JP2983973B1 - Oral fast disintegrating solid preparation - Google Patents
Oral fast disintegrating solid preparationInfo
- Publication number
- JP2983973B1 JP2983973B1 JP10290634A JP29063498A JP2983973B1 JP 2983973 B1 JP2983973 B1 JP 2983973B1 JP 10290634 A JP10290634 A JP 10290634A JP 29063498 A JP29063498 A JP 29063498A JP 2983973 B1 JP2983973 B1 JP 2983973B1
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- Japan
- Prior art keywords
- parts
- preparation
- solid preparation
- lactose
- crystalline cellulose
- Prior art date
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Abstract
【要約】
【課題】 水が無くても簡単に服用できる、服用し易い
口腔内速崩壊性の製剤を提供すること。
【解決手段】 薬物を結晶セルロース及び乳糖、並びに
カンテン末、さらに低置換度ヒドロキシプロピルセルロ
ースまたは／及びヒドロプロピルスターチと混合し、直
接打錠等により固形製剤とする。An object of the present invention is to provide a rapidly disintegrating preparation in the oral cavity which can be easily taken without water and is easy to take. SOLUTION: The drug is mixed with microcrystalline cellulose and lactose, agar powder, and low-substituted hydroxypropylcellulose or / and hydropropylstarch to obtain a solid preparation by direct tableting or the like.
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、口腔内の唾液又は
少量の水によって、直ちに崩壊し、薬物の服用を可能と
する、口腔内速崩壊性固形製剤及びその製造法に関する
ものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a rapidly disintegrating solid preparation in the oral cavity which can be rapidly disintegrated by saliva or a small amount of water in the oral cavity and can take a drug, and a method for producing the same.
【０００２】[0002]
【従来の技術および発明が解決しようとする課題】製剤
設計が製造、管理、販売する者の立場から、単なる成型
技術に終始していた時代を経て、薬理的な効用を指向す
る、いわゆるドラッグデリバリーシステム(必要なとき
に、必要なところへ、必要な量だけ薬物を送る)の重要
性が浸透して久しい。そのような経緯のなかで、近年高
年齢化社会の到来となり、薬物の正確な投与形態の一環
として、服用性の難易度が極めて重大な課題としてとり
あげられるようになってきた。2. Description of the Related Art The so-called drug delivery, which aims at pharmacological utility after the era where the formulation design has been from the point of view of the manufacture, management, and sale to simple molding technology. The importance of the system (delivery of the necessary amount of drug to the required place when needed) has long been infiltrated. Under such circumstances, the aging society has come in recent years, and as a part of an accurate administration form of a drug, difficulty in taking a drug has been taken up as a very important issue.
【０００３】すなわち、高齢者にとっては、従来の錠
剤、カプセル剤、散剤などの剤形では服用が困難な場合
があり、適切な薬物投与の障害ともなっているといわれ
てきた。したがって、服用し易い製剤の一つとして、水
が無くても簡単に服用できる、いわゆる口腔内速崩壊性
の製剤開発が急務となっている。[0003] That is, it has been said that it may be difficult for elderly people to take conventional tablets, capsules, powders and the like in dosage forms, which is an obstacle to proper drug administration. Therefore, there is an urgent need to develop a so-called rapidly disintegrating preparation in the oral cavity that can be easily taken without water as one of the preparations that can be easily taken.
【０００４】口腔内の唾液又は少量の水によって、直ち
に崩壊して服用を可能にする製剤形態としては、粒子間
結合力が弱く空隙率の大きい固形製剤が示唆されてい
る。例えば、溶解熱が小さい(−６０KJ/kg以下)キシリ
トールやエリスリトールなどの糖アルコールを薬物成分
と混合し、ヒドロキシプロピルセルロースやポリビニー
ルピロリドンなど水溶性結合剤を用いて流動層造粒する
方法(特開平８−９９９０４)、薬物成分を成形性のよい
結晶セルロースと崩壊剤の低置換度ヒドロキシプロピル
セルロースに混合し、比較的低い成型荷重(１００〜３
００kgf)で直接打錠する方法(特開平９−７１５２３)、
薬物成分をブドウ糖、果糖、デキストリン、ポリビニー
ルピロリドンのような湿潤性の糖アルコールや水溶性高
分子と混合し、２０kgf/杵以下で加圧成型後、多湿条件
下で吸湿させたのち乾燥して空隙率の大きい固形製剤を
得る方法(特開平９−４８７２６)などがある。[0004] As a preparation form which can be disintegrated immediately by saliva or a small amount of water in the oral cavity and can be taken, a solid preparation having a low porosity and a high porosity has been suggested. For example, a method of mixing a sugar alcohol such as xylitol or erythritol with a small heat of dissolution (-60 KJ / kg or less) with a drug component and granulating the mixture with a water-soluble binder such as hydroxypropylcellulose or polyvinylpyrrolidone (particularly, Japanese Patent Application Laid-Open No. 8-99904), a drug component is mixed with crystalline cellulose having good moldability and a low-substituted hydroxypropylcellulose as a disintegrant, and a relatively low molding load (100 to 3)
00 kgf) directly tableting (JP-A-9-71523),
The drug component is mixed with a moist sugar alcohol or a water-soluble polymer such as glucose, fructose, dextrin, or polyvinylpyrrolidone, press-molded with a pressure of 20 kgf / punch or less, dried under high humidity conditions, and then dried. There is a method of obtaining a solid preparation having a large porosity (JP-A-9-48726).
