JPH09175999A - Spherical granule and its production - Google Patents
Spherical granule and its productionInfo
- Publication number
- JPH09175999A JPH09175999A JP34943295A JP34943295A JPH09175999A JP H09175999 A JPH09175999 A JP H09175999A JP 34943295 A JP34943295 A JP 34943295A JP 34943295 A JP34943295 A JP 34943295A JP H09175999 A JPH09175999 A JP H09175999A
- Authority
- JP
- Japan
- Prior art keywords
- water
- fine powder
- filler
- aqueous solution
- soluble carbohydrate
- 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.)
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は水溶性炭水化物を主
成分とする球形顆粒に関する。また、本発明は、核の外
側に水溶性炭水化物からなる層部を球形に形成させる転
動造粒方法による球形顆粒の製造方法に関する。TECHNICAL FIELD The present invention relates to spherical granules containing a water-soluble carbohydrate as a main component. The present invention also relates to a method for producing spherical granules by a tumbling granulation method in which a layer of water-soluble carbohydrate is formed into a spherical shape on the outside of the nucleus.
【０００２】[0002]
【従来の技術】医薬品の溶出制御技術の一つとして、微
小な球形顆粒の表面に薬剤と溶出制御層とをコーティン
グし、必要なら何種類かのかかるコーティング物を混合
して所望の溶出特性に設定する方法が広く行なわれてい
る。2. Description of the Related Art As one of the elution control technologies for pharmaceuticals, the surface of fine spherical granules is coated with a drug and an elution control layer, and if necessary, several kinds of such coatings are mixed to obtain desired elution characteristics. The setting method is widely used.
【０００３】このような顆粒状医薬品の製造に使用され
る球形顆粒としては、通常蔗糖または蔗糖と澱粉との混
合物から製造されたものが広く用いられている。この球
形顆粒は通常、蔗糖の結晶を核として遠心転動造粒装置
に仕込み、蔗糖または蔗糖と澱粉との微粉混合物を振り
かけながら蔗糖水溶液を噴霧し、核の外側に蔗糖または
蔗糖と澱粉の外層部を形成させて製造されるものであっ
て、該外層部の上層部は遠心転動作用によって外形が球
形になるから、これを所望の粒度にまで成長させること
により製造されている。As the spherical granules used for producing such granular pharmaceutical products, those produced from sucrose or a mixture of sucrose and starch are widely used. The spherical granules are usually charged into a centrifugal tumbling granulator with sucrose crystals as the core, sprayed with a sucrose aqueous solution while sprinkling sucrose or a fine powder mixture of sucrose and starch, and the outer layer of sucrose or sucrose and starch is applied to the outside of the nucleus. The outer layer portion has a spherical outer shape due to the centrifugal rolling operation, and is manufactured by growing the outer layer portion to a desired grain size.
【０００４】上記の蔗糖単独、または蔗糖と澱粉からな
る球形顆粒は広く実用に供されているものであるが、蔗
糖の球形顆粒は、蔗糖の吸湿性のため、ブロッキングし
易い欠点があり、製造、輸送、保管等において取扱い難
いだけでなく、強度的にも充分とは言えない。また、水
に対する蔗糖の溶解速度が大きすぎるため、球形粒子の
表面に薬剤層や溶出制御層をコーティングする際に水系
の液を用いると、粒子同士が凝集したり、造粒装置の器
壁に付着したりすることがある。The above-mentioned spherical granules consisting of sucrose alone or sucrose and starch have been widely put to practical use, but the spherical granules of sucrose have a drawback that they tend to be blocked due to the hygroscopicity of sucrose, In addition to being difficult to handle in transportation, storage, etc., it is not sufficient in terms of strength. Further, since the dissolution rate of sucrose in water is too high, if a water-based liquid is used when coating the surface of the spherical particles with the drug layer or the elution control layer, the particles may aggregate with each other or on the vessel wall of the granulating device. It may adhere.
【０００５】これに対して蔗糖と澱粉の球形顆粒は、ブ
ロッキングし難く、取扱いが容易であるが、硬度（圧潰
強度）が小さく、輸送中や、使用に際してこの球形顆粒
上に薬物をコーティングする工程等で崩壊、破損する欠
点があった。On the other hand, spherical granules of sucrose and starch are difficult to block and are easy to handle, but have low hardness (crush strength) and are coated with a drug on the spherical granules during transportation or during use. There was a defect that it would collapse and break due to such reasons.
