JPH1053538A - Easily administrable solid preparation of h2-blocker having reduced bitterness - Google Patents
Easily administrable solid preparation of h2-blocker having reduced bitternessInfo
- Publication number
- JPH1053538A JPH1053538A JP14479497A JP14479497A JPH1053538A JP H1053538 A JPH1053538 A JP H1053538A JP 14479497 A JP14479497 A JP 14479497A JP 14479497 A JP14479497 A JP 14479497A JP H1053538 A JPH1053538 A JP H1053538A
- Authority
- JP
- Japan
- Prior art keywords
- blocker
- bitterness
- solid preparation
- sugar alcohol
- heat
- 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.)
- Pending
Links
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は，溶解熱が−６０ｋＪ／
ｋｇ以下好ましくは−１００ｋＪ／ｋｇ以下の糖アルコ
ールを添加してなる，苦味改善易服用性Ｈ2ブロッカー
固形製剤及びその製造法に関するものである。BACKGROUND OF THE INVENTION The present invention relates to a method for producing a material having a heat of dissolution of -60 kJ /
The present invention relates to an easy-to-take bitterness improving H 2 blocker solid preparation comprising a sugar alcohol of not more than 100 kg / kg, preferably not more than -100 kJ / kg, and a method for producing the same.
【０００２】[0002]
【従来の技術】従来、医薬品を用いた治療においては，
その効果に重点がおかれた方法がとられていた。現在は
高度に経済が発達し，様々な物質があふれ，豊かな暮ら
しができるようになり，老齢人口の増加や，ストレス等
が問題となってくるにつれ，快適さ，好適さが要求さ
れ，人々の生活の質（Quality of life）の向上が唱え
られてきている。治療においても同じ医薬品を投与する
ならば，患者にとってより好ましい，苦味，苦痛等を伴
わない製剤，服用時に多量の水を摂取することを要しな
い，利用しやすい製剤の開発が望まれている。正確な服
薬は薬物療法を行なう前提であり，患者が服薬を守らな
い限り，薬物治療効果をあげることはできない。しか
し，患者が服薬を正確にしていない比率は驚く程高く，
患者が服薬を守っていると答えたにもかかわらず，薬物
血中濃度を測定した結果，服薬していないことが判明し
た事例もある。2. Description of the Related Art Conventionally, in the treatment using pharmaceuticals,
A method was used that emphasized its effects. At present, the economy is highly developed, various substances are overflowing, and we can live a rich life. As the elderly population increases and stress becomes a problem, comfort and suitability are required. Improvement of the quality of life has been advocated. If the same drug is administered in the treatment, there is a demand for the development of a formulation that is more favorable for patients, does not involve bitterness, pain, etc., and does not require a large amount of water when taken, and is easy to use. Precise medication is a prerequisite for drug therapy, and unless the patient adheres to the medication, the drug therapy cannot be effective. However, the rate at which patients do not take medication accurately is surprisingly high,
In some cases, patients have responded that they are taking medication, but have determined that they have not taken medication by measuring drug blood levels.
【０００３】よって患者のコンプライアンス（服薬遵
守），つまり投薬後患者がどの程度真面目に指示どおり
服用しているかが重要となってくる。口に合わない製剤
は患者が服用を怠る原因にもなり得，その改善はコンプ
ライアンスの向上につながる。ファモチジン，シメチジ
ン，塩酸ラニチジン，ニザチジン，塩酸ロキサチジンア
セタート等のＨ2ブロッカーは，カプセル剤，錠剤及び
散剤として処方されている。水に極めて溶けにくいもの
の，散剤，顆粒剤及び咀嚼可能な錠剤など表面積が広
く，口腔内に暫時滞留する剤型においては苦味のため服
用時に抵抗感が生じる。[0003] Therefore, it is important to determine the patient's compliance, that is, how seriously the patient is taking it as instructed after the medication. Unpalatable preparations can also cause patients to fail to take them, and their improvement leads to increased compliance. Famotidine, cimetidine, ranitidine hydrochloride, nizatidine, H 2 blockers such as hydrochloric acid roxatidine acetate are capsules are formulated as tablets and powders. Although it is extremely insoluble in water, it has a large surface area, such as powders, granules, and chewable tablets, and in dosage forms that stay in the oral cavity for a while, bitterness causes a feeling of resistance when taken.