【０００５】その他、一般的に空隙率の大きい低結合性
固形物を得るには、糖類や水溶性高分子化合物を用い、
凍結乾燥やドライスプレー法によって非晶質化すること
が行われているが、特殊な製剤機器と労力を必要とする
ため、生産段階における経済性に難点があり、より効率
的な製造方法の開発が望まれている。[0005] In addition, generally, in order to obtain a low binding solid having a high porosity, a saccharide or a water-soluble polymer compound is used.
Amorphization is performed by freeze-drying or dry spraying.However, special formulation equipment and labor are required, so there are difficulties in economics at the production stage, and development of more efficient manufacturing methods Is desired.
【０００６】[0006]
【課題を解決するための手段】本発明は、水無しで容易
に服用できる、しかも製造容易な口腔内速崩壊性固形製
剤であり、薬物を結晶セルロース及び乳糖、並びにカン
テン末、さらに低置換度ヒドロキシプロピルセルロース
または／及びヒドロプロピルスターチと混合し、緩衝打
圧０.５ｔ以下で直接打錠(錠剤硬度３.５〜４.５kg/c
m2)して得られる製剤である。DISCLOSURE OF THE INVENTION The present invention is a solid preparation rapidly disintegrating in the oral cavity which can be easily taken without water, and is easily manufactured. Mix with hydroxypropylcellulose and / or hydropropylstarch and directly compress the tablet with a buffer compression pressure of 0.5t or less (tablet hardness: 3.5-4.5kg / c
m 2 ).
【０００７】本発明では、製剤ベースの基本的な構成要
素である、賦形剤、結合剤及び崩壊剤について、機能、
安全性、経済性等の視点から材質の選定を行い、特にカ
ンテン末を結合剤として使用することにより、最も良好
な性能の口腔内速崩壊性固形製剤を得ることに成功した
ものである。最もシンプルで取り扱い易い直接打錠法で
製造できる利点がある。In the present invention, the functions of excipients, binders and disintegrants, which are the basic components of the formulation base,
By selecting the material from the viewpoints of safety, economy, and the like, and using a powder of agar as a binder, we have succeeded in obtaining a fast-disintegrating solid preparation in the oral cavity with the best performance. It has the advantage that it can be manufactured by the simplest and easy-to-handle direct compression method.
【０００８】本発明製剤の賦形剤としては、溶解性と圧
縮成型の観点から乳糖と結晶セルロースが選択され、そ
れらの配合量は合計で錠剤重量の６５％以上と設定し
た。結晶セルロースと乳糖の配合比は結晶セルロースが
半量以上となるようにするのが好ましい。直接打錠の関
係で成分混合末の流動性が要求されるため、乳糖は粒状
化された平均粒子径が１００ミクロン以上のものを、ま
た結晶セルロースも同様平均粒子径が８０ミクロン以上
のものを使用するのが好ましい。[0008] As the excipient of the preparation of the present invention, lactose and crystalline cellulose were selected from the viewpoint of solubility and compression molding, and their blending amount was set at 65% or more of the tablet weight in total. It is preferable that the mixing ratio of crystalline cellulose and lactose be such that crystalline cellulose is at least half the amount. Since the fluidity of the ingredient mixture powder is required for direct compression, lactose should have a granulated average particle size of 100 microns or more, and crystalline cellulose should have a mean particle size of 80 microns or more. It is preferred to use.
【０００９】結合剤としては、結合能力が比較的弱く、
しかも水分と接触すると直ちに膨潤して崩壊剤としての
機能をも発揮するカンテン末を選択した。その膨潤度
(カンテン末１.０gを試験管に入れ、精製水３０mlを加
え２４時間後の膨潤量を測定する)は１０ml以上の品質
のものが好ましく、カンテン末の配合量は錠剤重量の
０.５〜１３％、殊に１〜１０％とするのが実用上好ま
しい。As a binder, the binding ability is relatively weak,
In addition, a powdered agar powder was selected which swells immediately upon contact with water and also functions as a disintegrant. Its swelling degree
(Put 1.0 g of agar powder in a test tube, add 30 ml of purified water and measure the swelling amount after 24 hours) is preferably 10 ml or more, and the content of agar powder is 0.5 to tablet weight. It is practically preferable to set it to 13%, especially 1 to 10%.
【００１０】崩壊剤としては、流動性改善の機能もかね
備えた低置換度ヒドロキシプロピルセルロースと、水気
のない直接打錠法でその崩壊能力を最大限に発揮するヒ
ドロキシプロピルスターチを用いた。その配合量は錠剤
重量の１〜１３％、殊に３〜１０％とするのが実用上好
ましい。またこれらの崩壊剤は、それぞれ単独で充分効
果をあげ得るが、場合によっては両者を同時に併用する
こともできる。As disintegrants, low-substituted hydroxypropylcellulose, which also has a function of improving fluidity, and hydroxypropyl starch, which exerts its disintegration ability to the maximum by a direct compression method without moisture, were used. It is practically preferable that the compounding amount is 1 to 13%, particularly 3 to 10% of the tablet weight. These disintegrants can be sufficiently effective alone, but in some cases, both can be used simultaneously.
