JP2009001520A - Solid preparation containing diphenhydramine - Google Patents

Solid preparation containing diphenhydramine Download PDF

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JP2009001520A
JP2009001520A JP2007163754A JP2007163754A JP2009001520A JP 2009001520 A JP2009001520 A JP 2009001520A JP 2007163754 A JP2007163754 A JP 2007163754A JP 2007163754 A JP2007163754 A JP 2007163754A JP 2009001520 A JP2009001520 A JP 2009001520A
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diphenhydramine
solid preparation
mass
salt
carmellose calcium
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Yuichiro Kano
祐一郎 狩野
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Kowa Co Ltd
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Kowa Co Ltd
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Priority to JP2007163754A priority Critical patent/JP2009001520A/en
Priority to KR1020080049615A priority patent/KR20080112937A/en
Priority to CNA2008101099964A priority patent/CN101327184A/en
Publication of JP2009001520A publication Critical patent/JP2009001520A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for suppressing the reduction of an initial content of diphenhydramine at production, and to provide a solid preparation containing the diphenhydramine and prepared by suppressing the reduction of the initial content of the diphenhydramine. <P>SOLUTION: The method for suppressing the reduction of the initial content of the diphenhydramine or a salt thereof includes allowing the solid preparation containing the diphenhydramine or the salt thereof to contain ≥3.5 mass% of carmellose calcium. The solid preparation contains 10-60 mass% of the diphenhydramine or the salt thereof, and ≥3.5 mass% of the carmellose calcium. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

本発明は、ジフェンヒドラミンを含有する固形製剤に関する。   The present invention relates to a solid preparation containing diphenhydramine.

ジフェンヒドラミンは、強い抗ヒスタミン作用を有することから、じんましん、湿疹、皮膚炎に伴うかゆみ、アレルギー性鼻炎等に有効であり、感冒薬等にも広く用いられている。また近年では、緩和な催眠、鎮静剤としても用いられている、極めて有用な化合物である。   Since diphenhydramine has a strong antihistamine action, it is effective for urticaria, eczema, itching associated with dermatitis, allergic rhinitis and the like, and is widely used for cold medicine and the like. In recent years, it is a very useful compound that is also used as a mild hypnotic and sedative agent.

したがって、現在、ジフェンヒドラミンを含有する固形製剤（以下、ジフェンヒドラミン含有固形製剤）の薬理効果の向上、医薬製剤としての利便性の向上等について、盛んに研究開発が行われている。   Therefore, active research and development are currently underway for improving the pharmacological effect of diphenhydramine-containing solid preparations (hereinafter, diphenhydramine-containing solid preparations), improving convenience as pharmaceutical preparations, and the like.

例えば、ジフェンヒドラミンには苦味があり、ジフェンヒドラミンを含有する製剤の苦味の解決手段として、（１）平均粒子径３０〜５００μmのジフェンヒドラミンを用いる（特許文献１）、（２）遮光性物質と水溶性高分子物質を含有する皮膜で被覆する（特許文献２）、（３）低膨潤性高分子及び高膨潤性高分子を併用する（特許文献３）等が報告されている。
特開２００４−９９５１０号公報 特開２００３−３００８７２号公報 特開２００４−１０７２５８号公報 For example, diphenhydramine has a bitter taste, and as means for solving the bitter taste of a preparation containing diphenhydramine, (1) diphenhydramine having an average particle size of 30 to 500 μm is used (Patent Document 1), (2) a light-shielding substance and a high water-soluble substance. Coating with a film containing a molecular substance (Patent Document 2), (3) Using a low-swelling polymer and a high-swelling polymer in combination (Patent Document 3) has been reported.
JP 2004-99510 A Japanese Patent Laid-Open No. 2003-300872 JP 2004-107258 A

ジフェンヒドラミン含有固形製剤を製造し、その含有量、保存安定性等について検討してきたところ、ジフェンヒドラミンが、製造過程において製造装置の壁面（ＳＵＳ素材等）等に付着し、製造時におけるジフェンヒドラミン初期含量が低下することが判明した。   We have manufactured diphenhydramine-containing solid preparations and studied their content, storage stability, etc., and diphenhydramine adheres to the walls of the manufacturing equipment (SUS materials, etc.) during the manufacturing process, and the initial content of diphenhydramine decreases during manufacturing. Turned out to be.

