 However for the elderly and children might its swallowing is difficult, there is orally disintegrating tablet as a dosage form suitable for such patients. この剤形は水を同時に飲用しなくても口腔内で嚥液により速やかに崩壊し、老齢者や小児でも容易に嚥下し得るようになっている。 The dosage form is not drinking water at the same time rapidly disintegrated by aspiration fluid in the oral cavity, and is able to easily swallowed even elderly and children. しかしながら口腔内崩壊錠剤といえども包装工程を含む生産過程、出荷およびその後の医療現場での取扱い過程において外力によってたやすく崩壊することがないように十分な破壊強度(錠剤の硬度)を持つことが必要である。 However the production process comprising an orally disintegrating tablet and survive even the packaging process, to have a sufficient breaking strength (hardness of a tablet) so as not to easily disrupted by external force in the handling process of the shipment and subsequent medical field is necessary. しかしながら口腔内崩壊速度と錠剤強度とは一般に両立しないから、両者を程よくバランスさせなければならない。 However because incompatible generally the oral disintegration rate and tablet strength, must moderately to balance the two.
【0003】 [0003]
これまで提案された数多くの口腔内崩壊錠剤の中で、WO95/20380は乳糖、マンニトール、ブドウ糖、白糖及びキシリットからなる群から選択された成形性の低い糖類を、マルトース、マルチトール、ソルビトール及びオリゴ糖からなる群から選択された成形性の高い糖類で造粒し、得られた造粒物を圧縮成形してなる口腔内崩壊錠剤を開示する。 Among the many orally disintegrating tablets proposed heretofore, WO95 / 20380 is lactose, mannitol, glucose, sucrose and low saccharide moldability selected from the group consisting of xylitol, maltose, maltitol, sorbitol and oligosaccharides granulated with high selected moldability from the group consisting of sugars saccharides, discloses an orally disintegrating tablet obtained by compression molding granules obtained. これらの造粒に用いられる成形性の高い糖類はいずれも水溶性であり、その水溶液を低成形性の糖類の粒子に噴霧して造粒物がつくられる。 Any high moldability used in these granulation saccharides are also water soluble, granules are made by spraying the aqueous solution to a low moldability saccharide particles. そのため成形性の高い糖類は乾燥後造粒物内に無定形もしくは非晶質の形で存在し、成形性の低い糖類の粒子を強固に結合もしくは少なくとも一部を固溶していると考えられるから、口腔内崩壊速度と錠剤硬度の適度のバランスを得るためにはその低成形性糖類に対する相対的割合、液量、噴霧条件等の造粒条件について厳密なコントロールを必要とする。 Therefore high moldability saccharides are present in amorphous or amorphous form after drying granulation in believed to be strongly bonded or solid solution at least a portion of the lower saccharide particle moldability from, in order to obtain an adequate balance of orally disintegrating speed and tablet hardness relative ratio thereof low moldability saccharides, liquid volume, and requires strict control over granulation conditions such as spray conditions. さらにこの方法は賦形成分が高成形性糖類の場合には適用できない。 This method is not applicable to the case excipient content of high moldability saccharide further. 従って成形性に関係なく錠剤の賦形成分一般に広く適用でき、かつ簡単に口腔内崩壊速度と硬度を最適にバランスさせることができる口腔内崩壊錠剤の開発が望まれる。 Therefore moldability widely applied can turn excipient fraction general tablet regardless and easy development of orally disintegrating tablets orally disintegrating speed and hardness can be optimally balance desired.
