JPH1059842A - Composition for tablet and making tablet - Google Patents
Composition for tablet and making tabletInfo
- Publication number
- JPH1059842A JPH1059842A JP23147796A JP23147796A JPH1059842A JP H1059842 A JPH1059842 A JP H1059842A JP 23147796 A JP23147796 A JP 23147796A JP 23147796 A JP23147796 A JP 23147796A JP H1059842 A JPH1059842 A JP H1059842A
- Authority
- JP
- Japan
- Prior art keywords
- tablet
- composition
- physiologically active
- active ingredient
- tableting
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、低融点の生理活性
成分を含有する錠剤組成物及び打錠方法に関し、更に詳
述すると、製錠時の障害となる該生理活性成分の杵付着
を防止した錠剤用組成物及び打錠方法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a tablet composition and a tableting method containing a low-melting-point physiologically active ingredient, and more particularly, to the prevention of sticking of the physiologically active ingredient to a punch, which hinders tableting. And a tableting method.
【０００２】[0002]
【従来の技術及び発明が解決しようとする課題】従来、
生理活性成分を錠剤とする場合、この生理活性成分又は
これを造粒したものに結合剤、崩壊剤、崩壊助剤、賦形
剤、滑沢剤、有機溶媒等を加えて圧縮成形することによ
って製造されている。この場合、汎用されている打錠機
においては回転盤上の臼に錠剤原料が撹拌型の供給機に
より機械的に供給され、上杵と下杵の間で圧縮成形され
るが、この際、生理活性成分の融点が低い場合において
はこれが杵の先端部に付着し、打錠障害の一つである杵
付着（スティッキング）の原因となることが知られてい
る。2. Description of the Related Art
When the bioactive ingredient is made into a tablet, a binder, a disintegrant, a disintegration aid, an excipient, a lubricant, an organic solvent, and the like are added to the bioactive ingredient or a granulated product thereof, and compression-molded. Being manufactured. In this case, in a commonly used tableting machine, the tablet raw material is mechanically supplied to a die on a rotating plate by a stirring-type supply machine, and is compression-molded between an upper punch and a lower punch. It is known that when the melting point of a physiologically active component is low, it adheres to the tip of a punch and causes sticking (sticking), which is one of tableting obstacles.
【０００３】そこで、このようなスティッキング対策と
して、例えば、滑沢剤を増量して杵先と組成物との滑り
を良くする方法、賦形剤を増量して組成物中の低融点生
理活性成分の付着の確率を低減する方法、結合剤を増量
して杵先と組成物との結合力よりも強固な結合力を組成
物に与える方法、及び低融点生理活性成分を造粒する
際、該低融点生理活性成分に付着しにくい成分と賦形剤
を共に配合して造粒を行う方法等が採用されている。[0003] As a countermeasure against such sticking, for example, a method of increasing the amount of a lubricant to improve the sliding between the punch tip and the composition, and a method of increasing the amount of an excipient to increase the low melting point bioactive component in the composition. A method of reducing the probability of adhesion of the composition, a method of increasing the amount of the binder to give a stronger bonding force to the composition than the bonding force between the punch tip and the composition, and granulating the low melting point bioactive component. A method in which a component that is hardly adhered to the low-melting-point physiologically active component and an excipient are mixed together to perform granulation is adopted.
【０００４】しかしながら、滑沢剤の増量においては、
組成物の結合力の低下による製錠不良や、本来疎水性で
ある滑沢剤が増量されることにより、崩壊時間が遅延
し、生理活性成分の吸収が遅れる等の問題があった。ま
た、賦形剤の増量においては、製剤の大きさを必要以上
に大きくすることにつながり、使用者の服用性を悪化さ
せてしまう不具合があり、結合剤の増量による方法にお
いては、生理活性成分の製剤からの溶出を著しく遅延さ
せることから生体内利用能を低下させ、速効性を狙いと
する薬剤には重大な問題があった。更に、生理活性成分
を賦形剤と共に造粒する方法においては、賦形剤量を多
量に必要とするのみならず、造粒時の課題として、乾式
造粒法では製錠時の杵先付着と同様の付着の問題が生
じ、低融点生理活性成分が顆粒表面に残存し、スティッ
キングが解消できなかったり、湿式造粒法では低融点生
理活性成分の乾燥時の制約や、有機溶媒使用時の作業環
境での問題があった。このような状況下で製錠された錠
剤は、外観が好ましくないばかりか、コーティングを行
う場合にあっては被覆膜の均一性を損なう等、製品とし
ても重大な欠点につながることとなる。このような状況
からスティッキングの抜本的な解決が望まれている。However, in increasing the amount of lubricant,
There were problems such as poor tableting due to a decrease in the binding strength of the composition, and an increase in the amount of the lubricant that was originally hydrophobic, resulting in a delay in disintegration time and a delay in absorption of a physiologically active ingredient. In addition, increasing the amount of excipients leads to an increase in the size of the preparation more than necessary, which may deteriorate the user's ability to take the medicine. There is a serious problem with a drug aiming for rapid efficacy because it significantly delays the dissolution of the drug from the preparation, thereby reducing its bioavailability. Furthermore, the method of granulating a physiologically active ingredient together with an excipient not only requires a large amount of excipient, but also has a problem in granulation. The same adhesion problem as above occurs, the low melting point bioactive component remains on the granule surface, sticking cannot be eliminated, or the wet granulation method restricts the drying of the low melting point bioactive component, There was a problem in the working environment. Under such circumstances, tablets produced under such circumstances not only have an unfavorable appearance, but also impair the uniformity of the coating film when coating is performed, leading to serious drawbacks as products. Under such circumstances, a drastic solution to sticking is desired.
