WO2012153383A1 - Manufacturing method for tablet - Google Patents

Abstract

The present invention addresses the problem of providing a manufacturing method for a tablet which uses citric acid, maintains the tablet-shape thereof even when conveyed, does not generate carbon dioxide gas when stored, and completely dissolves in water when used. The solution to this problem is a manufacturing method wherein a granulated substance (A) obtained, using a mechanical fluidized-bed granulator which is not substantially used for air agitation, by raising the temperature of a powder which is a mixture of citric acid and polyethylene glycol to 60-65°C and then cooling, and a granulated substance (B) obtained, using a mechanical fluidized-bed granulator which is not substantially used for air agitation, by raising the temperature of a powder which is a mixture of sodium hydrogencarbonate and polyethylene glycol to 60-65°C and then cooling, are mixed in a manner such that the ratio of the second granulated substance (B) relative to the first granulated substance (A) is 1:2-1:10, and then the mixture is compression molded into a tablet.

Description

錠剤の製造方法Tablet manufacturing method

　本発明は、商品としての長期間の保存性が良く、かつ水中で炭酸ガスを発泡しつつ速やかに溶解する発泡性組成物である錠剤の製造方法に関する。 The present invention relates to a method for producing a tablet, which is a foamable composition that has good long-term storage stability as a commercial product and quickly dissolves while foaming carbon dioxide in water.

　炭酸塩又は重炭酸塩と、有機酸とを含む混合物を打錠等によって成型し、発泡性組成物（固形物）とすることは、洗浄剤、浴剤、風呂水清浄剤、プール用殺菌剤等の製品に適用されている。これらの製品（固形物）は、水に投入すると、その成分が反応して炭酸ガスを発生しつつ速やかに溶解する利点を有すると同時に、消費者に快適な使用感を与えるので商品価値を高める効果があり、特に浴剤においては、発生する炭酸ガスの血行促進効果が積極的に利用されている。 Molding a mixture containing carbonate or bicarbonate and an organic acid by tableting or the like to form an effervescent composition (solid) is a cleaning agent, bath agent, bath water cleaner, pool disinfectant It is applied to such products. These products (solids) have the advantage of quickly dissolving while generating carbon dioxide when they react with water, and at the same time increase the commercial value because they give consumers a comfortable feeling of use. In particular, in bath preparations, the blood circulation promoting effect of the generated carbon dioxide gas is actively used.

　しかしながら、炭酸塩又は重炭酸塩と有機酸とを共存させると、微量の水分の存在であっても反応が起きてしまうので、炭酸ガスが発生してしまい、錠剤（固形物）の形状が崩れたり、包装容器の内圧が高まり、容器が膨れたり、場合によっては、破損を引き起こすことがある。このような事態が発生すると、商品価値が著しく損なわれるばかりでなく、消費者の信用をも失墜する恐れさえあった。 However, if carbonate or bicarbonate and an organic acid coexist, a reaction occurs even in the presence of a small amount of water, so that carbon dioxide gas is generated and the shape of the tablet (solid material) is destroyed. Or the internal pressure of the packaging container may increase, causing the container to swell and possibly cause damage. When this happened, not only was the merchandise value significantly impaired, but there was also the risk of losing consumer confidence.

　このように炭酸塩又は重炭酸塩と有機酸を混合した上で安定な製品を得るためには、水分の混入を厳格に防ぐことが最も重要である。そこで製造時に原料及び工程の管理を厳重に行い、水分の混入を防ぐことに細心の注意が払われている。更に製造してから消費者が使用するまで安定に保つために密封包装をし、製品の吸湿を防いでいる。それにも拘らず、問題が解決されたとは言いがたい現状にある。 Thus, in order to obtain a stable product after mixing carbonate or bicarbonate with an organic acid, it is most important to strictly prevent moisture from being mixed. Therefore, careful attention is paid to the management of raw materials and processes at the time of production to prevent the mixing of moisture. Furthermore, it is sealed and sealed to prevent moisture absorption of the product so that it can be kept stable from use to consumer use. Nevertheless, it is difficult to say that the problem has been solved.

　この現状を解決するために、炭酸塩と芒硝の復塩を予め調整しておき、これに有機酸を調整する方法が提案されている（特許文献１）。 In order to solve this situation, a method has been proposed in which the salt of carbonate and sodium sulfate is adjusted in advance and the organic acid is adjusted to this (Patent Document 1).

　又、平均分子量９５０～３，７００のポリエチレングリコール（以下「ＰＥＧ」と略記する。）３０～７０質量％と他の発泡性成分７０～３０質量％とを配合した後、加熱してＰＥＧを溶融せしめ、発泡成分をＰＥＧ中に埋め込む方法が提案されている（特許文献２）。 Also, after blending 30 to 70% by mass of polyethylene glycol (hereinafter abbreviated as “PEG”) with an average molecular weight of 950 to 3,700 and 70 to 30% by mass of other foamable components, the mixture is heated to melt the PEG. A method of embedding a foaming component in PEG has been proposed (Patent Document 2).

　しかし、これらの方法では、製品の安定化のために、多量の成分を混合することは、炭酸ガスの発生量がそれだけ低下し、消費者の快適な使用感を損なうのみならず、製品目的を発現する有効成分の配合量が減少することになるので、発生する炭酸ガス量が減少し、一回あたりの使用量も増えるため、結局コストが高くなる。更に発生する炭酸ガスを積極的に利用する浴剤や、発生する泡沫を利用する洗浄剤では、発生する炭酸ガス量の低下は、致命的な欠点とも言える。 However, in these methods, mixing a large amount of components to stabilize the product not only reduces the amount of carbon dioxide generated, thereby deteriorating the consumer's comfortable feeling of use, but also improving the product purpose. Since the amount of the active ingredient to be expressed is reduced, the amount of generated carbon dioxide gas is reduced, and the amount of use per use is increased, resulting in an increase in cost. Further, in a bath agent that positively uses generated carbon dioxide and a cleaning agent that uses generated foam, a decrease in the amount of generated carbon dioxide is a fatal defect.