【0004】 [0004]
【本発明の開示】 SUMMARY OF THE INVENTION
本発明は、成形性すなわち単独で実用上満足な硬度を持つ錠剤に圧縮成形できる否かを問わず、広く錠剤の賦形成分に使用される糖または糖アルコールを用いる。 The present invention is, regardless of whether that can be compressed into moldability i.e. tablets having a practically satisfactory hardness alone, using a sugar or sugar alcohol is used widely excipient component of the tablet. 先行技術とは対照的に、本発明では水溶性の造粒成分を使用せず、親水性であるがしかし水に溶けない造粒成分を主たる賦形成分の造粒のために用いる。 In contrast to the prior art, the present invention without the use of granulating ingredients of the water-soluble, but hydrophilic but using granulating component which is insoluble in water for granulation of principal excipient component. このため造粒成分は乾燥後の造粒物において賦形成分と独立して存在し、親水性のため口腔内の唾液が錠剤の内部まで速やかに浸透し、錠剤の速やかな崩壊を助ける。 Granulating ingredients for this exists independently of the excipient component in the granulated product after drying, saliva in the oral cavity for the hydrophilic to penetrate rapidly into the interior of the tablet, assist in rapid disintegration of the tablet. この水不溶性親水性造粒成分の使用は、圧縮成形した錠剤の口腔内崩壊速度と錠剤硬度の間の適度なバランスを達成するために複雑な条件設定を必要としない。 The use of water-insoluble hydrophilic granulation components does not require a complex condition settings in order to achieve an appropriate balance between orally disintegrating speed and tablet hardness of tablets by compression molding.
【0005】 [0005]
このため本発明は、錠剤の賦形成分として用いられる糖または糖アルコールを賦形成分とし、水不溶性であるが親水性の造粒成分を用いて造粒した造粒物の圧縮成形物よりなる口腔崩壊錠剤を提供する。 Thus the present invention, a sugar or sugar alcohol is used as the excipient component of the tablet as excipient component, is water insoluble consisting compression molded product of the granulated product was granulated with granulating components of the hydrophilic to provide the orally disintegrating tablet.
【0006】 [0006]
【好ましい実施態様】 [Preferred embodiment]
本発明において造粒成分に用いることができる好ましい糖の例は、乳糖、トレハロースなどであり、糖アルコールはマンニトールである。 Examples of preferred sugar that can be used in the granulating ingredients in the present invention, lactose, trehalose and the like, sugar alcohol is mannitol. 先に引用したWO95/20380によれば、乳糖およびマンニトールは低成形性の糖類に分類される。 According to the above-cited WO95 / 20380, lactose and mannitol are classified as low moldability saccharides. トレハロースについては記載はないが、単独で実用上十分な硬度を有する錠剤に打錠することができるので、高成形性糖類に分類すべきである。 Without describe trehalose, it is possible to compressed into tablets having a practically sufficient hardness alone, it should be classified as high moldability saccharide. しかしこれらの糖または糖アルコールを水または水溶性高分子結合剤の水溶液を用いて造粒し、造粒物を圧縮成形して錠剤としても、硬度が実用に耐えない程低いか、又は口腔内崩壊に不適となる程高いかのどちらかである。 But these sugars or sugar alcohols granulated with water or an aqueous solution of a water-soluble polymeric binder, even tablets by compression molding granules, or low enough hardness unpractical, or buccal it is either high or enough to become unsuitable for collapse. しかしながらこれらの糖または糖アルコールを水不溶性の親水性造粒成分を用いて造粒し、造粒物を圧縮成形することにより、口腔内崩壊速度と硬度が適度にバランスした錠剤を得ることができる。 However these sugars or sugar alcohols granulated with a hydrophilic granulation components of water-insoluble, by compression molding granules can be oral disintegration rate and hardness to obtain a reasonably Tablets balance . 本発明において使用する造粒成分は親水性であるがしかし水には不溶である。 Granulating the ingredients used in the present invention are insoluble in but however water is hydrophilic. 一般に打錠用の造粒物には水溶性の高分子物質の水溶液が結合液として使用されるが、水不溶性物質の水分散液が使用されることはない。 In general the granules for tableting but an aqueous solution of a water-soluble polymeric substance is used as a binding solution, no water dispersion of water-insoluble substance is used. しかしこれらの水分散液を使用して造粒する時は、乾燥後賦形成分と分離した状態で造粒物中に分布し、もし存在しなければ高過ぎる硬度の錠剤を口腔内崩壊性とし、反対に低過ぎる硬度の錠剤を実用上満足な硬度を持つように働く。 However, when granulated using these aqueous dispersions, distributed in granules in a state separated after drying excipient content, the tablets of too high hardness and intraoral disintegrating If not present act to have practically satisfactory hardness tablet hardness too low the opposite.