【００１１】口腔内崩壊性製剤で問題になるのは苦味で
ある。したがって苦味をマスキングするために、苦味成
分そのものをコーティングしたり、甘味の強い糖類や酸
味剤を添加して苦味を軽減する方法が講じられている。A problem with orally disintegrating preparations is bitterness. Therefore, in order to mask bitterness, a method of coating the bitter component itself or adding a sugar or a sour agent having a strong sweetness to reduce the bitterness has been taken.
【００１２】本発明者らは、特にアルカロイド塩や他の
含窒素塩基塩の苦味のマスキングにはタンニン酸や縮合
リン酸塩が有効であることを見出した。また、崩壊剤と
して医薬品製剤に一般的に用いられている、カルボキシ
メチルスターチナトリウム、例えば、クロスカルメロー
スナトリウム（米国ＮＦ収載）が意外にも或種の薬剤の
苦味に対し、マスキング効果のあることを見出して本発
明に応用した。これらの苦味軽減剤の配合量は錠剤重量
の１〜１５％、殊に、３〜１０％とするのが実用上好ま
しい。The present inventors have found that tannic acid and condensed phosphate are particularly effective for masking the bitterness of alkaloid salts and other nitrogen-containing base salts. Also, sodium carboxymethyl starch, for example, croscarmellose sodium (listed in the US NF), which is generally used in pharmaceutical preparations as a disintegrant, has a surprisingly masking effect on the bitter taste of certain drugs. And applied to the present invention. It is practically preferable that the compounding amount of these bitterness reducing agents is 1 to 15%, particularly 3 to 10% of the tablet weight.
【００１３】なお、本発明の製剤には、必要に応じ、さ
らに薬物の苦味や不快臭をマスキングする目的で適当な
甘味料、酸味剤や香料を、またその他、発泡剤、着色
剤、安定化剤、流動化剤、滑沢剤などを任意に追加配合
することもできる。The preparations of the present invention may contain, if necessary, sweeteners, sour agents and flavors suitable for the purpose of masking the bitterness and unpleasant odor of the drug, as well as other foaming agents, coloring agents and stabilizing agents. An agent, a fluidizing agent, a lubricant and the like may be optionally added.
【００１４】本発明の錠剤の圧縮成型に際しては、取扱
い上不都合のない成形性を保持しつつ、しかも錠剤構成
粒子間の結合力を弱めて崩壊性を向上するため、緩衝打
圧を０.５ｔ以下に設定し、錠剤硬度を３.５〜４.５kg/
cm2の範囲にとどめるようにするのが好ましい。In the compression molding of the tablet of the present invention, the buffering pressure is set at 0.5 t to maintain the moldability without inconvenience in handling and to improve the disintegration by weakening the bonding force between the particles constituting the tablet. The tablet hardness is set to 3.5 to 4.5 kg /
It is preferred to keep it in the cm 2 range.
【００１５】本発明の製剤は、多種の薬物に応用でき
る。例えば、現在医療機関から「水無しでも服用可能な
剤形」として提供が要望されている、Ｃａ受容体拮抗剤
(塩酸ニカルジピン、塩酸ジルチアゼム、ニバジピン、
ニフェジピン、ニトレンジピン、ニゾルジピンなどを含
む)、Ｈ2受容体拮抗剤(フェモチジン、シメチジン、塩
酸ラニチジン、塩酸ロキサジンアセテートなどを含
む)、気管支拡張剤(フマル酸フォルモテロール、硫酸サ
ルブタモール、塩酸プロカテロールなどを含む)、脳機
能改善剤(ニセルゴリン、ビンポセチン、酒石酸イフェ
ンプロジルなどを含む)等の薬物に応用できる。また錠
剤に限らず、顆粒剤や細粒剤等にも適用出来る。The preparation of the present invention can be applied to various kinds of drugs. For example, a Ca receptor antagonist currently required by medical institutions to be provided as a “dosage form that can be taken without water”
(Nicardipine hydrochloride, diltiazem hydrochloride, nivadipine,
Comprising nifedipine, nitrendipine, and the like Nizorujipin), H 2 receptor antagonists (Femochijin, cimetidine, ranitidine hydrochloride, and the like hydrochloric Loki Sa Jin acetate), bronchodilators (formoterol fumarate, salbutamol sulfate, and the like procaterol hydrochloride ), Brain function improving agents (including nicergoline, vinpocetine, ifenprodil tartrate, etc.) and the like. Further, the present invention can be applied not only to tablets but also to granules and fine granules.
【００１６】[0016]
【実施例】以下に参考例、実施例、及び試験例を示し、
本発明をさらに詳しく説明するが、これらは本発明を何
ら限定するものではない。EXAMPLES Reference examples, examples, and test examples are shown below.