【０００５】本発明は、上記事情を改善したもので、低
融点の生理活性成分を配合した錠剤を製造する場合にお
いて、スティッキングを可及的に防止して打錠すること
ができる錠剤用組成物及び打錠方法を提供することを目
的とする。[0005] The present invention is an improvement of the above-mentioned circumstances, and in the case of producing a tablet containing a low-melting-point physiologically active ingredient, a tableting composition which can be pressed while preventing sticking as much as possible. And a tableting method.
【０００６】[0006]
【課題を解決するための手段及び発明の実施の形態】本
発明者らは、上記目的を達成するため、鋭意検討を行っ
た結果、融点が７０〜１５０℃である低融点の生理活性
成分に平均粒子径が１〜１００μｍの結晶性粉末を配合
して打錠した場合、長時間連続的に打錠を続けても杵先
端に組成物が付着するスティッキングが防止され、安定
した打錠が継続することを見出し、本発明をなすに至っ
た。Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result, have found that low-melting-point physiologically active ingredients having a melting point of 70 to 150 ° C. When tableting is performed by compounding a crystalline powder having an average particle diameter of 1 to 100 μm, sticking of the composition to the tip of the punch is prevented even if tableting is continuously performed for a long time, and stable tableting continues. To accomplish the present invention.
【０００７】従って、本発明は、融点が７０〜１５０℃
の生理活性成分に平均粒子径が１〜１００μｍの結晶性
粉末を配合してなることを特徴とする錠剤用組成物、及
び、融点が７０〜１５０℃の生理活性成分を含む錠剤を
製造するに際し、上記生理活性成分を平均粒子径が１〜
１００μｍの結晶性粉末の存在下に打錠することを特徴
とする打錠方法を提供する。[0007] Accordingly, the present invention provides a melting point of 70 to 150 ° C.
In producing a tablet composition characterized by comprising a crystalline powder having an average particle size of 1 to 100 μm mixed with a physiologically active ingredient, and a tablet containing a physiologically active ingredient having a melting point of 70 to 150 ° C. The average particle size of the physiologically active component is 1 to 1.
A tableting method characterized by tableting in the presence of a 100 μm crystalline powder.
【０００８】以下、本発明につき更に詳しく説明する
と、本発明の錠剤用組成物は、上述したように、融点が
７０〜１５０℃の比較的低い融点を有する生理活性成分
を含有してなるもので、この低融点生理活性成分として
は、上記融点範囲のものであればいずれのものであって
もよい。具体的には、下記の生理活性成分が代表例とし
て挙げられるが、これらに限定されるものではない。Hereinafter, the present invention will be described in further detail. As described above, the tablet composition of the present invention comprises a physiologically active ingredient having a relatively low melting point of 70 to 150 ° C. The low-melting-point physiologically active ingredient may be any one as long as it has the above-mentioned melting point range. Specifically, the following physiologically active components are mentioned as typical examples, but the present invention is not limited to these.
【０００９】 [0009]
【００１０】上記低融点生理活性成分は、その１種を単
独で又は２種以上を併用して使用することができるが、
特に、アスピリン、エテンザミド、アルクロフェナッ
ク、及びイブプロフェンから選ばれる１種又は２種以上
の組み合わせにおいて効果が顕著である。The above-mentioned low-melting-point physiologically active ingredients can be used alone or in combination of two or more.
In particular, the effect is remarkable in one or a combination of two or more selected from aspirin, etensamide, alclofenac, and ibuprofen.
【００１１】本発明の組成物において、上記低融点生理
活性成分の配合量は、特に制限されるものではなく、製
剤する錠剤の用途によって適宜調整されるが、通常は、
錠剤全体に対して１〜９９重量％、好ましくは５〜９０
重量％、更に好ましくは１０〜８０重量％である。In the composition of the present invention, the amount of the low-melting-point physiologically active ingredient is not particularly limited, and is appropriately adjusted depending on the use of the tablet to be prepared.
1 to 99% by weight, preferably 5 to 90% by weight based on the whole tablet
%, More preferably 10 to 80% by weight.
【００１２】なお、上記低融点生理活性成分の配合態様
は特に制限されるものではなく、そのまま配合したり、
乾式法或いは湿式法等の常法に従い、造粒、あるいは、
脂肪酸、グリセリン又はこれらの誘導体、結晶性高分子
（水溶性、水不溶性、腸溶性、胃溶性等）などの有機化
合物、あるいは１〜３価の金属塩であるケイ酸塩、炭酸
塩、酸化物、水酸化物等の無機化合物などで被覆したも
の又は表面改質したものを使用することができる。この
場合、造粒物としては平均粒子径１０００μｍ以下、特
に８５０〜５０μｍに形成したものを使用することが好
ましい。平均粒子径が１０００μｍを超えると、含有量
において不均一を生じたり、打錠成形に適さなくなる場
合がある。The mode of blending the low-melting-point physiologically active ingredient is not particularly limited.