【0007】 [0007]
使用し得る水不溶性の親水性造粒成分としては、デンプン、小麦粉のようなデンプンを含む穀粉、微粒子無水ケイ酸、ヒドロキシプロピルスターチ、クロスポビドンおよびそれらの混合物がある。 The hydrophilic granulation components of water-insoluble may be used, starch, flour containing starch, such as flour, particulate silicic anhydride, hydroxypropyl starch, there is a crospovidone and mixtures thereof. デンプンはトウモロコシデンプンおよびバレイショデンプンが好ましい。 Starch is preferably corn starch and potato starch. 微粒子無水ケイ酸としては、疎水化処理を施されていない軽質無水ケイ酸または粒径0.1ミクロン以下の非晶質シリカ微粒子が用いられる。 The particulate silicic anhydride, the following amorphous silica particles of light anhydrous silicic acid or having a particle size of 0.1 microns not subjected to hydrophobic treatment are used. これら微粒子無水ケイ酸は細孔を有し、大きい比表面積を有するのが特色である。 These fine silicic anhydride having pores, it is featured to have a large specific surface area. 賦形成分に対するこれら造粒成分の比は、重量で0.01〜1.0であることが適切である。 The ratio of these granulating ingredients for excipient component is suitably a 0.01 to 1.0 by weight. 任意の造粒方法を採用し得るが、流動層造粒法が好ましい。 May employ any granulation methods, fluidized bed granulation method is preferred. この場合、糖または糖アルコールの賦形成分の粉末粒子を流動させ、それへ造粒成分の水分散液を噴霧するか、または賦形成分と造粒成分を粉末状態であらかじめ混合し、この混合物へ水を噴霧して造粒することができる。 In this case, the powder particles of the excipient content of sugar or sugar alcohol is fluidized, either spraying an aqueous dispersion of the granulated ingredients to it, or excipient component and granulating ingredients were premixed in a powder state, the mixture it can be granulated by spraying with water to. 流動層造粒装置内で乾燥した造粒物は、必要により整粒後、ステアリン酸マグネシウムのような滑沢剤と混和した後、打錠機により錠剤に圧縮成形する。 Granulated product was dried in a fluid layer granulator after sizing as required, after admixture with a lubricant such as magnesium stearate, and compressed into tablets by a tablet machine. その際造粒に用いる造粒成分の一部を粉状状態で造粒物と混和し、打錠しても良い。 Admixed with granules Some powdery state of the granulation component used in this case granulation may be tableted.
【0008】 [0008]
このようにして製造された錠剤は、一般に口腔内崩壊時間が10秒以上60秒未満の範囲内にあり、硬度は少なくとも1.5kgであることが好ましい。 Tablets prepared in this way is generally oral disintegration time is within the range of less than 60 seconds 10 seconds, it is preferable hardness is at least 1.5 kg. 先に述べたように、一般に口腔内崩壊速度と硬度とは両立し難いので、あまり高い硬度例えば5.0kg以上になると口腔内崩壊速度が許容できないほど延長するであろう。 As mentioned earlier, since the general incompatibilities and oral disintegration rate and hardness, it will extend unacceptably intraoral disintegration rate becomes more than too high hardness example 5.0 kg.
【0009】 [0009]
本発明の口腔内崩壊錠剤は勿論薬物を含まなければならない。 Orally disintegrating tablet of the present invention must contain a course drug. その添加方法はいくつか考えられ、1錠あたりの薬物の含量および性格などによって適切な方法を選ぶことができる。 The addition method is considered some, can choose an appropriate method such as by content and character of each weighing drugs. 最も一般的な方法は少なくとも造粒物の一部分へ薬物を添加する方法である。 The most common method is the method of adding the drug to a portion of at least granules. また打錠前に造粒物と混合して打錠することもできる。 It is also possible to tabletting is mixed with granules to tableting. 薬物の種類によっては錠剤は主薬の安定剤や矯味剤(甘味剤)を含むことがある。 Depending on the type of drug tablets may contain agent stabilizers and flavoring agents (sweeteners). これらの補助成分についても上に述べた添加方法を適用し得る。 These auxiliary ingredients may apply added method described above.
【0010】 [0010]
【実施例】 【Example】
以下の実施例は例証目的であって本発明をこれらに実施例に限定することを意図しない。 The following examples are not intended to be limited to the embodiments in these present invention there illustrative purposes. また口腔内崩壊錠剤の製剤学的特性が添加した薬物によって有意に影響されるものではないので、多くの実施例においては薬物の添加なしで実験を行なった。 Since pharmaceutical properties of orally disintegrating tablets is not intended to be significantly affected by the drug was added, an experiment was conducted without the addition of drug in many embodiments.