The present invention will be described in more detail, but they do not limit the present invention in any way.
【００１７】以下の参考例及び実施例１及び２は、薬物
を含有しない製剤例である。 (参考例１)結晶セルロース（旭化成：アビセルPH 102）
３４.２９部、乳糖（メグレジャパン：タブレトース以
下同）５１.４３部、低置換度ヒドロキシプロピルセル
ロース（信越化学：LH-11以下同）５.７部、エリスリト
ール微紛５.７部、クロスカルメロースナトリウム（旭
化成：アクチゾル以下同）２.２部、アスパルテーム０.
１１部及びステアリン酸マグネシウム０.５７部を混合
して打錠用剤を得る。ロータリー打錠機を用い、緩衝打
圧０.１〜０.３ｔで径８mm、重量１７０mgの速崩壊性錠
剤(硬度３.４〜４.３kg/cm2)を得る。The following Reference Examples and Examples 1 and 2 are preparation examples containing no drug. (Reference Example 1) Crystalline cellulose (Asahi Kasei: Avicel PH 102)
34.29 parts, lactose (Megure Japan: the following tablelets) 51.43 parts, low substituted hydroxypropylcellulose (Shin-Etsu Chemical: LH-11 and below) 5.7 parts, erythritol fine powder 5.7 parts, croscarme Loose sodium (Asahi Kasei: Actizol and below) 2.2 parts, aspartame 0.
11 parts and 0.57 part of magnesium stearate are mixed to obtain a tableting agent. Using a rotary tableting machine, a rapidly disintegrating tablet (hardness: 3.4 to 4.3 kg / cm 2 ) having a diameter of 8 mm and a weight of 170 mg is obtained at a buffer compression pressure of 0.1 to 0.3 t.
【００１８】(参考例２)結晶セルロース３４.２９部、
乳糖５１.４部、低置換度ヒドロキシプロピルセルロー
ス５.７部、エリスリトール微紛末５.７部、精製寒天
（伊奈食品：タイプＩ以下同）１.７部、アスパルテー
ム０.１１部及びステアリン酸マグネシウム１.１部を混
合して打錠用剤を得る。参考例１と同様に打錠して径８
mm、重量１７０mgの速崩壊性錠剤(硬度３.８〜４.８kg/
cm2)を得る。Reference Example 2 34.29 parts of crystalline cellulose,
51.4 parts of lactose, 5.7 parts of low-substituted hydroxypropylcellulose, 5.7 parts of erythritol fine powder, 1.7 parts of purified agar (Ina Food: Type I and below), 0.11 part of aspartame and stearic acid A tableting preparation is obtained by mixing 1.1 parts of magnesium. Compressed as in Reference Example 1 to obtain a diameter of 8
mm, quick disintegrating tablet weighing 170 mg (hardness: 3.8-4.8 kg /
cm 2 ).
【００１９】(参考例３)結晶セルロース２０.３部、乳
糖４５.３部、ヒドロキシプロピルスターチ（フロイン
ト産業：HPS101以下同）１５部、精製寒天１４.５部、
クロスカルメロースナトリウム３.５部、アスパルテー
ム０.２部、軽質無水ケイ酸（フロイント産業：アドソ
リダー101以下同）０.２部及びステアリン酸マグネシウ
ム１部を混合して打錠用剤を得る。参考例１と同様に打
錠して径８mm、重量１７０mgの速崩壊性錠剤(硬度３.９
〜４.４kg/cm2)を得る。Reference Example 3 20.3 parts of crystalline cellulose, 45.3 parts of lactose, 15 parts of hydroxypropyl starch (Freund Corporation: HPS101 and below), 14.5 parts of purified agar,
Tableting agents are obtained by mixing 3.5 parts of croscarmellose sodium, 0.2 parts of aspartame, 0.2 parts of light anhydrous silicic acid (Freund Corporation: Adsolider 101 and below) and 1 part of magnesium stearate. Tablets were pressed in the same manner as in Reference Example 1 to obtain a rapidly disintegrating tablet having a diameter of 8 mm and a weight of 170 mg (hardness: 3.9).
~4.4kg / cm 2) obtained.
【００２０】(実施例１)結晶セルロース４５.３部、乳
糖４０.８部、低置換度ヒドロキシプロピルセルロース
５.５部、精製寒天３.５部、クロスカルメロースナトリ
ウム３.５部、アスパルテーム０.２部、軽質無水ケイ酸
０.２部及びステアリン酸マグネシウム１部を混合して
打錠用剤を得る。ロータリー打錠機を用い、緩衝打圧
０.１〜０.３ｔで径８mm、重量１７０mgの速崩壊性錠剤
(硬度３.５〜４.１kg/cm2)を得る。(Example 1) 45.3 parts of crystalline cellulose, 40.8 parts of lactose, 5.5 parts of low-substituted hydroxypropylcellulose, 3.5 parts of purified agar, 3.5 parts of croscarmellose sodium, 0 aspartame .2 parts, light anhydrous silicic acid 0.2 parts and magnesium stearate 1 part are mixed to obtain a tableting agent. Using a rotary tableting machine, buffering pressure 0.1 to 0.3t, diameter 8mm, weight 170mg fast disintegrating tablet
(Hardness 3.5-4.1 kg / cm 2 ).