【０００４】従来，散剤及び顆粒剤の添加剤としては，
造粒作業性，安定性並びに経済性などの点から，乳糖，
澱粉及び少量の甘味剤が使用されているが，Ｈ2ブロッ
カーの苦味を消すことはできない。また，乳糖，澱粉な
どは口腔内の少量の唾液で粘着性が出現することから，
服用感は決してよいとはいえない。通常，苦味物質の味
を改善するため，セルロース系，ポリアクリル酸系など
の腸溶性高分子，水不溶性高分子，胃溶性高分子ＡＥＡ
などの他，脂肪酸及びその誘導体，油脂などを用い，苦
味物質あるいは苦味物質と乳糖などからなる芯物質に被
覆し苦味のマスキングを行う方法がとられる。特開平６
−２１９９３９号公報ではファモチジンの苦味隠蔽法と
して，ファモチジン，乳糖，ＰＶＰからなる粒に，セル
ロースアセテート及びまたはセルロースアセテートブチ
レート及びＰＶＰからなる被覆剤を被覆してマスキング
が行なわれている。しかしながら，製造工程が多く複雑
であるうえ，アセトン，メタノールや塩化メチレンなど
有機溶媒を用いることによる作業環境の悪化が予想され
る。[0004] Conventionally, additives for powders and granules include
From the viewpoints of granulation workability, stability and economy, lactose,
Starch and a small amount of sweetening agent is used, it can not be erased of H 2 blockers bitter. In addition, lactose, starch, etc. become sticky with a small amount of saliva in the oral cavity,
The feeling of taking is by no means good. Usually, enteric polymers such as cellulosic and polyacrylic acids, water-insoluble polymers, and gastric-soluble polymers AEA are used to improve the taste of bitter substances.
In addition to these methods, a method is used in which a bitter substance or a core substance comprising a bitter substance and lactose is coated with a fatty acid and its derivatives, oils and fats to mask bitterness. JP 6
In JP-A-219939, as a method of masking the bitterness of famotidine, masking is performed by coating a particle composed of famotidine, lactose, and PVP with a coating material composed of cellulose acetate and / or cellulose acetate butyrate and PVP. However, the production process is complicated and complicated, and the use of an organic solvent such as acetone, methanol or methylene chloride is expected to deteriorate the working environment.
【０００５】[0005]
【発明が解決しようとする課題】本発明の目的は，工程
数の多い複雑な製造法を用いず，また，有機溶媒を使用
せずに，Ｈ2ブロッカーの苦味を改善した易服用性の固
形製剤及びその製造法を提供することにある。SUMMARY OF THE INVENTION It is an object of the present invention, without using the process a large number of complicated manufacturing process, also without the use of organic solvents, easy taking of solid having improved of H 2 blockers bitter An object of the present invention is to provide a preparation and a method for producing the same.
【０００６】[0006]
【課題を解決するための手段】本発明者らは，Ｈ2ブロ
ッカーの固形製剤について鋭意検討を重ねた結果，砂
糖，ブドウ糖等の様々な糖を添加しても苦味は改善され
なかったが，意外にも特定の糖アルコールを組み合わせ
ることで，Ｈ2ブロッカーにあらかじめ被覆マスキング
をする等の工程数の多い複雑な製造法を必要とせず，苦
味が改善され，かつ，易服用性の固形製剤が得られるこ
とを発見し，本発明を完成するに至った。 Means for Solving the Problems As a result of intensive studies on the solid preparation of H 2 blocker, the present inventors did not improve the bitterness by adding various sugars such as sugar and glucose. by combining a specific sugar alcohol surprisingly does not require a complicated production process with many number of steps, such that the pre-coated masking in H 2 blockers, bitterness is improved, and is easily taken of the solid preparation The inventors have found that the present invention can be obtained, and have completed the present invention.
【０００７】[0007]
【発明の実施の形態】本発明でいう特定の糖アルコール
とは，溶解熱が−６０ｋＪ／ｋｇ以下好ましくは−１０
０ｋＪ／ｋｇ以下のものであり，これらは苦味が改善さ
れなかった砂糖，ブドウ糖と同程度のあるいはそれ以下
の甘味しかもたないにもかかわらず，Ｈ2ブロッカーの
苦味改善効果を示すものである。溶解熱とは溶質を溶媒
（水）に溶かすときに吸収又は発生する熱量で，吸収す
る場合を−，発生する場合を＋であらわす。溶解熱が−
６０ｋＪ／ｋｇ以下とは６０ｋＪ／ｋｇよりも吸収熱量
が大きいことをいう。BEST MODE FOR CARRYING OUT THE INVENTION The specific sugar alcohol referred to in the present invention has a heat of dissolution of -60 kJ / kg or less, preferably -10 kJ / kg or less.
