JP2016222651A - Miglitol-containing orally disintegrable tablet - Google Patents
Miglitol-containing orally disintegrable tablet Download PDFInfo
- Publication number
- JP2016222651A JP2016222651A JP2016100795A JP2016100795A JP2016222651A JP 2016222651 A JP2016222651 A JP 2016222651A JP 2016100795 A JP2016100795 A JP 2016100795A JP 2016100795 A JP2016100795 A JP 2016100795A JP 2016222651 A JP2016222651 A JP 2016222651A
- Authority
- JP
- Japan
- Prior art keywords
- miglitol
- orally disintegrating
- disintegrating tablet
- tablet
- hardness
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Images
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Abstract
Description
本発明は、ミグリトールを含有する口腔内崩壊錠に関する。特に多湿条件下での保存時に必要な硬度を備えるミグリトールを含有する口腔内崩壊錠に関する。 The present invention relates to an orally disintegrating tablet containing miglitol. In particular, the present invention relates to an orally disintegrating tablet containing miglitol having a hardness required for storage under humid conditions.
ミグリトール（（−）-（2R,3R,4R,5S）-1-（2-hydroxyethyl）-2-（hydroxymethyl）piperidine-3,4,5-triol）は、二糖類水解酵素（α-グルコシダーゼ）を阻害し、二糖類から単糖への分解を抑制して、糖質の消化・吸収を遅延させることにより食後の過血糖を改善する効能を有し、ミグリトール含有錠であるセイブル（登録商標）錠を毎食直前に経口投与することにより、食後高血糖改善効果を食事開始直後から発現することが、非特許文献１に記載されている。 Miglitol ((-)-(2R, 3R, 4R, 5S) -1- (2-hydroxyethyl) -2- (hydroxymethyl) piperidine-3,4,5-triol) is a disaccharide hydrolase (α-glucosidase) Sable (registered trademark), a miglitol-containing tablet that has the effect of improving postprandial hyperglycemia by inhibiting the degradation of disaccharides to monosaccharides and delaying digestion and absorption of carbohydrates Non-patent document 1 describes that the effect of improving postprandial hyperglycemia is exhibited immediately after the start of a meal by orally administering the tablet immediately before each meal.
糖尿病患者において適切なタイミングで糖尿病治療薬を服用し、血糖値を好ましい値にコントロールすることが重要であり、ミグリトール含有錠を服用する場合、服用するタイミングが食事の直前であることや患者の服用時の利便性等を考慮して、水なしで簡便に服用できるミグリトールの口腔内崩壊錠が、特に有用であり、最近、ミグリトール含有口腔内崩壊錠であるセイブル（登録商標）ＯＤ錠の製造販売承認がなされた。 It is important to take antidiabetic drugs at an appropriate timing in diabetic patients and control the blood glucose level to a desirable level.When taking miglitol-containing tablets, the timing of taking should be just before meals or the patient's Considering convenience at times, miglitol orally disintegrating tablets that can be easily taken without water are particularly useful. Recently, manufacture and sales of Sable (registered trademark) OD tablets, which are miglitol-containing orally disintegrating tablets, are available. Approval was made.
しかし、非特許文献１には、ミグリトール含有口腔内崩壊錠であるセイブル（登録商標）ＯＤ錠が無包装状態で高湿度により錠剤の硬度低下が認められることが記載されており、開封後も湿気を避けて保存する旨の指示がある。 However, Non-Patent Document 1 describes that Sable (registered trademark) OD tablet, which is a miglitol-containing orally disintegrating tablet, shows a decrease in the hardness of the tablet due to high humidity in an unwrapped state. There is an instruction to avoid saving.
また、特許文献１および特許文献２においてミグリトールを有効成分として含有する口腔内崩壊錠が記載されているが、いずれも湿度に対する影響を改善する効果を有することは記載されていない。
Moreover, although patent document 1 and
本発明は、多湿条件下での保存時に必要な硬度を備え、さらに口腔内での良好な崩壊性を備えるミグリトール含有口腔内崩壊錠を提供する。 The present invention provides a miglitol-containing orally disintegrating tablet that has the necessary hardness during storage under humid conditions and also has good disintegration properties in the oral cavity.
本発明の一実施形態によると、ミグリトールと、水不溶性ポリマーを含有することを特徴とする、ミグリトール含有口腔内崩壊錠が提供される。 According to one embodiment of the present invention, there is provided a miglitol-containing orally disintegrating tablet characterized by containing miglitol and a water-insoluble polymer.
前記ミグリトール含有口腔内崩壊錠において、前記水不溶性ポリマーが、エチルセルロースである。 In the miglitol-containing orally disintegrating tablet, the water-insoluble polymer is ethyl cellulose.
前記ミグリトール含有口腔内崩壊錠において、前記ミグリトールに対して１０質量％以上２５質量％以下の前記エチルセルロースを含有する。 The miglitol-containing orally disintegrating tablet contains 10% by mass or more and 25% by mass or less of the ethyl cellulose with respect to the miglitol.
本発明によると、多湿条件下での保存時に必要な硬度を備えるミグリトール含有口腔内崩壊錠が提供される。また、口腔内での良好な崩壊性を備えるミグリトール含有口腔内崩壊錠が提供される。 According to the present invention, there is provided a miglitol-containing orally disintegrating tablet having a hardness necessary for storage under humid conditions. Moreover, the miglitol containing orally disintegrating tablet provided with the favorable disintegration property in an oral cavity is provided.
以下、本発明に係るミグリトール含有口腔内崩壊錠について説明する。但し、本発明のミグリトール含有口腔内崩壊錠は、以下に示す実施の形態及び実施例の記載内容に限定して解釈されるものではない。本発明において「後添加」とは、有効成分を含有する粒子を造粒・乾燥・整粒した後に添加混合することをいう。また、本発明において「口腔内での良好な崩壊性」とは、口腔内の唾液のみ又は少量の水で約３０秒前後、もしくはそれ以下の時間で速やかに崩壊することをいう。 Hereinafter, the miglitol-containing orally disintegrating tablet according to the present invention will be described. However, the miglitol-containing orally disintegrating tablet of the present invention is not construed as being limited to the description of the following embodiments and examples. In the present invention, “post-addition” refers to addition and mixing after granulating, drying and sizing particles containing an active ingredient. In the present invention, “good disintegration property in the oral cavity” means that it rapidly disintegrates in about 30 seconds or less with only saliva in the oral cavity or a small amount of water.