　一方、生産性の面からは、特に打錠製品において、錠剤の機械的強度を得ること、及び臼や杵への付着が問題となり、結合剤や離型剤の使用が不可欠であるが、これらの成分も、炭酸ガスの発生量の低下をもたらす一因となる。しかも、一般に使われる離型剤としての金属石鹸の微粉末は、水に不溶のために使用時に不快感を与える恐れさえも懸念された。これらの問題を解決する手段として、実質的に水を含まないか或いは５０℃以下で結晶水を遊離しない有機酸とＰＥＧとを６０～１００℃で加熱溶融混合後、内部にパドル又はプロペラ状の攪拌翼を取り付けた空気式流動層で攪拌しながら冷却、粉末化し、これに重炭酸ナトリウムと炭酸ナトリウムを添加して打錠成型する錠剤の製造方法が提案されており、前記実質的に水を含まないか或いは５０℃以下で結晶水を遊離しない有機酸として、フマル酸、酒石酸、蓚酸、クエン酸、コハク酸、グルコン酸又はアジピン酸が挙げられている（特許文献３）。 On the other hand, from the viewpoint of productivity, especially in tableting products, obtaining the mechanical strength of tablets and adhesion to mortars and ridges are problematic, and the use of binders and mold release agents is indispensable. This component also contributes to a decrease in the amount of carbon dioxide generated. In addition, there is a concern that the fine powder of metal soap as a release agent that is generally used may be uncomfortable during use because it is insoluble in water. As means for solving these problems, an organic acid that does not substantially contain water or does not liberate crystal water at 50 ° C. or less and PEG are heated and melted and mixed at 60 to 100 ° C. There has been proposed a method for producing a tablet that is cooled and powdered while stirring in an air fluidized bed equipped with a stirring blade, and then added with sodium bicarbonate and sodium carbonate to form a tablet. Examples of organic acids that do not contain or do not liberate crystal water at 50 ° C. or lower include fumaric acid, tartaric acid, succinic acid, citric acid, succinic acid, gluconic acid, and adipic acid (Patent Document 3).

特開昭５８－２１３７１４号公報JP 58-213714 A 特開昭５８－１０５９１０号公報JP 58-105910 A 特公平７－４７５３２号公報Japanese Patent Publication No. 7-47532

　そこで、本発明の目的は、有機酸として、疲労回復作用があり、きれいな血管を作る血液サラサラ効果があるクエン酸を使用するという条件下において、輸送しても錠剤の形状を維持でき、錠剤が崩壊するという問題がなく、保存による炭酸ガスの発生も無く、使用に際し、水中での、気泡が細かく良好な発泡により、溶解する炭酸イオン濃度が高く、全部が水に溶解する錠剤の製造方法を提供することにある。 Therefore, an object of the present invention is to maintain the shape of the tablet even if it is transported under the condition that citric acid is used as an organic acid, which has a fatigue recovery action and has a blood smoothing effect that creates a clean blood vessel. There is no problem of disintegration, no generation of carbon dioxide gas due to storage, and in use, a method for producing a tablet in which bubbles are fine in water and fine foaming, so that the concentration of dissolved carbonate ions is high and all is dissolved in water. It is to provide.

　上記課題を解決する本発明は、下記構成を有する。
１．実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、クエン酸とポリエチレングリコールの混合物の粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ａと、実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、炭酸水素ナトリウムとポリエチレングリコールの混合物の粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ｂとを、前記造粒物Ａ対前記造粒物Ｂが、１対２～１対１０の比率となるように混合して圧縮成型する錠剤の製造方法。 The present invention for solving the above problems has the following configuration.
1. A granulated product obtained by using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, raising the powder temperature of a mixture of citric acid and polyethylene glycol to 60 to 65 ° C., and then cooling. Using A and a mechanical fluidized bed granulator that does not substantially use air as a stirring action, the powder temperature of the mixture of sodium bicarbonate and polyethylene glycol is raised to 60 to 65 ° C., and then cooled. A tablet manufacturing method in which the granulated product B is mixed and compression-molded so that the granulated product A and the granulated product B have a ratio of 1: 2 to 1:10.

２．実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、クエン酸とポリエチレングリコールの混合物の粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ａと、実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、炭酸水素ナトリウムとポリエチレングリコールの混合物の粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ｂとを、前記造粒物Ａ対前記造粒物Ｂが、１対４～１対６の比率となるように混合して圧縮成型する錠剤の製造方法。 2. A granulated product obtained by using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, raising the powder temperature of a mixture of citric acid and polyethylene glycol to 60 to 65 ° C., and then cooling. Using A and a mechanical fluidized bed granulator that does not substantially use air as a stirring action, the powder temperature of the mixture of sodium bicarbonate and polyethylene glycol is raised to 60 to 65 ° C., and then cooled. A tablet manufacturing method in which the granulated product B is mixed and compressed so that the granulated product A and the granulated product B have a ratio of 1: 4 to 1: 6.

３．実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、クエン酸とポリエチレングリコールの混合物にエタノールを添加し、粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ａと、実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、炭酸水素ナトリウムとポリエチレングリコールの混合物にエタノールを添加し、粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ｂとを、前記造粒物Ａ対前記造粒物Ｂが、１対２～１対１０の比率となるように混合して圧縮成型する錠剤の製造方法。 3. Using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, ethanol is added to a mixture of citric acid and polyethylene glycol, the powder temperature is raised to 60-65 ° C., and then cooled. Using the obtained granulated product A and a mechanical fluidized bed granulator which does not substantially use air as a stirring action, ethanol was added to a mixture of sodium hydrogen carbonate and polyethylene glycol, and the powder temperature was adjusted to 60 to 65. The granulated product B obtained by raising the temperature to 0 ° C. and then cooling is mixed and compression molded so that the granulated product A and the granulated product B have a ratio of 1 to 2 to 1 to 10. Tablet manufacturing method.

４．造粒物Ｂの作成に際し、炭酸水素ナトリウム量の１／１０から１／３０までの量の無水炭酸ナトリウムを含有させることを特徴とする前記１～３のいずれかに記載の錠剤の製造方法。 4). 4. The method for producing a tablet according to any one of 1 to 3 above, wherein the granulated product B contains anhydrous sodium carbonate in an amount of 1/10 to 1/30 of the amount of sodium bicarbonate.

　請求項１に示す発明によれば、
　流動層のうち実質的に空気を攪拌作用として使用しない機械式流動層を用いることによって，及び、有機酸とPEG、炭酸水素ナトリウムとPEGからなる前記造粒物ＡとＢとの混合比率の特定によって上記本発明の目的を達成する効果がより顕著となり、有機酸の中でもクエン酸を用いた上で、輸送しても錠剤が崩壊するという問題がなく、硬度が高い錠剤が得られ、保存中も安定で、炭酸ガスの発生も無く、錠剤が使用に際し水に完全に溶解する効果が得られる。また、浴中での溶解後の溶解炭酸イオン濃度が高く、皮膚を通した炭酸イオン吸収が高まり、血流向上が見られ、糖尿病やリュウマチ、腎臓病等の症状改善効果が期待出来たり、疲労時に発生する乳酸をクエン酸が分解し、疲労回復作用があるとか、腎臓の働きを助け老廃物を排出するため、きれいな血管を作る血液サラサラ効果があるとかの利点を発揮する。 According to the invention shown in claim 1,
By using a mechanical fluidized bed that does not substantially use air as a stirring action in the fluidized bed, and specifying the mixing ratio of the granulated products A and B composed of organic acid and PEG, sodium bicarbonate and PEG The effect of achieving the above-mentioned object of the present invention becomes more remarkable, and there is no problem that the tablet disintegrates even when transported using citric acid among organic acids, and a tablet with high hardness is obtained and stored. Is stable, no carbon dioxide is generated, and the tablet is completely dissolved in water when used. In addition, the dissolved carbonate ion concentration after dissolution in the bath is high, absorption of carbonate ions through the skin is increased, blood flow is improved, and symptoms such as diabetes, rheumatism, and kidney disease can be expected to be improved. Citric acid decomposes the lactic acid that is sometimes produced, and it has the effect of recovering from fatigue, and it helps blood function and discharges waste products.