【0011】 [0011]
実施例1 Example 1
トレハロース355gを流動層造粒装置(マルチプレックスMP−01)に投入し、トウモロコシデンプン40gを水500mLに分散した液をスプレーし造粒した。 Trehalose 355g was placed in a fluid bed granulator (Multiplex MP-01), a liquid obtained by dispersing corn starch 40g water 500mL was sprayed and granulated. 得られた造粒物395gに、トウモロコシデンプン100gを混合し、さらにステアリン酸マグネシウム5gを加え、ロータリー式打錠機を用い、それぞれ打錠圧8kNおよび10kNにおいて打錠し、直径9.0mm,重量250mgの錠剤を得た。 The obtained granules 395 g, was mixed with corn starch 100 g, further adding magnesium stearate 5g, using a rotary tableting machine, and tableted at a tableting pressure 8kN and 10kN respectively, diameter 9.0 mm, weight to obtain tablets of 250mg.
【0012】 [0012]
実施例2 Example 2
トレハロース355gを流動層造粒装置に投入し、トウモロコシデンプン140gを水500mLに分散した液をスプレーし造粒した。 Trehalose 355g was placed in a fluid bed granulator, and the corn starch 140g granulated by spraying a dispersed solution in water 500 mL. 得られた造粒物495gにステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧8kNおよび10kNにおいて打錠し、直径9.0mm、重量250mgの錠剤を得た。 Obtained granules 495g was mixed with magnesium stearate 5g, using a rotary tableting machine, each was tableted in a tableting pressure 8kN and 10 kN, to give a diameter of 9.0 mm, the tablet weight 250 mg.
【0013】 [0013]
実施例3 Example 3
トレハロース355gとトウモロコシデンプン140gの混合物を流動層造粒装置に投入し、精製水300mLをスプレーして造粒した。 A mixture of trehalose 355g corn starch 140g was placed in a fluid bed granulator and granulated by spraying purified water 300 mL. 得られた造粒物495gにステアリン酸マグネシウム5gを加え、ロータリー式打錠機を用い、それぞれ打錠圧8kNおよび10kNにおいて打錠し、直径9.0mm、重量250mgの錠剤を得た。 Obtained granules 495g Magnesium stearate 5g was added to, using a rotary tableting machine, each was tableted in a tableting pressure 8kN and 10 kN, to give a diameter of 9.0 mm, the tablet weight 250 mg.
【0014】 [0014]
実施例4 Example 4
乳糖355gを流動層造粒装置に投入し、トウモロコシデンプン140gを水500mLに分散した液をスプレーして造粒した。 Lactose 355g was placed in a fluid bed granulator and granulated corn starch 140g by spraying a dispersed solution in water 500 mL. 得られた造粒物495gに、軽質水ケイ酸4gと、ステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧8kNおよび10kNにおいて打錠し、直径9.0mm、重量252mgの錠剤を得た。 The obtained granules 495 g, and the light water silicic acid 4g, was mixed with magnesium stearate 5g, using a rotary tableting machine, and tableted at a tableting pressure 8kN and 10kN respectively, diameter 9.0 mm, weight to obtain tablets of 252mg.
【0015】 [0015]
実施例5 Example 5
D−マンニトール355gを流動層造粒装置に投入し、トウモロコシデンプン140gを水500mLに分散した液をスプレーして造粒した。 D- mannitol 355g was placed in a fluid bed granulator and granulated corn starch 140g by spraying a dispersed solution in water 500 mL. 得られた造粒物495gに、軽質無水ケイ酸4gと、ステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧10kNおよび12kNにおいて打錠し、直径9.0mm、重量252mgの錠剤を得た。 The obtained granules 495 g, and light anhydrous silicic acid 4g, was mixed with magnesium stearate 5g, using a rotary tableting machine, and tableted at a tableting pressure 10kN and 12kN respectively, diameter 9.0 mm, weight to obtain tablets of 252mg.