本発明者らは、多湿条件下での保存時に必要な硬度を備えるミグリトール含有口腔内崩壊錠について検討を行ったところ、水不溶性ポリマーを添加することで、ミグリトールが水不溶性ポリマーによりコーティングされ、ミグリトール含有口腔内崩壊錠の硬度を得られることを新たに見出した。 The present inventors have examined a miglitol-containing orally disintegrating tablet having a hardness necessary for storage under humid conditions. As a result, by adding a water-insoluble polymer, the miglitol is coated with the water-insoluble polymer. It was newly found that the hardness of the contained orally disintegrating tablet can be obtained.
本発明に係るミグリトール含有口腔内崩壊錠は、ミグリトールと、水不溶性ポリマーを含有する。本実施形態において、ミグリトール含有口腔内崩壊錠は、所定量のミグリトールを含み、ミグリトールの含有量は、例えば、２５ｍｇ／錠、５０ｍｇ／錠又は７５ｍｇ／錠である。 The miglitol-containing orally disintegrating tablet according to the present invention contains miglitol and a water-insoluble polymer. In the present embodiment, the miglitol-containing orally disintegrating tablet contains a predetermined amount of miglitol, and the content of miglitol is, for example, 25 mg / tablet, 50 mg / tablet, or 75 mg / tablet.
本発明に係るミグリトール含有口腔内崩壊錠に添加する水不溶性ポリマーとしては、ｐＨ非依存型水不溶性ポリマー及びｐＨ依存型水不溶性ポリマーの何れも用いることができる。例えば、ｐＨ非依存型水不溶性ポリマーとしては、エチルセルロース、アミノアルキルメタクリレートコポリマーＲＳ、ｐＨ依存型水不溶性ポリマーとしては、アミノアルキルメタクリレートコポリマーＥ、メタクリル酸コポリマーＬ、ポリビニルアセタールジエチルアミノアセテート等を用いることができるが、これらに限定されるものではない。 As the water-insoluble polymer to be added to the miglitol-containing orally disintegrating tablet according to the present invention, any of a pH-independent water-insoluble polymer and a pH-dependent water-insoluble polymer can be used. For example, ethyl cellulose and aminoalkyl methacrylate copolymer RS can be used as the pH-independent water-insoluble polymer, and aminoalkyl methacrylate copolymer E, methacrylic acid copolymer L, polyvinyl acetal diethylaminoacetate, and the like can be used as the pH-dependent water-insoluble polymer. However, it is not limited to these.
一実施形態において、ミグリトール含有口腔内崩壊錠の製造時に水不溶性ポリマーとしてエチルセルロースを添加する場合、ミグリトールに対して１０質量％以上２５質量％以下の範囲でエチルセルロースを添加することが好ましい。エチルセルロースの含有量は、ミグリトールの含有量及び他の添加物に応じて、この範囲で適宜調節可能である。また、エチルセルロースの含有量がミグリトールに対して１０質量％より少ないと、崩壊時間が遅くなり、口腔内で溶けるまでに時間がかかる。また、ミグリトールに対するエチルセルロースの含有量が２５質量％を超えると、多湿条件下での保存時に必要な硬度が得られるものの、ミグリトール含有口腔内崩壊錠からのミグリトールの溶出性が低下するため、好ましくない。 In one embodiment, when ethylcellulose is added as a water-insoluble polymer during production of a miglitol-containing orally disintegrating tablet, it is preferable to add ethylcellulose in a range of 10% by mass to 25% by mass with respect to miglitol. The content of ethyl cellulose can be appropriately adjusted within this range depending on the content of miglitol and other additives. Moreover, when content of ethyl cellulose is less than 10 mass% with respect to miglitol, disintegration time will become slow and it will take time until it melt | dissolves in an oral cavity. Further, if the content of ethylcellulose with respect to miglitol exceeds 25% by mass, the necessary hardness during storage under humid conditions can be obtained, but the dissolution of miglitol from the miglitol-containing orally disintegrating tablet decreases, which is not preferable. .
なお、本明細書において、多湿条件下で口腔内崩壊錠を保存した場合に必要な硬度とは、２５℃、湿度７５％に１週間、開封状態で保存した口腔内崩壊錠の硬度が２０ Ｎ以上となることを意味する。 In the present specification, the hardness required when the orally disintegrating tablet is stored under humid conditions means that the hardness of the orally disintegrating tablet stored in an opened state at 25 ° C. and 75% humidity for 1 week is 20 N. That means that
本発明に係るミグリトール含有口腔内崩壊錠は、水不溶性ポリマーを添加することにより、ミグリトールが水不溶性ポリマーによりコーティングされ、多湿条件下に保存しても、口腔内崩壊錠の硬度を十分に維持することができる。また、硬度とともに、口腔内崩壊錠に必要な崩壊性と、ミグリトールの溶出性をも得ることができる。 In the miglitol-containing orally disintegrating tablet according to the present invention, by adding a water-insoluble polymer, miglitol is coated with the water-insoluble polymer, and the hardness of the orally disintegrating tablet is sufficiently maintained even when stored under humid conditions. be able to. In addition to the hardness, the disintegrability necessary for the orally disintegrating tablet and the dissolution property of miglitol can also be obtained.
本実施形態のミグリトール含有口腔内崩壊錠は、賦形剤、結合剤、崩壊剤、乳化剤、安定剤、矯味矯臭剤、可塑剤、滑沢剤等の添加剤をさらに添加することができる。 The miglitol-containing orally disintegrating tablet of this embodiment may further contain additives such as excipients, binders, disintegrants, emulsifiers, stabilizers, flavoring agents, plasticizers, lubricants and the like.