　請求項２に示す発明によれば、前記造粒物ＡとＢとの混合比率の特定によって上記本発明の効果がより顕著となる。 According to the invention described in claim 2, the effect of the present invention becomes more remarkable by specifying the mixing ratio of the granulated products A and B.

　請求項３に示す発明によれば、エタノールの添加により、更に本発明の効果が向上して発揮される。 According to the invention shown in claim 3, the effects of the present invention are further improved and exhibited by the addition of ethanol.

　以下、本発明について説明する。
　本発明で使用する実質的に空気を攪拌作用として使用しない機械式流動層造粒機とは、横型ドラムの中にすき状ショベルを配し、遠心拡散及び渦流作用を起こさせ三次元流動させる混合機の事で、例えば、ドイツレーディゲ社製又は松坂技研社製として市場で販売されている。これを利用し造粒する場合は、充填する粉体の体積比率は、４０％以上８０％以下が、本発明の効果を奏する上で特に好ましい。本造粒機には、減圧するための真空ポンプが付いていることが好ましい。即ち、冷却時に減圧し、少しでも水分が飛ぶように操作して、本発明の効果をより向上させる上で好ましい。更に、造粒した顆粒が冷却時に粗大粒子になるのを防止するためのチョッパーが付いていることが好ましい。即ち、チョッパーを冷却時に作動させて、整粒することにより、本発明の効果をより向上させる上で好ましい。 The present invention will be described below.
The mechanical fluidized bed granulator which does not substantially use air as the stirring action used in the present invention is a mixing in which a chamfered shovel is arranged in a horizontal drum to cause centrifugal diffusion and vortex action to flow three-dimensionally. For example, it is sold in the market as a product made in Germany Redige or Matsuzaka Giken. When granulating using this, the volume ratio of the powder to be filled is particularly preferably 40% or more and 80% or less in view of the effects of the present invention. The granulator is preferably provided with a vacuum pump for reducing the pressure. That is, it is preferable in order to further improve the effect of the present invention by reducing the pressure during cooling and operating so that even a little moisture can fly. Furthermore, it is preferable to have a chopper for preventing the granulated granules from becoming coarse particles upon cooling. That is, it is preferable to improve the effect of the present invention by operating the chopper at the time of cooling to adjust the particle size.

　打錠用造粒機としては、例えば、前記特許文献３に開示された空気を攪拌作用に利用したものが知られているが、この造粒機は、いわゆる湿式破壊造粒及び攪拌造粒が基本的技術である打錠用顆粒製造であって、空気により粉体を浮遊させ造粒する構成であり、造粒した顆粒は、ポーラスで、この顆粒を打錠すると硬度が出て、高速で打錠できるメリットがある。即ち、コーディングするためには、極めて優れた技術であり、ポーラスな顆粒なので硬度が出やすく、溶解性も良い。 As a granulator for tableting, for example, one using air disclosed in Patent Document 3 for stirring action is known. This granulator has so-called wet fracture granulation and stirring granulation. The basic technology is granulation for tableting, which is a structure in which powder is suspended by air and granulated. The granulated granule is porous, and when this granule is tableted, the hardness is increased and the granulation is performed at high speed. There is merit that can be tableted. That is, it is an extremely excellent technique for coding, and since it is a porous granule, it is easy to obtain hardness and has good solubility.

　ところが、本発明者らが検討した結果、この技術は有機酸として、例えば、コハク酸やフマル酸などでは良好な錠剤を形成できるが、本発明が対象とするクエン酸に適用すると次のような欠点ないし不都合がある事が判明した。即ち、エアーで流動させるため、完全に水分が除去できず、ランニングコストが多大にかかかってしまう。かつ、空気から水分を完全に除去することは難しく　微量の水分を含んだ空気であっても、流動させると、多量の空気中の水分で、造粒中にクエン酸及び炭酸水素ナトリウムが吸湿してしまい、製造中はもとより、製品の保存中や流通中であっても、いろいろな問題が起こることが明らかになった。即ち、フマル酸やコハク酸等では問題とならない水分であっても、クエン酸を使用する場合においては、この現象が顕著であり、水分が少しでもあると、打錠時に付着等が発生し、生産性が悪化するばかりか、錠剤保存中に炭酸ガスが発生し、最悪の場合、錠剤が輸送中の振動で崩壊してしまい、商品価値がなくなることが判明した。 However, as a result of investigations by the present inventors, this technique can form a good tablet with an organic acid, for example, succinic acid or fumaric acid. However, when applied to citric acid targeted by the present invention, the technique is as follows. It turns out that there are drawbacks and inconveniences. That is, since it is made to flow with air, moisture cannot be completely removed, and the running cost is greatly increased. Moreover, it is difficult to completely remove moisture from the air. Even if the air contains a small amount of moisture, when it is flowed, citric acid and sodium bicarbonate absorb moisture during granulation with a large amount of moisture in the air. As a result, it became clear that various problems occur not only during production but also during storage and distribution of products. That is, even if the moisture is not a problem with fumaric acid, succinic acid, etc., when citric acid is used, this phenomenon is prominent. It has been found that not only the productivity deteriorates, but carbon dioxide gas is generated during tablet storage. In the worst case, the tablet collapses due to vibration during transportation, and the commercial value is lost.

　この点、本発明に用いられる実質的に空気を攪拌作用として使用しない機械式流動層造粒機は、空気で流動することなく、ショベルと言われる羽根を用い機械式にて流動させるため、造粒中に水分を吸湿する事もなく、特に、クエン酸の造粒にはベストであるし、加えて、造粒中に減圧ポンプで真空にすることが可能となり、乾燥効果を上げることさえできるため、クエン酸が吸湿することなく、崩壊を抑制できる錠剤として造粒することができるという利点がある。 In this respect, the mechanical fluidized bed granulator which does not substantially use air as the stirring action used in the present invention is made to flow mechanically using blades called excavators without flowing with air. There is no moisture absorption in the grain, especially the best for granulation of citric acid, and in addition, it is possible to vacuum with a vacuum pump during granulation, and even increase the drying effect Therefore, there is an advantage that it can be granulated as a tablet capable of suppressing disintegration without absorbing citric acid.

