JPH01175936A - Tablet containing 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-4-methyl-1-pi-perazinyl)-4-oxo-3-quinolinecarboxylic acid as active component - Google Patents
Tablet containing 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-4-methyl-1-pi-perazinyl)-4-oxo-3-quinolinecarboxylic acid as active componentInfo
- Publication number
- JPH01175936A JPH01175936A JP33492487A JP33492487A JPH01175936A JP H01175936 A JPH01175936 A JP H01175936A JP 33492487 A JP33492487 A JP 33492487A JP 33492487 A JP33492487 A JP 33492487A JP H01175936 A JPH01175936 A JP H01175936A
- Authority
- JP
- Japan
- Prior art keywords
- tablet
- weight
- tablets
- fluoroethyl
- difluoro
- 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
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 20
- 239000000843 powder Substances 0.000 claims abstract description 18
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 13
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 10
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 10
- 239000007884 disintegrant Substances 0.000 claims abstract description 9
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000007888 film coating Substances 0.000 claims abstract description 8
- 238000009501 film coating Methods 0.000 claims abstract description 8
- 239000008101 lactose Substances 0.000 claims abstract description 8
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000314 lubricant Substances 0.000 claims abstract description 7
- 239000011230 binding agent Substances 0.000 claims abstract description 5
- 229920002472 Starch Polymers 0.000 claims abstract description 4
- 229920002678 cellulose Polymers 0.000 claims abstract description 4
- 239000001913 cellulose Substances 0.000 claims abstract description 4
- 238000000748 compression moulding Methods 0.000 claims abstract description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims abstract description 4
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 4
- 239000008107 starch Substances 0.000 claims abstract description 4
- 235000019698 starch Nutrition 0.000 claims abstract description 4
- XBJBPGROQZJDOJ-UHFFFAOYSA-N fleroxacin Chemical compound C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(CCF)C2=C1F XBJBPGROQZJDOJ-UHFFFAOYSA-N 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 3
- 238000005507 spraying Methods 0.000 claims description 2
- 238000007907 direct compression Methods 0.000 abstract description 8
- 238000000465 moulding Methods 0.000 abstract description 7
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 abstract description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 abstract description 3
- 239000011248 coating agent Substances 0.000 abstract description 2
- 238000000576 coating method Methods 0.000 abstract description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
- 230000000996 additive effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 82
- 229960003306 fleroxacin Drugs 0.000 description 21
- 238000000034 method Methods 0.000 description 15
- 238000010998 test method Methods 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000007922 dissolution test Methods 0.000 description 4
- 230000000704 physical effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000011812 mixed powder Substances 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000007941 film coated tablet Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000004898 kneading Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 238000004513 sizing Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- YCAZALSUJDPQPP-UHFFFAOYSA-N 4-oxo-3h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2C(=O)C(C(=O)O)C=NC2=C1 YCAZALSUJDPQPP-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920003114 HPC-L Polymers 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960003368 croscarmellose sodium type a Drugs 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は６．８−ジフルオロ−１−（２−フルオロエチ
ル）−１，４−ジヒドロ−７−（４−メチル−１−ピペ
ラジニル）−４−オキソ−３−キノリンカルボン酸（以
下−数名に従いフレロキサシンと称す）を含む粉末を直
接圧縮し成形して得られる錠剤に関する。Detailed Description of the Invention [Industrial Application Field] The present invention relates to 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)- The present invention relates to a tablet obtained by directly compressing and molding a powder containing 4-oxo-3-quinolinecarboxylic acid (hereinafter referred to as fleroxacin according to some names).
フレロキサシンは大傘らが新たに合成し、合成抗菌剤と
して開発したものである（特開昭５６−３０４４号）。Fleroxacin was newly synthesized by Okasa et al. and developed as a synthetic antibacterial agent (Japanese Patent Application Laid-open No. 3044/1983).
フレロキサシンは極めて広い抗菌スペクトラムを示し、
ダラム陽性菌及びダラム陰性菌に対し強い抗菌活性を示
し、これらの病原体に起因する病気の予防と治療に極め
て有効である。Fleroxacin exhibits an extremely broad antibacterial spectrum;
It exhibits strong antibacterial activity against Durham-positive bacteria and Durham-negative bacteria, and is extremely effective in preventing and treating diseases caused by these pathogens.
［従来の技術とその問題点］
医薬品製剤の錠剤を製する場合、その製造法は、古くか
ら湿式造粒法が用いられてきた。この湿式造粒法は混合
−加水練合一造粒一乾燥一整粒一打錠と複雑な工程を経
るものである。しかしこの工程中には水その他の溶媒に
よる湿潤、加熱による溶媒の乾燥等、不安定な医薬品成
分を過酷な条件にさらさなければならず、このため錠剤
化工程で、変色、分解等の変質が避は難いという問題が
ある。[Prior Art and its Problems] When manufacturing tablets of pharmaceutical preparations, a wet granulation method has been used for a long time. This wet granulation method involves a complex process of mixing, hydration, kneading, granulation, drying, sizing, and tableting. However, during this process, unstable pharmaceutical ingredients must be exposed to harsh conditions such as wetting with water and other solvents and drying of solvents by heating, which can lead to changes in quality such as discoloration and decomposition during the tabletting process. There is a problem that is difficult to avoid.