Granulation, or according to a conventional method such as a dry method or a wet method, or
Organic compounds such as fatty acids, glycerin or derivatives thereof, crystalline macromolecules (water-soluble, water-insoluble, enteric-soluble, gastric-soluble, etc.), or silicates, carbonates and oxides, which are monovalent to trivalent metal salts Coated with an inorganic compound such as hydroxide, hydroxide or the like or surface-modified. In this case, it is preferable to use granules having an average particle diameter of 1000 μm or less, particularly 850 to 50 μm. If the average particle size exceeds 1000 μm, the content may become non-uniform or may not be suitable for tableting.
【００１３】次に、本発明の錠剤用組成物は、上記低融
点生理活性成分と共に、平均粒子径１〜１００μｍ、好
ましくは１〜５０μｍ、更に好ましくは１〜３０μｍ、
最も好ましくは１〜２０μｍの結晶性粉末を配合するも
のである。ここで、結晶性粉末の平均粒子径が１μｍ未
満であると、組成物の流動性が不十分になる上、製剤時
に供給機から漏れたり、飛散性、供給ラインでの選択的
吸着による含有量の不均一化を招き、不均一化が生ずる
原因になる。一方、１００μｍを超えると、長時間の製
剤により発生する摩擦熱により杵への付着防止効果がな
くなり、本発明の目的を達成し得ない。なお、ここでい
う平均粒子径はレーザー光散乱方式粒度分布測定による
値である。Next, the composition for tablets of the present invention, together with the low-melting-point physiologically active ingredient, has an average particle size of 1 to 100 μm, preferably 1 to 50 μm, more preferably 1 to 30 μm.
Most preferably, a crystalline powder of 1 to 20 μm is blended. Here, if the average particle diameter of the crystalline powder is less than 1 μm, the fluidity of the composition becomes insufficient, and it leaks from the feeder at the time of formulation, flies, and the content due to selective adsorption in the feed line. Is caused to cause unevenness. On the other hand, if it exceeds 100 μm, the effect of preventing adhesion to a punch is lost due to frictional heat generated by a long-term preparation, and the object of the present invention cannot be achieved. Here, the average particle size is a value obtained by a laser light scattering type particle size distribution measurement.
【００１４】上記結晶性粉末としては、乳糖、無水乳
糖、マンニトール、ソルビトール、白糖、精製白糖、二
酸化ケイ素、無水ケイ酸、合成ケイ酸アルミニウム、合
成ヒドロタルサイト、乾燥水酸化アルミニウム、リン酸
水素カルシウム、無水リン酸水素カルシウム、キシリト
ール、エリスリトール、その他の単糖類、少糖類、多糖
類、糖アルコール類等を挙げることができ、これらは１
種を単独で又は２種以上を混合して使用することができ
るが、特に糖類（糖アルコール類を含む）から選ばれる
結晶性粉末を使用することが好ましい。なおまた、これ
ら結晶性粉末を上記平均粒子径にする方法は、公知の方
法でよく、例えば、粉砕機で粉砕後、孔径１００μｍ以
下のふるいにかけ、ふるいを通過した粉末だけを使用す
る方法などを挙げることができる。The crystalline powder includes lactose, anhydrous lactose, mannitol, sorbitol, sucrose, purified sucrose, silicon dioxide, silicic anhydride, synthetic aluminum silicate, synthetic hydrotalcite, dry aluminum hydroxide, calcium hydrogen phosphate , Anhydrous calcium hydrogen phosphate, xylitol, erythritol, other monosaccharides, oligosaccharides, polysaccharides, sugar alcohols and the like.
The seeds can be used alone or as a mixture of two or more, but it is particularly preferable to use a crystalline powder selected from sugars (including sugar alcohols). In addition, the method of making these crystalline powders the above average particle diameter may be a known method, for example, a method of pulverizing with a pulverizer, sieving with a pore size of 100 μm or less, and using only the powder that has passed through the sieve. Can be mentioned.
【００１５】上記結晶性粉末の配合量は同時に配合する
低融点生理活性成分の配合量により適宜調整されるが、
通常、錠剤全体に対して０．５〜９０重量％、好ましく
は２〜５０重量％、更に好ましくは５〜３０重量％配合
することが推奨される。配合量が少なすぎると杵付着防
止効果が不十分であり、多きずると製剤が多くなるので
服用性が問題となる場合がある。The amount of the crystalline powder is appropriately adjusted depending on the amount of the low-melting-point physiologically active ingredient to be added at the same time.
Usually, it is recommended to add 0.5 to 90% by weight, preferably 2 to 50% by weight, and more preferably 5 to 30% by weight based on the whole tablet. If the amount is too small, the effect of preventing sticking of punches is insufficient, and if the amount is too small, the amount of the preparation increases, which may cause a problem in ingestion.
【００１６】本発明の錠剤用組成物には、必要に応じセ
ルロース及びその誘導体、デンプン及びその誘導体等の
崩壊剤、ヒドロキシプロピルセルロース（置換度５３．
４〜７７．５％）、メチルセルロース、ゼラチン、ビニ
ルピロリドン、部分α化デンプン等の結合剤、ステアリ
ン酸マグネシウム、硬化油、グリセリン又はその誘導体
等の滑沢剤、天然高分子化合物、合成高分子化合物、脂
肪酸又はその誘導体、アルコール、多価アルコール又は
これらの誘導体、界面活性剤（特にノニオン）等の賦形
剤、その他崩壊助剤、色素、矯味剤などを生理活性成分
の種類に応じた常用量で配合することができる。The tablet composition of the present invention may contain, if necessary, disintegrants such as cellulose and its derivatives, starch and its derivatives, hydroxypropylcellulose (substitution degree 53.