　本発明者らは、上記特許文献３に記載の空気攪拌式流動層造粒機以前の技術についても、種々検討した。即ち、例えば、空気を使用しないヘンシェル造粒機（湿式破壊造粒機）が知られているが、これは流動させる事ができず、作成する顆粒の粒度分布が広く、打錠するためには、分級する等の工程が必要で、時間がかかるばかりか、コスト的にデメリットとなってしまう。また、顆粒は、密度が高く、よって硬度が出せず、輸送程度の衝撃で割れたり、粉々になったりした。また、密度が高いため、溶解発泡しにくく、ダマになり沈殿してしまうという不都合があり、有機酸の中でクエン酸に適用するのは困難であることが、本発明者らによって突き止められた。 The inventors of the present invention have also studied various techniques prior to the air-stirring fluidized bed granulator described in Patent Document 3 above. That is, for example, a Henschel granulator (wet breaking granulator) that does not use air is known, but this cannot be flowed, and the granule size distribution of the granules to be produced is wide, so that tableting is possible. This requires a process such as classification, which takes time and is disadvantageous in terms of cost. Moreover, the granule was high in density, and therefore could not give hardness, and was cracked or shattered by the impact of the transportation level. In addition, the present inventors have found out that it is difficult to apply to citric acid among organic acids because it has a high density and is difficult to dissolve and foam, resulting in lumps and precipitation. .

　本発明における粉体温度とは、実質的に空気を攪拌作用として使用しない機械式流動層造粒機の缶体中に粉体温度を測定するための熱電対を設け、これで測定し、表示された温度を示す。この粉体温度は、ジャケットに温度をコントロールできる温水タンクから温水を流しコントロールする事ができ、かつ冷却し、粉体温度を短時間で下げるために、冷水（約５℃）を予め準備した冷水タンクと、切り替えができる構成である事が好ましい。 The powder temperature in the present invention is provided with a thermocouple for measuring the powder temperature in the can of a mechanical fluidized bed granulator that does not substantially use air as a stirring action, and is measured and displayed. The measured temperature. This powder temperature can be controlled by flowing hot water from a hot water tank that can control the temperature to the jacket, and cold water (about 5 ° C) prepared in advance for cooling and lowering the powder temperature in a short time. It is preferable that the tank can be switched.

　本発明の粉体温度は、６０℃以上６５℃以下が本発明の効果を奏する上で好ましい。６０℃未満であると粉体の摩擦によりＰＥＧの一部が融け、造粒が進むが時間が掛かり効率が悪いし、一方、６５℃超であると造粒終了後、完全にＰＥＧが溶解しているため表面が固化しても内部がなかなか固化せず、冷却するのに時間が掛かり製造効率が悪い。 The powder temperature of the present invention is preferably 60 ° C. or higher and 65 ° C. or lower for achieving the effects of the present invention. If the temperature is lower than 60 ° C, a part of the PEG melts due to the friction of the powder, and the granulation proceeds. However, it takes time and the efficiency is poor. Therefore, even if the surface is solidified, the inside does not solidify easily, and it takes time to cool down and the production efficiency is poor.

　本発明で使用するＰＥＧは、平均分子量が４０００～８０００のものが本発明の効果を奏する点で好ましい。ロータリー式打錠機の如き圧縮成形打錠機による成形安定性、杵付着耐性、キャッピング、錠剤成型速度の向上の点より、平均分子量６０００程度のＰＥＧが、最も好ましい。 The PEG used in the present invention is preferably one having an average molecular weight of 4000 to 8000 because the effects of the present invention are exhibited. PEG having an average molecular weight of about 6000 is most preferred from the viewpoint of improvement in molding stability, wrinkle adhesion resistance, capping, and tablet molding speed by a compression molding tableting machine such as a rotary tableting machine.

　造粒物Ａにおけるクエン酸１００質量部に対するＰＥＧの比率は、１～２０質量部、好ましくは２～１０質量部であり、ＰＥＧの比率が上記量よりも少ないと、品質安定性及び打錠性が劣ることとなり、一方、ＰＥＧの比率が上記量よりも多いと、品質安定性及び製造コストの点で劣る。 The ratio of PEG to 100 parts by mass of citric acid in the granulated product A is 1 to 20 parts by mass, preferably 2 to 10 parts by mass. When the ratio of PEG is less than the above amount, quality stability and tabletability On the other hand, when the ratio of PEG is larger than the above-mentioned amount, it is inferior in terms of quality stability and manufacturing cost.

　造粒物ＢにおけるＰＥＧの比率は、炭酸水素ナトリウム１００質量部当り１～２０質量部、好ましくは２～１０質量部であり、ＰＥＧの比率が上記量よりも少ないと、品質安定性及び打錠性が劣ることとなり、一方、ＰＥＧの比率が上記量よりも多いと、品質安定性及び製造コストの点で劣る。
また、前記造粒物Ｂが炭酸水素ナトリウム単独でＰＥＧを含まない場合は、打錠後の商品を常温で２ヶ月位経過すると炭酸ガスが自然に発生し崩壊してしまう欠点がある。 The ratio of PEG in the granulated product B is 1 to 20 parts by mass, preferably 2 to 10 parts by mass per 100 parts by mass of sodium hydrogen carbonate. When the ratio of PEG is less than the above amount, quality stability and tableting On the other hand, if the ratio of PEG is larger than the above-mentioned amount, it is inferior in terms of quality stability and production cost.
Further, when the granulated product B is sodium hydrogen carbonate alone and does not contain PEG, there is a drawback that carbon dioxide gas is spontaneously generated and disintegrated after about 2 months at room temperature after the product after tableting.

　更に、前記造粒物Ｂは、炭酸水素ナトリウムと共に、炭酸ナトリウムを含有してもよく、炭酸ナトリウムとしては、１０水和物、１水和物及び無水塩が挙げられるが、本発明の効果を奏する上で無水塩が好ましい。即ち、後記実施例における操作１１において無水炭酸ナトリウムを、炭酸水素ナトリウム量の１／１０～１／３０量だけ使用することにより、後記実施例中のサンプルＮｏ．１４と同等の効果が得られた。更にこのサンプルＮｏ．１４のように、エタノールによる噴霧を併用することにより、本発明の効果が、より良く発揮された。
　前記造粒物Ａに対する前記造粒物Ｂの比率は、１対４から１対６質量部であることが本発明の効果を得る上で特に望ましい。 Furthermore, the granulated product B may contain sodium carbonate together with sodium hydrogen carbonate. Examples of sodium carbonate include decahydrate, monohydrate and anhydrous salt. An anhydrous salt is preferred for performance. That is, by using anhydrous sodium carbonate in an amount of 1/10 to 1/30 of the amount of sodium hydrogen carbonate in operation 11 in the examples described later, sample No. The effect equivalent to 14 was obtained. Further, this sample No. As shown in FIG. 14, the effect of the present invention was better exhibited by using spraying with ethanol together.
The ratio of the granulated product B to the granulated product A is particularly preferably 1 to 4 to 1 to 6 parts by mass for obtaining the effects of the present invention.