【0016】 [0016]
実施例6 Example 6
D−マンニトール470gを流動層造粒装置に投入し、軽質無水ケイ酸25gを水500mLに分散した液をスプレーして造粒した。 The D- mannitol 470g was placed in a fluid bed granulator and granulated light silicic anhydride 25g by spraying a solution obtained by dispersing in water 500 mL. 得られた造粒物495gにステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧4kNおよび6kNにおいて打錠し、直径9.0mm、重量250mgの錠剤を得た。 Obtained granules 495g was mixed with magnesium stearate 5g, using a rotary tableting machine, each was tableted in a tableting pressure 4kN and 6 kN, to give a diameter of 9.0 mm, the tablet weight 250 mg.
【0017】 [0017]
実施例7 Example 7
テオフィリン10gとトレハロース345gの混合物を流動層造粒装置に投入し、トウモロコシデンプン140gを水500mLに分散した液をスプレーして造粒した。 The mixture of theophylline 10g trehalose 345g was placed in a fluid bed granulator and granulated corn starch 140g by spraying a dispersed solution in water 500 mL. 得られた造粒物495gに、アスパルテーム6gと、ステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用いそれぞれ打錠圧8kNおよび10kNにおいて打錠し、直径9.0mm、重量253mgの錠剤を得た。 The obtained granules 495 g, and aspartame 6 g, was mixed with magnesium stearate 5g, into tablets in each compression force 8kN and 10kN using a rotary tableting machine, diameter 9.0 mm, the tablet weight 253mg Obtained.
【0018】 [0018]
実施例8 Example 8
プラバスタチンナトリウム50gとトレハロース650gの混合物を流動層造粒装置に投入し、軽質無水ケイ酸100gを水1000mLに分散した液をスプレーして造粒した。 The mixture of pravastatin sodium 50g trehalose 650g was placed in a fluid bed granulator and granulated light silicic anhydride 100g by spraying a dispersed solution in water 1000 mL. 得られた造粒物をAとする。 The obtained granules and A.
【0019】 [0019]
別にトレハロース500gを流動層造粒装置に投入し、トウモロコシデンプン100gを水1250mLに分散した液をスプレーして造粒した。 Separately trehalose 500g was placed in a fluid bed granulator and granulated corn starch 100g by spraying a dispersed solution in water 1250 mL. 得られた造粒物をBとする。 The obtained granules and B.
【0020】 [0020]
A造粒物800gと、B造粒物1200gと、トウモロコシデンプン50gと、アスパルテーム5gを混合し、さらにステアリン酸マグネシウム25gを加え、ロータリー式打錠機を用い、それぞれ打錠圧6kNおよび8kNにおいて打錠し、直径9.0mm、重量253mgの錠剤を得た。 Striking a A granulate 800 g, it was mixed with B granules 1200 g, and corn starch 50 g, aspartame 5g, further adding magnesium stearate 25 g, using a rotary tableting machine, in each tableting pressure 6kN and 8kN and tablets, to obtain a diameter of 9.0 mm, the tablet weight 253 mg.
【0021】 [0021]
実施例9 Example 9
D−マンニトール235gおよびトレハロース120gを流動層造粒装置に投入し、トウモロコシデンプン140gを水500mLに分散した液をスプレーして造粒した。 D- mannitol 235g and trehalose 120g was placed in a fluid bed granulator and granulated corn starch 140g by spraying a dispersed solution in water 500 mL. 得られた造粒物495gにステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧8kNおよび10kNにおいて打錠し、直径9.0mm,重量250mgの錠剤を得た。 Obtained granules 495g was mixed with magnesium stearate 5g, using a rotary tableting machine, each was tableted in a tableting pressure 8kN and 10 kN, to give a diameter of 9.0 mm, the tablet weight 250 mg.
【0022】 [0022]
実施例10 Example 10
D−マンニトール267gおよびトレハロース88gを流動層造粒装置に投入し、ヒドロキシプロピルスターチ140gを水500mLに分散した液をスプレーして造粒した。 D- mannitol 267g and trehalose 88g was placed in a fluid bed granulator, and the hydroxypropyl starch 140g granulated by spraying a dispersed solution in water 500 mL. 得られた造粒物495gにステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧8kNおよび10kNにおいて打錠し、直径9.0mm,重量250mgの錠剤を得た。 Obtained granules 495g was mixed with magnesium stearate 5g, using a rotary tableting machine, each was tableted in a tableting pressure 8kN and 10 kN, to give a diameter of 9.0 mm, the tablet weight 250 mg.