賦形剤は、例えば、糖誘導体、澱粉誘導体、セルロース誘導体、アラビアゴム、デキストラン、プルラン、ケイ酸塩誘導体、燐酸塩、炭酸塩及び硫酸塩等から選択することができる。糖誘導体としては、例えば、乳糖、白糖、葡萄糖、マンニトール、エリスリトール、トレハロース、マルトース、キシリトール及びソルビトール等を例示することができる。また、澱粉誘導体としては、トウモロコシデンプン、バレイショデンプン、α−澱粉、デキストリン等を例示することができる。セルロース誘導体としては、結晶セルロース等を例示することができる。また、ケイ酸塩誘導体としては、軽質無水ケイ酸、合成ケイ酸アルミニウム、ケイ酸カルシウム、メタケイ酸アルミン酸マグネシウム等を例示することができる。燐酸塩としては、燐酸水素カルシウム等を例示することができる。炭酸塩としては、炭酸カルシウム、炭酸マグネシウム、炭酸水素ナトリウム等を例示することができる。硫酸塩としては、硫酸カルシウム等を例示することができる。これらの賦形剤は、単独又は二種以上組み合わせて使用できる。 The excipient can be selected from, for example, sugar derivatives, starch derivatives, cellulose derivatives, gum arabic, dextran, pullulan, silicate derivatives, phosphates, carbonates and sulfates. Examples of sugar derivatives include lactose, sucrose, sucrose, mannitol, erythritol, trehalose, maltose, xylitol, and sorbitol. Examples of starch derivatives include corn starch, potato starch, α-starch, and dextrin. As the cellulose derivative, crystalline cellulose and the like can be exemplified. Examples of the silicate derivative include light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, magnesium aluminate metasilicate, and the like. Examples of the phosphate include calcium hydrogen phosphate. Examples of carbonates include calcium carbonate, magnesium carbonate, sodium hydrogen carbonate and the like. Examples of sulfates include calcium sulfate. These excipients can be used alone or in combination of two or more.
崩壊剤は、例えば、クロスポビドン、カルメロースカルシウム、カルメロースナトリウム、クロスカルメロースナトリウム、カルメロース、架橋化ポリビニルピロリドン、低置換度ヒドロキシプロピルセルロース、各種デンプン類等から選択することができる。これらの崩壊剤は、単独又は二種以上組み合わせて使用できる。 The disintegrant can be selected from, for example, crospovidone, carmellose calcium, carmellose sodium, croscarmellose sodium, carmellose, crosslinked polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, various starches, and the like. These disintegrants can be used alone or in combination of two or more.
結合剤は、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、ポリビニルアルコール、マクロゴール及び上記に賦形剤として示した化合物等から選択することができる。これらの結合剤は、単独又は二種以上組み合わせて使用できる。 The binder can be selected from, for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, macrogol and the compounds shown above as excipients. These binders can be used alone or in combination of two or more.
乳化剤は、例えば、コロイド性粘土、金属水酸化物、陰イオン界面活性剤、陽イオン界面活性剤及び非イオン界面活性剤等から選択することができる。コロイド性粘土としては、ベントナイト、ビーガム等を例示することができる。金属水酸化物としては、水酸化マグネシウム、水酸化アルミニウム等を例示することができる。陰イオン界面活性剤としては、ラウリル硫酸ナトリウム、等を例示することができる。陽イオン界面活性剤としては、塩化ベンザルコニウム等を例示することができる。また、非イオン界面活性剤としては、ポリオキシエチレンアルキルエーテル、ポリオキシエチレンソルビタン脂肪酸エステル、ショ糖脂肪酸エステル等を例示することができる。これらの乳化剤は、単独又は二種以上組み合わせて使用できる。 The emulsifier can be selected from, for example, colloidal clay, metal hydroxide, anionic surfactant, cationic surfactant and nonionic surfactant. Examples of colloidal clay include bentonite and bee gum. Examples of the metal hydroxide include magnesium hydroxide and aluminum hydroxide. Examples of the anionic surfactant include sodium lauryl sulfate. Examples of the cationic surfactant include benzalkonium chloride. Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, and sucrose fatty acid ester. These emulsifiers can be used alone or in combination of two or more.
安定剤は、例えば、パラヒドロキシ安息香酸エステル類、アルコール類、フェノール類、チメロサール、デヒドロ酢酸及びソルビン酸等から選択することができる。パラヒドロキシ安息香酸エステル類としては、メチルパラベン、プロピルパラベン等を例示することができる。アルコール類としては、クロロブタノール、ベンジルアルコール、フェニルエチルアルコール等を例示することができる。これらの安定剤は、単独又は二種以上組み合わせて使用できる。 Stabilizers can be selected from, for example, parahydroxybenzoates, alcohols, phenols, thimerosal, dehydroacetic acid, sorbic acid, and the like. Examples of parahydroxybenzoic acid esters include methyl paraben and propyl paraben. Examples of alcohols include chlorobutanol, benzyl alcohol, and phenylethyl alcohol. These stabilizers can be used alone or in combination of two or more.
矯味矯臭剤は、例えば、甘味料、酸味料及び香料等から選択することができる。甘味料としては、サッカリンナトリウム、スクラロース、タウマチン、アセスルファムカリウム、ステビア抽出物、白糖、アスパルテーム等を例示することができる。酸味料としては、クエン酸、リンゴ酸、酒石酸等を例示することができる。また、香料としては、メントール、レモンエキス、オレンジエキス等を例示することができる。これらの矯味矯臭剤は、単独又は二種以上組み合わせて使用できる。 The flavoring agent can be selected from, for example, sweeteners, acidulants, and fragrances. Examples of sweeteners include saccharin sodium, sucralose, thaumatin, acesulfame potassium, stevia extract, sucrose, aspartame and the like. Examples of the sour agent include citric acid, malic acid, tartaric acid and the like. Examples of the fragrances include menthol, lemon extract, orange extract and the like. These flavoring agents can be used alone or in combination of two or more.
可塑剤は、例えば、クエン酸トリエチル、グリセリン脂肪酸エステル、トリアセチン、プロピレングリコール、マクロゴール、モノステアリン酸グリセリン等を例示することができる。これらの可塑剤は、単独又は二種以上組み合わせて使用できる。 Examples of the plasticizer include triethyl citrate, glycerin fatty acid ester, triacetin, propylene glycol, macrogol, and glyceryl monostearate. These plasticizers can be used alone or in combination of two or more.
滑沢剤は、例えば、ステアリン酸、ステアリン酸金属塩（ステアリン酸カルシウム、ステアリン酸マグネシウム等）、タルク、コロイドシリカ、ワックス類（ビーズワックス、ゲイ蝋等）、硼酸、アジピン酸、硫酸塩（硫酸ナトリウム等）、グリコール、フマル酸、フマル酸ステアリルナトリウム、安息香酸ナトリウム、Ｄ，Ｌ−ロイシン、ラウリル硫酸塩（ラウリル硫酸ナトリウム、ラウリル硫酸マグネシウム等）、酸類（無水ケイ酸、ケイ酸水和物等）及び上記に賦形剤として示した化合物等から選択することができる。これらの滑沢剤は、単独又は二種以上組み合わせて使用できる。 Lubricants include, for example, stearic acid, metal stearates (calcium stearate, magnesium stearate, etc.), talc, colloidal silica, waxes (bead wax, gay wax, etc.), boric acid, adipic acid, sulfate (sodium sulfate) Etc.), glycol, fumaric acid, sodium stearyl fumarate, sodium benzoate, D, L-leucine, lauryl sulfate (sodium lauryl sulfate, magnesium lauryl sulfate, etc.), acids (anhydrous silicic acid, silicic acid hydrate, etc.) And from the compounds shown above as excipients. These lubricants can be used alone or in combination of two or more.