【０００６】このような欠点のない球形顆粒について
は、幾つかの提案がなされている。例えば、結晶セルロ
ース単独の球形顆粒について、特開昭６１−２１３２０
１号公報や「第７回 製剤と粒子設計シンポジウム講演
要旨集（１９９０年１０月２４・２５日）ｐ．８９」、
あるいは特開平７−１７３０５０号公報等に開示があ
り、商品も市販されている。Several proposals have been made for spherical granules which do not have such drawbacks. For example, for spherical granules containing only crystalline cellulose, see Japanese Patent Application Laid-Open No. 61-21320.
No. 1 gazette and "7th Formulation and Particle Design Symposium Abstracts (Oct. 24, 25, 1990) p.89",
Alternatively, it is disclosed in Japanese Patent Application Laid-Open No. 7-173050, and the products are commercially available.
【０００７】結晶セルロースと乳糖などの水溶性物質を
併用したものについては、特開平５−２２９９６１号公
報、特開平４−２８３５２０号公報および前記特開昭６
１−２１３２０１号公報、特開平７−１７３０５０号公
報等に記載があり、結晶セルロース３０％と乳糖７０％
の混合球形顆粒が最近上市されている。また、乳糖単独
の球形顆粒も特開平６−２０５９５９号公報に開示され
ている。Regarding a combination of crystalline cellulose and a water-soluble substance such as lactose, JP-A-5-229961, JP-A-4-283520, and JP-A-6-26520 are used.
It is described in JP-A 1-213201, JP-A-7-173050 and the like, and crystalline cellulose 30% and lactose 70%.
Mixed spherical granules of are commercially available recently. Further, spherical granules containing only lactose are disclosed in JP-A-6-205959.
【０００８】これらの球形顆粒のうち、結晶セルロース
を含むものは、崩壊、溶出に長時間を要することがあ
り、溶出制御層が不適当であると、薬剤の完全溶出を期
せないことがあったり、消化されないで***されるセル
ロースがあって患者に薬効についての疑念を抱かせるこ
とがあるほか、製造原価が高いなどの問題点がある。ま
た、乳糖単独のものは、乳糖の結合力が弱くて硬度が低
いことと、乳糖の結晶性状が針状であるため、顆粒表面
の凹凸が大きく、摩損度が大きいという難点がある。Of these spherical granules, those containing crystalline cellulose may take a long time to disintegrate and dissolve, and if the dissolution control layer is inadequate, complete dissolution of the drug may not be achieved. In addition, there is a problem that the excretion of cellulose that is not digested may cause the patient to doubt about the medicinal effect and that the manufacturing cost is high. In addition, lactose alone has the drawbacks that the binding strength of lactose is weak and the hardness is low, and that the crystalline form of lactose is acicular, and therefore the surface of the granules has large irregularities and friability.
【０００９】[0009]
【発明が解決しようとする課題】本発明は、溶解性能が
よく、硬度が高く、表面が平滑でブロッキング等が生じ
ない球形顆粒を安価に製造することを目的とするもので
ある。SUMMARY OF THE INVENTION The present invention has as its object to inexpensively produce spherical granules having good dissolution performance, high hardness, smooth surface and free from blocking and the like.
【００１０】[0010]
【課題を解決するための手段】本発明者らは、従来の球
形顆粒にみられる前記の欠点を解決するため、各種の処
方を検討した結果、従来の球形顆粒の外層部の蔗糖の一
部または全部に替えて、澱粉の種々の程度の糖化物（加
水分解物）、またはその還元物である糖アルコールを用
いると、良好な物性を有する球形顆粒を得ることができ
ることを発見して本発明を完成した。[Means for Solving the Problems] The inventors of the present invention have studied various formulations in order to solve the above-mentioned drawbacks of conventional spherical granules. As a result, a part of the sucrose in the outer layer portion of the conventional spherical granules has been investigated. It was discovered that spherical granules having good physical properties can be obtained by using saccharified products (hydrolysates) of various degrees of starch or sugar alcohols, which are reduction products thereof, in place of all of them, or the present invention. Was completed.