Binders such as methylcellulose, gelatin, vinylpyrrolidone and partially pregelatinized starch, lubricants such as magnesium stearate, hydrogenated oil, glycerin or derivatives thereof, natural polymer compounds and synthetic polymer compounds , Fatty acids or derivatives thereof, alcohols, polyhydric alcohols or derivatives thereof, excipients such as surfactants (especially nonionics), other disintegration aids, pigments, flavoring agents, etc., in a normal dose depending on the type of physiologically active ingredient. Can be blended.
【００１７】本発明の錠剤用組成物は、公知の打錠機を
用い、通常の打錠条件で打錠することができ、直径３〜
１２ｍｍ、厚さ（中央部）１〜１０ｍｍの錠剤を得るこ
とができるが、この場合０．１〜４ｔ程度の打錠圧で連
続的に打錠しても杵にスティッキングが生じることが可
及的に防止され、安定した打錠が行われる。錠剤は、円
形錠、変形錠等、特に形状は限定されない。The tablet composition of the present invention can be tableted using a known tableting machine under ordinary tableting conditions and has a diameter of 3 to 3.
A tablet having a thickness of 12 mm and a thickness (central portion) of 1 to 10 mm can be obtained. In this case, even if the tablet is continuously compressed with a compression pressure of about 0.1 to 4 t, sticking may occur in the punch. Is prevented and stable tableting is performed. The shape of the tablet is not particularly limited, such as a round tablet and a deformed tablet.
【００１８】なお、打錠後は、必要に応じて糖衣錠とし
たり、フィルムコーティングを行うことができる。After tableting, sugar-coated tablets and film coating can be applied as necessary.
【００１９】[0019]
【発明の効果】本発明によれば、低融点生理活性成分を
錠剤化する場合において、打錠機の杵に低融点生理活性
成分が付着することが可及的に防止され、長時間に亘っ
て連続的に安定して打錠を行うことができるものであ
る。According to the present invention, when a low-melting-point bioactive ingredient is made into a tablet, the low-melting-point bioactive ingredient is prevented from adhering to a punch of a tableting machine as much as possible and can be used for a long time. Thus, tableting can be performed continuously and stably.
【００２０】[0020]
【実施例】以下、実施例及び比較例を示し、本発明を具
体的に説明するが、本発明は下記実施例に制限されるも
のではない。なお、下記の例において、使用した結晶性
粉末は表１に示す通りであり、これら結晶性粉末は、必
要に応じて粉砕機で微粉末とした後、ふるいに通過さ
せ、実施例、比較例に使用する結晶性粉末とした。EXAMPLES Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples, the crystalline powders used are as shown in Table 1. These crystalline powders were finely ground with a pulverizer if necessary, and then passed through a sieve. Crystalline powder used for
【００２１】[0021]
【表１】 [Table 1]
【００２２】［実施例１、比較例１］低融点生理活性物
質としてアスピリン、結晶性粉末として無水リン酸カル
シウムを用い、下記組成の錠剤を下記方法で製造した。組 成 アスピリン ６３０重量部 コーンスターチ ７０重量部 結晶セルロース ２００重量部 無水リン酸水素カルシウム ９０重量部 硬化ヒマシ油 １０重量部Example 1, Comparative Example 1 Using aspirin as a low melting point physiologically active substance and anhydrous calcium phosphate as a crystalline powder, tablets having the following composition were produced by the following method. Composition Aspirin 630 parts by weight Corn starch 70 parts by weight Microcrystalline cellulose 200 parts by weight Calcium hydrogen phosphate anhydrous 90 parts by weight Hardened castor oil 10 parts by weight
【００２３】実施例１ アスピリン１８０００ｇ及びコーンスターチ２０００ｇ
をＶ型混合機（（株）特寿工作所製）にて５分間混合し
た後、乾式造粒機にて造粒し、これを整粒した後、平均
粒子径２５０μｍの顆粒を得た。 Example 1 18000 g of aspirin and 2000 g of corn starch
Was mixed for 5 minutes with a V-type mixer (manufactured by Tokuju Kosakusho Co., Ltd.), and then granulated with a dry granulator. After granulating the granules, granules having an average particle diameter of 250 μm were obtained.
【００２４】次いで、得られた顆粒７０００ｇに結晶セ
ルロース２０００ｇ及び平均粒子径２０μｍの無水リン
酸水素カルシウム９００ｇを加え、Ｖ型混合機で１５分
間混合した。更に、硬化ヒマシ油１００ｇを添加して５
分間混合し、錠剤用組成物を得た。Next, 2000 g of crystalline cellulose and 900 g of anhydrous calcium hydrogen phosphate having an average particle size of 20 μm were added to 7000 g of the obtained granules, and mixed with a V-type mixer for 15 minutes. Further, 100 g of hydrogenated castor oil was added to
After mixing for a minute, a composition for tablets was obtained.
【００２５】得られた組成物を、打錠機（Ｌ−４１型：
（株）畑鐵工所製）にて直径８ｍｍ、杵先半径１５ｍｍ
の杵を用い、打錠圧１．２ｔで打錠し、錠剤の製造を行
った。その結果、約２時間の打錠においても杵への付着
が見られず、スティッキングの傾向は認められなかっ
た。The obtained composition was converted into a tableting machine (model L-41:
8mm in diameter, punch tip radius 15mm
The tablets were pressed at a tableting pressure of 1.2 tonnes using a pestle of No. 1 to produce tablets. As a result, no sticking to the punch was observed even after tableting for about 2 hours, and no sticking tendency was observed.