　本発明において、離型剤を使用することができ、この離型剤としては、ｎ－ヘキサンスルホン酸ソーダ及びｎ－オクタンスルホン酸ソーダが、本発明の効果を奏する上で好ましい。特にｎ－オクタンスルホン酸ソーダは、本発明に係る錠剤を安定に連続で、かつ高速で成型するために最も好ましい。 In the present invention, a mold release agent can be used, and as this mold release agent, n-hexane sulfonate sodium and n-octane sulfonate sodium are preferable for achieving the effects of the present invention. In particular, sodium n-octane sulfonate is most preferable for stably and continuously molding the tablet according to the present invention at a high speed.

　エタノールは、市販されている９９％エチルアルコールを原料に、三井造船社製ゼオライト膜を使用し、９９．９％エチルアルコールを作成し、これを使用することが本発明の効果を奏する上で好ましい。
　尚、エタノールは、水と共沸し、水の沸点を下げる効果があるが、メタノールには無い。即ち、エタノールがあると、水が飛び易く乾燥しやすいが、メタノールには、その効果が無いので、本発明においてはエタノールを用いることがより好ましい効果を発揮する。 Ethanol is preferably 99% ethyl alcohol as a raw material, using a zeolite membrane manufactured by Mitsui Engineering & Shipbuilding Co., Ltd. to produce 99.9% ethyl alcohol, and using this is preferable for achieving the effects of the present invention. .
Ethanol azeotropes with water and has the effect of lowering the boiling point of water, but methanol does not. That is, when ethanol is present, water can easily fly and dry, but methanol does not have the effect. Therefore, in the present invention, it is more preferable to use ethanol.

　造粒物Ａにおけるクエン酸１００質量部に対するエタノールの比率は、０．０５～５質量部、好ましくは０．１～１質量部であり、エタノールの比率が上記量よりも少ないと、品質安定性が劣ることとなり、一方、エタノールの比率が上記量よりも多いと、品質安定性及び製造コストの点で劣る。 The ratio of ethanol to 100 parts by mass of citric acid in the granulated product A is 0.05 to 5 parts by mass, preferably 0.1 to 1 part by mass. If the ethanol ratio is less than the above amount, quality stability On the other hand, when the ratio of ethanol is larger than the above amount, it is inferior in terms of quality stability and production cost.

　前記造粒物Ｂにおけるエタノールの比率は、クエン酸１００質量部当り０．０５～５質量部、好ましくは０，１～１質量部であり、エタノールの比率が上記量よりも少ないと、品質安定性及び打錠性が劣ることとなり、エタノールの比率が上記量よりも多いと、品質安定性及び製造コストの点で劣る。 The ratio of ethanol in the granulated product B is 0.05 to 5 parts by mass, preferably 0.1 to 1 part by mass per 100 parts by mass of citric acid. If the ethanol ratio is less than the above amount, the quality is stable. When the ratio of ethanol is larger than the above amount, the quality stability and production cost are inferior.

　本発明には、その他の成分を必要に応じて混合することができる。その他の成分としては、造粒物Ａには　香料、色素、界面活性剤等が挙げられる。造粒物Ｂには　炭酸ナトリウムや、香料、色素、界面活性剤等が挙げられる。 In the present invention, other components can be mixed as necessary. As other components, the granulated product A includes fragrances, pigments, surfactants and the like. The granulated product B includes sodium carbonate, fragrances, pigments, surfactants and the like.

　前記造粒物Ａと前記造粒物Ｂとの混合比率は、１対２～１対１０、好ましくは１対４～１対６であり、この範囲外であると、本発明の効果が得られない（後記実施例におけるサンプルＮｏ．８、９及び１１参照）。
　錠剤を作製する圧縮成形には、公知の圧縮成形機を特別の制限なく使用でき、例えば、油圧プレス機、単発式打錠機、ロータリー式打錠機、ブリケッティングマシンなどを用いることができる。 The mixing ratio of the granulated product A and the granulated product B is 1: 2 to 1:10, preferably 1: 4 to 1: 6, and if it is outside this range, the effects of the present invention can be obtained. (Refer to sample Nos. 8, 9, and 11 in the examples described later).
For compression molding for producing tablets, a known compression molding machine can be used without any particular limitation. For example, a hydraulic press machine, a single shot tableting machine, a rotary tableting machine, a briquetting machine, etc. can be used. .

　以下、実施例を挙げ本発明を詳細に説明するが、本発明の態様は、これらに限定されない。
　実施例１
１．比較錠剤Ａの作成
　Ｐｏｗｒｅｘ社製流動層造粒機ＧＰＣＧ－３００ＣＴを用いて下記操作を行った。
　（操作１）比較用の顆粒Ａの作成
　２３℃６０％に空調された造粒室に設置されたＰｏｗｒｅｘ社製流動層造粒機ＧＰＣＧ－３００ＣＴに無水クエン酸３９０Ｋｇ及びＰＥＧ＃６０００、２０Ｋｇを投入し、６５℃に設定した流動エアーで粉体を流動させ、粉体温度が６５℃に到達したら、流動エアーを１５℃に設定し、粉体を冷却する。粉体温度が約３５℃に到達したら、造粒を終了し、密閉容器に粉体を排出し、保管、顆粒Ａを得た。 EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, the aspect of this invention is not limited to these.
Example 1
1. Preparation of Comparative Tablet A The following operation was performed using a fluidized bed granulator GPCG-300CT manufactured by Powerex.
(Operation 1) Preparation of comparative granule A 390 kg of anhydrous citric acid and PEG # 6000, 20 kg were added to a Porex fluidized bed granulator GPCG-300CT installed in a granulation chamber air-conditioned at 23 ° C. and 60%. Then, the powder is flowed with flowing air set at 65 ° C. When the powder temperature reaches 65 ° C., the flowing air is set at 15 ° C. and the powder is cooled. When the powder temperature reached about 35 ° C., the granulation was finished, the powder was discharged into an airtight container, stored, and granules A were obtained.

　（操作２）比較用の顆粒Ｂの作成
　２３℃６０％に空調された造粒室に設置されたＰｏｗｒｅｘ社製流動層造粒機ＧＰＣＧ－３００ＣＴに炭酸水素ナトリウム３９０Ｋｇ及びＰＥＧ＃６０００、２０Ｋｇを６５℃に設定した流動エアーで粉体を流動させ、粉体温度が６５℃に到達したら、流動エアーを１５℃に設定し、粉体を冷却する。粉体温度が約３５℃に到達したら、造粒を終了し、密閉容器に粉体を排出し、保管し、顆粒Ｂを得た。 (Operation 2) Preparation of Comparative Granule B A Porex fluidized bed granulator GPCG-300CT installed in a granulation chamber conditioned at 23 ° C. and 60% was charged with 390 Kg of sodium hydrogen carbonate and PEG # 6000, 20 Kg. When the powder is flowed with flowing air set at 0 ° C. and the powder temperature reaches 65 ° C., the flowing air is set at 15 ° C. to cool the powder. When the powder temperature reached about 35 ° C., the granulation was completed, the powder was discharged into a sealed container and stored, and Granule B was obtained.