【００２１】(実施例２）結晶セルロース７１.１部、乳
糖１５部、ヒドロキシプロピルスターチ５.５部、精製
寒天３.５部、クロスカルメロースナトリウム３.５部、
アスパルテーム０.２部、軽質無水ケイ酸０.２部及びス
テアリン酸マグネシウム１部を混合して打錠用剤を得
る。実施例１と同様に打錠して径８mm、重量１７０mgの
速崩壊性錠剤(硬度４〜４.５kg/cm2)を得る。Example 2 71.1 parts of crystalline cellulose, 15 parts of lactose, 5.5 parts of hydroxypropyl starch, 3.5 parts of purified agar, 3.5 parts of croscarmellose sodium,
A tableting preparation is obtained by mixing 0.2 part of aspartame, 0.2 part of light anhydrous silicic acid and 1 part of magnesium stearate. Tableting was performed in the same manner as in Example 1 to obtain a rapidly disintegrating tablet having a diameter of 8 mm and a weight of 170 mg (hardness: 4 to 4.5 kg / cm 2 ).
【００２２】以下は薬物含有製剤の実施例である。 (実施例３）ニセルゴリン５部、結晶セルロース４０.３
部、乳糖４０部、ヒドロキシプロピルスターチ５.５
部、精製寒天３.５部、クロスカルメロースナトリウム
３.５部、アスパルテーム１部、軽質無水ケイ酸０.２部
及びステアリン酸マグネシウム１部を混合して打錠用剤
を得る。実施例１と同様に打錠して径６mm、重量１００
mgの速崩壊性錠剤(硬度３.２〜３.５kg/cm2)を得る。The following are examples of drug-containing preparations. (Example 3) Nicergoline 5 parts, crystalline cellulose 40.3
Parts, lactose 40 parts, hydroxypropyl starch 5.5
, 3.5 parts of purified agar, 3.5 parts of croscarmellose sodium, 1 part of aspartame, 0.2 parts of light anhydrous silicic acid and 1 part of magnesium stearate to obtain a tableting agent. Tableting was performed in the same manner as in Example 1, and the diameter was 6 mm,
mg of rapidly disintegrating tablets (hardness 3.2-3.5 kg / cm 2 ) are obtained.
【００２３】(実施例４）塩酸アンブロキソール１２.５
部、結晶セルロース３８.６部、乳糖３４.２部、ヒドロ
キシプロピルスターチ５.５部、精製寒天３.５部、クロ
スカルメロースナトリウム３.５部、アスパルテーム１
部、軽質無水ケイ酸０.２部及びステアリン酸マグネシ
ウム１部を混合して打錠用剤を得る。実施例１と同様に
打錠して径７mm、重量１２０mgの速崩壊性錠剤(硬度３.
２〜３.８kg/cm2)を得る。Example 4 Ambroxol Hydrochloride 12.5
Part, crystalline cellulose 38.6 parts, lactose 34.2 parts, hydroxypropyl starch 5.5 parts, purified agar 3.5 parts, croscarmellose sodium 3.5 parts, aspartame 1
, 0.2 parts of light anhydrous silicic acid and 1 part of magnesium stearate to obtain a tableting agent. Tablets were compressed in the same manner as in Example 1 to obtain a rapidly disintegrating tablet having a diameter of 7 mm and a weight of 120 mg (hardness: 3.
2 to 3.8 kg / cm 2 ).
【００２４】(実施例５）ファモチジン５.９部、結晶セ
ルロース４３.８部、乳糖３７.１部、ヒドロキシプロピ
ルスターチ５.５部、精製寒天３.５部、メタリン酸ナト
リウム２部、アスパルテーム１部、軽質無水ケイ酸０.
２部及びステアリン酸マグネシウム１部を混合して打錠
用剤を得る。実施例１と同様に打錠して径８mm、重量１
７０mgの苦味を抑制した速崩壊性錠剤(硬度３.１〜４.
０kg/cm2)を得る。Example 5 5.9 parts of famotidine, 43.8 parts of crystalline cellulose, 37.1 parts of lactose, 5.5 parts of hydroxypropyl starch, 3.5 parts of purified agar, 2 parts of sodium metaphosphate, aspartame 1 Parts, light anhydrous silicic acid
2 parts and 1 part of magnesium stearate are mixed to obtain a tableting agent. Tableting 8 mm in diameter and weight 1 as in Example 1.
70 mg of rapidly disintegrating tablet with suppressed bitterness (hardness 3.1 to 4.
0 kg / cm 2 ).