【００２６】比較例１ 平均粒子径２０μｍの無水リン酸水素カルシウム９００
ｇの代わりに、平均粒子径２００μｍの無水リン酸水素
カルシウムを９００ｇ用いた以外は、実施例１と同様の
方法で組成物を得、製剤を行った。打錠開始後、約５分
で打錠機の杵にスティッキングが生じた。 Comparative Example 1 Anhydrous calcium hydrogen phosphate 900 having an average particle diameter of 20 μm
The composition was obtained and formulated in the same manner as in Example 1 except that 900 g of anhydrous calcium hydrogen phosphate having an average particle size of 200 μm was used instead of g. Approximately 5 minutes after the start of tableting, sticking occurred in the punch of the tableting machine.
【００２７】［実施例２、比較例２］低融点生理活性物
質としてエテンザミド、結晶性粉末として無水ケイ酸を
用い、下記組成の錠剤を下記方法で製造した。組 成 エテンザミド ６６５重量部 部分α化デンプン ３５重量部 結晶セルロース １００重量部 カルボキシメチルセルロース １００重量部 無水ケイ酸 ９０重量部 ステアリン酸マグネシウム １０重量部Example 2, Comparative Example 2 Tablets having the following composition were produced by the following method using ethenzamide as a low-melting-point physiologically active substance and silicic anhydride as a crystalline powder. Composition Ethenzamide 665 parts by weight Partially pregelatinized starch 35 parts by weight Crystalline cellulose 100 parts by weight Carboxymethyl cellulose 100 parts by weight Silicic anhydride 90 parts by weight Magnesium stearate 10 parts by weight
【００２８】実施例２ エテンザミド１９０００ｇ及び部分α化デンプン１００
０ｇをＶ型混合機（（株）特寿工作所製）にて５分間混
合した後、乾式造粒機にて造粒し、これを整粒した後、
平均粒子径２５０μｍの顆粒を得た。 Example 2 19000 g of ethenzamide and partially pregelatinized starch 100
After mixing 0 g for 5 minutes with a V-type mixer (manufactured by Tokushou Co., Ltd.), the mixture was granulated with a dry granulator, and this was sized.
Granules having an average particle size of 250 μm were obtained.
【００２９】次いで、得られた顆粒７０００ｇに結晶セ
ルロース１０００ｇ、カルボキシメチルセルロース１０
００ｇ及び平均粒子径１９μｍの無水ケイ酸９００ｇを
加え、Ｖ型混合機で１５分間混合した。更に、ステアリ
ン酸マグネシウム１００ｇを添加して５分間混合し、錠
剤用組成物を得た。Then, 7000 g of the obtained granules were added to 1000 g of crystalline cellulose and 10 g of carboxymethyl cellulose.
Then, 00 g and 900 g of silicic anhydride having an average particle diameter of 19 μm were added, followed by mixing with a V-type mixer for 15 minutes. Further, 100 g of magnesium stearate was added and mixed for 5 minutes to obtain a composition for tablets.
【００３０】得られた組成物を打錠機（Ｌ−４１型：
（株）畑鐵工所製）にて直径６ｍｍ、杵先半径７．５ｍ
ｍの杵を用い、打錠圧０．８ｔで打錠し、錠剤の製造を
行った。その結果、約２時間の打錠においても杵への付
着が見られず、スティッキングの傾向は認められなかっ
た。A tableting machine (model L-41:
6mm in diameter, 7.5m radius of punch tip
The tablets were pressed at a tableting pressure of 0.8 t using a m.punch to produce tablets. As a result, no sticking to the punch was observed even after tableting for about 2 hours, and no sticking tendency was observed.
【００３１】比較例２ 平均粒子径１９μｍの無水ケイ酸９００ｇの代わりに、
平均粒子径２００μｍの無水ケイ酸水素カルシウムを９
００ｇ用いた以外は、実施例２と同様の方法で組成物を
得、製剤を行った。打錠開始後、約５分で打錠機の杵に
スティッキングが生じた。 Comparative Example 2 Instead of 900 g of silicic anhydride having an average particle size of 19 μm,
Anhydrous calcium hydrogen silicate having an average particle size of 200 μm was added to 9
A composition was obtained and formulated in the same manner as in Example 2 except that 00 g was used. Approximately 5 minutes after the start of tableting, sticking occurred in the punch of the tableting machine.
【００３２】［実施例３、比較例３］低融点生理活性物
質としてイブプロフェン、結晶性粉末としてマンニトー
ルを用い、下記組成の錠剤を下記方法で製造した。組 成 イブプロフェン ８００重量部 コーンスターチ １５０重量部 ヒドロキシプロピルセルロース ５０重量部 無水カフェイン ４００重量部 結晶セルロース ４００重量部 マンニトール １６０重量部 ステアリン酸マグネシウム ４０重量部Example 3, Comparative Example 3 Tablets having the following composition were produced by the following method using ibuprofen as a low-melting-point physiologically active substance and mannitol as a crystalline powder. Composition Ibuprofen 800 parts by weight Corn starch 150 parts by weight Hydroxypropylcellulose 50 parts by weight Anhydrous caffeine 400 parts by weight Crystalline cellulose 400 parts by weight Mannitol 160 parts by weight Magnesium stearate 40 parts by weight
【００３３】実施例３ 流動層造粒機にイブプロフェン２４００ｇ、コーンスタ
ーチ４５０ｇをとり、予めヒドロキシプロピルセルロー
ス２００ｇを水に溶解し４０００ｇとした溶液を６５℃
で噴霧し、造粒した。これを乾燥した後、目開きが８５
０μｍのふるいにかけて粒度を調整した。 Example 3 2400 g of ibuprofen and 450 g of corn starch were placed in a fluidized bed granulator, and 200 g of hydroxypropyl cellulose was previously dissolved in water to make 4000 g, and a solution was prepared at 65 ° C.