　（操作３）比較用の混合物Ａの作成
　松坂技研社製レディゲミキサーＶＴ１２００改良型に顆粒Ａ１００Ｋｇ、顆粒Ｂ５００Ｋｇ、及び無水炭酸ナトリウム２５Ｋｇ及びｎ－オクタンスルホン酸ソーダ１．５Ｋｇを投入し、回転数１１５ｒｐｍで３分攪拌し、混合物Ａを得た。
　（操作４）錠剤Ａの作成
　操作３で作成した混合物Ａを菊水製作所社製タフプレスコレクト１５２７ＨＵ（錠剤製造機）により、直径３０ｍｍで重量１２ｇの錠剤Ａを作成した。 (Operation 3) Preparation of Comparative Mixture A 100 kg of granules A, 500 kg of granules B, 25 kg of anhydrous sodium carbonate, and 1.5 kg of sodium n-octanesulfonate were added to an improved version of the REDGE MIXER VT1200 manufactured by Matsuzaka Giken Co., Ltd. For 3 minutes to obtain a mixture A.
(Operation 4) Preparation of Tablet A Tablet A having a diameter of 30 mm and a weight of 12 g was prepared from the mixture A prepared in Operation 3 using a tough press collect 1527HU (tablet making machine) manufactured by Kikusui Seisakusho.

　（操作５）評価サンプル１の作成
　操作４で作成した錠剤Ａをアルミバリア袋（ポリエチレンフィルム・アルミニウム箔・ポリエチレンフィルムの積層フィルムからなる酸素バリア密封袋。以下、同じ。）に５０ケ入れ、減圧、密閉し、評価用サンプルＮｏ．１（比較例）を作成した。 (Operation 5) Preparation of Evaluation Sample 1 50 tablets of Tablet A prepared in Operation 4 are placed in an aluminum barrier bag (an oxygen barrier sealed bag made of a laminated film of polyethylene film, aluminum foil, and polyethylene film; the same applies hereinafter). , Hermetically sealed, evaluation sample No. 1 (comparative example) was prepared.

２．比較錠剤Ｂの作成
　Ｐｏｗｒｅｘ社製流動層造粒機ＧＰＣＧ－３００ＣＴを用いて下記操作を行った。
　（操作６）比較用の顆粒Ｃの作成
　２３℃６０％に空調された造粒室に設置されたＰｏｗｒｅｘ社製流動層造粒機ＧＰＣＧ－３００ＣＴに無水クエン酸３９０Ｋｇ及びＰＥＧ＃６０００、２０Ｋｇを投入し、６５℃に設定した流動エアーで粉体を流動させ、粉体温度が６５℃に到達したら、流動エアーを１５℃に設定し、粉体を冷却する。粉体温度が約３５℃に到達したら、造粒を終了し、密閉容器に粉体を排出し、保管、顆粒Ｃを得た。 2. Preparation of Comparative Tablet B The following operation was performed using a fluidized bed granulator GPCG-300CT manufactured by Powerex.
(Operation 6) Preparation of Comparative Granule C Charged with 390 kg of anhydrous citric acid and PEG # 6000, 20 kg into a Porex fluidized bed granulator GPCG-300CT installed in a granulation chamber conditioned at 60 ° C. at 23 ° C. Then, the powder is flowed with flowing air set at 65 ° C. When the powder temperature reaches 65 ° C., the flowing air is set at 15 ° C. and the powder is cooled. When the powder temperature reached about 35 ° C., the granulation was finished, the powder was discharged into an airtight container, stored, and granules C were obtained.

　（操作７）比較用の混合物Ｂの作成
　松坂技研社製レディゲミキサーＶＴ１２００改良型に顆粒Ｃ１００Ｋｇ、及び炭酸水素ナトリウム５００Ｋｇ、及び無水炭酸ナトリウム２５Ｋｇ及びｎ－オクタンスルホン酸ソーダ１．５Ｋｇを投入し、回転数１１５ｒｐｍで３分攪拌し、混合物Ｂを得た。
　（操作８）錠剤Ｂの作成
　操作７で作成した混合物Ｂを菊水製作所社製タフプレスコレクト１５２７ＨＵ（錠剤製造機）により、直径３０ｍｍで重量１２ｇの錠剤Ｂを作成した。 (Operation 7) Preparation of Mixture B for Comparison To a modified model of RED 1200 manufactured by Matsuzaka Giken, 100 kg of granules C, 500 kg of sodium hydrogen carbonate, 25 kg of anhydrous sodium carbonate and 1.5 kg of sodium n-octanesulfonate were added. Stirring was performed at 115 rpm for 3 minutes to obtain a mixture B.
(Operation 8) Preparation of tablet B Tablet B having a diameter of 30 mm and a weight of 12 g was prepared from the mixture B prepared in operation 7 using a tough press collect 1527HU (tablet manufacturing machine) manufactured by Kikusui Seisakusho.

　（操作９）評価サンプル２の作成
　操作８で作成した錠剤Ｂをアルミバリア袋に５０ケ入れ、減圧、密閉し、評価用サンプルＮｏ．２（比較例）を作成した。 (Operation 9) Preparation of Evaluation Sample 2 50 tablets of Tablet B prepared in Operation 8 are placed in an aluminum barrier bag, depressurized and sealed. 2 (comparative example) was prepared.

３．本発明に係る錠剤の作成
　（操作１０）顆粒Ａ２の作成
　２３℃６０％に空調された造粒室に設置された松坂技研社製レディゲミキサーＶＴ１２００改良型（横型ドラムの中にすき状ショベル及び減圧するための真空ポンプを有し、かつ造粒した顆粒が冷却時に粗大粒子になるのを防止するためのチョッパーを有し、しかもジャケットに温度をコントロールできる温水タンクから温水を流しコントロールする事ができるし、かつ、冷却し、粉体温度を短時間で下げるために、冷水（約５℃）を予め準備した冷水タンクと切り替えができる構成を有する。以下、同じ。）に、無水クエン酸３９０Ｋｇを投入し、回転数１１５ｒｐｍで攪拌しながら、約６５℃の温水を循環させ加温した。粉体温度が約６０℃に到達したところで、ＰＥＧ＃６０００、２０Ｋｇを投入し、粉体温度が６５℃に到達したら、水温１５℃の水でジャケット内の温水を置き換え、加えて１０トールの減圧下で冷却した。粉体温度が約３５℃に到達したら、底部排出口より、粉体を排出し、密閉容器に保管し、顆粒Ａ２を得た。 3. Preparation of tablet according to the present invention (Operation 10) Preparation of granule A2 Matsudaka Giken-made Readyge Mixer VT1200 installed in a granulation chamber air-conditioned at 23 ° C. and 60% (a horizontal excavator in a horizontal drum and It has a vacuum pump for depressurization, and has a chopper for preventing granulated granules from becoming coarse particles during cooling, and it can be controlled by flowing hot water from a hot water tank that can control the temperature to the jacket. In addition, in order to cool and lower the powder temperature in a short time, it has a configuration in which cold water (about 5 ° C.) can be switched to a cold water tank prepared in advance. The hot water at about 65 ° C. was circulated and heated while stirring at 115 rpm. When the powder temperature reached about 60 ° C., PEG # 6000, 20 Kg was added. When the powder temperature reached 65 ° C., the hot water in the jacket was replaced with water at a water temperature of 15 ° C., and the pressure was reduced to 10 Torr. Cooled down. When the powder temperature reached about 35 ° C., the powder was discharged from the bottom outlet and stored in an airtight container to obtain granules A2.