【００１１】すなわち、本発明は、層部が填料と結合剤
とから成り、該填料は少くともその一部が水溶性炭水化
物の微粉末であり、該結合剤は該填料と同一または異な
る水溶性炭水化物であって、前記填料または結合剤の水
溶性炭水化物の少くとも一方は澱粉糖化物またはその還
元物であるような前記層部を有することを特徴とする球
形顆粒に関するものである。That is, according to the present invention, the layer portion comprises a filler and a binder, and at least a part of the filler is a fine powder of a water-soluble carbohydrate, and the binder has the same or different water solubility as the filler. A spherical granule characterized in that it has a layer part such that at least one of the water-soluble carbohydrates of said filler or binder is a starch saccharified product or its reduced product.
【００１２】本発明は、前記層部が、層部と異なる組成
の核の外側に形成されている球形顆粒に関するものであ
る。また本発明は、上記球形顆粒の外側に薬効成分およ
び溶出制御成分を含有する医薬品に関する。The present invention relates to spherical granules in which the layer portion is formed outside a nucleus having a composition different from that of the layer portion. The present invention also relates to a pharmaceutical product containing a medicinal component and an elution control component on the outside of the spherical granules.
【００１３】本発明は、接粉部の水平断面が円形の容器
の底部に回転円板を有する遠心転動造粒装置に核を仕込
み、水溶性炭水化物を含む微粉末を散布しつつ、該微粉
末と同一または異なる水溶性炭水化物を含む水溶液を添
加して前記核の外側に層部を球形に形成させて転動造粒
し、その際、前記微粉末と水溶液の水溶性炭水化物の少
くとも一方を澱粉糖化物またはその還元物とすることを
特徴とする前記球形顆粒の製造方法に関する。According to the present invention, a core is charged into a centrifugal tumbling granulating apparatus having a rotating disk at the bottom of a container having a horizontal cross section of a powder contacting portion, and fine particles containing a water-soluble carbohydrate are dispersed while An aqueous solution containing the same or different water-soluble carbohydrate as the powder is added to form a spherical layer on the outside of the core to roll-granulate, and at this time, at least one of the fine powder and the water-soluble carbohydrate of the aqueous solution. Is a saccharified starch or a reduced product thereof, and relates to a method for producing the spherical granules.
【００１４】なお、本発明にいう「水溶性炭水化物」と
は、室温の水に容易に溶解する炭水化物を意味するもの
であり、澱粉のように加熱しないと溶解しないものは含
まない。The "water-soluble carbohydrate" referred to in the present invention means a carbohydrate that is easily dissolved in water at room temperature, and does not include those that do not dissolve unless heated, such as starch.
【００１５】[0015]
【発明の実施の形態】現在、本発明が改良の対象として
いる従来の蔗糖と澱粉より成る球形顆粒は、蔗糖の結晶
を核として、遠心転動造粒装置で転動させつつ、蔗糖と
澱粉の微粉末を散布し、蔗糖の５０〜６０％水溶液を噴
霧してこれらの微粉末を核上に付着させて造粒すること
により得られている。この方法では、蔗糖微粉末の一部
は、蔗糖水溶液に溶解して飽和水溶液となり、一部は溶
け残って微粉末のまゝこの蔗糖水溶液を結合剤として蔗
糖の結晶からなる核に固着する。それ故、この外層部は
蔗糖微粉末と澱粉を填料とし、蔗糖を結合剤とした構造
となっている。かゝる構造の球形顆粒において、填料と
結合剤の双方が蔗糖を主としたものであると強度が小さ
く、グルコースやソルビトールのような単糖類を使用し
たときも同様に低強度である。BEST MODE FOR CARRYING OUT THE INVENTION The conventional spherical granules comprising sucrose and starch, which are the object of the present invention to improve, are sucrose and starch while being rolled by a centrifugal tumbling granulator using sucrose crystals as cores. It is obtained by spraying the fine powder of 1., spraying a 50-60% aqueous solution of sucrose, and adhering these fine powder on the core for granulation. In this method, a part of the sucrose fine powder is dissolved in a sucrose aqueous solution to become a saturated aqueous solution, and a part of the fine powder remains undissolved and adheres to the nucleus made of sucrose crystals using the fine sucrose aqueous solution as a binder. Therefore, this outer layer portion has a structure in which sucrose fine powder and starch are used as a filler and sucrose is used as a binder. In the spherical granules having such a structure, the strength is low when both the filler and the binder are mainly sucrose, and the strength is also low when a monosaccharide such as glucose or sorbitol is used.