And granulated. After drying this, the aperture is 85
The particle size was adjusted by passing through a 0 μm sieve.
【００３４】次いで、得られた造粒物１０００ｇに無水
カフェイン４００ｇ、結晶セルロース４００ｇ及び平均
粒子径１８μｍのマンニトール１６０ｇを加え、Ｖ型混
合機（（株）特寿工作所製）で１５分間混合した。更
に、ステアリン酸マグネシウム４０ｇを添加して５分間
混合し、錠剤用組成物を得た。Next, 400 g of anhydrous caffeine, 400 g of crystalline cellulose, and 160 g of mannitol having an average particle diameter of 18 μm were added to 1000 g of the obtained granules, and mixed for 15 minutes using a V-type mixer (manufactured by Tokuju Corp.). did. Further, 40 g of magnesium stearate was added and mixed for 5 minutes to obtain a composition for tablets.
【００３５】得られた組成物を打錠機（クリーンプレス
コレクト１２ＨＵＫ：（株）菊水製作所製）にて直径８
ｍｍ、杵先半径２０ｍｍの杵を用い、打錠圧１．０ｔで
打錠し、錠剤の製造を行った。その結果、約２時間の打
錠において、杵先端への付着がなく、スティッキングは
発生しなかった。The obtained composition was subjected to a tableting machine (Clean Press Collect 12HUK: manufactured by Kikusui Seisakusho) to have a diameter of 8
Tablets were produced at a tableting pressure of 1.0 t using a punch having a diameter of 20 mm and a tip radius of 20 mm to produce tablets. As a result, in the tableting for about 2 hours, there was no sticking to the tip of the punch and sticking did not occur.
【００３６】比較例３ 平均粒子径１８μｍのマンニトール１６０ｇの代わり
に、平均粒子径１３０μｍのマンニトールを１６０ｇ用
いた以外は、実施例３と同様の方法で組成物を得、製剤
を行った。打錠開始後、約１０分で、杵先端にスティッ
キング発生が認められ、２０分後には杵先端全域にステ
ィッキングが認められた。 Comparative Example 3 A composition was obtained and prepared in the same manner as in Example 3, except that 160 g of mannitol having an average particle size of 130 μm was used instead of 160 g of mannitol having an average particle size of 18 μm. About 10 minutes after the start of tableting, sticking occurred at the tip of the punch, and 20 minutes later, sticking was observed at the entire area of the tip of the punch.
【００３７】［実施例４、比較例４］低融点生理活性物
質としてイブプロフェン、結晶性粉末としてソルビトー
ルを用い、下記組成の錠剤を下記方法で製造した。組 成 イブプロフェン ８００重量部 結晶セルロース １５０重量部 ヒドロキシプロピルセルロース ５０重量部 アリルイソプロピルアセチル尿素 ３００重量部 乳糖 ４００重量部 ソルビトール １６０重量部 ステアリン酸マグネシウム ４０重量部Example 4, Comparative Example 4 Tablets having the following composition were produced by the following method using ibuprofen as a low melting point physiologically active substance and sorbitol as a crystalline powder. Composition Ibuprofen 800 parts by weight Microcrystalline cellulose 150 parts by weight Hydroxypropylcellulose 50 parts by weight Allylisopropylacetyl urea 300 parts by weight Lactose 400 parts by weight Sorbitol 160 parts by weight Magnesium stearate 40 parts by weight
【００３８】実施例４ 流動層造粒機にイブプロフェン２４００ｇ、結晶セルロ
ース４５０ｇをとり、予めヒドロキシプロピルセルロー
ス２００ｇを水に溶解し４０００ｇとした溶液を６５℃
で噴霧し、造粒した。これを乾燥した後、目開きが８５
０μｍのふるいにかけて粒度を調整した。 Example 4 2400 g of ibuprofen and 450 g of crystalline cellulose were placed in a fluidized bed granulator, and 200 g of hydroxypropyl cellulose was dissolved in water in advance to obtain a 4000 g solution.
And granulated. After drying this, the aperture is 85
The particle size was adjusted by passing through a 0 μm sieve.
【００３９】次いで、得られた造粒物１０００ｇにアリ
ルイソプロピルアセチル尿素３００ｇ、乳糖４００ｇ及
び平均粒子径１８μｍのソルビトール１６０ｇを加え、
Ｖ型混合機（（株）特寿工作所製）で１５分間混合し
た。更に、ステアリン酸マグネシウム４０ｇを添加して
５分間混合し、錠剤用組成物を得た。Next, 300 g of allylisopropylacetyl urea, 400 g of lactose and 160 g of sorbitol having an average particle diameter of 18 μm were added to 1000 g of the obtained granules,
The mixture was mixed for 15 minutes using a V-type mixer (manufactured by Tokushou Kosakusho). Further, 40 g of magnesium stearate was added and mixed for 5 minutes to obtain a composition for tablets.