　（操作１１）顆粒Ｂ２の作成
　２３℃６０％に空調された造粒室に設置された松坂技研社製レディゲミキサーＶＴ１２００改良型に、炭酸水素ナトリウム３９０Ｋｇを投入し、回転数１１５ｒｐｍで攪拌しながら、約６５℃の温水を循環させた。粉体温度が約６０℃に到達したところで、ＰＥＧ＃６０００、２０Ｋｇを投入し、粉体温度が６５℃に到達したら、水温１５℃の水でジャケット内の温水を置き換え、加えて１０トールの減圧下で冷却した。粉体温度が約３５℃に到達したら、底部排出口より、粉体を排出し、密閉容器に保管し、顆粒Ｂ２を得た。 (Operation 11) Preparation of granule B2 390 Kg of sodium hydrogen carbonate was added to a modified model of Rot 1200 made by Matsuzaka Giken Co., Ltd. installed in a granulation chamber which was air-conditioned at 23 ° C. and 60%, while stirring at 115 rpm. About 65 ° C. warm water was circulated. When the powder temperature reached about 60 ° C., PEG # 6000, 20 Kg was added. When the powder temperature reached 65 ° C., the hot water in the jacket was replaced with water at a water temperature of 15 ° C., and the pressure was reduced to 10 Torr. Cooled down. When the powder temperature reached about 35 ° C., the powder was discharged from the bottom outlet and stored in an airtight container to obtain granules B2.

（操作１２）混合物Ａ２の作成
　松坂技研社製レディゲミキサーＶＴ１２００改良型に顆粒Ａ２を１００Ｋｇ、顆粒Ｂ２を５００Ｋｇ及びｎ－オクタンスルホン酸ソーダ１．５Ｋｇを投入し、回転数１１５ｒｐｍで３分攪拌し、混合物Ａ２を得た。
　（操作１３）錠剤Ａ２の作成
　操作１２で作成した混合物Ａ２を菊水製作所社製タフプレスコレクト１５２７ＨＵ（錠剤製造機）により、直径３０ｍｍで重量１２ｇの錠剤Ａ２を作成した。 (Operation 12) Preparation of mixture A2 100 kg of granule A2, 500 kg of granule B2 and 1.5 kg of n-octane sulfonic acid soda were added to an improved model of Matsuegi Giken's Readyge Mixer VT1200 and stirred for 3 minutes at 115 rpm. A mixture A2 was obtained.
(Operation 13) Preparation of Tablet A2 A tablet A2 having a diameter of 30 mm and a weight of 12 g was prepared from the mixture A2 prepared in Operation 12 using a tough press collect 1527HU (tablet making machine) manufactured by Kikusui Seisakusho.

　（操作１４）評価サンプル３の作成
　操作１３で作成した錠剤Ａ２をアルミバリア袋に５０ケ入れ、減圧、密閉し、評価用サンプルＮｏ．３（本発明例）を作成した。 (Operation 14) Preparation of Evaluation Sample 3 50 tablets A2 prepared in Operation 13 were put in an aluminum barrier bag, and the pressure was reduced and sealed. 3 (Example of the present invention) was prepared.

　（評価方法）
　アルミバリア袋入り評価用サンプルＮｏ．１、２及び３を４５℃で１０日保存し、開封後下記の評価を行った。
　振動試験：
　アイデックス社製振動試験機ＢＦ－５０ＵＣを用い、ＪＩＳＺ０２３２の条件で２０００Ｋｍ輸送相当の振動を与え、開封後の錠剤について、割れ及び欠けが発生した錠剤の個数を数えた。尚、３ヶ以下であれば、実用に耐え、市販品として問題はない。 (Evaluation methods)
Sample No. for evaluation with aluminum barrier bag 1, 2 and 3 were stored at 45 ° C. for 10 days, and the following evaluation was performed after opening.
Vibration test:
A vibration tester BF-50UC manufactured by IDEX Co., Ltd. was used, and vibration equivalent to 2000 km transportation was given under the conditions of JISZ0232, and the number of tablets with cracks and chippings after opening was counted. In addition, if it is 3 or less, it will be practical and there is no problem as a commercial product.

　発泡試験：
　４５℃保存前と保存後のアルミバリア袋の体積変化を測定した。尚、５ｍｌ以下であれば、実用に耐え、市販品として問題はない。
　溶解試験：
　４０℃に保温した水１０００ｍｌに錠剤１ヶを入れ、錠剤が溶解するまでの様子を観察し、以下の基準で評価した。 Foam test:
The volume change of the aluminum barrier bag before and after storage at 45 ° C. was measured. In addition, if it is 5 ml or less, it will be practical and there is no problem as a commercial product.
Dissolution test:
One tablet was placed in 1000 ml of water kept at 40 ° C., and the state until the tablet was dissolved was observed and evaluated according to the following criteria.

　◎：８分以内に激しく発砲しながら全部溶解した。
　○：１０分以内に発砲しながら全部溶解した。
　△：１０分以内に発砲しなくなり、２０分経過後微量の固形物が残っていた。
　×：１０分以内に発砲しなくなり、２０分経過して残っている固形物の量が多かった。
　××：×の数が増えると２０分経過後の残っている固形物の量が多いことを示す。
　尚、○以上であれば、実用に耐え、市販品として問題はない。 A: All dissolved while firing vigorously within 8 minutes.
○: All dissolved while firing within 10 minutes.
(Triangle | delta): It did not shoot within 10 minutes, and trace amount solid matter remained after 20 minutes progress.
X: No firing occurred within 10 minutes, and a large amount of solids remained after 20 minutes.
XX: When the number of X increases, it shows that there is much quantity of the solid substance which remains after 20-minute progress.
In addition, if it is (circle) or more, it will be practical use and there is no problem as a commercial item.

　表１の結果より、本発明は、クエン酸と炭酸水素ナトリウムを含有する錠剤が、輸送しても崩壊するという問題がなく、即ち、錠剤の形状を維持することができ、保存による炭酸ガスの発生もなく、更に、使用に際して錠剤が完全に溶解する事がわかる。尚、保存期間を２０日まで延長すると本発明以外のサンプルは、アルミバリア袋が破裂することを確認した。 From the results shown in Table 1, the present invention has no problem that tablets containing citric acid and sodium hydrogen carbonate are disintegrated even when transported, that is, the shape of the tablets can be maintained, and carbon dioxide gas due to storage can be maintained. There is no occurrence and it can be seen that the tablet is completely dissolved in use. When the storage period was extended to 20 days, it was confirmed that the samples other than the present invention ruptured the aluminum barrier bag.