従って、本発明の目的は、ジフェンヒドラミン含有固形製剤の製造過程によるジフェンヒドラミン初期含量の低下が抑制された、ジフェンヒドラミン含有固形製剤を提示するものである。   Accordingly, an object of the present invention is to provide a diphenhydramine-containing solid preparation in which a decrease in the initial diphenhydramine content during the production process of the diphenhydramine-containing solid preparation is suppressed.

そこで、本発明者は、ジフェンヒドラミン含有固形製剤の初期含量低下防止手段について鋭意研究を行った結果、意外にも、カルメロースカルシウムをジフェンヒドラミン含有固形製剤中に３．５質量％以上含有させると、ジフェンヒドラミンの製造時の初期含量の低下が抑制される固形製剤が得られることを見出し、本発明を完成した。   Therefore, as a result of intensive studies on the means for preventing the initial content of the diphenhydramine-containing solid preparation from being diminished, the present inventors surprisingly found that when carmellose calcium was contained in the diphenhydramine-containing solid preparation at 3.5% by mass or more, diphenhydramine was added. As a result, it was found that a solid preparation capable of suppressing a decrease in the initial content at the time of production was obtained, and the present invention was completed.

すなわち、本発明は、ジフェンヒドラミン又はその塩を１０〜６０質量％、及びカルメロースカルシウムを３．５質量％以上含有する固形製剤を提供するものである。   That is, the present invention provides a solid preparation containing 10 to 60% by mass of diphenhydramine or a salt thereof and 3.5% by mass or more of carmellose calcium.

また、本発明は、ジフェンヒドラミン又はその塩を含有する固形製剤において、カルメロースカルシウムを３．５質量％以上含有させることを特徴とする、ジフェンヒドラミン又はその塩の初期含量の低下を抑制する方法を提供するものである。   The present invention also provides a method for suppressing a decrease in the initial content of diphenhydramine or a salt thereof, characterized in that in a solid preparation containing diphenhydramine or a salt thereof, carmellose calcium is contained in an amount of 3.5% by mass or more. To do.

本発明によれば、製造過程によるジフェンヒドラミン初期含量の低下が抑制され、効率良く、しかも簡便に、ジフェンヒドラミン含有固形製剤を製造することができる。   ADVANTAGE OF THE INVENTION According to this invention, the fall of the diphenhydramine initial content by a manufacture process is suppressed, A diphenhydramine containing solid formulation can be manufactured efficiently and simply.

本発明のジフェンヒドラミン含有固形製剤（以下、「本発明固形製剤」という）は、ジフェンヒドラミン又はその塩を１０〜６０質量％含有し、カルメロースカルシウム（カルボキシメチルセルロースカルシウムともいう）をジフェンヒドラミン含有固形製剤全質量に対して３．５質量％以上含有する。   The diphenhydramine-containing solid preparation of the present invention (hereinafter referred to as “the present invention solid preparation”) contains 10 to 60% by mass of diphenhydramine or a salt thereof, and carmellose calcium (also referred to as carboxymethylcellulose calcium) is the total mass of the diphenhydramine-containing solid preparation. It contains 3.5 mass% or more with respect to.

本発明において、ジフェンヒドラミンの塩としては、塩酸ジフェンヒドラミン、硫酸ジフェンヒドラミン、クエン酸ジフェンヒドラミン、サリチル酸ジフェンヒドラミン、タンニン酸ジフェンヒドラミン、ラウリル硫酸ジフェンヒドラミン等が挙げられるが、塩酸ジフェンヒドラミンが好ましい。   In the present invention, examples of the salt of diphenhydramine include diphenhydramine hydrochloride, diphenhydramine sulfate, diphenhydramine citrate, diphenhydramine salicylate, diphenhydramine tannate, diphenhydramine lauryl sulfate, and diphenhydramine hydrochloride is preferable.

本発明固形製剤の剤形としては、錠剤、散剤、顆粒剤、細粒剤、丸剤、カプセル剤等が挙げられるが、錠剤、カプセル剤が好ましい。   Examples of the dosage form of the solid preparation of the present invention include tablets, powders, granules, fine granules, pills, capsules and the like, and tablets and capsules are preferable.