（製造方法）
本発明に係るミグリトール含有口腔内崩壊錠は、薬学分野において公知の製造方法に従って製造することができる。例えば、ミグリトール及び必要に応じて、上記各種添加剤などを含む混合物に、水不溶性ポリマーを含む溶液をスプレーしつつ流動層造粒又は転動流動層造粒する。
(Production method)
The miglitol-containing orally disintegrating tablet according to the present invention can be produced according to a known production method in the pharmaceutical field. For example, fluidized bed granulation or rolling fluidized bed granulation is performed while spraying a solution containing a water-insoluble polymer onto a mixture containing miglitol and, if necessary, the above-described various additives.
本発明の製造方法において、流動層造粒装置としては、「ＭＰ−１」（パウレック社製）、「ＦＬＯ−５」（フロイント社製）等の市販機を用いることができる。また、「ＭＰ−１」（パウレック社製）は、転動流動層造粒装置として用いることもできる。 In the production method of the present invention, commercially available machines such as “MP-1” (manufactured by POWREC) and “FLO-5” (manufactured by Freund) can be used as the fluidized bed granulator. Further, “MP-1” (manufactured by POWREC) can also be used as a rolling fluidized bed granulator.
湿式造粒工程で得られた造粒物は乾燥し整粒した後、崩壊剤、滑沢剤及び必要に応じて、上記各種添加剤などを添加して混合する。混合した組成物を打錠して一実施形態に係るミグリトール含有口腔内崩壊錠を得ることができる。 The granulated product obtained in the wet granulation step is dried and sized, and then added with a disintegrant, a lubricant, and, if necessary, the above-mentioned various additives and mixed. The mixed composition can be tableted to obtain the miglitol-containing orally disintegrating tablet according to one embodiment.
なお、一実施形態において、湿式造粒工程後の造粒物に、上記の添加剤の何れかを混合し成形するようにしてもよい（後添加）。 In one embodiment, the granulated product after the wet granulation step may be mixed with any of the above-described additives (post-addition).
（硬度）
本明細書において、硬度は、シュロイニゲル錠剤硬度計（MODEL6D、シュロイニゲル社製）により各錠剤５錠について硬度を測定し、その平均値を錠剤硬度とする。
(hardness)
In this specification, the hardness is measured for 5 tablets with a Schleunigel tablet hardness tester (MODEL6D, manufactured by Schleunigel), and the average value is taken as the tablet hardness.
（口腔内崩壊時間）
本明細書において、口腔内崩壊時間は、試験液として人口唾液を用い、トリコープテスタ（岡田精工社製）により評価する。
(Oral disintegration time)
In the present specification, the oral disintegration time is evaluated by a tricope tester (Okada Seiko Co., Ltd.) using artificial saliva as a test solution.
（溶出試験）
本明細書において、溶出試験は、第十六改正日本薬局方 溶出試験法 パドル法に準じ、パドル回転数：５０回転、試験液：水９００ｍｌの条件にて、試験開始後１５分の溶出率を測定することにより評価する。
(Dissolution test)
In this specification, the dissolution test is based on the 16th revised Japanese Pharmacopoeia dissolution test method, paddle method, paddle rotation number: 50 rotations, test solution: 900 ml water, 15 minutes after the start of the test. Evaluate by measuring.
（類縁物質）
本明細書において、安定性の評価として、液体クロマトグラフィーを用いてミグリトールの純度を評価する。ミグリトール由来の類縁物質のピーク面積からミグリトールのピーク面積に対する比率を算出し、総類縁物質とする。
(Related substances)
In this specification, as an evaluation of stability, the purity of miglitol is evaluated using liquid chromatography. The ratio to the peak area of miglitol is calculated from the peak area of the related substance derived from miglitol, and is defined as the total related substance.
上述した本発明に係るミグリトール含有口腔内崩壊錠の具体的な実施例及び試験結果を示して、より詳細に説明する。 Specific examples and test results of the above-described miglitol-containing orally disintegrating tablet according to the present invention will be described in more detail.
（実施例１）
流動層造粒装置（パウレック社製、機種：MP-01）にて、ミグリトール４５０ｇに、エチルセルロース（エトセル７ＦＰ、ダウケミカル）４５ｇを溶解させたエタノール溶液をスプレーし、転動流動層造粒を行った。転動流動層造粒工程で得られた造粒物を、６０℃で乾燥した。
Example 1
Using a fluidized bed granulator (Poulex, model: MP-01), sprayed with an ethanol solution in which 45 g of ethylcellulose (Ethocel 7FP, Dow Chemical) was dissolved in 450 g of miglitol to perform rolling fluidized bed granulation. It was. The granulated product obtained in the rolling fluidized bed granulation step was dried at 60 ° C.
乾燥した造粒物を篩２２号で整粒した後、整粒品４９．５ｇにプレミックス添加剤（Ｄ−マンニトール、カルメロース、結晶セルロース及びクロスポビドンの混合物）１２１．３２ｇ、スクラロース（三栄源エフ・エフ・アイ）０．１８ｇ、結晶セルロース（セオラスＵＦ７１１、旭化成ケミカルズ）１．８ｇ、メタケイ酸アルミン酸マグネシウム（ノイシリンＵＦＬ２、富士化学工業）５．４ｇを加えビニール袋で混合した。さらに、ステアリン酸マグネシウム（太平化学）１．８ｇを添加して混合し、ミグリトールを含む打錠前粉末を得た。打錠機（VELA5、菊水製作所社製）を用い、重量３００ｍｇとなるよう打錠前粉末を打錠し、実施例１のミグリトール含有口腔内崩壊錠を得た。 The dried granulated product is sized with sieve No. 22, and then 49.5 g of the sized product is added to premixed additives (mixture of D-mannitol, carmellose, crystalline cellulose and crospovidone), 121.32 g, sucralose (San-Eigen F) -F8) 0.18 g, crystalline cellulose (Theolas UF711, Asahi Kasei Chemicals) 1.8 g, magnesium aluminate metasilicate (Neusilin UFL2, Fuji Chemical Industry) 5.4 g was added and mixed in a plastic bag. Furthermore, 1.8 g of magnesium stearate (Taihei Chemical) was added and mixed to obtain a pre-tablet powder containing miglitol. Using a tableting machine (VELA5, manufactured by Kikusui Seisakusho Co., Ltd.), the powder before tableting was tableted to a weight of 300 mg, and the miglitol-containing orally disintegrating tablet of Example 1 was obtained.