　実施例２
　表２に、実施例１のサンプル３の操作１２で顆粒Ａ２に対する顆粒Ｂ２の比率を変え、その後の操作は、同様に行いサンプルを作成し、評価を行った結果をまとめた。尚、サンプルＮｏ．１及び３についても併記した。 Example 2
In Table 2, the ratio of the granule B2 to the granule A2 was changed in the operation 12 of the sample 3 of Example 1, and the subsequent operation was performed in the same manner to prepare a sample, and the evaluation results were summarized. Sample No. 1 and 3 are also shown.

　表２の結果より、顆粒Ｂの顆粒Ａに対する比率が４～６の場合、本発明の効果をさらに良好に奏する事が分かる。 From the results of Table 2, it can be seen that when the ratio of the granule B to the granule A is 4 to 6, the effect of the present invention is further improved.

　実施例３
　（操作１５）エタノールの作成
　市販されている９９％エチルアルコールを三井造船製ゼオライト膜を使用し、９９．９％エチルアルコール（以下エタノールという）を作成した。
　表３に、実施例１のサンプルＮｏ．３の操作１０及び１１において、ＰＥＧ＃６０００を投入した後、操作１５で作成したエタノールをクエン酸１００質量部当り０．３質量部となる量だけ２００ｍｌ／ｍｉｎの速度で噴霧する。
　その後は同様に操作し顆粒を作成した。その他は、実施例１と同様にサンプルを作成し、評価した。結果をまとめて表３に示す。尚、サンプルＮｏ．１及び３についても併記した。 Example 3
(Operation 15) Preparation of ethanol 99.9% ethyl alcohol (hereinafter referred to as ethanol) was prepared from commercially available 99% ethyl alcohol using a zeolite membrane manufactured by Mitsui Engineering & Shipbuilding.
Table 3 shows the sample No. of Example 1. In the operations 10 and 11 of 3, after the introduction of PEG # 6000, the ethanol prepared in the operation 15 is sprayed at an amount of 0.3 parts by mass per 100 parts by mass of citric acid at a rate of 200 ml / min.
Thereafter, the same operation was performed to prepare granules. Others were prepared and evaluated in the same manner as in Example 1. The results are summarized in Table 3. Sample No. 1 and 3 are also shown.

　表３の結果より、本発明におけるエタノールの噴霧が有る場合が、本発明の効果をより良く奏することが分かる。 From the results of Table 3, it can be seen that the effects of the present invention are better achieved when there is spraying of ethanol in the present invention.

　実施例４
　実施例１におけるサンプルＮｏ．３の作成において、以下の操作を行ったことのみ異ならせ、他は同様とした。即ち、操作１１において、無水炭酸ナトリウムを炭酸水素ナトリウム量の１／１０量又は１／３０量だけ加えた。
　評価結果は、いずれも前記サンプルＮｏ．１４と同等であった。 Example 4
Sample No. 1 in Example 1 In the preparation of No. 3, only the following operations were performed, and the others were the same. That is, in operation 11, anhydrous sodium carbonate was added in an amount of 1/10 or 1/30 of the amount of sodium bicarbonate.
As for the evaluation results, the sample No. It was equivalent to 14.

　洗浄剤、浴剤、風呂水清浄剤、プール用殺菌剤など、固形物としての発泡組成物の利用分野に用いることができる。 It can be used in the fields of application of foamed compositions as solid materials such as cleaning agents, bath agents, bath water cleaners, and pool disinfectants.

Claims (4)

1. 　実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、クエン酸とポリエチレングリコールの混合物の粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ａと、
   　実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、炭酸水素ナトリウムとポリエチレングリコールの混合物の粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ｂとを、
   　前記造粒物Ａ対前記造粒物Ｂが、１対２～１対１０の比率となるように混合して圧縮成型する錠剤の製造方法。 A granulated product obtained by using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, raising the powder temperature of a mixture of citric acid and polyethylene glycol to 60 to 65 ° C., and then cooling. A and
   Granulation obtained by using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, raising the powder temperature of the mixture of sodium bicarbonate and polyethylene glycol to 60-65 ° C. and then cooling. Object B
   A method for producing a tablet, wherein the granulated product A and the granulated product B are mixed and compression-molded so as to have a ratio of 1: 2 to 1:10.
2. 　実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、クエン酸とポリエチレングリコールの混合物の粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ａと、
   　実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、炭酸水素ナトリウムとポリエチレングリコールの混合物の粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ｂとを、
   　前記造粒物Ａ対前記造粒物Ｂが、１対４～１対６の比率となるように混合して圧縮成型する錠剤の製造方法。 A granulated product obtained by using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, raising the powder temperature of a mixture of citric acid and polyethylene glycol to 60 to 65 ° C., and then cooling. A and
   Granulation obtained by using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, raising the powder temperature of the mixture of sodium bicarbonate and polyethylene glycol to 60-65 ° C. and then cooling. Object B
   A method for producing a tablet, wherein the granulated product A and the granulated product B are mixed and compression-molded so as to have a ratio of 1: 4 to 1: 6.
3. 　実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、クエン酸とポリエチレングリコールの混合物にエタノールを添加し、粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ａと、
   　実質的に空気を攪拌作用として使用しない機械式流動層造粒機を使用し、炭酸水素ナトリウムとポリエチレングリコールの混合物にエタノールを添加し、粉体温度を６０～６５℃に上げ、その後、冷却して得た造粒物Ｂとを、
   　前記造粒物Ａ対前記造粒物Ｂが、１対２～１対１０の比率となるように混合して圧縮成型する錠剤の製造方法。 Using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, ethanol is added to a mixture of citric acid and polyethylene glycol, the powder temperature is raised to 60-65 ° C., and then cooled. The obtained granulated product A,
   Using a mechanical fluidized bed granulator that does not substantially use air as a stirring action, add ethanol to the mixture of sodium bicarbonate and polyethylene glycol, raise the powder temperature to 60-65 ° C, and then cool. Granule B obtained by
   A method for producing a tablet, wherein the granulated product A and the granulated product B are mixed and compression-molded so as to have a ratio of 1: 2 to 1:10.
4. 　造粒物Ｂの作成に際し、炭酸水素ナトリウム量の１／１０から１／３０までの量の無水炭酸ナトリウムを含有させることを特徴とする請求項１～３のいずれかに記載の錠剤の製造方法。 The method for producing a tablet according to any one of claims 1 to 3, wherein an anhydrous sodium carbonate in an amount of 1/10 to 1/30 of the amount of sodium hydrogen carbonate is contained in the production of the granulated product B. .