本発明固形製剤中のジフェンヒドラミン又はその塩の含有量は、１回投与量としては１０〜５０ｍｇが好ましく、２５〜５０ｍｇがさらに好ましく、５０ｍｇがさらに好ましい。   The content of diphenhydramine or a salt thereof in the solid preparation of the present invention is preferably 10 to 50 mg, more preferably 25 to 50 mg, and further preferably 50 mg as a single dose.

例えば、本発明固形製剤の剤形が錠剤やカプセル剤の場合、１錠又は１カプセル中のジフェンヒドラミン又はその塩の含有量は、１回あたり１錠又は１カプセル投与する場合は上記と同様であり、１回あたり２錠又は２カプセル投与する場合は上記の１／２となる。 また、ジフェンヒドラミン又はその塩の平均粒子径は、３０〜５００μｍであることが好ましく、５０〜３００μｍであることがさらに好ましい。   For example, when the dosage form of the solid preparation of the present invention is a tablet or capsule, the content of diphenhydramine or a salt thereof in one tablet or one capsule is the same as described above when one tablet or one capsule is administered per time. When 2 tablets or 2 capsules are administered at a time, it is 1/2 of the above. Moreover, it is preferable that the average particle diameter of diphenhydramine or its salt is 30-500 micrometers, and it is further more preferable that it is 50-300 micrometers.

本発明固形製剤中のカルメロースカルシウムの含有量は、固形製剤製造時のジフェンヒドラミン初期含量の低下抑制の点から、本発明固形製剤中に３．５質量％以上が好ましく、４〜２０質量％がより好ましく、５〜２０質量％がさらに好ましい。
また、ジフェンヒドラミン又はその塩の含有量は、製剤の小型化及び初期含量低下抑制効果を得る点から、固形製剤中に１０〜６０質量％が好ましく、１５〜５０質量％がさらに好ましい。
また、ジフェンヒドラミン又はその塩とカルメロースカルシウムの質量比は、初期含量低下抑制の点から、１０：１〜１：２が好ましく、特に５：１〜１：１が好ましい。 The content of carmellose calcium in the solid preparation of the present invention is preferably 3.5% by mass or more, preferably 4 to 20% by mass in the solid preparation of the present invention, from the viewpoint of suppressing a decrease in the initial content of diphenhydramine during solid preparation production. More preferred is 5 to 20% by mass.
In addition, the content of diphenhydramine or a salt thereof is preferably 10 to 60% by mass in the solid formulation and more preferably 15 to 50% by mass from the viewpoint of obtaining a reduction in the size of the formulation and an effect of suppressing an initial content decrease.
In addition, the mass ratio of diphenhydramine or a salt thereof and carmellose calcium is preferably 10: 1 to 1: 2 and particularly preferably 5: 1 to 1: 1 from the viewpoint of suppressing a decrease in the initial content.

本発明固形製剤は、常法により製造することができる。すなわち、ジフェンヒドラミン又はその塩、カルメロースカルシウム、及び通常用いられる製剤添加物を用いて、日本薬局方製剤総則等に基づいて製造することができる。   The solid preparation of the present invention can be produced by a conventional method. That is, it can be produced based on the Japanese Pharmacopoeia General Formulation etc. using diphenhydramine or a salt thereof, carmellose calcium, and a commonly used formulation additive.

製剤添加物としては、通常用いられるものであれば特に限定されることはなく、例えば、乳糖、結晶セルロース、ヒドロキシプロピルセルロース、マンニトール、キシリトール、デキストリン、ソルビトール、プルラン、部分アルファー化デンプン、ポビドン等の賦形剤、ポリビニルアルコール、ヒドロキシプロピルセルロース等の結合剤、ステアリン酸マグネシウム、ステアリン酸カルシウム等の滑沢剤等が挙げられる。また、これらの製剤添加物は１種又は２種以上を使用することができる。   The formulation additive is not particularly limited as long as it is usually used. For example, lactose, crystalline cellulose, hydroxypropyl cellulose, mannitol, xylitol, dextrin, sorbitol, pullulan, partially pregelatinized starch, povidone, etc. Examples include excipients, binders such as polyvinyl alcohol and hydroxypropyl cellulose, and lubricants such as magnesium stearate and calcium stearate. Moreover, these formulation additives can use 1 type (s) or 2 or more types.