【0023】 [0023]
実施例11 Example 11
トレハロース355gを流動層造粒装置に投入し、ヒドロキシプロピルスターチ140gを水500mLに分散した液をスプレーして造粒した。 Trehalose 355g was placed in a fluid bed granulator and granulated with hydroxypropyl starch 140g by spraying a dispersed solution in water 500 mL. 得られた造粒物495gにステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧8kNおよび10kNにおいて打錠し、直径9.0mm,重量250mgの錠剤を得た。 Obtained granules 495g was mixed with magnesium stearate 5g, using a rotary tableting machine, each was tableted in a tableting pressure 8kN and 10 kN, to give a diameter of 9.0 mm, the tablet weight 250 mg.
【0024】 [0024]
実施例12 Example 12
D−マンニトール355gを流動層造粒装置に投入し、ヒドロキシプロピルスターチ140gを水500mLに分散した液をスプレーして造粒した。 D- mannitol 355g was placed in a fluid bed granulator, and the hydroxypropyl starch 140g granulated by spraying a dispersed solution in water 500 mL. 得られた造粒物495gにステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧10kNおよび12kNにおいて打錠し、直径9.0mm,重量250mgの錠剤を得た。 Obtained granules 495g was mixed with magnesium stearate 5g, using a rotary tableting machine, each was tableted in a tableting pressure 10kN and 12 kN, to give a diameter of 9.0 mm, the tablet weight 250 mg.
【0025】 [0025]
実施例13 Example 13
D−マンニトール475gを流動層造粒装置に投入し、クロスポピドン20gを水500mLに分散した液をスプレーして造粒した。 D- mannitol 475g was placed in a fluid bed granulator, and the crospovidone 20g granulated by spraying a dispersed solution in water 500 mL. 得られた造粒物495gにステアリン酸マグネシウム5gを混合し、ロータリー式打錠機を用い、それぞれ打錠圧7kNおよび9kNにおいて打錠し、直径9.0mm,重量250mgの錠剤を得た。 Obtained granules 495g was mixed with magnesium stearate 5g, using a rotary tableting machine, each was tableted in a tableting pressure 7kN and 9 kN, to give a diameter of 9.0 mm, the tablet weight 250 mg.
【0026】 [0026]
実施例14 Example 14
D−マンニトール475gを流動層造粒装置に投入し、小麦粉20gを水500mLに分散した液をスプレーし造粒した。 The D- mannitol 475g was placed in a fluid bed granulator, and the flour 20g granulated by spraying a liquid prepared by dispersing in water 500 mL. 得られた造粒物475gに軽質無水ケイ酸4gを混合し、さらにステアリン酸マグネシウム5gを加え、ロータリー式打錠機を用い、それぞれ打錠圧6kN及び8kNにおいて打錠し、直径9.0mm,重量252mgの錠剤を得た。 The resulting granules light anhydrous silicic acid 4g was mixed with 475 g, further adding magnesium stearate 5g, using a rotary tableting machine, and tableted at a tableting pressure 6kN and 8kN respectively, diameter 9.0 mm, to give tablets weighing 252 mg.
【0027】 [0027]
実施例15 Example 15
D−マンニトール475gを流動層造粒装置に投入し、小麦粉20gを水200mLに分散した液をスプレーし造粒した。 The D- mannitol 475g was placed in a fluid bed granulator, and the flour 20g granulated by spraying a liquid prepared by dispersing in water 200 mL. 得られた造粒物475gに軽質無水ケイ酸4gを混合し、さらにステアリン酸マグネシウム5gを加え、ロータリー式打錠機を用い、それぞれ打錠圧6kN及び8kNにおいて打錠し、直径9.0mm,重量252mmの錠剤を得た。 The resulting granules light anhydrous silicic acid 4g was mixed with 475 g, further adding magnesium stearate 5g, using a rotary tableting machine, and tableted at a tableting pressure 6kN and 8kN respectively, diameter 9.0 mm, to give tablets weighing 252 mm.