この湿式造粒法に代り、加温、練合、乾燥を行わない方
法として医薬品粉末を直接圧縮成形し錠剤を得る方法が
とられ、これは直打法と呼ばれる。直打法は医薬品粉末
を直接成形し錠剤化できるので製造が簡便である利点を
有するが同法の適用可否はその主成分の医薬品成分の圧
縮成形性に負うところが大きく、全ての医薬品成分に直
接法を採用できるものではない。例えば本発明において
対象とするフレロキサシンの粉末はそのまま成形圧力を
かけて成形できるものではない。Instead of this wet granulation method, there is a method that does not require heating, kneading, or drying, and involves directly compressing pharmaceutical powder to obtain tablets, which is called the direct compression method. The direct compression method has the advantage of being easy to manufacture because the pharmaceutical powder can be directly molded into tablets, but the applicability of this method largely depends on the compression moldability of the main pharmaceutical ingredient. It is not something that can be enacted by law. For example, the powder of fleroxacin, which is the object of the present invention, cannot be molded as it is by applying molding pressure.
［本発明が解決しようとする問題点］
この発明は、フレロキサシンの粉末から前記直打法によ
って錠剤を調整することを目的としてなされたものであ
る。[Problems to be Solved by the Present Invention] The present invention has been made for the purpose of preparing tablets from fleroxacin powder by the above-mentioned direct compression method.
［問題を解決するための手段及び作用］本発明者は、前
記の問題を解決するため、フレロキサシンに添加する種
々の直打用添加剤を鋭意研究した。その結果、このフレ
ロキサシンについての直打しやすい粉末組成を見出し、
この粉末に基づいてフレロキサシンの錠剤を製すること
を可能としたものである。[Means and effects for solving the problem] In order to solve the above-mentioned problem, the present inventor has intensively researched various additives for direct injection to be added to fleroxacin. As a result, we found a powder composition for fleroxacin that was easy to apply directly,
This made it possible to manufacture fleroxacin tablets based on this powder.
本発明によって得られたフレロキサシン錠剤は、製造工
程が簡略化されたばかりでなく、崩壊又は溶出試験にお
いて良好な崩壊性と、溶出性を示す。The fleroxacin tablet obtained by the present invention not only has a simplified manufacturing process, but also exhibits good disintegration and dissolution properties in disintegration or dissolution tests.
フレロキサシン粉末からの直打法により錠剤を製するに
は、適当な添加剤を添加することが必要であり、添加剤
にはその作用により賦形剤、崩壊剤、結合剤及び滑沢剤
が選択される。To manufacture tablets by direct compression from fleroxacin powder, it is necessary to add appropriate additives, and excipients, disintegrants, binders, and lubricants are selected depending on their functions. be done.
賦形剤には例えば、乳糖が用いられるが、通常のもので
は成形性の良い錠剤が得られにくい。このため流動性の
良い直打用乳糖 （例えば商品名；タブレトーズ、太陽
化学産業社製）、噴られる。その他の賦形剤として結晶
セルロース（例えば商品名；アビセル、旭化成工業社製
）が用いられる。これらの添加量は錠剤重量の５〜４０
重量％とされる。この添加量が５％以下の場合は、成形
性の良い錠剤が得られず、又４０％以上では成形性が良
くなる反面、錠剤が大きくなる欠点を有する。For example, lactose is used as an excipient, but it is difficult to obtain tablets with good moldability using ordinary excipients. For this reason, lactose for direct injection with good fluidity (for example, trade name: Tabletose, manufactured by Taiyo Kagaku Sangyo Co., Ltd.) is used. As another excipient, crystalline cellulose (for example, trade name: Avicel, manufactured by Asahi Kasei Industries, Ltd.) is used. The amount added is 5 to 40 of the tablet weight.
% by weight. If the amount added is less than 5%, tablets with good moldability cannot be obtained, and if it is more than 40%, moldability is improved, but the tablets have the disadvantage of becoming larger.