And a 0kJ / kg the following, these sugar did not improve the bitterness, even though only have comparable or less sweet and glucose, shows the bitterness-improving effect of the H 2 blocker. The heat of dissolution is the amount of heat absorbed or generated when a solute is dissolved in a solvent (water). Absorbing is represented by-and generating is represented by +. Heat of dissolution
60 kJ / kg or less means that the heat absorption is greater than 60 kJ / kg.
【０００８】本発明で用いられる糖アルコールとしては
溶解熱が−６０ｋＪ／ｋｇ以下のものであれば特に制限
はなく，−１００ｋＪ／ｋｇ以下であればより好まし
い，例としては，キシリトール，ソルビトール，マンニ
トール，エリスリトールなどが挙げられる。糖アルコー
ルの溶解熱が−６０ｋＪ／ｋｇ以下でない場合には，清
涼感よりも糖アルコールの甘味が重たく感じられ，Ｈ2
ブロッカーの苦味と相まって複雑な味となり，良好な服
用感を得ることができない。例えば溶解熱が−６０ｋＪ
／ｋｇ以下でないマルチトール，ラクチトール等では苦
味改善効果は得られなかった。しかし、溶解熱が−６０
ｋＪ／ｋｇ以下好ましくは−１００ｋＪ／ｋｇ以下の糖
アルコールを用いることにより，苦味が改善され，清涼
感があり，口中ですみやかに溶解，崩解しうる易服用性
のＨ2ブロッカー固形製剤が提供し得た。これらの糖ア
ルコールは水に極めてとけ易く，甘味があるがインスリ
ン作用を要することなく細胞内に取り込まれるので血糖
値を上昇させることはない。本発明における「Ｈ2ブロ
ッカー」とは，例えばファモチジン，シメチジン，塩酸
ラニチジン，ニザチジン，塩酸ロキサチジンアセタート
等があげられる。このうち特に好ましいものとしてはフ
ァモチジンがあげられる。The sugar alcohol used in the present invention is not particularly limited as long as it has a heat of solution of -60 kJ / kg or less, and is more preferably -100 kJ / kg or less. Examples thereof include xylitol, sorbitol and mannitol. And erythritol. When the heat of dissolution of the sugar alcohol is not less than -60 kJ / kg, the sweetness of the sugar alcohol is heavier than the refreshing feeling, and H 2
The taste becomes complicated in combination with the bitterness of the blocker, and a good feeling of taking cannot be obtained. For example, the heat of dissolution is -60 kJ
Maltitol, lactitol, etc., which were not less than / kg / kg, did not provide an effect of improving bitterness. However, the heat of solution is -60.
By kJ / kg or less, preferably using the following sugar alcohol -100kJ / kg, bitterness is improved, there is refreshing feel, rapidly dissolves in the mouth, provide easy dosing of the H 2 blocker solid preparation which can disintegrate I got it. These sugar alcohols are very easy to dissolve in water and have a sweet taste, but they are taken up into cells without the need for insulin action, so they do not raise blood sugar levels. The “H 2 blocker” in the present invention includes, for example, famotidine, cimetidine, ranitidine hydrochloride, nizatidine, roxatidine hydrochloride acetate and the like. Among them, famotidine is particularly preferred.
【０００９】又，本発明における「固形製剤」には，散
剤，顆粒剤，咀嚼可能な錠剤等が含まれる。好ましくは
散剤，顆粒剤であり，最も好ましくは散剤である。そし
て本発明でいう散剤は細粒剤をも含むものである。本発
明で用いられる「易服用性」とは，清涼感があり，口中
ですみやかに溶解，崩解し，服用する際にざらつき感等
を伴わず，口当たりの良い服用し易い形態を提供しうる
ものである。The "solid preparation" of the present invention includes powders, granules, chewable tablets and the like. Preferred are powders and granules, and most preferred are powders. The powder according to the present invention also includes fine granules. "Easy-to-take" as used in the present invention means that it has a refreshing sensation, dissolves and disintegrates quickly in the mouth, does not have a feeling of roughness when taken, and can provide a palatable, easy-to-take form. Things.