【００４０】得られた組成物を打錠機（クリーンプレス
コレクト１２ＨＵＫ：（株）菊水製作所製）にて直径１
０ｍｍ、杵先半径１３ｍｍの杵を用い、打錠圧１．２ｔ
で打錠し、錠剤の製造を行った。その結果、約２時間の
打錠において、杵先端への付着がなく、スティッキング
は発生しなかった。The obtained composition was subjected to a tableting machine (Clean Press Collect 12HUK: manufactured by Kikusui Seisakusho) to have a diameter of 1
0mm, punch pressure 1.2t using a punch with a 13mm tip radius
To produce tablets. As a result, in the tableting for about 2 hours, there was no sticking to the tip of the punch and sticking did not occur.
【００４１】比較例４ 平均粒子径１８μｍのソルビトール１６０ｇの代わり
に、平均粒子径１３０μｍのソルビトールを１６０ｇ用
いた以外は、実施例４と同様の方法で組成物を得、製剤
を行った。打錠開始後、約５分で、杵先端にスティッキ
ング発生が認められ、１５分後には杵先端全域にスティ
ッキングが認められた。 Comparative Example 4 A composition was obtained and formulated in the same manner as in Example 4 except that 160 g of sorbitol having an average particle diameter of 130 μm was used instead of 160 g of sorbitol having an average particle diameter of 18 μm. About 5 minutes after the start of tableting, sticking occurred at the tip of the punch, and 15 minutes later, sticking was observed at the entire area of the tip of the punch.
【００４２】［実施例５、比較例５］低融点生理活性物
質としてアスピリン、結晶性粉末として乳糖を用い、下
記組成の錠剤を下記方法で製造した。組 成 アスピリン ５００重量部 無水カフェイン １２０重量部 ヒドロキシプロピルスターチ ８０重量部 結晶セルロース １５０重量部 乳糖 ２００重量部 ステアリン酸マグネシウム ３０重量部Example 5, Comparative Example 5 Using aspirin as a low-melting-point physiologically active substance and lactose as a crystalline powder, tablets having the following composition were produced by the following method. Composition Aspirin 500 parts by weight Anhydrous caffeine 120 parts by weight Hydroxypropyl starch 80 parts by weight Microcrystalline cellulose 150 parts by weight Lactose 200 parts by weight Magnesium stearate 30 parts by weight
【００４３】実施例５ アスピリン１７５００ｇ及びヒドロキシプロピルスター
チ２８００ｇをＶ型混合機（（株）特寿工作所製）にて
５分間混合した後、乾式造粒機にて造粒し、整粒した
後、平均粒子径２３０μｍの顆粒を得た。 Example 5 Aspirin (17500 g) and hydroxypropyl starch (2800 g) were mixed in a V-type mixer (manufactured by Tokushou Kogyo Co., Ltd.) for 5 minutes, then granulated in a dry granulator and sized. Thus, granules having an average particle diameter of 230 μm were obtained.
【００４４】次いで、得られた顆粒５８００ｇに無水カ
フェイン１２００ｇ、結晶セルロース１５００ｇ及び平
均粒子径３５μｍの乳糖２０００ｇを加え、Ｖ型混合機
で１５分間混合した。更に、ステアリン酸マグネシウム
３００ｇを添加して５分間混合し、錠剤用組成物を得
た。Next, 1200 g of anhydrous caffeine, 1500 g of crystalline cellulose, and 2000 g of lactose having an average particle diameter of 35 μm were added to 5800 g of the obtained granules, and mixed for 15 minutes using a V-type mixer. Further, 300 g of magnesium stearate was added and mixed for 5 minutes to obtain a composition for tablets.
【００４５】得られた組成物を打錠機（Ｌ−４１型：
（株）畑鐵工所製）にて直径１０ｍｍ、杵先半径８ｍｍ
の杵を用い、打錠圧１．５ｔで打錠し、錠剤の製造を行
った。その結果、約２時間の打錠においても杵への付着
が見られず、スティッキングの傾向は認められなかっ
た。A tableting machine (model L-41:
(Manufactured by Hata Iron Works) with a diameter of 10 mm and a tip radius of 8 mm
The tablets were pressed at a tableting pressure of 1.5 t using a pestle to produce tablets. As a result, no sticking to the punch was observed even after tableting for about 2 hours, and no sticking tendency was observed.
【００４６】比較例５ 平均粒子径３５μｍの乳糖２０００ｇの代わりに、平均
粒子径１８０μｍの乳糖２０００ｇ用いた以外は、実施
例５と同様の方法で組成物を得、製剤を行った。打錠開
始後、約５分で打錠機の杵にスティッキングが生じた。 Comparative Example 5 A composition was obtained and prepared in the same manner as in Example 5, except that 2000 g of lactose having an average particle size of 180 μm was used instead of 2000 g of lactose having an average particle size of 35 μm. Approximately 5 minutes after the start of tableting, sticking occurred in the punch of the tableting machine.
Claims (2)
平均粒子径が１〜１００μｍの結晶性粉末を配合してな
ることを特徴とする錠剤用組成物。1. A tablet composition comprising a physiologically active ingredient having a melting point of 70 to 150 ° C. and a crystalline powder having an average particle size of 1 to 100 μm.