崩壊剤として一般的にはカルボキシメチルセルロースカ
ルシウム（例えば商品名、 ＥＣＧ、。５、五徳薬品社
製）、カルボキシメチルセルロース（例えば商品名、
ＮＳ−３００、ニチリン化学社製）、クロスカルメロー
スナトリウム・Ａ型（例えば商品名； Ａｃ−Ｄｉ−５
％ｏｌ、旭化成工業社製）などが用いられているが、こ
れらの崩壊剤はフレロキサシンの分解を促進するため本
発明においては用いることができない。そこで本発明に
おいては崩壊剤として例えば低置換度ヒドロキシプロピ
ルセルロース （例えば商品名、 Ｌ−ＮＰＣ１信越化
学社製）、トウモロコシデンプン、バレイショデンブン
、部分アルファー化デンプン（例えば商品名、 ｐｃｓ
、旭化成工業社製）が用いの成形性を低下させるばかり
でなく、錠剤を大型化する欠点を有する。As disintegrants, carboxymethyl cellulose calcium (for example, trade name, ECG, .5, manufactured by Gotoku Pharmaceutical Co., Ltd.), carboxymethyl cellulose (for example, trade name,
NS-300, manufactured by Nichirin Kagaku Co., Ltd.), croscarmellose sodium type A (e.g., trade name: Ac-Di-5)
%ol, manufactured by Asahi Kasei Industries, Ltd.), but these disintegrants accelerate the decomposition of fleroxacin and cannot be used in the present invention. Therefore, in the present invention, as disintegrants, for example, low-substituted hydroxypropyl cellulose (for example, trade name, L-NPC1 manufactured by Shin-Etsu Chemical Co., Ltd.), corn starch, potato starch, partially pregelatinized starch (for example, trade name, pcs) are used.
(manufactured by Asahi Kasei Kogyo Co., Ltd.) has the drawback of not only reducing the moldability but also increasing the size of the tablet.
結合剤としてはヒドロキシプロピルセルロース（例えば
ＨＰＣ−Ｌ、日本曹達社製）等を必要に応じて例えば錠
剤重量の０〜４重量％を混合することができる。As a binder, hydroxypropyl cellulose (for example, HPC-L, manufactured by Nippon Soda Co., Ltd.) or the like can be mixed as necessary, for example, in an amount of 0 to 4% by weight of the tablet weight.
滑沢剤にはステアリン酸マグネシウム、含水ケイ酸 （
例えば商品名；カープレックス、塩野義製薬社製）を用
いることができる。その添加量は錠剤重量の０．２〜５
重量％とすることがよい。０．２％以下では滑沢効果を
示さないし、５％以上では錠剤の結合性が低下し、成形
性の良い錠剤が得られない欠点を有する。Lubricants include magnesium stearate and hydrated silicic acid (
For example, the product name: Carplex (manufactured by Shionogi & Co., Ltd.) can be used. The amount added is 0.2 to 5 of the tablet weight.
It is preferable to express it in weight%. If it is less than 0.2%, no lubricating effect will be exhibited, and if it is more than 5%, the binding properties of the tablet will decrease, resulting in the disadvantage that tablets with good moldability cannot be obtained.
これらの１種か、又は２ ｆ１以上と、フレロキサシン
粉末と混合し、この混合粉末を通常の打錠機を用いて圧
縮成形して錠剤を製することができる。Tablets can be produced by mixing one or more of these with fleroxacin powder and compressing the mixed powder using a common tablet machine.
この錠剤にフィルムコーティングを施す場合には、医薬
品に用いられるフィルムコーティング剤が用いられる０
例えば、ヒドロキシプロピルメチルセルロース（例えば
商品名、 ＴＣ−５、信越化学工業社製）を錠剤に対し
て３〜１０重量％、あるいは酸化チタン０．１〜０．５
重量％を通常の方法でフィルムコーティングすることが
できる。When film coating these tablets, a film coating agent used for pharmaceuticals is used.
For example, 3 to 10% by weight of hydroxypropyl methylcellulose (eg, trade name: TC-5, manufactured by Shin-Etsu Chemical Co., Ltd.) based on the tablet, or 0.1 to 0.5% of titanium oxide.
% by weight can be film coated in a conventional manner.
［実 施 例］
以下、実施例により発明具体化の諸態様を説明するが、
例示は当然説明のものであって、発明精神の限定を意図
するものではない。[Example] Hereinafter, various aspects of embodiment of the invention will be explained using Examples.
The examples are, of course, for illustration only and are not intended to limit the spirit of the invention.
実施例 １
フレロキサシン粉末１０００ｇをＶ型混合機にとり、タ
ブレトーズ（商品名） １４０ｇ、アビセル（商品名）
２７２ｇ、Ｌ−）ＩＰＣ（商品名）５０ｇ、ステアリ
ン酸マグネシウム２３ｇ及びカープレックス（商品名）
１５ｇ（いずれも前出）を加えて１０分間混合した。こ
の混合粉末を錠径７．５ｍｍの打錠機セットを用い、１
錠１５０ｍｇ （フレロキサシンとして１００ｍｇ）の
錠剤に圧縮成形（成形圧力９００ｋｇ、錠厚２．５ｍｍ
） シた。これにより何ら打錠障害なく液）１分１７
秒、溶出試験（日局第１法１１００ｒｐ、試験液：ｐｔ
＋ｓ、、ｏの酢酸緩衝液９００ｍ１ ）で３０分に９３
％が溶出し、これにより優れた圧縮成形性と、崩壊性、
溶出性を示す錠剤が得られた。Example 1 1000 g of fleuroxacin powder was placed in a V-type mixer, and 140 g of Tabletose (trade name) and Avicel (trade name) were added.