【００１６】本発明の球形顆粒の層部形成に使用する結
合剤としては、粘着力が大きく、或る程度分子量の大き
なオリゴ糖やオリゴ糖アルコールが適しており、特に安
価で容易に入手しうる澱粉糖化物即ち通常水飴と言われ
ているものや、還元麦芽糖などのようなその還元物が好
ましい。上記の結合剤を用いると、散布した微粉末のう
ち、水溶性の物質は噴霧される水溶性炭水化物の水溶液
に一部溶解して結合剤として機能するから、散布する微
粉末として上記澱粉糖化物やその還元物を使用しても好
結果が得られる。As the binder used for forming the layer portion of the spherical granules of the present invention, oligosaccharides and oligosaccharide alcohols having a large adhesive force and a certain large molecular weight are suitable, and are particularly inexpensive and easily available. Preference is given to saccharified starch, that is, what is commonly called starch syrup, and its reduced products such as reduced maltose. When the above-mentioned binder is used, the water-soluble substance out of the fine powder that has been sprayed partially dissolves in the aqueous solution of water-soluble carbohydrate that is sprayed, and functions as a binder. Good results can be obtained by using or reduced products thereof.
【００１７】本発明に用いられる澱粉糖化物としては、
酸糖化物でも酵素糖化物でもよく、３糖から６糖程度の
オリゴ糖が多いものが好ましく、その還元物についても
同様である。糖化が進みすぎて、グルコースやソルビト
ールなどの単糖やマルトースやマルチトールなどの２糖
が多くなると強度が小さく、逆に糖化が不十分なものは
高粘度となって、噴霧時の水溶液濃度を高くできず、ま
た溶解速度が小さくて散布微粉末が結合剤として作用し
難くなる。適当な糖化の程度は、糖化方法や条件によっ
て異なるので一概に定めるのは困難であるが、糖化程度
の指標として３糖、即ちマルトトリオースやマルトトリ
イトールが２〜８０％で単糖が２０％以下、かつ４糖以
上が８０％以下であるものが好ましい。The saccharified starch used in the present invention includes:
It may be an acid saccharified product or an enzymatic saccharified product, and those having many oligosaccharides of about 3 to 6 saccharides are preferable, and the reduced products thereof are also the same. When saccharification proceeds too much and monosaccharides such as glucose and sorbitol and disaccharides such as maltose and maltitol increase, the strength is low, and on the contrary, those with insufficient saccharification have high viscosity, and the concentration of the aqueous solution during spraying is It cannot be increased, and the dissolution rate is low, and it becomes difficult for the finely divided powder to act as a binder. The appropriate degree of saccharification varies depending on the saccharification method and conditions, so it is difficult to determine it unconditionally. However, as an index of the degree of saccharification, trisaccharides, ie, maltotriose and maltotriitol are 2 to 80% and monosaccharides are % Or less and 80% or less of tetrasaccharides or more are preferable.
【００１８】本発明球形顆粒の填料と結合剤とは、同一
の澱粉糖化物またはその還元物であってもよく、この場
合は本発明方法における散布微粉末中の水溶性炭水化物
は噴霧される水溶性炭水化物と同一のものとなる。ま
た、填料と結合剤とは異っていてもよく、この場合は散
布微粉末中の水溶性炭水化物と噴霧される水溶性炭水化
物とは異なるものを使用するが、前述のように結合剤中
には散布微粉末中の水溶性炭水化物成分をも含有するも
のとなる。The filler of the spherical granules of the present invention and the binder may be the same starch saccharified product or its reduced product, in which case the water-soluble carbohydrate in the finely divided powder in the method of the present invention is sprayed in water. It is the same as sex carbohydrate. Further, the filler and the binder may be different, and in this case, the water-soluble carbohydrate in the finely divided powder and the water-soluble carbohydrate to be sprayed are different from each other. Will also contain water soluble carbohydrate components in the finely divided powder.
【００１９】本発明球形顆粒の填料には、水溶性炭水化
物以外の微粉末を含有していてよく、これには薬効成分
や澱粉、微結晶セルロース、粉末セルロース、二酸化チ
タンなどの顔料などが例示される。結合剤中には、水溶
性炭水化物のほか、他種の結合剤や薬効成分を含有して
いてもよい。The filler of the spherical granules of the present invention may contain fine powders other than water-soluble carbohydrates, and examples thereof include medicinal ingredients and pigments such as starch, microcrystalline cellulose, powdered cellulose and titanium dioxide. It In addition to the water-soluble carbohydrate, the binder may contain other types of binders and medicinal components.