【００１０】本発明において，溶解熱が−６０ｋＪ／ｋ
ｇ以下好ましくは−１００ｋＪ／ｋｇ以下の糖アルコー
ルはＨ2ブロッカー１部に対し，２５部以上，好ましく
は４０部以上であり，かつ，製剤全重量に対し，５０％
〜９９．９％，好ましくは８０〜９９．９％用いるのが
よい。これを外れると清涼感が薄れ，口中ですみやかに
溶解，崩解し得なくなり，良好な服用感が得られない。
また，本発明で用いるこれらの糖アルコールは，単独で
用いるのみでなく，２種以上を組み合わせることもでき
る。特に咀嚼可能な錠剤の様に適度な成形性を必要とす
る剤型には良好な成形性を有するソルビトールの添加が
望ましい。In the present invention, the heat of solution is -60 kJ / k.
g or less preferably the following sugar alcohol -100kJ / kg whereas H 2 blockers 1 part, 25 parts or more, preferably not less than 40 parts, and, relative to total weight of the preparation, 50%
９９99.9%, preferably 80-99.9%. If it is removed, the refreshing sensation will be weakened, it will not dissolve or disintegrate quickly in the mouth, and a good feeling of taking it will not be obtained.
These sugar alcohols used in the present invention can be used alone or in combination of two or more. In particular, it is desirable to add sorbitol having a good formability to a dosage form requiring an appropriate formability such as a chewable tablet.
【００１１】更に，本発明において，１−メントールを
添加することで，溶解熱が−６０ｋＪ／ｋｇ以下好まし
くは−１００ｋＪ／ｋｇ以下の糖アルコールによるＨ2
ブロッカーの苦味改善効果を更に向上することができ
る。１−メントールの添加量としては通常１％以下好ま
しくは０．１％以下である。本発明で製したＨ2ブロッ
カーと溶解熱が−６０ｋＪ／ｋｇ以下好ましくは−１０
０ｋＪ／ｋｇ以下の糖アルコールまたは，Ｈ2ブロッカ
ーと溶解熱が−６０ｋＪ／ｋｇ以下好ましくは−１００
ｋＪ／ｋｇ以下の糖アルコール及び１−メントールから
なる組成物は，通常製剤化において用いられる賦形剤，
安定化剤，結合剤，滑沢剤，流動化剤，香料，甘味剤，
色素などを添加し，常法により，散剤，顆粒剤あるいは
錠剤好ましくは咀嚼可能な錠剤とすることができる。本
発明のＨ2ブロッカー固形製剤は，工程数の多い複雑な
製造法を要せず，しかも有害な有機溶媒を使わず，通常
行なわれている製造法を用い，少ない工程で製造するこ
とができる。Further, in the present invention, by adding 1-menthol, H 2 by sugar alcohol having a heat of dissolution of -60 kJ / kg or less, preferably -100 kJ / kg or less is added.
The effect of improving the bitterness of the blocker can be further improved. The amount of 1-menthol added is usually 1% or less, preferably 0.1% or less. H 2 blockers and dissolution heat of manufacturing in the present invention is -60kJ / kg or less, preferably -10
0kJ / kg or less of sugar alcohol or, H 2 blockers and heat of dissolution preferably less -60kJ / kg -100
Compositions consisting of kJ / kg or less of sugar alcohols and 1-menthol are used as excipients ordinarily used in formulation,
Stabilizers, binders, lubricants, fluidizers, flavors, sweeteners,
By adding a pigment or the like, powders, granules or tablets, preferably chewable tablets, can be prepared by a conventional method. H 2 blockers solid preparation of the present invention, without requiring more complex manufacturing process of the number of steps, moreover without using harmful organic solvents, usually conducted are using the production method, can be produced in fewer steps .
【００１２】（製造法）造粒方法として，通常の製造方
法である流動層造粒法，攪拌造粒法，高速攪拌造粒法，
転動流動造粒法などを用いて製造することができる。好
ましくは流動層造粒法，転動流動造粒法であり，中でも
流動層造粒法が最も適している。本発明で用いられる溶
解熱が−６０ｋＪ／ｋｇ以下好ましくは−１００ｋＪ／
ｋｇ以下の糖アルコールは，水に極めてとけ易いことか
ら，造粒中に水分過多による好ましくない粗粒子や塊が
できやすい。流動層造粒法は水分制御が簡単なため造粒
物の粒径制御が行ないやすく本発明の製造に最適であ
る。流動層造粒法を用いた製造方法を詳細に説明する
が，これらは本発明を限定するものではない。(Production method) As the granulation method, fluidized bed granulation method, stirring granulation method, high-speed stirring granulation method, which is a usual production method,
It can be manufactured using a tumbling fluidized-granulation method or the like. The fluidized bed granulation method and the tumbling fluidized granulation method are preferred, and the fluidized bed granulation method is most suitable. The heat of dissolution used in the present invention is -60 kJ / kg or less, preferably -100 kJ / kg.