（実施例２）
実施例１においてはミグリトールに対して１０質量％となるようエチルセルロース溶解液をスプレーしたが、実施例２においては、ミグリトールに対して２５質量％となるようエチルセルロース溶解液をスプレーした。実施例２においては、エチルセルロース（エトセル７ＦＰ、ダウケミカル）１１２．５ｇ、整粒品５６．２５ｇ、プレミックス添加剤（Ｄ−マンニトール、カルメロース、結晶セルロース及びクロスポビドンの混合物）１１６．３７ｇとし、結晶セルロースを添加しなかったこと以外は、実施例１と同様に口腔内崩壊錠を得た。
(Example 2)
In Example 1, the ethylcellulose solution was sprayed so as to be 10% by mass with respect to miglitol, but in Example 2, the ethylcellulose solution was sprayed so as to be 25% by mass with respect to miglitol. In Example 2, 112.5 g of ethyl cellulose (Ethocel 7FP, Dow Chemical), 56.25 g of a sized product, 116.37 g of a premix additive (a mixture of D-mannitol, carmellose, crystalline cellulose and crospovidone) and crystals An orally disintegrating tablet was obtained in the same manner as in Example 1 except that cellulose was not added.
（実施例３）
実施例３においては、ミグリトールに対して２０質量％となるようエチルセルロース溶解液をスプレーした。流動層造粒装置（パウレック社製、機種：MP-01）にて、ミグリトール４５０ｇに、エチルセルロース（エトセル７ＦＰ、ダウケミカル）９０ｇを溶解させたエタノール溶液をスプレーし、流動層造粒を行った。流動層造粒工程で得られた造粒物を、６０℃で乾燥した。
Example 3
In Example 3, the ethylcellulose solution was sprayed so that it might become 20 mass% with respect to miglitol. In a fluidized bed granulator (Paurec, model: MP-01), an ethanol solution in which 90 g of ethylcellulose (Ethocel 7FP, Dow Chemical) was dissolved in 450 g of miglitol was sprayed to perform fluidized bed granulation. The granulated product obtained in the fluidized bed granulation step was dried at 60 ° C.
乾燥した造粒物を篩２２号で整粒した後、整粒品４５ｇにプレミックス添加剤（Ｄ−マンニトール、カルメロース、結晶セルロース及びクロスポビドン混合物）６２．７３ｇ、スクラロース（三栄源エフ・エフ・アイ）０．１５ｇ、メタケイ酸アルミン酸マグネシウム（ノイシリンＵＦＬ２、富士化学工業）３．５ｇを加えビニール袋で混合した。さらに、ステアリン酸マグネシウム（太平化学）１．１３ｇを添加して混合し、ミグリトールを含む打錠前粉末を得た。打錠機（VELA5、菊水製作所社製）を用い、重量２２５ｍｇとなるよう打錠前粉末を打錠し、実施例３のミグリトール含有口腔内崩壊錠を得た。 After the dried granulated product is sized with sieve No. 22, the premixed additive (D-mannitol, carmellose, crystalline cellulose and crospovidone mixture) 62.73 g, sucralose (San-Eigen EF Eye) 0.15 g and magnesium aluminate metasilicate (Neusilin UFL2, Fuji Chemical Industries) were added and mixed in a plastic bag. Furthermore, 1.13 g of magnesium stearate (Taihei Chemical) was added and mixed to obtain a pre-tablet powder containing miglitol. Using a tableting machine (VELA5, manufactured by Kikusui Seisakusho Co., Ltd.), the powder before tableting was tableted to a weight of 225 mg, and the miglitol-containing orally disintegrating tablet of Example 3 was obtained.
（実施例４）
実施例４においては、実施例３に対して、後添加するプレミックス添加剤（Ｄ−マンニトール、カルメロース、結晶セルロース及びクロスポビドン混合物）を別のプレミックス添加剤（Ｄ−マンニトール及びコーンスターチ混合物）に変更した。実施例３と同様に乾燥した造粒物を篩２２号で整粒した後、整粒品にプレミックス添加剤（Ｄ−マンニトール及びコーンスターチ混合物）６４．５５ｇ、クロスポビドン（コリドンＣＬ−Ｆ、ＢＡＳＦ）１．６９ｇ、スクラロース（三栄源エフ・エフ・アイ）０．１５ｇを加えビニール袋で混合した。さらに、ステアリン酸マグネシウム（太平化学）１．１３ｇを添加して混合し、ミグリトールを含む打錠前粉末を得た。打錠機（VELA5、菊水製作所社製）を用い、重量２２５ｍｇとなるよう打錠前粉末を打錠し、実施例４のミグリトール含有口腔内崩壊錠を得た。
Example 4
In Example 4, the premix additive (D-mannitol, carmellose, crystalline cellulose and crospovidone mixture) to be added later to Example 3 was added to another premix additive (D-mannitol and corn starch mixture). changed. After granulating the dried granulated product in the same manner as in Example 3 using sieve No. 22, 64.55 g of a premix additive (D-mannitol and corn starch mixture) and crospovidone (Collidon CL-F, BASF) ) 1.69 g and 0.15 g of sucralose (Sanyogen F.F.I.) were added and mixed in a plastic bag. Furthermore, 1.13 g of magnesium stearate (Taihei Chemical) was added and mixed to obtain a pre-tablet powder containing miglitol. Using a tableting machine (VELA5, manufactured by Kikusui Seisakusho Co., Ltd.), the powder before tableting was tableted to a weight of 225 mg, and the miglitol-containing orally disintegrating tablet of Example 4 was obtained.