含む錠剤を製造するに際し、上記生理活性成分を平均粒
子径が１〜１００μｍの結晶性粉末の存在下に打錠する
ことを特徴とする打錠方法。2. A tablet containing a physiologically active ingredient having a melting point of 70 to 150 ° C., wherein the physiologically active ingredient is tableted in the presence of a crystalline powder having an average particle size of 1 to 100 μm. Tableting method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23147796A JPH1059842A (en) | 1996-08-13 | 1996-08-13 | Composition for tablet and making tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23147796A JPH1059842A (en) | 1996-08-13 | 1996-08-13 | Composition for tablet and making tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH1059842A true JPH1059842A (en) | 1998-03-03 |
Family
ID=16924115
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP23147796A Pending JPH1059842A (en) | 1996-08-13 | 1996-08-13 | Composition for tablet and making tablet |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH1059842A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7799351B2 (en) | 1997-09-19 | 2010-09-21 | Ineos Healthcare Limited | Metal compounds, mixed or sulphated, as phosphate binders |
| US8697125B2 (en) | 2007-02-01 | 2014-04-15 | Takeda Pharmaceutical Company Limited | Tablet preparation without causing a tableting trouble |
| JP2015036374A (en) * | 2013-08-13 | 2015-02-23 | ライオン株式会社 | Ibuprofen-containing tablet and method for producing the same |
| US9066917B2 (en) | 2009-08-03 | 2015-06-30 | Cytochroma Development Inc. | Mixed metal compound |
| US9168270B2 (en) | 2006-01-31 | 2015-10-27 | Opko Ireland Global Holdings, Ltd. | Water-insoluble, iron-containing mixed metal, granular material |
| WO2015186729A1 (en) * | 2014-06-03 | 2015-12-10 | カルピス株式会社 | Immediate-release tablet formulation, composition for tablets and method for manufacturing immediate-release tablet formulation |
| US9566302B2 (en) | 2010-02-04 | 2017-02-14 | Opko Ireland Global Holdings, Ltd. | Composition comprising mixed metal compounds and xanthan gum |
| US10155040B2 (en) | 2007-10-16 | 2018-12-18 | Opko Ireland Global Holdings, Ltd. | Mixed metal compounds for treatment of hyperphosphataemia |
| US10201501B2 (en) | 2007-07-27 | 2019-02-12 | Opko Ireland Global Holdings, Ltd. | Mixed metal compounds used as antacids |
-
1996
- 1996-08-13 JP JP23147796A patent/JPH1059842A/en active Pending
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9242869B2 (en) | 1997-09-19 | 2016-01-26 | Opko Ireland Global Holdings, Ltd. | Metal compounds mixed or sulphated, as phosphate binders |
| US8568792B2 (en) | 1997-09-19 | 2013-10-29 | Cytochroma Development Inc. | Metal compounds, mixed or sulphated, as phosphate binders |
| US7799351B2 (en) | 1997-09-19 | 2010-09-21 | Ineos Healthcare Limited | Metal compounds, mixed or sulphated, as phosphate binders |
| US9168270B2 (en) | 2006-01-31 | 2015-10-27 | Opko Ireland Global Holdings, Ltd. | Water-insoluble, iron-containing mixed metal, granular material |
| US9907816B2 (en) | 2006-01-31 | 2018-03-06 | Opko Ireland Global Holdings, Ltd. | Water-insoluble, iron-containing mixed metal, granular material |
| US8697125B2 (en) | 2007-02-01 | 2014-04-15 | Takeda Pharmaceutical Company Limited | Tablet preparation without causing a tableting trouble |
| US10201501B2 (en) | 2007-07-27 | 2019-02-12 | Opko Ireland Global Holdings, Ltd. | Mixed metal compounds used as antacids |
| US10155040B2 (en) | 2007-10-16 | 2018-12-18 | Opko Ireland Global Holdings, Ltd. | Mixed metal compounds for treatment of hyperphosphataemia |
| US9066917B2 (en) | 2009-08-03 | 2015-06-30 | Cytochroma Development Inc. | Mixed metal compound |
| US9314481B2 (en) | 2009-08-03 | 2016-04-19 | Opko Ireland Global Holdings, Ltd. | Method |
| US9566302B2 (en) | 2010-02-04 | 2017-02-14 | Opko Ireland Global Holdings, Ltd. | Composition comprising mixed metal compounds and xanthan gum |
| JP2015036374A (en) * | 2013-08-13 | 2015-02-23 | ライオン株式会社 | Ibuprofen-containing tablet and method for producing the same |
| CN106535916A (en) * | 2014-06-03 | 2017-03-22 | 朝日可尔必思健康株式会社 | Immediate-release tablet formulation, composition for tablets and method for manufacturing immediate-release tablet formulation |
| US9675666B2 (en) | 2014-06-03 | 2017-06-13 | Asahi Calpis Wellness Co., Ltd. | Immediate-release tablet formulation, composition for tablets and method for manufacturing immediate-release tablet formulation |
| JP2016011285A (en) * | 2014-06-03 | 2016-01-21 | カルピス株式会社 | Tablet type immediate release formulation and production method thereof |
| WO2015186729A1 (en) * | 2014-06-03 | 2015-12-10 | カルピス株式会社 | Immediate-release tablet formulation, composition for tablets and method for manufacturing immediate-release tablet formulation |
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