これらの製剤添加物の本発明固形製剤中の含有量は、適宜検討・決定すればよいが、３０〜９０質量％が好ましく、４０〜８０質量％がさらに好ましく、５０〜７５質量％が特に好ましい。   The content of these preparation additives in the solid preparation of the present invention may be appropriately examined and determined, but is preferably 30 to 90% by mass, more preferably 40 to 80% by mass, and particularly preferably 50 to 75% by mass.

本発明固形製剤が錠剤の場合、その製造方法としては、特に限定されるものではないが、直接粉末圧縮打錠法、湿式造粒打錠法等が挙げられる。含量の均一性の観点より湿式造粒打錠法が望ましい。湿式造粒打錠法の造粒手段としては噴霧造粒法、撹拌造粒法、流動造粒法、転動造粒法、転動流動造粒法等が挙げられる。   When the solid preparation of the present invention is a tablet, the production method is not particularly limited, and examples thereof include a direct powder compression tableting method and a wet granulation tableting method. The wet granulation tableting method is desirable from the viewpoint of uniformity of content. Examples of granulation means of the wet granulation tableting method include spray granulation method, stirring granulation method, fluidized granulation method, rolling granulation method, rolling fluidization granulation method and the like.

得られた錠剤には、フィルムコーティングを施すこともできる。フィルムコーティングは、ジフェンヒドラミン又はその塩の溶出性を妨げないものであればよく、例えばパンコーティング、流動層コーティング、転動コーティング、ドライコーティング等により行うことができる。コーティング層には、ヒドロキシプロピルメチルセルロース、マクロゴール、含水二酸化ケイ素、軽質無水ケイ酸等のコーティング剤、黄色三二酸化鉄、酸化チタン、三二酸化鉄、食用青色１号、食用黄色５号、食用赤色２号等の着色剤、オレンジ、カラメル、ハッカ油、バニラフレーバー、ミントフレーバー、ｌ−メントール等の香料を配合することができる。さらにカルナウバロウ、サラシミツロウ、セラック等により艶出し層を設けてもよい。 The obtained tablets can be subjected to film coating. The film coating is not particularly limited as long as it does not interfere with the dissolution property of diphenhydramine or a salt thereof, and can be performed by pan coating, fluidized bed coating, rolling coating, dry coating, or the like. For coating layer, coating agent such as hydroxypropylmethylcellulose, macrogol, hydrous silicon dioxide, light anhydrous silicic acid, yellow ferric oxide, titanium oxide, ferric oxide, edible blue No. 1, edible yellow No. 5, edible red 2 A coloring agent such as No. 1, orange, caramel, peppermint oil, vanilla flavor, mint flavor, l-menthol and the like can be blended. Further, a polishing layer may be provided by carnauba wax, white beeswax, shellac or the like.

以下に実施例を挙げて本発明を詳細に説明するが、本発明はこれら実施例に何ら限定されるものではない。   EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

実施例１ カルメロースカルシウム５質量％含有錠剤
塩酸ジフェンヒドラミン；７５０ｇ、乳糖；２４５２．５ｇ、結晶セルロース；３７５ｇ、ヒドロキシプロピルセルロース；９０ｇ、カルメロースカルシウム；１９５ｇを高速攪拌造粒機（深江工業：ＦＳ−１０型）に投入して混合後、精製水を添加して練合した。この造粒物を流動層乾燥機（フロイント産業：ＦＬＯ−５型）に投入して乾燥後、整粒機（岡田精工：ＮＤ−１０型）を用いて整粒した。この整粒物；２５７５ｇ及びステアリン酸マグネシウム；２５ｇを混合機（朝日工業：Ｂ２／１０９型）に投入して混合した後、直径７ｍｍの杵を取り付けた打錠機（畑鉄工所：ＨＴ−ＡＰ１８ＳＳ型）を用いて打錠し、１錠の重量が１３０ｍｇの錠剤２００００錠を得た。 Example 1 Tablet containing 5% by mass of carmellose calcium Diphenhydramine hydrochloride; 750 g, lactose; 2452.5 g, crystalline cellulose; 375 g, hydroxypropyl cellulose; 90 g, carmellose calcium; 195 g were mixed with a high-speed stirring granulator (Fukae Kogyo: FS- 10 type), and after mixing, purified water was added and kneaded. This granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type) and dried, and then granulated using a granulator (Okada Seiko: ND-10 type). This granulated product; 2575 g and magnesium stearate; 25 g were charged into a blender (Asahi Kogyo: B2 / 109 type) and mixed, and then a tableting machine equipped with a 7 mm diameter punch (Hatetsu Works: HT-AP18SS) Type) was used to obtain 20000 tablets each weighing 130 mg.