（実施例５）
実施例５においては、ミグリトールに対して２０質量％となるようエチルセルロース溶解液をスプレーするともに、滑沢剤としてタルクを添加して転動流動層造粒により造粒物を製した。流動層造粒装置（パウレック社製、機種：MP-01）にて、ミグリトール４５０ｇに、エチルセルロース（エトセル７ＦＰ、ダウケミカル）９０ｇ及びタルク（日本タルク）９ｇを溶解及び分散させたエタノールと水を８対２の割合で混合した溶解液をスプレーし、転動流動層造粒を行った。転動流動層造粒工程で得られた造粒物を、６０℃で乾燥した。
(Example 5)
In Example 5, while spraying an ethylcellulose solution so that it might become 20 mass% with respect to miglitol, talc was added as a lubricant and the granulated material was manufactured by rolling fluidized bed granulation. In a fluidized bed granulator (manufactured by Paulek, model: MP-01), 8 g of ethanol and water in which 90 g of ethylcellulose (Etocel 7FP, Dow Chemical) and 9 g of talc (Japanese talc) were dissolved and dispersed in 450 g of miglitol. The solution mixed in the ratio of 2 was sprayed to perform rolling fluidized bed granulation. The granulated product obtained in the rolling fluidized bed granulation step was dried at 60 ° C.
乾燥した造粒物を篩２２号で整粒した後、整粒品４５．７５ｇにプレミックス添加剤（Ｄ−マンニトール、カルメロース、結晶セルロース及びクロスポビドンの混合物）９６．６ｇ、スクラロース（三栄源エフ・エフ・アイ）０．１５ｇ、結晶セルロース（セオラスＵＦ７１１、旭化成ケミカルズ）１．５ｇ、メタケイ酸アルミン酸マグネシウム（ノイシリンＵＦＬ２、富士化学工業）４．５ｇを加えビニール袋で混合した。さらに、ステアリン酸マグネシウム（太平化学）１．５ｇを添加して混合し、ミグリトールを含む打錠前粉末を得た。打錠機（VELA5、菊水製作所社製）を用い、重量３００ｍｇとなるよう打錠前粉末を打錠し、実施例５のミグリトール含有口腔内崩壊錠を得た。 After the dried granulated product is sized with sieve No. 22, the premixed additive (mixture of D-mannitol, carmellose, crystalline cellulose and crospovidone) 96.6 g, sucralose (San-Eigen F) -F eye (0.15 g), crystalline cellulose (Theolas UF711, Asahi Kasei Chemicals) 1.5 g, and magnesium aluminate metasilicate (Neusilin UFL2, Fuji Chemical Industries) were added and mixed in a plastic bag. Furthermore, 1.5 g of magnesium stearate (Taihei Chemical) was added and mixed to obtain a pre-tablet powder containing miglitol. Using a tableting machine (VELA5, manufactured by Kikusui Seisakusho Co., Ltd.), the powder before tableting was tableted to a weight of 300 mg, and the miglitol-containing orally disintegrating tablet of Example 5 was obtained.
（実施例６）
実施例６においては、実施例５のタルクに替えて、ヒプロメロース（ＴＣ−５Ｅ、信越化学）を添加して溶媒としてエタノールと水を８対２の割合の混合液に溶解したこと以外は、実施例５と同様にミグリトール含有口腔内崩壊錠を得た。
(Example 6)
In Example 6, it replaced with the talc of Example 5, and it implemented except having added hypromellose (TC-5E, Shin-Etsu Chemical), and melt | dissolving ethanol and water in the liquid mixture of the ratio of 8 to 2 as a solvent. A miglitol-containing orally disintegrating tablet was obtained in the same manner as in Example 5.
（実施例７）
実施例７においては、ミグリトール４５０ｇに、ポリビニルアセタールジエチルアミノアセテート（ＡＥＡ（登録商標）、三菱化学フーズ株式会社）９０ｇを溶解させたエタノールと水を８対２の割合で混合した溶解液をスプレーし、転動流動層造粒を行ったこと以外は、実施例３と同様にミグリトール含有口腔内崩壊錠を得た。
(Example 7)
In Example 7, a solution obtained by mixing ethanol and water, in which 90 g of polyvinyl acetal diethylaminoacetate (AEA (registered trademark), Mitsubishi Chemical Foods)) was dissolved in 450 g of miglitol, at a ratio of 8 to 2, was sprayed. A miglitol-containing orally disintegrating tablet was obtained in the same manner as in Example 3 except that the rolling fluidized bed granulation was performed.
（実施例８）
実施例８においては、流動層造粒装置（パウレック社製、機種：MP-01）にて、ミグリトール４５０ｇに、アミノアルキルメタクリレートコポリマーＲＳ（オイドラギット（登録商標）ＲＳ、EVONIK）９０ｇ、マクロゴール６０００（日油株式会社）９ｇ及びタルク（日本タルク）８１ｇを溶解させたエタノールと水を８対２の割合で混合した溶解液をスプレーし、流動層造粒を行った。流動層造粒工程で得られた造粒物を、６０℃で乾燥した。
(Example 8)
In Example 8, in a fluidized bed granulator (manufactured by Paulek, model: MP-01), 450 g of miglitol, 90 g of aminoalkyl methacrylate copolymer RS (Eudragit (registered trademark) RS, EVONIK), Macrogol 6000 ( (Nissho Corporation) 9g and 81g of talc (Nihon Talc) in which ethanol and water were mixed at a ratio of 8 to 2 were sprayed to perform fluidized bed granulation. The granulated product obtained in the fluidized bed granulation step was dried at 60 ° C.
乾燥した造粒物を篩２２号で整粒した後、整粒品５２．５ｇにプレミックス添加剤（Ｄ−マンニトール、カルメロース、結晶セルロース及びクロスポビドン混合物）５５．２３ｇ、スクラロース（三栄源エフ・エフ・アイ）０．１５ｇ、メタケイ酸アルミン酸マグネシウム（ノイシリンＵＦＬ２、富士化学工業）３．５ｇを加えビニール袋で混合した。さらに、ステアリン酸マグネシウム（太平化学）１．１３ｇを添加して混合し、ミグリトールを含む打錠前粉末を得た。打錠機（VELA5、菊水製作所社製）を用い、重量２２５ｍｇとなるよう打錠前粉末を打錠し、実施例８のミグリトール含有口腔内崩壊錠を得た。 After the dried granulated product is sized with sieve No. 22, 55.23 g of premixed additive (mixture of D-mannitol, carmellose, crystalline cellulose and crospovidone) is added to 52.5 g of sized product, F.I.) 0.15 g and magnesium aluminate metasilicate (Neusilin UFL2, Fuji Chemical) were added and mixed in a plastic bag. Furthermore, 1.13 g of magnesium stearate (Taihei Chemical) was added and mixed to obtain a pre-tablet powder containing miglitol. Using a tableting machine (VELA5, manufactured by Kikusui Seisakusho), the powder before tableting was tableted to a weight of 225 mg to obtain a miglitol-containing orally disintegrating tablet of Example 8.