【0028】 [0028]
実施例16 Example 16
D−マンニトール475gを流動層造粒装置に投入し、小麦粉20gを水100mLに分散した液をスプレーし造粒した。 The D- mannitol 475g was placed in a fluid bed granulator, and the flour 20g granulated by spraying a liquid prepared by dispersing in water 100 mL. 得られた造粒物475gに軽質無水ケイ酸4gを混合し、さらにステアリン酸マグネシウム5gを加え、ロータリー式打錠機を用い、それぞれ打錠圧8kN及び10kNにおいて打錠し、直径9.0mm,重量252mgの錠剤を得た。 The resulting granules light anhydrous silicic acid 4g was mixed with 475 g, further adding magnesium stearate 5g, using a rotary tableting machine, and tableted at a tableting pressure 8kN and 10kN respectively, diameter 9.0 mm, to give tablets weighing 252 mg.
【0029】 [0029]
比較例1 Comparative Example 1
トレハロース568gを流動層造粒装置に投入し、精製水300mLをスプレーして造粒した。 Trehalose 568g was placed in a fluid bed granulator and granulated by spraying purified water 300 mL. 得られた造粒物426gにトウモロコシデンプン168gを混合し、さらにステアリン酸マグネシウム6gを加え、ロータリー式打錠機を用いて直径9.0mm、重量250mgの錠剤に打錠した。 The resulting granules of corn starch 168g were mixed in 426 g, further adding magnesium 6g stearate, and compressed into tablets with a diameter of 9.0 mm, weight 250mg using a rotary tableting machine. 打錠圧8kNにおいては脆い錠剤(硬度0.2kg)が得られたが、打錠圧10kNにおいてはキャッピングが著しく、打錠不可能であった。 Tableting pressure friable tablet in 8 kN (hardness 0.2 kg) was obtained, significantly capping in tableting pressure 10 kN, were tableting impossible.
【0030】 [0030]
比較例2 Comparative Example 2
比較例1において得た造粒物495gに、ステアリン酸マグネシウム5gを混合し、ロータリー打錠機を用い、それぞれ打錠圧3kNおよび5kNにおいて打錠し、直径9.0mm、重量250mgの錠剤を得た。 Obtained granules 495g obtained in Comparative Example 1, were mixed with magnesium stearate 5g, using a rotary tableting machine, and tableted at a tableting pressure 3kN and 5kN respectively, diameter 9.0 mm, the tablet weight 250mg It was.
【0031】 [0031]
【硬度および崩壊性試験】 [Hardness and disintegration test]
実施例および比較例で得た錠剤について、常法により硬度を測定した。 For the tablets obtained in Examples and Comparative Examples, the hardness was measured by a conventional method. 崩壊試験は水を使用して第14改正薬局方記載の方法に従って水中崩壊時間を測定し、口腔内崩壊時間は健康な成人男子の口腔内に試験錠剤を含ませ、噛まない状態で完全に崩壊するまでの時間を測定した。 Disintegration test the water disintegration time measured according to the method of the 14th Pharmacopoeia using water, the oral disintegration time included a test tablet in the oral cavity of a healthy adult male, completely disintegrated in the absence bite the time was measured until the. なお比較例1の錠剤については水中および口腔内崩壊時間を測定しなかった。 Note that although the tablet of Comparative Example 1 was not measured in water and oral disintegration time. 結果を表1から表6に示す。 The results are shown in Tables 1 to 6.
【0032】 [0032]
表1 Table 1
【0033】 [0033]
表2 Table 2
【0034】 [0034]
表3 Table 3
【0035】 [0035]
表4 Table 4
【0036】 [0036]
表5 Table 5
【0037】 [0037]
表6 Table 6
【0038】 [0038]
表7 Table 7
【0039】 [0039]
【考察】 [Discussion]
比較例1および2から理解し得るように、トレハロースを水のみで造粒し、造粒物にデンプンおよび滑沢剤を混合して打錠した場合、許容できる硬度に達しないか又はキャッピングのため打錠できない。 As can be seen from Comparative Examples 1 and 2, granulated trehalose in water alone, when tableting a mixture of starch and lubricant in the granulated product, or not reached an acceptable hardness or for capping I can not tableting. トレハロースを水のみで造粒した造粒物へ滑沢剤を加えて打錠すると低い打錠圧で硬い錠剤となり、口腔内崩壊錠剤は得られない。 Trehalose becomes hard tablet in granulated added a lubricant to the granulated product is tableted When low tableting pressure in water alone, orally disintegrating tablets can not be obtained. これと対照的に糖又は糖アルコールを水不溶性の親水性造粒成分の水分散液を用いて造粒するか、あるいは両者の混合物を水で造粒した場合は、実施例から理解されるように、口腔内崩壊速度と硬度が適度にバランスした錠剤が得られる。 In contrast, the one sugar or sugar alcohol is granulated with an aqueous dispersion of hydrophilic granulation components of water-insoluble, or if the mixture of both were granulated with water, to be understood from the examples the tablets orally disintegrating speed and hardness were appropriately balanced is obtained.