【００２５】(実施例６）ファモチジン５.９部、結晶セ
ルロース５０部、乳糖２０部、精製寒天１０部、カルボ
キシメチルスターチナトリウム（木村産業：エキスプロ
タブ）７.３部、クロスカルメロースナトリウム３.５
部、アスパルテーム１部、エリスリトール微粉末１部、
軽質無水ケイ酸０.３部及びステアリン酸マグネシウム
１部を混合して打錠用剤を得る。実施例１と同様に打錠
して径６mm、重量１００mgの速崩壊性錠剤(硬度３.６〜
４.２kg/cm2)を得る。Example 6 5.9 parts of famotidine, 50 parts of crystalline cellulose, 20 parts of lactose, 10 parts of purified agar, 7.3 parts of sodium carboxymethyl starch (Kimura Sangyo: Expprotab), croscarmellose sodium 3 .5
Part, aspartame 1 part, erythritol fine powder 1 part,
A tableting preparation is obtained by mixing 0.3 part of light anhydrous silicic acid and 1 part of magnesium stearate. Tablets were tabletted in the same manner as in Example 1 to obtain a rapidly disintegrating tablet having a diameter of 6 mm and a weight of 100 mg (hardness of 3.6 to
4.2 kg / cm 2 ).
【００２６】(実施例７）ブロチゾラム０.１７部、結晶
セルロース４５.１３部、乳糖４０部、ヒドロキシプロ
ピルスターチ５.５部、精製寒天３.５部、クロスカルメ
ロースナトリウム３.５部、アスパルテーム１部、軽質
無水ケイ酸０.２部及びステアリン酸マグネシウム１部
を混合して打錠用剤を得る。実施例１と同様に打錠して
径８mm、重量１５０mgの速崩壊性錠剤（硬度３.４〜４.
０kg/cm2)を得る。Example 7 0.17 parts of brotizolam, 45.13 parts of crystalline cellulose, 40 parts of lactose, 5.5 parts of hydroxypropyl starch, 3.5 parts of purified agar, 3.5 parts of croscarmellose sodium, aspartame One part, 0.2 parts of light anhydrous silicic acid and 1 part of magnesium stearate are mixed to obtain a tableting agent. Tablets were pressed in the same manner as in Example 1 to obtain a rapidly disintegrating tablet having a diameter of 8 mm and a weight of 150 mg (hardness of 3.4 to 4.
0 kg / cm 2 ).
【００２７】(実施例８）塩酸プロカテロール０.０５
部、結晶セルロース４５.２５部、乳糖３７部、低置換
度ヒドロキシプロピルセルロース６部、精製寒天６部、
クロスカルメロースナトリウム３.５部、アスパルテー
ム１部、軽質無水ケイ酸０.２部及びステアリン酸マグ
ネシウム１部を混合して打錠用剤を得る。実施例１と同
様に打錠して径６mm、重量１００mgの速崩壊性錠剤（硬
度２.８〜３.６kg/cm2)を得る。Example 8 Procaterol Hydrochloride 0.05
Part, crystalline cellulose 45.25 parts, lactose 37 parts, low-substituted hydroxypropylcellulose 6 parts, purified agar 6 parts,
A tableting preparation is obtained by mixing 3.5 parts of croscarmellose sodium, 1 part of aspartame, 0.2 part of light anhydrous silicic acid and 1 part of magnesium stearate. Tableting is performed in the same manner as in Example 1 to obtain a rapidly disintegrating tablet (hardness: 2.8 to 3.6 kg / cm 2 ) having a diameter of 6 mm and a weight of 100 mg.
【００２８】(実施例９）マレイン酸エナラプリル５
部、結晶セルロース６５.３部、乳糖１６部、低置換度
ヒドロキシプロピルセルロース６部、精製寒天２部、ク
ロスカルメロースナトリウム３.５部、アスパルテーム
１部、軽質無水ケイ酸０.２部及びステアリン酸マグネ
シウム１部を混合して打錠用剤を得る。実施例１と同様
に打錠して径６mm、重量１００mgの速崩壊性錠剤（硬度
３.７〜４.１kg/cm2)を得る。Example 9 Enalapril Maleate 5
Parts, crystalline cellulose 65.3 parts, lactose 16 parts, low substituted hydroxypropyl cellulose 6 parts, purified agar 2 parts, croscarmellose sodium 3.5 parts, aspartame 1 part, light anhydrous silicic acid 0.2 parts and stearin One part of magnesium acid is mixed to obtain a tableting agent. Tableting is performed in the same manner as in Example 1 to obtain a rapidly disintegrating tablet (hardness: 3.7 to 4.1 kg / cm 2 ) having a diameter of 6 mm and a weight of 100 mg.