272g, L-) IPC (trade name) 50g, magnesium stearate 23g and Carplex (trade name)
15 g (all from above) were added and mixed for 10 minutes. Using a tablet press set with a tablet diameter of 7.5 mm, this mixed powder was
Compression molding into 150 mg tablets (100 mg as fleroxacin) (molding pressure 900 kg, tablet thickness 2.5 mm)
) Shita. As a result, there was no tableting problem and liquid) 1 minute 17
seconds, dissolution test (Japanese Pharmacopoeia Method 1 1100rp, test solution: pt
+s,,o acetate buffer (900 ml) for 30 min.
% is eluted, which results in excellent compression moldability, disintegration properties,
Tablets exhibiting dissolution properties were obtained.
実施例 ２
フレロキサシン粉末１０００ｇを■型混合機にとり、タ
ブレトーズ（商品名） ２４０ｇ、アビセル（商品名）
１５０ｇ、 Ｌ−ＮＰＣ（商品名） ５０ｇ、）ＩＰ
ｃ−Ｌ（商品名）３０ｇを加え、さらに、ステアリン酸
マグネシウム１５ｇ及びカープレックス（商品名）１５
ｇ（いずれも前出）を添加して１５分間混合し、通常の
ロータリー打錠機を用いて直径７．０ｍｍ 、 １錠
重量１５０ｍｇ（フレロキサシンとして１００ｍｇ）の
錠剤に圧縮成形（成形圧力８００ｋｇ、ｉ厚２．５ｍｍ
） した。この錠剤の硬度（試験法は前出）は９．８
ｋｐ、崩壊時間（試験法は前出）１分２８秒で、打錠障
害は全く見られず、硬度の高い、しかも崩壊性の優れた
錠剤が得られた。Example 2 1000g of fleuroxacin powder was placed in a type mixer, and 240g of Tabletose (trade name) and Avicel (trade name) were added.
150g, L-NPC (product name) 50g, )IP
Add 30g of c-L (trade name), and further add 15g of magnesium stearate and 15g of Carplex (trade name).
g (all mentioned above), mixed for 15 minutes, and compressed into tablets with a diameter of 7.0 mm and a tablet weight of 150 mg (100 mg as fleroxacin) using an ordinary rotary tablet machine (molding pressure 800 kg, i Thickness 2.5mm
) did. The hardness of this tablet (test method is mentioned above) is 9.8
kp, disintegration time (test method described above) was 1 minute 28 seconds, no tableting failure was observed, and tablets with high hardness and excellent disintegration properties were obtained.
実施例 ３
フレロキサシン粉末２０００ｇを混合機にとり、ＳＤ−
ラクトース２８０ｇ、アビセル （商品名）５４４ｇ、
Ｌ−ＲＰＣ（商品名−） １００ｇ、ステアリン酸マグ
ネシウム４６ｇ及びカープレックス（商品名） ３０ｇ
（いずれも前出）を加えて１５分間混合した。この混合
粉末を直径９ 、０ｍｍの打錠機をセットしたロータリ
ー打錠機を用いて、成形圧力６００ｋｇ、錠厚４．３ｍ
ｍで打錠し、１錠３００ｍｇ（フレロキサシンとして２
００ｍｇ）の錠剤に圧縮成形した。この硬度（試験法は
前出）は１３．Ｏｋｐ、崩壊時間（試験法は前出）は３
７秒であり、打錠時のトラブルは見られず、硬度の高い
、しかも崩壊性の優れた錠剤が得られた。Example 3 2000g of fleloxacin powder was placed in a mixer and SD-
Lactose 280g, Avicel (trade name) 544g,
L-RPC (trade name) 100g, magnesium stearate 46g and Carplex (trade name) 30g
(both described above) were added and mixed for 15 minutes. This mixed powder was molded using a rotary tablet machine equipped with a tablet machine with a diameter of 9.0 mm, at a pressure of 600 kg and a tablet thickness of 4.3 m.
Each tablet is 300 mg (2 mg as fleroxacin).
00 mg) tablets. This hardness (the test method is mentioned above) is 13. Okp, disintegration time (test method mentioned above) is 3
The tableting time was 7 seconds, no trouble was observed during tableting, and tablets with high hardness and excellent disintegration properties were obtained.