【００２０】本発明球形顆粒は上記填料と結合剤とから
成る層部のみで形成されていてもよいが、製造上の便宜
さからは、中心の層部と異なる組成の核の外側に層部が
形成されているものがよく、この核としては蔗糖や乳糖
などの炭水化物の結晶や、所望の直径より小さな直径の
球形顆粒が用いられる。核は、最長部が０．２〜０．６
ｍｍのものが好ましい。The spherical granules of the present invention may be formed only by the layer portion consisting of the above-mentioned filler and binder, but for the convenience of production, the layer portion outside the core having a composition different from that of the central layer portion. Are preferably formed, and as the nucleus, crystals of carbohydrates such as sucrose and lactose, and spherical granules having a diameter smaller than a desired diameter are used. The longest part of the nucleus is 0.2 to 0.6
mm is preferred.
【００２１】本発明の方法に用いられる造粒装置として
は、市販の遠心転動造粒装置（例えばフロイント産業株
式会社製の「ＣＦ造粒装置」）、即ち接粉部の水平断面
が円形の容器の底部に回転円板を有する装置が好適であ
る。この装置の接粉部は通常円筒形であるが、截頭逆円
錐形や球の一部のような形状でもよい。回転円板は平面
板である必要はなく、縁部が上に反った皿状をなしてい
てもよく、また円板中央部が円錐状や山型に盛り上った
形をしていてもよい。回転円板は前記ＣＦ造粒装置のよ
うに接粉部が平滑であるのが好ましい。この装置の容器
の内壁と回転円板との間は０．２〜１ｍｍの間隙となっ
ていて、内容物の落下防止と乾燥作用を果すため、下方
から気体が送入される。As the granulating apparatus used in the method of the present invention, a commercially available centrifugal tumbling granulating apparatus (for example, "CF granulating apparatus" manufactured by Freund Sangyo Co., Ltd.), that is, a horizontal cross section of the powder contacting portion is circular. A device having a rotating disc at the bottom of the container is suitable. The powder contacting part of this device is usually cylindrical, but it may be shaped like a truncated cone or a part of a sphere. The rotating disc does not have to be a flat plate, and may have a dish-like shape with the edge warped upward, or the center of the disc may have a conical or mountain-like shape. Good. It is preferable that the powder contact portion of the rotating disk is smooth as in the CF granulator. There is a gap of 0.2 to 1 mm between the inner wall of the container of this device and the rotating disk, and gas is introduced from below in order to prevent the contents from falling and to dry them.
【００２２】本発明の造粒方法を実施するには、前記し
た遠心転動造粒装置に核を仕込んで回転円板を回転し、
前記気体を送入する。次に、水溶性炭水化物を含む微粉
末を散布しながら、水溶性炭水化物を含む水溶液を噴霧
する。この水溶液の濃度は、噴霧に適した粘度であるこ
とが必要であり、水溶性炭水化物の溶解度により個々に
異なるが、普通は約１０〜７０％の濃度とする。散布す
る微粉末と水溶液との添加速度は、核上の微粉末の溶解
残部と水溶液との比（液／固比）が一定の範囲となるよ
うに制御する公知の技術（例えば「月刊薬事３１， No.
１１，８３〜８９，（１９８９）」により行うのがよ
い。To carry out the granulating method of the present invention, the above-mentioned centrifugal tumbling granulating apparatus is charged with nuclei and the rotary disc is rotated,
Introduce the gas. Next, an aqueous solution containing water-soluble carbohydrate is sprayed while sprinkling a fine powder containing water-soluble carbohydrate. The concentration of this aqueous solution needs to be a viscosity suitable for spraying and varies depending on the solubility of the water-soluble carbohydrate, but is usually about 10 to 70%. The rate of addition of the fine powder to be sprayed and the aqueous solution is controlled by a known technique (for example, "Monthly Pharmaceutical Affairs 31 ， No.
11, 83-89, (1989) ".