比較例１ カルメロースカルシウム２質量％含有錠剤
塩酸ジフェンヒドラミン；７５０ｇ、乳糖；２５６９．５ｇ、結晶セルロース；３７５ｇ、ヒドロキシプロピルセルロース；９０ｇ、カルメロースカルシウム；７８ｇを高速攪拌造粒機（深江工業：ＦＳ−１０型）に投入して混合後、精製水を添加して練合した。この造粒物を流動層乾燥機（フロイント産業：ＦＬＯ−５型）に投入して乾燥後、整粒機（岡田精工：ＮＤ−１０型）を用いて整粒した。この整粒物；２５７５ｇ及びステアリン酸マグネシウム；２５ｇを混合機（朝日工業：Ｂ２／１０９型）に投入して混合した後、直径７ｍｍの杵を取り付けた打錠機（畑鉄工所：ＨＴ−ＡＰ１８ＳＳ型）を用いて打錠し、１錠の重量が１３０ｍｇの錠剤２００００錠を得た。 Comparative Example 1 Carmellose Calcium 2 mass% tablet Diphenhydramine hydrochloride; 750 g, lactose; 2569.5 g, crystalline cellulose; 375 g, hydroxypropylcellulose; 90 g, carmellose calcium; 78 g are mixed with a high-speed agitation granulator (Fukae Kogyo: FS- 10 type), and after mixing, purified water was added and kneaded. This granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type) and dried, and then granulated using a granulator (Okada Seiko: ND-10 type). This granulated product; 2575 g and magnesium stearate; 25 g were charged into a blender (Asahi Kogyo: B2 / 109 type) and mixed, and then a tableting machine equipped with a 7 mm diameter punch (Hatetsu Works: HT-AP18SS) Type) was used to obtain 20000 tablets each weighing 130 mg.

試験例１ 製造時におけるジフェンヒドラミン初期含量
実施例１及び比較例１で得られた製造直後の錠剤中のジフェンヒドラミン含量をＨＰＬＣ法にて測定し、仕込み量から理論値としてのジフェンヒドラミン残存率を算出した。結果を表１に示す。 Test Example 1 Diphenhydramine initial content during production The diphenhydramine content in the tablets immediately after production obtained in Example 1 and Comparative Example 1 was measured by the HPLC method, and the diphenhydramine residual rate as a theoretical value was calculated from the charged amount. The results are shown in Table 1.

Figure 2009001520
Figure 2009001520

（結果）
カルメロースカルシウムを２質量％配合した比較例１のジフェンヒドラミン含有錠剤では、製造直後のジフェンヒドラミン含量は９５質量％を示し、理論値より低値であった。一方、カルメロースカルシウムを５質量％配合した実施例１のジフェンヒドラミン含有錠剤では、製造直後のジフェンヒドラミン含量は１００質量％を示し、理論値通りの値であった。
また実施例１のジフェンヒドラミン含有錠剤をガラス瓶に入れ蓋をした後、保存安定性試験（４０℃、６箇月間）を実施したところ、変色は全く認められなかった。
ジフェンヒドラミン含有錠剤において、カルメロースカルシウムを３．５質量％以上配合して製することで、製造直後のジフェンヒドラミン含量も理論値通りの極めて良好な製剤とすることができることがわかる。 (result)
In the diphenhydramine-containing tablet of Comparative Example 1 containing 2% by mass of carmellose calcium, the diphenhydramine content immediately after production was 95% by mass, which was lower than the theoretical value. On the other hand, in the diphenhydramine-containing tablet of Example 1 containing 5% by mass of carmellose calcium, the diphenhydramine content immediately after production was 100% by mass, which was a theoretical value.
Further, after the diphenhydramine-containing tablet of Example 1 was put in a glass bottle and capped, a storage stability test (40 ° C., 6 months) was performed, and no discoloration was observed.
It can be seen that the diphenhydramine-containing tablet can be prepared by blending 3.5% by mass or more of carmellose calcium, and the diphenhydramine content immediately after the production can be a very good preparation as the theoretical value.