この錠剤３ｋｇをフィルムコーティング装置にとり、５
重量％ＴＣ−５（商品名）水溶液に０．５重量％酸化チ
タンを懸濁した液を常法にしたがって噴Ｈし、１錠重量
３１０ｍｇのフィルムコーティング錠を製した。この錠
剤の硬度（試験法は前出）は２７．０ｋｐ、崩壊（試験
法は前出）５分３０秒と、物性の優れた錠剤を得た。Take 3 kg of this tablet into a film coating device and
A suspension of 0.5 wt % titanium oxide in a wt % TC-5 (trade name) aqueous solution was sprayed in a conventional manner to prepare film-coated tablets each weighing 310 mg. The hardness of this tablet (the test method is described above) was 27.0 kp, and the tablet disintegrated (the test method was described above) in 5 minutes and 30 seconds, giving a tablet with excellent physical properties.
実施例 ４
フレロキサシン粉末１０００ｇを混合機にとり、乳糖２
７２ｇ、アビセル（商品名） ２７２ｇ、 トウモロ
コシデンプン５０ｇ、ステアリン酸マグネシウム２３ｇ
及びカープレックス（商品名） １５ｇ（いずれも前
出）を加えて１０分間混合し、通学のロータリー打錠機
を用いて直径７．０ｍｍ、１錠重量１５０ｍｇ（フレロ
キサシンとして１００ａ＋ｇ）の錠剤に圧縮成形（成形
圧力８００ｋｇ、ｉ厚３．５ｍｍ ） シた。この錠剤
の硬度（試験法は前出）は８．８ｋｇ 、崩壊（試験法
は前出）６分４７秒、溶出試験３０分に８６％であり、
錠剤として優れた物性を示した。Example 4 1000g of fleroxacin powder was placed in a mixer, and lactose 2
72g, Avicel (trade name) 272g, corn starch 50g, magnesium stearate 23g
and Carplex (trade name) 15g (both listed above) were added, mixed for 10 minutes, and compressed into tablets with a diameter of 7.0mm and a tablet weight of 150mg (100a+g as fleroxacin) using a school rotary tablet press. (Molding pressure 800 kg, thickness 3.5 mm) Shita. The hardness of this tablet (test method is listed above) was 8.8 kg, disintegration (test method listed above) was 6 minutes 47 seconds, dissolution test was 86% in 30 minutes,
It showed excellent physical properties as a tablet.
実施例 ５
フレロキサシン粉末１０００ｇを混合機にとり、タブレ
トーズ（商品名） ２７２ｇ、アビセル（商品名） ２
７２ｇ、 ＰＯ２（商品名） ５０ｇ、ステアリン酸マ
グネシウム２３ｇ及びカープレックス（商品名）１５ｇ
（いずれも前出）を加えて１０分間混合し、ロータリー
打錠機を用いて直径７．０ｍｍ、１錠重量１５０ｍｇ（
フレロキサシンとして１ｏＯｎ＋ｇ）の錠剤に圧縮成形
（成形圧力８００ｋｇ、錠厚３，４ｍｍ ） Ｌ／た。Example 5 1000g of fleloxacin powder was placed in a mixer, 272g of Tabletose (trade name), and 272g of Avicel (trade name) were added.
72g, PO2 (trade name) 50g, magnesium stearate 23g and Carplex (trade name) 15g
(all mentioned above) and mixed for 10 minutes, using a rotary tablet press to make tablets with a diameter of 7.0 mm and a weight of 150 mg (1 tablet).
It was compression molded into tablets (molding pressure 800 kg, tablet thickness 3.4 mm) of 10On+g as fleroxacin.
得られた錠剤の硬度（試験法は前出）は、９．９ｋｐ、
崩壊（試験法は前出）１分７秒と優れた錠剤か得られた
。The hardness of the obtained tablets (the test method is described above) is 9.9kp,
An excellent tablet was obtained which disintegrated in 1 minute and 7 seconds (the test method is described above).
この錠剤をフィルムコーティング装置にとり、５重量％
のＴ（ニー５水溶液に０．５重量％の酸化チタンを懸濁
した液を常法にしたがって噴霧し、１錠重量２０５ｍｇ
のフィルムコーティング錠を製した。錠剤の溶出（試験
法は前出）３０分値８２％と優れた錠剤を得た。This tablet was placed in a film coating device and 5% by weight was coated.
A suspension of 0.5% by weight of titanium oxide in an aqueous solution of T (nee 5) was sprayed according to a conventional method, and each tablet weighed 205 mg.
A film-coated tablet was produced. Excellent tablets with a 30-minute dissolution value of 82% were obtained (the test method is described above).