【００２３】このようにして造粒を続けると、核上に次
第に外層部が形成され、転動作用のために、核として結
晶などの非球形粒子を用いたものも球形に近づいて行
く。核と微粉末の粒度を適当に選択すれば、最小限の外
層量で、所望の粒子径を有する球形度の良好な顆粒を得
ることができる。When the granulation is continued in this way, the outer layer portion is gradually formed on the core, and the one using non-spherical particles such as crystals as the core approaches the spherical shape for the rolling operation. By appropriately selecting the particle size of the core and the fine powder, it is possible to obtain granules having a desired sphericity and a desired particle size with a minimum outer layer amount.
【００２４】本発明の球形顆粒は硬度が大きく、ブロッ
キング性がない為取扱い易く、水溶性物質や消化可能な
物質のみで構成することができるので、未消化で***さ
れることもなく、また水溶性炭水化物を適宜選択すれば
所望の溶解速度の顆粒とすることができ、医薬品の溶出
制御用の基材として、従来にない、すぐれた性能を有し
ており、この他着色、着味等を施して食品の装飾や味付
けなどに利用することもできる。The spherical granules of the present invention have a large hardness and are easy to handle because they have no blocking property and can be composed of only a water-soluble substance or a digestible substance. Granules with a desired dissolution rate can be obtained by appropriately selecting a soluble carbohydrate, and it has excellent performance that has never been seen as a base material for controlling the elution of pharmaceuticals. It can also be used to decorate or season foods.
【００２５】[0025]
【実施例】以下に実施例および比較例に従って本発明を
より詳しく説明するが、本発明はこれらの実施例によっ
て限定されるものではない。The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to these examples.
【００２６】実施例１〜５、比較例１ 遠心転動造粒装置ＣＦ−３６０（フロイント産業株式会
社）に核として蔗糖結晶（グラニュー糖）の０．３〜
０．４２ｍｍ品５００ｇを仕込み、回転円板下方から空
気を送入しつつ１８０ＲＰＭで回転した。散布微粉末と
して蔗糖（粉糖）の粒径５〜３０μｍのもの６０％、コ
ーンスターチ４０％の混合粉末１，０００ｇを散布しつ
つ表１に示す水溶性炭水化物５０％水溶液２００ｇを噴
霧して造粒した。得られた球形顆粒の粒度は直径０．５
〜０．７ｍｍで、いずれも真球度は良好であった。岡本
精工（株）製の硬度測定装置「グラノ」により顆粒１個
づつの圧潰強度のピーク値（ｇ）を測定し、顆粒２０個
の平均値を得られた顆粒の硬度とした。これらの球形顆
粒の性質を表２に示す。Examples 1 to 5, Comparative Example 1 Centrifugal tumbling granulator CF-360 (Freund Sangyo Co., Ltd.) with 0.3 to sucrose crystals (granulated sugar) as the core.
A 0.42 mm product (500 g) was charged and rotated at 180 RPM while introducing air from below the rotating disk. Granulation by spraying 200 g of a 50% aqueous solution of water-soluble carbohydrate shown in Table 1 while spraying 1000 g of a mixed powder of 60% of sucrose (powdered sugar) having a particle size of 5 to 30 μm and 40% of corn starch as a fine powder. did. The particle size of the obtained spherical granules is 0.5.
In each case, the sphericity was good. The peak value (g) of the crushing strength of each granule was measured with a hardness measuring device "Grano" manufactured by Okamoto Seiko Co., Ltd., and the average value of 20 granules was taken as the hardness of the granules. The properties of these spherical granules are shown in Table 2.
【００２７】実施例６ 実施例４の散布微粉末を蔗糖の粒径５〜３０μｍのもの
６０％と、微結晶セルロース アビセルＰＨ−３０１
（旭化成工業（株）製）４０％の混合粉末１，０００ｇ
としたほか実施例４と同様に操作して直径０．５〜０．
７ｍｍの良好な球形顆粒を得た。その性質を表２に示
す。 実施例７ 実施例４の散布微粉末を蔗糖の粒径５〜３０μｍのもの
１，０００ｇとしたほか実施例４と同様に操作して直径
０．５〜０．７ｍｍの良好な球形顆粒を得た。その性質
を表２に示す。Example 6 60% of sucrose having a particle size of 5 to 30 μm was used as the finely dispersed powder of Example 4 and microcrystalline cellulose Avicel PH-301.
(Asahi Kasei Co., Ltd.) 40% mixed powder 1,000 g
In addition to the above, the same operation as in Example 4 was performed to obtain a diameter of 0.5 to 0.