【００２９】(実施例１０）塩酸カルテオロール５部、
エチルマルトール０.２部、乳糖５部、メタリン酸ナト
リウム０.９部及びタンニン酸（メルク製）０.１部をハ
イスピードミキサー（深江工業）中で混合、エタノール
（日局）を加えて練合後、６０℃（電気乾燥機）中で乾
燥する。得られた造粒物を３０メッシュ篩過処理して、
それに結晶セルロース５８.６部、低置換度ヒドロキシ
プロピルセルロース５.５部、精製寒天５部、クロスカ
ルメロースナトリウム３.５部、乳糖１０部、軽質無水
ケイ酸０.２部、エリスリトール微粉末５部及びステア
リン酸マグネシウム１部を混合して打錠用剤を得る。実
施例１と同様に打錠して径６mm、重量１００mgの主薬の
苦味を抑制した速崩壊性錠剤（硬度３.５〜４.１kg/c
m2)を得る。(Example 10) 5 parts of carteolol hydrochloride,
0.2 parts of ethyl maltol, 5 parts of lactose, 0.9 parts of sodium metaphosphate and 0.1 part of tannic acid (Merck) were mixed in a high-speed mixer (Fukae Kogyo), and kneaded with ethanol (JP). After the combination, the mixture is dried at 60 ° C. (electric dryer). The obtained granules are subjected to a 30 mesh sieving process,
58.6 parts of crystalline cellulose, 5.5 parts of low substituted hydroxypropyl cellulose, 5 parts of purified agar, 3.5 parts of croscarmellose sodium, 10 parts of lactose, 0.2 parts of light anhydrous silicic acid, and 5 parts of erythritol fine powder And 1 part of magnesium stearate are mixed to obtain a tableting agent. A rapidly disintegrating tablet having a diameter of 6 mm and a weight of 100 mg, which was compressed in the same manner as in Example 1 to suppress the bitterness of the active ingredient (hardness of 3.5 to 4.1 kg / c)
m 2 ).
【００３０】(試験例)崩壊性試験 本発明による錠剤の速崩壊性効果を確認するために以下
の試験方法を設定した。 １．口中法 健常人ボランティアに上記各例で製した速崩壊性錠剤１
錠を口中に含ませ、自然な状態で崩壊時間を確認する。
(１群各４名につき、その平均値と標準偏差を求めた) ２．振盪器法 精製水３０mlを入れた１００mlビーカーを振盪器（大洋
科学工業：RECIPRO SHAKER SR-II）へ固定し、これに上
記各例で製した速崩壊性錠剤１錠を入れて、室温下、一
定条件（振幅距離：４cm、振盪回数：４０回/１分間）
で振盪し、錠剤の崩壊時間を確認する。(各３錠につ
き、その平均値を求める) ３．水中静置法 １００mlビーカーへ精製水３０mlを入れ、これに上記各
例で製した速崩壊性錠剤１錠を静かに投入し、室温下、
静置状態にてビーカー側面及び上面より錠剤の崩壊時間
を確認する。(各３錠につき、その平均値を求める） ４．水中ＪＰ法 日本薬局方、一般試験法中の崩壊試験法、素錠の項に基
づき、上記各例で製した速崩壊性錠剤各１錠を用いて崩
壊性試験を行い崩壊時間を確認する。（各６錠につき、
その最短及び最長時間を記録する） 各試料についての試験結果は、第１表に示す。(Test Example) Disintegration Test The following test method was set in order to confirm the fast disintegrating effect of the tablet according to the present invention. 1. Oral method Fast disintegrating tablets 1 prepared in each of the above examples for healthy volunteers
Put the tablet in the mouth and check the disintegration time in a natural state.
(The average value and standard deviation were determined for each group of four subjects.) Shaker method A 100 ml beaker containing 30 ml of purified water was fixed to a shaker (Ocean Scientific Industry: RECIPRO SHAKER SR-II), and one rapidly disintegrating tablet produced in each of the above examples was added thereto. Constant conditions (amplitude distance: 4 cm, number of times of shaking: 40 times / 1 minute)
And check the disintegration time of the tablet. (Calculate the average value for each 3 tablets) 30 ml of purified water was put into a 100 ml beaker in water, and one rapidly disintegrating tablet prepared in each of the above examples was gently added thereto.
While still standing, the disintegration time of the tablet is checked from the side and top of the beaker. (Calculate the average value for each 3 tablets) In-water JP method Based on the disintegration test method in the Japanese Pharmacopoeia, General Test Methods, and the section on uncoated tablets, a disintegration test is performed using each of the quick disintegrating tablets produced in each of the above examples to confirm the disintegration time. (For each 6 tablets,
The shortest and longest times are recorded.) The test results for each sample are shown in Table 1.
【表１】 [Table 1]
【００３１】[0031]
【発明の効果】本発明の製剤は、第１表に示す崩壊試験
結果のとおり、口中崩壊試験法では、いずれも４０秒以
内に崩壊し、スムーズな呑み込みが可能で、服用に際し
てまったく水を必要としない。したがって、本発明の製
剤は、効用面においても極めて良好な口腔内速崩壊性固
形製剤ということができる。According to the disintegration test results shown in Table 1, all of the preparations of the present invention disintegrate within 40 seconds in the oral disintegration test method, can be swallowed smoothly, and require absolutely no water when taken. And not. Therefore, the preparation of the present invention can be said to be a very rapidly disintegrating solid preparation in the oral cavity in terms of utility.