［参 考 例］
フレロキサシン９００ｇＩ乳糖２１６ｇ、アビセル（商
品名） ９０ｇ、 Ｌ−ＲＰＣ（商品名）９０ｇを混合
し、これに６重量％のＨＰ（ニーＬ （商品名）水溶
液４５０ｇを加えて常法に従って練合、造粒し、５０℃
、４０分間乾燥した。これを２０メツシユスクリーンを
通し整粒した後、ステアリン酸マグネシウム１３．５ｇ
及びカープレックス（商品名）１３．５３を加えて混合
し、ロータリー打錠機にて直径７．５ｍｍ、１錠重量１
５０ｍｇ（フレロキサシンとして１００ｍｇ）に打錠し
た。硬度５．９ｋｐ、崩壊時間３分４８秒、溶出試験３
０分値８８％の錠剤を得た。錠剤物性として良好であっ
た。[Reference Example] Mix 900 g of fleroxacin, 216 g of lactose, 90 g of Avicel (trade name), and 90 g of L-RPC (trade name), add 450 g of a 6% by weight aqueous solution of HP (NieL (trade name)), and prepare in a conventional manner. Knead and granulate according to
, dried for 40 minutes. After passing this through a 20 mesh screen and sizing it, 13.5g of magnesium stearate
and Carplex (trade name) 13.53 were added and mixed, and a rotary tablet machine was used to make tablets with a diameter of 7.5 mm and a weight of 1 tablet.
It was compressed into 50 mg tablets (100 mg as fleroxacin). Hardness 5.9kp, disintegration time 3 minutes 48 seconds, dissolution test 3
Tablets with a 0 minute value of 88% were obtained. The tablet physical properties were good.
ここに得た湿式錠と本発明の実施例１で得た直打錠をそ
れぞれイヌに経口投与し、血清中濃度を測定したところ
、表１に示すように、最高血清中濃度到達時間（Ｔｍａ
ｘ）、最高血清中濃度（Ｃｍａｘ）、血清中濃度曲線下
面積（ＡＵＧ） ともに、直打錠は湿式錠と同等の結果
であり、優れた消化管吸収性を示した。The wet tablets obtained here and the direct compressed tablets obtained in Example 1 of the present invention were each orally administered to dogs, and the serum concentrations were measured. As shown in Table 1, the time to reach the maximum serum concentration (Tma)
x), maximum serum concentration (Cmax), and area under the serum concentration curve (AUG), the results of the direct compression tablets were equivalent to those of the wet tablets, indicating excellent gastrointestinal absorption.
表 １
湿式錠及び直打錠の吸収性（イヌ）
［発明の効果コ
この発明は、以上説明したように、フレロキサシンの錠
剤を直打法によって製することを可能となし得たことに
よって、錠剤製造時の省力化がはかれたばかりでなく、
得られた錠剤はきわめて良好な物性を示し、消化管吸収
性が高いという効果を有する。Table 1 Absorption properties of wet tablets and direct compression tablets (dogs) [Effects of the invention] As explained above, this invention has made it possible to produce fleroxacin tablets by the direct compression method, Not only was it possible to save labor during manufacturing, but
The obtained tablets exhibit extremely good physical properties and have the effect of being highly absorbable in the gastrointestinal tract.
手続補正書 、。Procedural amendment.
ｌ、事件の表示
昭和６２年特許ｕｖ＋３３４−９２を号４、代理 人
住 所 東京都千代田区丸の内２丁目６番２号丸の内
へ重洲ビル３３０８、補正の内容 別紙のとおり
補 正 書
本願明細豊中下記事項を補正致します。l, Indication of the case 1986 Patent UV+334-92 No. 4, Agent address: 3308 Marunouchi Building, 2-6-2 Marunouchi, Chiyoda-ku, Tokyo, Contents of the amendment: Amendment as shown in the attached document Specification of the original application Toyonaka We will correct the following matters.
記 １、特許請求の範囲を別紙の如く訂正する。Record 1. The scope of claims is amended as shown in the attached sheet.
２、第４頁下から７行目に 「直接法を採用できるｊとあるを 「直打法を採用できるノと訂正する。2. On the 7th line from the bottom of the 4th page ``It says that you can use the direct method.'' ``I'd like to correct you by saying that you can use the direct hit method.
３、第８頁８行目に
「あるいは酸化チタン０．１〜０．５重量％を」とある
を
「及び隠ぺい剤として酸化チタン０．１〜０．５重量％
を混合し、」と訂正する。3. On page 8, line 8, the text "or 0.1 to 0.5% by weight of titanium oxide" was replaced with "and 0.1 to 0.5% by weight of titanium oxide as a masking agent.
``mixed,'' corrected.
４、第１０頁８行目に 「ステアリン酸」とあるを 「ステアリン酸」と訂正する。4. On page 10, line 8 It says "stearic acid" Correct to "stearic acid."
特許請求の範囲
（１） ６．８−ジフルオロ−１−（２−フルオロエチ
ル）−１゜４−ジヒドロ−７−（４−メチル−１−ピペ
ラジニル）−４−オキソ−３−キノリンカルボン酸に医
薬用添加剤を混合した粉末を圧縮成形して得ることを特
徴とする錠剤。Claims (1) 6.8-difluoro-1-(2-fluoroethyl)-1゜4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid A tablet obtained by compression molding a powder mixed with a pharmaceutical additive.