Good spherical granules of 7 mm were obtained. The properties are shown in Table 2. Example 7 The finely divided powder of Example 4 was changed to 1,000 g of sucrose having a particle size of 5 to 30 μm, and the same operation as in Example 4 was carried out to obtain good spherical granules having a diameter of 0.5 to 0.7 mm. It was The properties are shown in Table 2.
【００２８】実施例８〜９ 散布微粉末として実施例１〜５の蔗糖に代えてアマルテ
ィ（表１参照）の粒径５〜５０μｍのものを用いたほか
実施例１〜５と同様に操作した。実施例８は水溶性炭水
化物水溶液として蔗糖水溶液を、実施例９はアマルティ
シロップを用いた。結果を表２に示す。Examples 8 to 9 The same operation as in Examples 1 to 5 was carried out, except that the sucrose of Examples 1 to 5 was replaced by Amarti (see Table 1) having a particle size of 5 to 50 μm as the finely divided powder. . In Example 8, a sucrose aqueous solution was used as the water-soluble carbohydrate aqueous solution, and in Example 9, amalti syrup was used. Table 2 shows the results.
【００２９】比較例２ 噴霧する水溶性炭水化物として蔗糖の５０％水溶液を用
いたほか実施例７と同様に操作して直径０．５〜０．７
ｍｍの良好な球形顆粒を得た。結果を表２に示す。Comparative Example 2 A 50% aqueous sucrose solution was used as the water-soluble carbohydrate to be sprayed, and the same procedure as in Example 7 was carried out to obtain a diameter of 0.5 to 0.7.
Good spherical granules of mm were obtained. Table 2 shows the results.
【００３０】[0030]
【表１】 註） １）加藤化学（株）製 酵素糖化水飴 ２） 〃 酸糖化水飴 ３）東和化成工業（株）製 還元澱粉糖化物[Table 1] Note) 1) Enzymatic saccharified starch syrup manufactured by Kato Chemical Co., Ltd. 2) Saccharified saccharified starch syrup 3) Reduced starch saccharified product manufactured by Towa Kasei Co., Ltd.
【００３１】[0031]
【表２】 [Table 2]
【００３２】[0032]
【発明の効果】表１および表２から明らかなように、本
発明の球形顆粒はさらに薬剤等からなる層をコーティン
グする際の操作に充分に耐え得る高い硬度を有してお
り、かつブロッキング性がないことから薬剤層等のコー
ティング操作がし易く、均質な医薬品顆粒を製造するた
めに適したものである。As is clear from Tables 1 and 2, the spherical granules of the present invention have a high hardness sufficient to withstand the operation of coating a layer comprising a drug or the like, and have blocking properties. Since it does not have such a substance, the coating operation of the drug layer and the like is easy, and it is suitable for producing homogeneous pharmaceutical granules.
フロントページの続き (72)発明者 坂田 有司 東京都新宿区高田馬場２丁目14番２号 フ ロイント産業株式会社内Front Page Continuation (72) Inventor Yuji Sakata 2-14-2 Takadanobaba, Shinjuku-ku, Tokyo Inside Freund Sangyo Co., Ltd.
Claims (5)
は少くともその一部が水溶性炭水化物の微粉末であり、
該結合剤は該填料と同一または異なる水溶性炭水化物で
あって、前記填料または結合剤の水溶性炭水化物の少く
とも一方は澱粉糖化物またはその還元物であることを特
徴とする、核の外側に層部が形成されている球形顆粒。1. The layer portion comprises a filler and a binder, the filler being at least a part of which is a fine powder of a water-soluble carbohydrate,
The binder is a water-soluble carbohydrate which is the same as or different from the filler, and at least one of the water-soluble carbohydrates of the filler or the binder is a starch saccharified product or a reduced product thereof. Spherical granules in which layers are formed.
側に形成されていることを特徴とする請求項１記載の球
形顆粒。2. The spherical granule according to claim 1, wherein the layer portion is formed outside a nucleus having a composition different from that of the layer portion.
糖と澱粉と、澱粉糖化物またはその還元物との混合物か
ら形成されていることを特徴とする請求項１または２記
載の球形顆粒。3. The spherical shape according to claim 1 or 2, wherein the layer portion formed outside the nucleus is formed of a mixture of sucrose and starch and a saccharified starch or a reduced product thereof. Granules.