【００３２】一方、本発明の製剤は、粉体の混合と圧縮
成型という極めてシンプルな工程から成り立つ乾式法で
製剤できるものであるから、製法面においても安全性や
経済性で有利といえる。本発明の製剤の打錠用剤は、流
動性に富んでいるから打錠時における障害は全く認めら
れず、また成形性も良好であることから、緩衝打圧が比
較的低いにもかかわらず、適切な錠剤硬度が得られ、打
錠後における取り扱いに何らの不都合を感じ得ない。On the other hand, since the preparation of the present invention can be prepared by a dry method comprising very simple steps of mixing and compression molding of powder, it can be said that the preparation is advantageous in terms of safety and economy in terms of production. Since the tableting agent of the preparation of the present invention is rich in fluidity, no obstacle at the time of tableting is recognized, and since it has good moldability, it has a relatively low buffering pressure. , Suitable tablet hardness is obtained, and no inconvenience can be felt in handling after tableting.
【００３３】以上説明のとおり、本発明の製剤はすぐれ
た口腔内速崩壊性を有し、またその製造方法も簡易であ
る。従って、今後迫り来る老齢社会の場において、医療
活動に大いに貢献し得るものである。As described above, the preparation of the present invention has excellent rapid disintegration in the oral cavity, and its production method is simple. Therefore, it can greatly contribute to medical activities in an aging society that is approaching in the future.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭60−241871（ＪＰ，Ａ) 特開 平９−316009（ＪＰ，Ａ) (58)調査した分野(Int.Cl.6，ＤＢ名) A61K 9/20 A61K 47/26 A61K 47/36 A61K 47/38 ────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-60-241871 (JP, A) JP-A-9-31609 (JP, A) (58) Fields investigated (Int. Cl. 6 , DB name) A61K 9/20 A61K 47/26 A61K 47/36 A61K 47/38
Claims (9)
カンテン末、さらに低置換度ヒドロキシプロピルセルロ
ースまたは／及びヒドロキシプロピルスターチを含有し
てなる、口腔内速崩壊性固形製剤。1. A rapidly disintegrating solid preparation in the oral cavity comprising a drug, crystalline cellulose and lactose, agar powder, and low-substituted hydroxypropylcellulose or / and hydroxypropylstarch.
ある請求項１記載の口腔内速崩壊性固形製剤。2. The rapidly disintegrating oral solid preparation according to claim 1, wherein the agar powder has a swelling degree of 10 ml or more.
５〜１３％である請求項１記載の口腔内速崩壊性固形製
剤。3. The agar powder content in the preparation is 0.5% by weight.
The oral solid rapidly disintegrating preparation according to claim 1, which is 5 to 13%.
ロン以上であり、乳糖の平均粒子径が１００ミクロン以
上である請求項１記載の口腔内速崩壊性固形製剤。4. The solid preparation according to claim 1, wherein the average particle size of the crystalline cellulose is 80 μm or more, and the average particle size of the lactose is 100 μm or more.
量が重量比で６５％以上であり、その半量以上が結晶セ
ルロースである請求項１記載の口腔内速崩壊性固形製
剤。5. The rapidly oral disintegrating solid preparation according to claim 1, wherein the total content of crystalline cellulose and lactose in the preparation is 65% or more by weight, and half or more of the preparation is crystalline cellulose.
ルロースまたは／及びヒドロキシプロピルスターチの含
量が重量比で１〜１３％である請求項１記載の口腔内速
崩壊性固形製剤。6. The solid preparation according to claim 1, wherein the content of low-substituted hydroxypropylcellulose and / or hydroxypropyl starch in the preparation is 1 to 13% by weight.
チルスターチナトリウム、タンニン酸及び縮合リン酸塩
の１種以上を含有する請求項１記載の口腔内速崩壊性固
形製剤。7. The rapidly oral disintegrating solid preparation according to claim 1, further comprising at least one of sodium carboxymethyl starch, tannic acid and condensed phosphate as a bitterness reducing agent.
〜１５％である請求項１記載の口腔内速崩壊性固形製
剤。8. The preparation according to claim 1, wherein the content of the bitterness reducing agent is 1 by weight.
The rapidly disintegrating solid preparation in the oral cavity according to claim 1, which has a content of from 15% to 15%.
ある請求項１記載の口腔内速崩壊性固形製剤。9. The rapidly disintegrating solid preparation in the oral cavity according to claim 1, wherein the buffer pressure during compression molding is 0.5 t or less.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10290634A JP2983973B1 (en) | 1998-10-13 | 1998-10-13 | Oral fast disintegrating solid preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10290634A JP2983973B1 (en) | 1998-10-13 | 1998-10-13 | Oral fast disintegrating solid preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2983973B1 true JP2983973B1 (en) | 1999-11-29 |
| JP2000119175A JP2000119175A (en) | 2000-04-25 |
Family
ID=17758523
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|---|---|---|---|
| JP10290634A Expired - Lifetime JP2983973B1 (en) | 1998-10-13 | 1998-10-13 | Oral fast disintegrating solid preparation |
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- 1998-10-13 JP JP10290634A patent/JP2983973B1/en not_active Expired - Lifetime
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113116852A (en) * | 2021-04-07 | 2021-07-16 | 海南普利制药股份有限公司 | Nicergoline orally disintegrating tablet |
| CN113116852B (en) * | 2021-04-07 | 2022-10-21 | 海南普利制药股份有限公司 | Nicergoline orally disintegrating tablet |
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