（比較例１）
比較例１として、エチルセルロースを添加せずに、口腔内崩壊錠を製した。ミグリトール２５ｇに、プレミックス添加剤（Ｄ−マンニトール、カルメロース、結晶セルロース及びクロスポビドン混合物）６９．９ｇ、スクラロース（三栄源エフ・エフ・アイ）０．１ｇ、結晶セルロース（セオラスＵＦ７１１、旭化成ケミカルズ）１ｇ、メタケイ酸アルミン酸マグネシウム（ノイシリンＵＦＬ２、富士化学工業）３ｇを加えビニール袋で混合した。さらに、ステアリン酸マグネシウム（太平化学）１ｇを添加して混合し、ミグリトールを含む打錠前粉末を得た。打錠機（VELA5、菊水製作所社製）を用い、重量３００ｍｇとなるよう打錠前粉末を打錠し、比較例１のミグリトール含有口腔内崩壊錠を得た。
(Comparative Example 1)
As Comparative Example 1, an orally disintegrating tablet was produced without adding ethylcellulose. 25 g of miglitol, 69.9 g of premix additives (D-mannitol, carmellose, crystalline cellulose and crospovidone mixture), 0.1 g of sucralose (Seiei Gen FFI), 1 g of crystalline cellulose (Seolas UF711, Asahi Kasei Chemicals) 3 g of magnesium aluminate metasilicate (Neusilin UFL2, Fuji Chemical) was added and mixed in a plastic bag. Furthermore, 1 g of magnesium stearate (Taipei Kagaku) was added and mixed to obtain a pre-tablet powder containing miglitol. Using a tableting machine (VELA5, manufactured by Kikusui Seisakusho Co., Ltd.), the powder before tableting was tableted to a weight of 300 mg, and the miglitol-containing orally disintegrating tablet of Comparative Example 1 was obtained.
（比較例２）
比較例２として、ミグリトールに対して５質量％となるようエチルセルロースと水を８対２の割合で混合した溶解液をスプレーし、実施例６に準じて口腔内崩壊錠を製した。流動層造粒装置（パウレック社製、機種：MP-01）にて、ミグリトール４５０ｇに、エチルセルロース（エトセル７ＦＰ、ダウケミカル）２２．５ｇ及びヒプロメロース（ＴＣ−５Ｅ、信越化学）２．２５ｇを溶解させたエタノール溶液をスプレーし、転動流動層造粒を行った。転動流動層造粒工程で得られた造粒物を、６０℃で乾燥した。
(Comparative Example 2)
As Comparative Example 2, an orally disintegrating tablet was produced in the same manner as in Example 6 by spraying a solution obtained by mixing ethyl cellulose and water at a ratio of 8 to 2 to 5% by mass with respect to miglitol. Dissolve 22.5 g of ethylcellulose (Etocel 7FP, Dow Chemical) and 2.25 g of hypromellose (TC-5E, Shin-Etsu Chemical) in 450 g of miglitol, using a fluidized bed granulator (Poulex, model: MP-01). The ethanol solution was sprayed to perform rolling fluidized bed granulation. The granulated product obtained in the rolling fluidized bed granulation step was dried at 60 ° C.
乾燥した造粒物を篩２２号で整粒した後、整粒品３９．５６ｇにプレミックス添加剤（Ｄ−マンニトール、カルメロース、結晶セルロース及びクロスポビドンの混合物）１０２．８５ｇ、スクラロース（三栄源エフ・エフ・アイ）０．１５ｇ、結晶セルロース（セオラスＵＦ７１１、旭化成ケミカルズ）１．５ｇ、メタケイ酸アルミン酸マグネシウム（ノイシリンＵＦＬ２、富士化学工業）４．５ｇを加えビニール袋で混合した。さらに、ステアリン酸マグネシウム（太平化学）１．５ｇを添加して混合し、ミグリトールを含む打錠前粉末を得た。打錠機（VELA5、菊水製作所社製）を用い、重量３００ｍｇとなるよう打錠前粉末を打錠し、比較例２のミグリトール含有口腔内崩壊錠を得た。 After the dried granulated product is sized with sieve No. 22, the premixed additive (mixture of D-mannitol, carmellose, crystalline cellulose and crospovidone) 102.85 g, sucralose (San-Eigen F) -F eye (0.15g), crystalline cellulose (Theolas UF711, Asahi Kasei Chemicals) 1.5g, magnesium metasilicate aluminate (Neusilin UFL2, Fuji Chemical Industry) 4.5g was added and mixed with a plastic bag. Furthermore, 1.5 g of magnesium stearate (Taihei Chemical) was added and mixed to obtain a pre-tablet powder containing miglitol. Using a tableting machine (VELA5, manufactured by Kikusui Seisakusho Co., Ltd.), the powder before tableting was tableted to a weight of 300 mg, and the miglitol-containing orally disintegrating tablet of Comparative Example 2 was obtained.
（比較例３）
比較例３においては、エチルセルロース溶解液に替えて、エタノールと水を８対２の割合で混合した溶液をミグリトールと粉末のエチルセルロースにスプレーした。ミグリトール４５０ｇに、エタノールと水を８対２の割合で混合した溶液をスプレーし、転動流動層造粒を行ったこと以外は、実施例３と同様に口腔内崩壊錠を得た。
(Comparative Example 3)
In Comparative Example 3, instead of the ethylcellulose solution, a solution in which ethanol and water were mixed at a ratio of 8 to 2 was sprayed on miglitol and powdered ethylcellulose. An orally disintegrating tablet was obtained in the same manner as in Example 3 except that 450 g of miglitol was sprayed with a solution in which ethanol and water were mixed at a ratio of 8 to 2, and subjected to rolling fluidized bed granulation.
（打錠障害）
打錠前粉末を打錠した際の、打錠障害（スティッキング）について評価した。評価結果を図１に示す。エチルセルロースを添加しない比較例１においては、スティッキングが生じ、比較例３に於いては、バインディングが生じた。一方、実施例１〜８の打錠前粉末においては、打錠障害が認められなかった。
(Tablet failure)
The tableting failure (sticking) when the powder before tableting was tableted was evaluated. The evaluation results are shown in FIG. In Comparative Example 1 where no ethylcellulose was added, sticking occurred, and in Comparative Example 3, binding occurred. On the other hand, in the powders before tableting of Examples 1 to 8, no tableting trouble was observed.
