JPS6346726B2 - - Google Patents
Info
- Publication number
- JPS6346726B2 JPS6346726B2 JP55024344A JP2434480A JPS6346726B2 JP S6346726 B2 JPS6346726 B2 JP S6346726B2 JP 55024344 A JP55024344 A JP 55024344A JP 2434480 A JP2434480 A JP 2434480A JP S6346726 B2 JPS6346726 B2 JP S6346726B2
- Authority
- JP
- Japan
- Prior art keywords
- ibuprofen
- granules
- content
- angle
- repose
- 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.)
- Expired
Links
- 239000008187 granular material Substances 0.000 claims description 72
- 239000000203 mixture Substances 0.000 claims description 31
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 30
- 229960001680 ibuprofen Drugs 0.000 claims description 29
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 24
- 239000002775 capsule Substances 0.000 claims description 22
- 239000007884 disintegrant Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 15
- 238000001816 cooling Methods 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 238000002844 melting Methods 0.000 claims description 6
- 230000008018 melting Effects 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229940126701 oral medication Drugs 0.000 claims 1
- 239000000843 powder Substances 0.000 description 27
- 238000009472 formulation Methods 0.000 description 20
- 238000000034 method Methods 0.000 description 20
- 239000002245 particle Substances 0.000 description 10
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 7
- 239000008116 calcium stearate Substances 0.000 description 7
- 235000013539 calcium stearate Nutrition 0.000 description 7
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 238000007907 direct compression Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000007902 hard capsule Substances 0.000 description 4
- 239000001341 hydroxy propyl starch Substances 0.000 description 4
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 4
- 239000011088 parchment paper Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229910002012 Aerosil® Inorganic materials 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 238000007908 dry granulation Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000010298 pulverizing process Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000002221 antipyretic Substances 0.000 description 2