Since sugar alcohols of less than kg are extremely soluble in water, undesired coarse particles and agglomerates due to excessive moisture are likely to be formed during granulation. The fluidized-bed granulation method is easy to control the particle size of the granulated material because the moisture control is simple, and is most suitable for the production of the present invention. Production methods using fluidized bed granulation will be described in detail, but these do not limit the present invention.
【００１３】１種あるいは２種以上の溶解熱が−６０ｋ
Ｊ／ｋｇ以下好ましくは−１００ｋＪ／ｋｇ以下の糖ア
ルコールと粉砕したＨ2ブロッカーを常法により，ＨＰ
Ｃ，ＰＶＰ等の結合剤水溶液を用いて流動層造粒機で造
粒し，所望の粒径に調製した後，粉砕した１−メントー
ル及び軽質無水ケイ酸等の流動化剤を混合機で配合し，
散剤あるいは顆粒剤とすればよい。また，得られた造粒
物にステアリン酸マグネシウム，タルク等の滑沢剤を必
要量添加し，混合機で混合した後，常法により打錠機で
打錠し，咀嚼可能な錠剤とすることもできる。この際，
溶解熱が−６０ｋＪ／ｋｇ以下好ましくは−１００ｋＪ
／ｋｇ以下の糖アルコールが大きな粒径の結晶であると
きは，造粒の前に少量の流動化剤とともに予め粉砕処理
をすることが望ましい。また，Ｈ2ブロッカーが低含量
の場合，製剤中の均一な含量を得るため，結合剤水溶液
中に分散した後，溶解熱が−６０ｋＪ／ｋｇ以下好まし
くは−１００ｋＪ／ｋｇ以下の糖アルコールに噴霧しな
がら造粒することが望ましい。[0013] One or more heats of dissolution are -60k
J / kg or less, preferably -100 kJ / kg or less, and crushed H 2 blocker are mixed with HP
After granulating with a fluidized bed granulator using an aqueous solution of a binder such as C or PVP and adjusting the particle size to a desired value, pulverized 1-menthol and a fluidizing agent such as light anhydrous silicic acid are blended with a mixer. And
Powders or granules may be used. Add the necessary amount of lubricant such as magnesium stearate, talc, etc. to the obtained granules, mix with a mixer, and tablet with a tableting machine by a conventional method to make chewable tablets. Can also. On this occasion,
Heat of dissolution is −60 kJ / kg or less, preferably −100 kJ / kg
When the sugar alcohol of less than / kg is a crystal having a large particle size, it is desirable to carry out a pulverizing treatment with a small amount of a fluidizing agent before granulation. Spray Also, if H 2 blockers low content, in order to obtain a uniform content in the formulation, was dispersed in a binder solution, heat of dissolution is less preferred -60kJ / kg on the following sugar alcohol -100kJ / kg It is desirable to granulate while performing.
【００１４】[0014]
【実施例】以下，本発明のＨ2ブロッカー含有固形製剤
及び製造法を実施例に基づいて更に詳細に説明するが，
本発明はこれらの実施例に限定されるものではない。EXAMPLES Hereinafter, described in more detail by of H 2 blockers containing solid preparation and a production method of the present invention in the Examples,
The present invention is not limited to these examples.
【００１５】実施例１ キシリトール粉末６６７．８部及び軽質無水ケイ酸３．
５部を粗混合した後，流動層造粒機ＦＬＯ−１にとり，
７．５％ＨＰＣ水溶液１４０部に１．０ｍｍスクリーン
付き微粉砕機で粉砕したファモチジン１４部を分散した
液を噴霧し造粒した。得られた造粒物を３０号篩いで篩
過し，軽質無水ケイ酸３．５部とともにＶ型混合機で１
０分間混合し，２％ファモチジン散剤を得た。Example 1 667.8 parts of xylitol powder and light anhydrous silicic acid
After roughly mixing 5 parts, the mixture is taken into a fluidized bed granulator FLO-1.
A liquid in which 14 parts of famotidine pulverized with a 1.0-mm screen pulverizer was dispersed and sprayed into 140 parts of a 7.5% HPC aqueous solution was granulated. The obtained granules were sieved with a No. 30 sieve, and mixed with 3.5 parts of light anhydrous silicic acid in a V-type mixer.
After mixing for 0 minutes, a 2% famotidine powder was obtained.
【００１６】実施例２ キシリトール粉末に替え，ソルビトール粉末６６７．８
部を用いた他は実施例１と同様にして２％ファモチジン
散剤を得た。Example 2 Instead of xylitol powder, sorbitol powder 667.8
A 2% famotidine powder was obtained in the same manner as in Example 1 except that the parts were used.