（硬度）
シュロイニゲル錠剤硬度計（MODEL6D、シュロイニゲル社製）により実施例１〜８及び比較例１〜３の口腔内崩壊錠、５錠について硬度を測定し、その平均値をそれぞれの錠剤硬度とした。硬度の測定結果を図１に示す。また、２５℃、湿度７５％に１週間、開封状態で保存した口腔内崩壊錠の硬度も同様に測定し、図１に示す。エチルセルロースを添加しない比較例１においては、製造直後では硬度が得られたものの、保存後の硬度が２０ Ｎを下回り、十分な硬度を維持できないことが明らかとなった。また、ミグリトールに対するエチルセルロースの添加量が５質量％の比較例２においては、保存後の硬度が２３ Ｎと実施例に比して著しく低下した。保存後の硬度は２０ Ｎ以上を維持していたが、後述するように口腔内崩壊時間が遅延した。粉末のエチルセルロースを添加し、エタノールと水の混合液を用いて造粒した比較例３においては、著しく低い硬度を示した。一方、実施例１〜８においては、保存後の硬度が２０ Ｎを上回り、十分な硬度を維持できていることが明らかとなった。
(hardness)
The hardness of the orally disintegrating tablets of Examples 1 to 8 and Comparative Examples 1 to 3 was measured with a Schleunigel tablet hardness tester (MODEL6D, manufactured by Schleunigel), and the average value was defined as each tablet hardness. The measurement result of hardness is shown in FIG. Further, the hardness of the orally disintegrating tablet stored in an open state at 25 ° C. and 75% humidity for 1 week was also measured and is shown in FIG. In Comparative Example 1 in which ethylcellulose was not added, although hardness was obtained immediately after production, the hardness after storage was less than 20 N, and it became clear that sufficient hardness could not be maintained. Further, in Comparative Example 2 in which the amount of ethyl cellulose added relative to miglitol was 5% by mass, the hardness after storage was 23 N, which was significantly lower than that in Examples. The hardness after storage was maintained at 20 N or more, but the oral disintegration time was delayed as described later. In Comparative Example 3 in which powdered ethylcellulose was added and granulated using a mixed solution of ethanol and water, extremely low hardness was exhibited. On the other hand, in Examples 1-8, it became clear that the hardness after storage exceeded 20 N and sufficient hardness was maintained.
（口腔内崩壊時間）
試験液として人口唾液を用い、実施例１〜８及び比較例１〜３の口腔内崩壊錠をトリコープテスタ（岡田精工社製）により、それぞれ２錠評価した。口腔内崩壊時間の測定結果を図１に示す。実施例１〜８の口腔内崩壊錠においては、３０秒以下の速やかな口腔内崩壊が確認された。一方、エチルセルロースを添加しない比較例１、ミグリトールに対するエチルセルロースの添加量が５質量％の比較例２及び粉末のエチルセルロースを添加し、エタノールと水の混合液を用いて造粒した比較例３においては、口腔内崩壊時間の著しい遅延が認められた。
(Oral disintegration time)
Using the artificial saliva as a test solution, each of the orally disintegrating tablets of Examples 1 to 8 and Comparative Examples 1 to 3 was evaluated by a tricope tester (Okada Seiko Co., Ltd.). The measurement results of the oral disintegration time are shown in FIG. In the orally disintegrating tablets of Examples 1 to 8, rapid oral disintegration of 30 seconds or less was confirmed. On the other hand, in Comparative Example 1 in which ethyl cellulose is not added, Comparative Example 2 in which the amount of ethyl cellulose added to miglitol is 5% by mass, and Comparative Example 3 in which powdered ethyl cellulose is added and granulated using a mixture of ethanol and water, A significant delay in the oral disintegration time was observed.
（溶出試験）
試験液として９００ｍｌの水を用い、実施例１〜８及び比較例１〜３の口腔内崩壊錠を第十六改正日本薬局方 溶出試験法 パドル法に準じ、１５分間撹拌し、溶出率を測定した。溶出率の測定結果を図１に示す。実施例１〜８の口腔内崩壊錠において、エチルセルロースを添加したことに伴う溶出率の低下は認められなかった。
(Dissolution test)
Using 900 ml of water as the test solution, the orally disintegrating tablets of Examples 1 to 8 and Comparative Examples 1 to 3 were stirred for 15 minutes according to the 16th revised Japanese Pharmacopoeia Dissolution Test Method, and the dissolution rate was measured. did. The measurement results of the dissolution rate are shown in FIG. In the orally disintegrating tablets of Examples 1 to 8, no decrease in dissolution rate due to the addition of ethyl cellulose was observed.
（類縁物質）
実施例１〜８の口腔内崩壊錠の安定性の評価として、液体クロマトグラフィーを用いてミグリトールの純度を評価した。ミグリトール由来の類縁物質のピーク面積からミグリトールのピーク面積に対する比率を算出し、総類縁物質とした。また、６０℃で２週間および、６０℃湿度６０％で２週間、開封状態で保存した口腔内崩壊錠の総類縁物質も同様に測定したが、実施例１〜８の口腔内崩壊錠において、保存前後での総類縁物質の増加は認められなかった。
(Related substances)
As an evaluation of the stability of the orally disintegrating tablets of Examples 1 to 8, the purity of miglitol was evaluated using liquid chromatography. The ratio to the peak area of miglitol was calculated from the peak area of the related substance derived from miglitol and used as the total related substance. Moreover, although the total related substance of the orally disintegrating tablet preserve | saved in the open state for 2 weeks at 60 degreeC and 60
以上説明したように、本発明に係るミグリトール含有口腔内崩壊錠は、水不溶性ポリマーを添加することにより、多湿条件下に保存しても、口腔内崩壊錠の硬度を十分に維持することができる。また、硬度とともに、口腔内崩壊錠に必要な崩壊性と、ミグリトールの溶出性をも得ることができる。 As described above, the miglitol-containing orally disintegrating tablet according to the present invention can sufficiently maintain the hardness of the orally disintegrating tablet by adding a water-insoluble polymer even when stored under humid conditions. . In addition to the hardness, the disintegrability necessary for the orally disintegrating tablet and the dissolution property of miglitol can also be obtained.
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