実施例２
塩酸ジフェンヒドラミン；８７５ｇ、乳糖；２３１７ｇ、結晶セルロース；４９０ｇ、ヒドロキシプロピルセルロース；１２９．５ｇ、カルメロースカルシウム；７００ｇを高速攪拌造粒機（深江工業：ＦＳ−１０型）に投入して混合後、精製水を添加して練合し、さらに整粒機（岡田精工：ＮＤ−１０型）を用いて破砕造粒した。この造粒物を流動層乾燥機（フロイント産業：ＦＬＯ−５型）に投入して乾燥後、整粒機（岡田精工：ＮＤ−１０型）を用いて整粒した。この整粒物；４５１１．５ｇにステアリン酸マグネシウム；３８．５ｇを混合機（朝日工業：Ｂ２／１０９型）に投入して混合した後、直径７ｍｍの杵を取り付けた打錠機（畑鉄工所：ＨＴ−ＡＰ１８ＳＳ型）を用いて打錠し、１錠の重量が１３０ｍｇの錠剤３５０００錠を得た。 Example 2
Diphenhydramine hydrochloride; 875 g, lactose; 2317 g, crystalline cellulose; 490 g, hydroxypropyl cellulose; 129.5 g, carmellose calcium; 700 g are charged into a high-speed agitation granulator (Fukae Kogyo: FS-10 type), mixed and purified. Water was added and kneaded, and further pulverized and granulated using a granulator (Okada Seiko: ND-10 type). This granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type) and dried, and then granulated using a granulator (Okada Seiko: ND-10 type). This sized product: 4511.5 g of magnesium stearate; 38.5 g was put into a blender (Asahi Kogyo: B2 / 109 type) and mixed, and then a tableting machine (Hata Iron Works) fitted with a 7 mm diameter punch. : HT-AP18SS type), and 35000 tablets each having a weight of 130 mg were obtained.

本発明のジフェンヒドラミン含有固形製剤は、製造時のジフェンヒドラミン初期含量の低下が抑制される。また、効率良く、しかも簡便に製造することができる。   In the diphenhydramine-containing solid preparation of the present invention, a decrease in the initial diphenhydramine content during production is suppressed. Further, it can be produced efficiently and simply.

Claims (3)

ジフェンヒドラミン又はその塩を１０〜６０質量％、及びカルメロースカルシウムを３．５質量％以上含有する固形製剤。   A solid preparation containing 10 to 60% by mass of diphenhydramine or a salt thereof and 3.5% by mass or more of carmellose calcium. ジフェンヒドラミン又はその塩を１０〜６０質量％、及びカルメロースカルシウムを４〜２０質量％含有する固形製剤。   A solid preparation containing 10 to 60% by mass of diphenhydramine or a salt thereof and 4 to 20% by mass of carmellose calcium. ジフェンヒドラミン又はその塩を含有する固形製剤において、カルメロースカルシウムを３．５質量％以上含有させることを特徴とするジフェンヒドラミン又はその塩の初期含量の低下抑制方法。   A solid preparation containing diphenhydramine or a salt thereof, containing 3.5% by mass or more of carmellose calcium, a method for suppressing a decrease in the initial content of diphenhydramine or a salt thereof.
JP2007163754A 2007-06-21 2007-06-21 Solid preparation containing diphenhydramine Pending JP2009001520A (en)

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JP2004107258A (en) * 2002-09-18 2004-04-08 Ss Pharmaceut Co Ltd Compression molded hypnotic preparation
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JP2001172201A (en) * 1999-12-20 2001-06-26 Basf Ag Use of film coating for masking the taste for oral administration, oral administration form and production thereof
JP2007091758A (en) * 2000-06-22 2007-04-12 Novartis Ag Solid valsartan pharmaceutical composition
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