【００１７】実施例３ 実施例１で得られた散剤２９９．７部に乳鉢粉砕した１
−メントール０．３部を加え，Ｖ型混合機で１０分間混
合し，２％ファモチジン散剤を得た。Example 3 299.7 parts of the powder obtained in Example 1 was ground with a mortar.
-0.3 part of menthol was added and mixed with a V-type mixer for 10 minutes to obtain a 2% famotidine powder.
【００１８】実施例４ ソルビトール粉末４５７．３部，エリスリトール粉末２
００部及び軽質無水ケイ酸３．５部を粗混合した後，流
動層造粒機ＦＬＯ−１にとり，１０％ＨＰＣ水溶液２１
０部に１．０ｍｍスクリーン付き微粉砕機で粉砕したフ
ァモチジン１４部を分散した液を噴霧し造粒した。得ら
れた造粒物を１２号篩いで篩過し，１−メントール０．
７部，軽質無水ケイ酸３．５部とともにＶ型混合機で１
０分間混合し，２％ファモチジン顆粒を得た。Example 4 457.3 parts of sorbitol powder, erythritol powder 2
After roughly mixing 00 parts and 3.5 parts of light anhydrous silicic acid, the mixture was placed in a fluidized bed granulator FLO-1, and a 10% HPC aqueous solution 21 was added.
A liquid in which 14 parts of famotidine pulverized by a pulverizer with a 1.0 mm screen was dispersed in 0 part was sprayed and granulated. The obtained granules were sieved with a No. 12 sieve to give 1-menthol 0.1.
7 parts, 3.5 parts of light anhydrous silicic acid with V-type mixer 1
Mixing was performed for 0 minutes to obtain 2% famotidine granules.
【００１９】実施例５ キシリトール粉末に替え，マンニトール粉末６６７．８
部を用いた他は実施例１と同様にして２％ファモチジン
散剤を得た。Example 5 Mannitol powder 667.8 was used instead of xylitol powder.
A 2% famotidine powder was obtained in the same manner as in Example 1 except that the parts were used.
【００２０】実施例６ 実施例５で得られた散剤２９９．７部に乳鉢粉砕したｌ
−メントール０．３部を加え，Ｖ型混合機で１０分間混
合し，２％ファモチジン散剤を得た。Example 6 299.7 parts of the powder obtained in Example 5 was crushed with a mortar.
-0.3 part of menthol was added and mixed with a V-type mixer for 10 minutes to obtain a 2% famotidine powder.
【００２１】実施例７ キシリトール粉末に替え，エリスリトール粉末６６７．
８部を用いた他は実施例１と同様にして２％ファモチジ
ン散剤を得た。Example 7 Erythritol powder was used instead of xylitol powder.
A 2% famotidine powder was obtained in the same manner as in Example 1 except that 8 parts were used.
【００２２】実施例８ 実施例７で得られた散剤２９９．７部に乳鉢粉砕したｌ
−メントール０．３部を加え，Ｖ型混合機で１０分間混
合し，２％ファモチジン散剤を得た。Example 8 299.7 parts of the powder obtained in Example 7 was crushed with a mortar.
-0.3 part of menthol was added and mixed with a V-type mixer for 10 minutes to obtain a 2% famotidine powder.
【００２３】実施例９ 軽質無水ケイ酸１．０部にレモンフレーバー０．５部を
加え乳鉢中でよく混合した後，実施例２で得られた散剤
４９９．５部とともにＶ型混合機で１０分間混合し，更
にステアリン酸マグネシウム１０部を加え１０分間混合
した後，単発型打錠機により１錠１０２２ｍｇ，直径１
５．０ｍｍ，厚さ５．５ｍｍの錠剤に打錠し，１錠中フ
ァモチジン２０ｍｇを含有する咀嚼可能な錠剤を得た。Example 9 0.5 part of lemon flavor was added to 1.0 part of light anhydrous silicic acid, mixed well in a mortar, and mixed with 499.5 parts of the powder obtained in Example 2 in a V-type mixer. After mixing for 10 minutes, 10 parts of magnesium stearate was further added and mixed for 10 minutes.
Tablets having a thickness of 5.0 mm and a thickness of 5.5 mm were tabletted to obtain chewable tablets containing 20 mg of famotidine in each tablet.