回転円板を有する遠心転動造粒装置に核を仕込み、水溶
性炭水化物を含む微粉末を散布しつつ、該微粉末と同一
または異なる水溶性炭水化物を含む水溶液を添加して前
記核の外側に層部を球形に形成させる転動造粒方法であ
って、前記微粉末と前記水溶液に含まれる水溶性炭水化
物の少くとも一方が澱粉糖化物またはその還元物である
ことを特徴とする、核の外側に層部が形成されている球
形顆粒の製造方法。4. A core is charged into a centrifugal tumbling granulator having a rotating disk at the bottom of a container having a horizontal cross section of the powder-contacting portion, and the fine powder containing water-soluble carbohydrate is sprayed while the fine powder and the fine powder are mixed with each other. A tumbling granulation method for forming a spherical layer outside the nucleus by adding an aqueous solution containing the same or different water-soluble carbohydrates, wherein at least one of the fine powder and the water-soluble carbohydrates contained in the aqueous solution is used. Is a saccharified starch or a reduced product thereof, and a method for producing spherical granules having a layer formed outside the nucleus.
またはその還元物は、前記水溶液に添加されていること
を特徴とする請求項３記載の球形顆粒の製造方法。5. The method for producing spherical granules according to claim 3, wherein the starch saccharified product or its reduced product used for forming the layer portion is added to the aqueous solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34943295A JPH09175999A (en) | 1995-12-22 | 1995-12-22 | Spherical granule and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34943295A JPH09175999A (en) | 1995-12-22 | 1995-12-22 | Spherical granule and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH09175999A true JPH09175999A (en) | 1997-07-08 |
Family
ID=18403711
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP34943295A Pending JPH09175999A (en) | 1995-12-22 | 1995-12-22 | Spherical granule and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH09175999A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999004760A1 (en) * | 1997-07-23 | 1999-02-04 | Freund Industrial Co., Ltd. | Spherical single-substance particles, medicines and foodstuffs containing the particles, and method of production thereof |
| EP1072612A1 (en) * | 1999-07-24 | 2001-01-31 | Cerestar Holding B.V. | Starch granulation |
| US7192608B2 (en) | 2001-03-07 | 2007-03-20 | Sumitomo Pharmaceuticals Company Limited | Method of manufacturing drug granules, the drug granules and pharmaceutical preparation containing the drug granules |
| JPWO2009072334A1 (en) * | 2007-12-03 | 2011-04-21 | 富田製薬株式会社 | Pharmaceutical core particles |
| WO2012091040A1 (en) | 2010-12-27 | 2012-07-05 | 富田製薬株式会社 | Decay-type nuclear particle for pharmaceutical formulation |
| JP5585920B2 (en) * | 2010-12-27 | 2014-09-10 | 富田製薬株式会社 | Particulate preparation |
-
1995
- 1995-12-22 JP JP34943295A patent/JPH09175999A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999004760A1 (en) * | 1997-07-23 | 1999-02-04 | Freund Industrial Co., Ltd. | Spherical single-substance particles, medicines and foodstuffs containing the particles, and method of production thereof |
| US6264989B1 (en) | 1997-07-23 | 2001-07-24 | Freund Industrial Co., Ltd. | Spherical single-substance particles, medicines and foodstuffs containing the particles, and method of production thereof |
| EP1072612A1 (en) * | 1999-07-24 | 2001-01-31 | Cerestar Holding B.V. | Starch granulation |
| US7192608B2 (en) | 2001-03-07 | 2007-03-20 | Sumitomo Pharmaceuticals Company Limited | Method of manufacturing drug granules, the drug granules and pharmaceutical preparation containing the drug granules |
| JPWO2009072334A1 (en) * | 2007-12-03 | 2011-04-21 | 富田製薬株式会社 | Pharmaceutical core particles |
| JP2014196361A (en) * | 2007-12-03 | 2014-10-16 | 富田製薬株式会社 | Core particle for pharmaceutical preparation |
| US9149434B2 (en) | 2007-12-03 | 2015-10-06 | Tomita Pharmaceutical Co., Ltd. | Core particle for pharmaceutical preparation |
| WO2012091040A1 (en) | 2010-12-27 | 2012-07-05 | 富田製薬株式会社 | Decay-type nuclear particle for pharmaceutical formulation |
| JP5585920B2 (en) * | 2010-12-27 | 2014-09-10 | 富田製薬株式会社 | Particulate preparation |
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