- 229940125716 antipyretic agent Drugs 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 208000015220 Febrile disease Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 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 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012768 molten material Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000012254 powdered material Substances 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
Landscapes
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Description
本発明はイブプロフエン含有粒状物およびそれ
を含有する内服剤に関する。さらに詳しくは、嵩
が低く流動性のすぐれたイブプロフエン含有粒状
物および該イブプロフエン含有粒状物を含有して
なる小型化された内服剤に関する。
イブプロフエン〔化学名：２―（4′―イソブチ
ルフエニル）プロピオン酸〕（以下、IPと略称す
る）は炎症性疼痛疾患から発熱性疾患にいたるま
で広範囲に使用されている医薬品であり、各種剤
形で用いられている。
しかしながら、従来より用いられているIP原
末は嵩が高く、流動性がわるくかつ水に不溶であ
るため、各種剤形の製剤の製造にさいし製剤化が
必らずしも容易でなく、取扱いが不便であるなど
の問題があり、またえられた製剤の崩壊性がわる
いなどの問題がある。従来においては、前記問題
の解決のために製剤中における賦形剤、崩壊剤な
どの量を多くしているが、そのため必然的に製剤
の大型化を余儀なくされている。とくに近年IP
の用量が増大する傾向にあり（１日量が600mgか
ら900〜1200mgへ）、IP製剤の小型化が重要な課
題となつている。かかる観点から、IP原末の嵩
の低減化、流動性の改善、およびその製剤におけ
る崩壊性の改善を達成することが希求されてい
る。
一般に粉体材料の嵩の低減化や流動性を改善す
る方法としては粉体材料をたとえばスラツグ打錠
による乾式造粒法あるいは水または有機溶剤を使
用する湿式造粒法などの方法で顆粒化することが
知られている。しかしながら、IP原末のごとく
嵩が高く、流動性のわるい粉体材料のばあい、前
記の乾式造粒法においてはIP原末単独ではもち
ろんのことこれに崩壊剤を添加しただけではスラ
ツグ打錠は困難であり、結合剤などの賦形剤を多
量に使用する必要があり、このため前記のごとく
製剤が大型化するという問題が生じる。また湿式
造粒法においても溶剤と賦形剤が必要であつて製
剤が大型化し、しかも工程が配合、練合、造粒、
乾燥と多く、煩雑で長時間を要しランニングコス
トが高くなるという問題がある。
しかるに本発明者らはIP原末の嵩の低減化、
流動性および崩壊性の改善を達成し、IP製剤を
小型化すべく鋭意研究を重ねた結果、IP原末を
加熱溶融したのち冷却固化し、ついで粉砕すると
きは嵩が低く、流動性および崩壊性にすぐれた
IP粒状物がえられること、およびこのIP粒状物
の製剤化するときはIP製剤の小型化がきわめて
容易に達成されうるというまつたく新たな事実を
見出し、本発明を完成するにいたつた。
すなわち本発明は、
(1) イブプロフエン単独またはこれと賦形剤およ
び崩壊剤の少なくとも１種との混合物を媒体を
不存在下で加熱溶融したのち冷却固化したもの
の粉砕物であつて、見掛比容積が9.3〜11.5
ml／５ｇ、安息角が40〜47゜、IP含有率が78％
（重量％、以下同様）以上である粒状物からな
ることを特徴とするIP含有粒状物、
(2) 前記IP含有粒状物を含有してなることを特
徴とする内服剤
に関する。
本発明のIP含有粒状物にはIP単独の粒状物、
IPと適宜の賦形剤との粒状物、IPと適宜の崩壊
剤との粒状物、さらにはIPと賦形剤と崩壊剤と
の粒状物が含まれる。また本発明にいう粒状物と
は粉状物をも含む概念である。
本発明のIP含有粒状物は見掛比容積が9.3〜
11.5ml／５ｇ、安息角が40〜47゜、IP含有率が78
％以上のものである。従来のIP原末は見掛比容
積が16ml／５ｇ以上、安息角が60゜以上であり、
これからにして、本発明のIP含有粒状物は嵩が
低くかつ流動性にすぐれていることがわかる。
従来のIP原末は単独では打錠が不可能であり、
多量の賦形剤を用いてはじめて打錠が可能であつ
たが、本発明のIP含有粒状物のうちIP単独の粒
状物のばあいそれ単独でも打錠が可能であるなど
IP単独でも製剤化が容易であり、製剤の小型化
が達成される。また本発明のIP含有粒状物のう
ちIPに加えて賦形剤を含有する粒状物のばあい
は賦形剤の量が22％未満と少なくても各種剤形の
製剤化が容易であり、製剤の小型化が達成され
る。たとえば本発明のIPと賦形剤との粒状物か
らえられる錠剤のばあい（IP含有量が100mgの錠
剤のばあい）、従来のIP錠剤にくらべて賦形剤量
にして65％減となり、杵径においても８mmから７
mmとなり、従来のIP錠剤にくらべて小型化され
ている。また本発明のIP単独またはIPと賦形剤
の混合物に加えて崩壊剤を含有する粒状物のばあ
いも同様に製剤の小型化が達成されるとともに、
えられる製剤は小型化されているにもかかわらず
崩壊性がすぐれているという特徴がある。
このように本発明のIP含有粒状物を用いるば
あいは製剤の小型化が達成されるのであるが、そ
れにともなつて従来のIP原末ではなしえなかつ
た高含有IP製剤の調製が可能である。たとえば
IP含有率が300mg〜400mg／錠の錠剤、IP含有率