【００２４】試験例１ 実施例１〜４及び下記の比較例で得られたファモチジン
含有内服固形製剤につき，１０名のパネラーの口中に２
０秒間含ませ，官能試験を行った。それぞれの苦味及び
清涼感，口当たり等の服用感につき，表１及び表２に示
す。 （比較例）１．０ｍｍスクリーン付き微粉砕機で粉砕し
たファモチジン２０部，乳糖８４５部，トウモロコシ澱
粉１００部を流動層造粒機ＦＬＯ−１にとり，１０％Ｈ
ＰＣ水溶液３００部を結合剤として造粒した後，３０号
篩いで篩過し，軽質無水ケイ酸５部とともにＶ型混合機
で１０分間混合し，２％ファモチジン散剤を得た。 Test Example 1 The oral preparation of famotidine-containing solid preparation obtained in Examples 1 to 4 and the following Comparative Example was placed in the mouth of 10 panelists.
The sensory test was performed by allowing the sample to be included for 0 second. Tables 1 and 2 show the bitterness, the refreshing sensation, and the feeling of taking such as mouthfeel. (Comparative Example) 20 parts of famotidine, 845 parts of lactose and 100 parts of corn starch pulverized by a pulverizer with a 1.0 mm screen were placed in a fluidized bed granulator FLO-1 and 10% H was added.
After granulating 300 parts of an aqueous PC solution as a binder, the mixture was sieved with a No. 30 sieve and mixed with 5 parts of light anhydrous silicic acid for 10 minutes in a V-type mixer to obtain a 2% famotidine powder.
【００２５】[0025]
【表１】 表１の結果から明らかなように，糖アルコール以外の糖
（乳糖）を用いた比較例に比べ，同含量％のＨ2ブロッ
カー（ファモチジン）を含む実施例１〜４の製剤は，い
ずれも苦味を改善した。 [Table 1] As is evident from the results in Table 1, all of the preparations of Examples 1 to 4 containing the same content of H 2 blocker (famotidine) in the same content as those of the comparative examples using sugar (lactose) other than sugar alcohol were bitter. Was improved.
【００２６】[0026]
【表２】 表２の結果から明らかなように，実施例１〜４では，清
涼感があり，口中ですみやかに溶解，崩解し服用される
際にざらつき感等を伴わず，口当たりが良好であるとの
結果を得た。一方，乳糖を用いた比較例では，清涼感は
伴わず，ざらつき，べとつき感を有し，良好な服用感は
得られなかった。[Table 2] As is evident from the results in Table 2, Examples 1-4 have a refreshing sensation, dissolve and disintegrate promptly in the mouth, and are not accompanied by a feeling of roughness when taken. The result was obtained. On the other hand, in the comparative example using lactose, there was no refreshing sensation, rough and sticky feeling, and good feeling of taking was not obtained.
【００２７】試験例２ 次の組成物９８部それぞれにファモチジン２部及び１−
メントール０．１部を加え粉砕処理して製した散剤の官
能試験を５名のパネラーで行なった。それぞれの結果を
表３に示す。 苦味を感じない ：０ 苦味を殆ど感じない ：１ 苦味をわずかに感じる：２ 苦味を感じる ：３Test Example 2 2 parts of famotidine and 1-
A powdery product produced by adding 0.1 part of menthol and pulverizing was subjected to a sensory test by five panelists. Table 3 shows the results. Bitter taste is not felt: 0 Bitter taste is hardly felt: 1 Bitter taste is slightly felt: 2 Bitterness is felt: 3
【００２８】[0028]
【表３】 これらの結果からファモチジンの苦味改善効果には製剤
中５０％以上の糖アルコールが有効であった。[Table 3] From these results, 50% or more of the sugar alcohol in the preparation was effective in improving the bitter taste of famotidine.
【００２８】試験例３ 次の組成物９８部それぞれにファモチジン２部あるいは
ファモチジン２部及び１−メントール０．１部を加え粉
砕処理して製した散剤の官能試験を５名のパネラーで行
なった。それぞれの結果を表４に示す。 苦味を感じない ：０ 苦味を殆ど感じない ：１ 苦味をわずかに感じる：２ 苦味を感じる ：３Test Example 3 A powdery product prepared by pulverizing 2 parts of famotidine or 2 parts of famotidine and 0.1 part of 1-menthol to 98 parts of each of the following compositions was subjected to a sensory test by five panelists. Table 4 shows the results. Bitter taste is not felt: 0 Bitter taste is hardly felt: 1 Bitter taste is slightly felt: 2 Bitterness is felt: 3
【００２９】[0029]
【表４】 結果から明らかなように，溶解熱が−６０ｋＪ／ｋｇ以
下の糖アルコールを用いた際には，苦味が改善された。
一方，溶解熱が−６０ｋＪ／ｋｇ以下でない糖アルコー
ル若しくはその他の糖類では，苦味改善効果はみられな
かった。また，溶解熱が−６０ｋＪ／ｋｇ以下の糖アル
コールを用い，さらにｌ−メントールを添加すること
で，苦味改善効果が向上した。[Table 4] As is clear from the results, the bitterness was improved when a sugar alcohol having a heat of solution of −60 kJ / kg or less was used.