（２） ６．８−ジフルオロ−１−（２−フルオロエチ
ル）−１゜４−ジヒドロ−７−（４−メチル−１−ピペ
ラジニル）＝４−オキソ−３−キノリンカルボン酸を少
なくとも６０重量％以上を含有する特許請求の範囲第（
１）項記載の錠剤。(2) At least 60% by weight of 6.8-difluoro-1-(2-fluoroethyl)-1゜4-dihydro-7-(4-methyl-1-piperazinyl)=4-oxo-3-quinolinecarboxylic acid Claim No. 1 containing the above (
Tablets described in section 1).
（３）医薬用添加剤が、賦形剤、崩壊剤、結合剤及び滑
沢剤であることを特徴とする特許請求の範囲第（１）項
記載の錠剤。(3) The tablet according to claim (1), wherein the pharmaceutical additives are an excipient, a disintegrant, a binder, and a lubricant.
（４）賦形剤が乳糖又は結晶セルロースであり、錠剤重
量の１０〜４０重量％を含有する特許請求の範囲第（３
）項記載の錠剤。(4) The excipient is lactose or crystalline cellulose, and it contains 10 to 40% by weight of the tablet weight.
Tablets listed in ).
（５）崩壊剤が低置換度ヒドロキシプロピルセルロース
、デンプン、部分アルファー化デンプンのいずれかであ
り、錠剤重量の０．２〜１５重量％を含有することを特
徴とする特許請求の範囲第（３）項記載の錠剤。(5) The disintegrant is one of low-substituted hydroxypropylcellulose, starch, and partially pregelatinized starch, and contains 0.2 to 15% by weight of the tablet weight. Tablets listed in ).
（６）滑沢剤がステアリン酸マグネシウム又は含水ケイ
酸であり、錠剤重量の０．２〜５重量％を含有すること
を特徴とする特許請求の範囲第（３）項記載の錠剤。(6) The tablet according to claim (3), wherein the lubricant is magnesium stearate or hydrated silicic acid, and contains 0.2 to 5% by weight of the tablet weight.
（７）錠剤がフィルムコーティング剤で被覆されたもの
であることを特徴とする特許請求の範囲第（１）項記載
の錠剤。(7) The tablet according to claim (1), characterized in that the tablet is coated with a film coating agent.
（８）フィルレムコーティング斉りが、ヒドロキシプロ
ピルメチルセルロースにμ酸化チタン１１合したもので
あり、錠剤重量の３〜１０重量％を噴霧法によりコーテ
ィングしたものであることを特徴とする特許請求の範囲
第（７）項記載の錠剤。(8) The scope of the claim characterized in that the fillem coating is made by combining hydroxypropyl methylcellulose with μ titanium oxide 11, and is coated by a spraying method in an amount of 3 to 10% by weight of the tablet weight. The tablet described in paragraph (7).
Claims (8)
）−１，４−ジヒドロ−７−（４−メチル−１−ピペラ
ジニル）−４−オキソ−３−キノリンカルボン酸に医薬
用添加剤を混合した粉末を圧縮成形して得ることを特徴
とする錠剤。(1) Pharmaceutical additive for 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid A tablet obtained by compression molding a powder mixed with.
）−１，４−ジヒドロ−７−（４−メチル−１−ピペラ
ジニル）−４−オキソ−３−キノリンカルボン酸を少な
くとも６０重量％以上を含有する特許請求の範囲第（１
）項記載の錠剤。(2) at least 60% by weight of 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid; Claim No. 1 (1) containing the above
Tablets listed in ).
沢剤であることを特徴とする特許請求の範囲第（１）項
記載の錠剤。(3) The tablet according to claim (1), wherein the pharmaceutical additives are an excipient, a disintegrant, a binder, and a lubricant.
量の１０〜４０重量％を含有する特許請求の範囲第（３
）項記載の錠剤。(4) The excipient is lactose or crystalline cellulose, and it contains 10 to 40% by weight of the tablet weight.
Tablets listed in ).
、デンプン、部分アルファー化デンプンのいずれかであ
り、錠剤重量の０．２〜１５重量％を含有することを特
徴とする特許請求の範囲第（３）項記載の錠剤。(5) The disintegrant is one of low-substituted hydroxypropylcellulose, starch, and partially pregelatinized starch, and contains 0.2 to 15% by weight of the tablet weight. Tablets listed in ).
酸であり、錠剤重量の０．２〜５重量％を含有すること
を特徴とする特許請求の範囲第（３）項記載の錠剤。(6) The tablet according to claim (3), wherein the lubricant is magnesium stearate or hydrated silicic acid, and contains 0.2 to 5% by weight of the tablet weight.