Claims (6)

  1. 錠剤の賦形成分として用いられる糖または糖アルコールを水に不溶であるが親水性の造粒成分を用いて造粒した造粒物の圧縮成形物よりなる口腔内崩壊錠剤。 Orally disintegrating tablet is a sugar or sugar alcohol is used as the excipient component of the tablet is insoluble in water consisting of compression molded product of the granulated product was granulated with granulating ingredients hydrophilic.
  2. 造粒成分はデンプン、デンプンを含む穀粉、微粒子無水ケイ酸、ヒドロキシプロピルスターチ、クロスポビドンおよびそれらの混合物よりなる群から選ばれる請求項1の口腔内崩壊錠剤。 Flour granulating ingredients containing starches, starch, fine silicic anhydride, hydroxypropyl starch, orally disintegrating tablet of claim 1 selected from the group consisting of crospovidone and mixtures thereof.
  3. 賦形成分はトレハロース、乳糖、マンニトールおよびそれらの混合物から選ばれる請求項1または2の口腔内崩壊錠剤。 Excipient fraction is trehalose, lactose, mannitol and orally disintegrating tablet of claim 1 or 2 selected from the mixtures thereof.
  4. 造粒物が薬物を含んでいる請求項1ないし3のいずれかの口腔内崩壊錠剤。 Either orally disintegrating tablets of claims 1 granulate contains a drug 3.
  5. 前記造粒物にさらに粉状の前記造粒成分を混合し、得られた混合物を圧縮成形してなる請求項1ないし4のいずれかの口腔内崩壊錠剤。 The granulation was further mixed powdery said granulating ingredients, claims 1 formed by compression molding a mixture obtained to any of the orally disintegrating tablet 4.
  6. 造粒物中の賦形成分に対する造粒成分の重量比が0.01ないし1.0である請求項1ないし5のいずれかの口腔内崩壊錠剤。 Either orally disintegrating tablet to the claims 1 1.0 0.01 weight ratio of granulating component to excipient fraction of granules 5.
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WO2008032767A1 (en) 2006-09-14 2008-03-20 Astellas Pharma Inc. Orally disintegrating tablet and process for production thereof
WO2009041651A1 (en) 2007-09-27 2009-04-02 Mitsubishi Tanabe Pharma Corporation Rapidly disintegrating solid preparation
WO2010061846A1 (en) 2008-11-25 2010-06-03 田辺三菱製薬株式会社 Orally rapidly disintegrating tablet, and process for producing same
JP2011513194A (en) * 2008-02-29 2011-04-28 大塚製薬株式会社 Orally disintegrating tablet
JP5004236B2 (en) * 2005-02-09 2012-08-22 キッセイ薬品工業株式会社 Orally disintegrating tablet
JP2016522272A (en) * 2013-03-29 2016-07-28 ロケット フレールRoquette Freres Film forming composition for film coating solids
JP2017008112A (en) * 2012-04-24 2017-01-12 第一三共株式会社 Orally disintegrating tablet, and production method of the same
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JP5004236B2 (en) * 2005-02-09 2012-08-22 キッセイ薬品工業株式会社 Orally disintegrating tablet
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JP2016522272A (en) * 2013-03-29 2016-07-28 ロケット フレールRoquette Freres Film forming composition for film coating solids
JP2017502060A (en) * 2014-01-10 2017-01-19 ジョンソン・アンド・ジョンソン・コンシューマー・インコーポレイテッド Manufacturing process of tablets using a high frequency and lossy coated particles

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