On the other hand, with sugar alcohols or other saccharides having a heat of dissolution of -60 kJ / kg or less, no bitterness improving effect was observed. In addition, by using a sugar alcohol having a heat of dissolution of −60 kJ / kg or less and further adding 1-menthol, the effect of improving bitterness was improved.
【００３０】[0030]
【発明の効果】本発明によれば，砂糖と同程度あるいは
それ以下の甘味度を有する−６０ｋＪ／ｋｇ好ましくは
−１００ｋＪ／ｋｇの糖アルコールにより、Ｈ2ブロッ
カーの苦味が改善された固形製剤が得られる。これらは
口中ですみやかに溶解，崩解し，服用する際にざらつき
感等を伴わず，口当たりのよい清涼感を伴った服用しや
すい製剤である。さらに、服用時に多量の水の摂取を必
要とせず，よりよい服用形態を提供し得るものである。
また，工程数の多い複雑な製造法を必要とせず，有機溶
媒による環境悪化もなく，一般の製造工程で製造される
ので，経済的で工業生産性の高いものである。According to the present invention, preferably -60kJ / kg with comparable or less sweetness and sugar by a sugar alcohol of -100kJ / kg, H 2 blockers solid preparation bitterness is improved of can get. These preparations dissolve and disintegrate promptly in the mouth, and are easy to take with a pleasant refreshing sensation without a feeling of roughness when taken. Further, the present invention can provide a better dosage form without requiring a large amount of water to be taken.
In addition, since it does not require a complicated manufacturing method having many steps, does not deteriorate the environment due to an organic solvent, and is manufactured in a general manufacturing process, it is economical and has high industrial productivity.
フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 45/00 ＡＥＭ Ａ６１Ｋ 9/14 Ｌ Continuation of the front page (51) Int.Cl. 6 Identification number Agency reference number FI Technical display location A61K 45/00 AEM A61K 9/14 L
Claims (5)
コールを添加してなる，苦味改善易服用性Ｈ2ブロッカ
ー固形製剤。1. A heat of dissolution become by adding the following sugar alcohol -60kJ / kg, bitter improved easily taking ability H 2 blocker solid preparation.
剤である請求項１記載の固形製剤。2. The solid preparation according to claim 1, wherein the solid preparation is a powder, a granule or a chewable tablet.
ルコールを添加してなる請求項１及び２記載の固形製
剤。3. The solid preparation according to claim 1, wherein a sugar alcohol having a heat of dissolution of -100 kJ / kg or less is added.
コールからなるＨ2ブロッカー固形製剤の苦味改善易服
用化剤。Wherein a heat of dissolution bitterness improved easy taking agents H 2 blocker solid preparation comprising the following sugar alcohol -60kJ / kg.
コールを添加することによるＨ2ブロッカー固形製剤の
苦味改善及び易服用化方法。5. A method for improving the bitterness of a solid preparation of H 2 blocker and making it easy to take by adding a sugar alcohol having a heat of dissolution of −60 kJ / kg or less.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14479497A JPH1053538A (en) | 1997-06-03 | 1997-06-03 | Easily administrable solid preparation of h2-blocker having reduced bitterness |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14479497A JPH1053538A (en) | 1997-06-03 | 1997-06-03 | Easily administrable solid preparation of h2-blocker having reduced bitterness |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6237963A Division JP2705787B2 (en) | 1994-09-30 | 1994-09-30 | Easy to take bitterness improving H 改善 2Ｈ blocker solid preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH1053538A true JPH1053538A (en) | 1998-02-24 |
Family
ID=15370616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14479497A Pending JPH1053538A (en) | 1997-06-03 | 1997-06-03 | Easily administrable solid preparation of h2-blocker having reduced bitterness |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH1053538A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007018190A1 (en) * | 2005-08-10 | 2007-02-15 | Shionogi & Co., Ltd. | Bitterness-reducing agent |
-
1997
- 1997-06-03 JP JP14479497A patent/JPH1053538A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007018190A1 (en) * | 2005-08-10 | 2007-02-15 | Shionogi & Co., Ltd. | Bitterness-reducing agent |
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