であることを特徴とする特許請求の範囲第（１）項記載
の錠剤。(7) The tablet according to claim (1), characterized in that the tablet is coated with a film coating agent.
メチルセルロース又は酸化チタンであり、錠剤重量の３
〜１０重量％を噴霧法によりコーティングしたものであ
ることを特徴とする特許請求の範囲第（７）項記載の錠
剤。(8) The film coating agent is hydroxypropyl methylcellulose or titanium oxide, and the tablet weight is 3
The tablet according to claim (7), characterized in that the tablet is coated by a spraying method in an amount of up to 10% by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33492487A JPH01175936A (en) | 1987-12-28 | 1987-12-28 | Tablet containing 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-4-methyl-1-pi-perazinyl)-4-oxo-3-quinolinecarboxylic acid as active component |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33492487A JPH01175936A (en) | 1987-12-28 | 1987-12-28 | Tablet containing 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-4-methyl-1-pi-perazinyl)-4-oxo-3-quinolinecarboxylic acid as active component |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01175936A true JPH01175936A (en) | 1989-07-12 |
Family
ID=18282762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP33492487A Pending JPH01175936A (en) | 1987-12-28 | 1987-12-28 | Tablet containing 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-4-methyl-1-pi-perazinyl)-4-oxo-3-quinolinecarboxylic acid as active component |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01175936A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995011022A1 (en) * | 1993-10-21 | 1995-04-27 | Rhone-Poulenc Rorer S.A. | Method for the preparation of quinolone-containing oral compositions |
| WO1997040828A1 (en) * | 1996-04-26 | 1997-11-06 | Shionogi & Co., Ltd. | Rapid-release s1452 tablets |
| JP2002529415A (en) * | 1998-11-10 | 2002-09-10 | バイエル アクチェンゲゼルシャフト | Pharmaceutical moxifloxacin preparation |
| CN100353943C (en) * | 2005-07-04 | 2007-12-12 | 广州固志医药科技有限公司 | Fleroxacin lactate dispersion tablet, and its prepn. method |
| WO2008072535A1 (en) * | 2006-12-07 | 2008-06-19 | Daiichi Sankyo Company, Limited | Pharmaceutical composition containing low-substituted hydroxypropylcellulose |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5630964A (en) * | 1979-08-22 | 1981-03-28 | Kyorin Pharmaceut Co Ltd | Novel substituted quinolinecarboxylic acid and its preparation |
-
1987
- 1987-12-28 JP JP33492487A patent/JPH01175936A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5630964A (en) * | 1979-08-22 | 1981-03-28 | Kyorin Pharmaceut Co Ltd | Novel substituted quinolinecarboxylic acid and its preparation |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995011022A1 (en) * | 1993-10-21 | 1995-04-27 | Rhone-Poulenc Rorer S.A. | Method for the preparation of quinolone-containing oral compositions |
| WO1995011023A1 (en) * | 1993-10-21 | 1995-04-27 | Rhone-Dpc Europe | Method for the preparation of quinolone-containing oral compositions |
| FR2711524A1 (en) * | 1993-10-21 | 1995-05-05 | Rhone Dpc Europ | Process for the preparation of oral compositions containing quinolones. |
| BE1007326A3 (en) * | 1993-10-21 | 1995-05-16 | Rhone Dpc Europ | Compositions method of preparing oral containing quinolones. |
| ES2126474A1 (en) * | 1993-10-21 | 1999-03-16 | Rhone Dpc Europ | Method for the preparation of quinolone-containing oral compositions |
| WO1997040828A1 (en) * | 1996-04-26 | 1997-11-06 | Shionogi & Co., Ltd. | Rapid-release s1452 tablets |
| US6056974A (en) * | 1996-04-26 | 2000-05-02 | Shionogi & Co., Ltd. | Rapid-release S1452 tablets |
| JP2002529415A (en) * | 1998-11-10 | 2002-09-10 | バイエル アクチェンゲゼルシャフト | Pharmaceutical moxifloxacin preparation |
| JP4809978B2 (en) * | 1998-11-10 | 2011-11-09 | バイエル・シエリング・フアーマ・アクチエンゲゼルシヤフト | Pharmaceutical Moxifloxacin Preparation |
| CN100353943C (en) * | 2005-07-04 | 2007-12-12 | 广州固志医药科技有限公司 | Fleroxacin lactate dispersion tablet, and its prepn. method |
| WO2008072535A1 (en) * | 2006-12-07 | 2008-06-19 | Daiichi Sankyo Company, Limited | Pharmaceutical composition containing low-substituted hydroxypropylcellulose |
| US9034860B2 (en) | 2006-12-07 | 2015-05-19 | Daiichi Sankyo Company, Limited | Pharmaceutical composition containing low-substituted hydroxypropyl cellulose |
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