が300mg〜400mg／カプセル（２号カプセル）のカ
プセル剤がはじめて可能となつた。
本発明のIP含有粒状物においては前記のごと
く製剤の小型化が達成され、それにともなつて賦
形剤、崩壊剤などの原料の使用量が低減され、ま
た製剤が小型であるため包装資材の量が低減さ
れ、運搬および保管が容易であるとともにそれら
の費用が低減される。このように本発明のIP含
有粒状物を用いるばあいは製剤化のスタートから
消費者へ渡る全流通過程を通した大巾なコストダ
ウンが可能となる。
しかして前記のごとき顕著な効果を奏するため
には見掛比容積が9.3〜11.5ml／５ｇ、なかんづ
く10.0〜11.0ml／５ｇ、安息角が40〜47゜、なかん
づく43〜47゜、IP含有率が78％以上であることが
必要である。見掛比容積が前記範囲より大きいば
あいは嵩が高く、本発明の所期の目的が達成され
ず、前記範囲より小さいばあいは粒状物の粒度が
大きすぎて製剤上好ましくない。安息角が前記範
囲より大きいと流動性がわるく製剤化が困難であ
り、前記範囲より小さいと粒状物の粒度が大きす
ぎて製剤上好ましくない。IP含有率が78％より
低いと製剤の小型化が達成されがたい。なお錠剤
に用いるばあいは79％以上、カプセル剤に用いる
ばあいは93％以上のIP含有率が好ましい。
本発明において所望により用いられる賦形剤と
してはたとえば微結晶性セルロース（カルボキシ
メチルセルロースナトリウムを含んでいてもよ
い）、スターチ、ヒドロキシプロピルスターチ、
ステアリン酸カルシウム、タルク、乳糖などがあ
げられる。本発明において所望により用いられる
崩壊剤としては、たとえば微結晶性セルロース
（カルボキシメチルセルロースナトリウムを含ん
でいてもよい）ヒドロキシプロピルスターチなど
があげられる。賦形剤および崩壊剤はIP含有率
が78％以上（錠剤に用いるばあいは好ましくは79
％以上、カプセル剤に用いるばあいは好ましくは
93％以上）になるように使用される。本発明の
IP含有粒状物は賦形剤および崩壊剤の量がこの
ように少なくても製剤化が容易であり、えられた
製剤の崩壊性がすぐれている。
本発明のIP含有粒状物はIP単独、さらに要す
ればこれに賦形剤および（または）崩壊剤を加え
て加熱溶融したのち冷却固化し、ついで粉砕し、
所望により適宜の粒度に分級することによりえら
れる。
本発明の方法は加熱溶融、冷却固化、粉砕とい
うきわめて簡便な工程よりなるものであり、用い
る溶融器および粉砕機も通常のものでもよい。本
発明の方法においてはかかる簡便な方法により従
来の乾式造粒法では賦形剤を使用しなければえら
れなかつたIP粒状物がIP単独またはこれに崩壊
剤のみを加えたものからもえられるという特徴が
ある。また本発明の方法においては水および有機
溶剤を使用しないため従来の湿式造粒法における
ごとき乾燥のための装置と時間が必要でなく、ま
た水分のバラツキなどもなく工程管理が容易であ
る。なお本発明の方法はIPの化学的性質に何ら
の影響も及ぼさないことが確認されている。
本発明の方法において、IPの加熱溶融はIPの
融点（約76℃）以上に加熱すればよい。加熱温度
の上限はIPなどの原料が分解、変質などを起さ
ない範囲であればとくに制限されないが、通常
100℃前後である。IPの溶融物に溶解しない賦形
剤、崩壊剤を用いるばあいにはこれらをIP溶融
物によく分散させる。溶融物の冷却固化は自然放
冷でも強制冷却（急冷および徐冷を含む）でも行
なえるが、特別の装置が不要で安価につく点かな
自然放冷が好ましい。固化物の粉砕は通常の粉砕
機で行なえばよく、たとえばロールクラツシヤ
ー、ハンマーミル、スクリーンミルなどが用いら
れる。粉砕の程度は前記特定範囲の見掛比容積、
安息角を有する粒状物をうる観点から12〜120メ
ツシユ（インチメツシユ、以下同様）、なかんづ
く20〜80メツシユとするのが好ましい。従来の
IP原末は微細で流動性がわるいため分級して適
宜の粒度のものをうるのが不可能であつたが、本
発明の方法によるときは分級により前記粒度範
囲、さらにはこの粒度範囲内でさらに粒度をそろ
えることができる。
本発明のIP含有粒状物は適宜の剤形に製剤化
して内服剤の非ステロイド抗炎症鎮痛解熱剤とし
て用いられる。剤形としては錠剤、カプセル剤、
粉剤、顆粒剤などがあげられ、これら製剤は一般
に用いられているキヤリヤーを用いあるいは用い
ることなく常法により製造することができる。と
くに錠剤およびカプセル剤として用いるとき本発
明におけるIP製剤の小型化、IPの高含有化とい
う特徴が顕著に発揮される。前述の賦形剤、崩壊
剤以外のキヤリヤーとしてはたとえば軽質無水ケ
イ酸などがあげられる。本発明のIP製剤には他
の抗炎症剤、鎮痛剤、解熱剤、鎮痛催眠剤、中枢
興奮剤、抗ヒスタミン剤、ビタミン剤などの薬剤
を配合してもよい。本発明のIP製剤は小型化あ
るいは高含有化されているにもかかわらず、従来
のIP製剤と同様な薬理効果を示す。
つぎに実施例をあげて本発明を説明する。
実施例 １
異なる３つのロツトＡ、ＢおよびＣのIP原末
をステンレス容器内に入れ、沸騰水浴中で加温し
た。IPの融点は76℃前後であるから、それ以上
の温度になるとステンレス容器内のIP原末は溶
融しはじめ、ついには完全な溶融液となつた。こ
の溶融液を硫酸紙上に流し込み、しばらくの間
（10〜20分程度）自然放冷して固化させた。この
固化物をスクリーンミルで粉砕し、24〜120メツ
シユの粒状物をえた。えられた粒状物の見掛比容
積は11.0ml／５ｇ、安息角は45゜であつた。
なお前記IP粒状物を分級して、第１表に示さ
れる粒度別のIP粒状物をえ、これらについて見
掛比容積を測定した。その結果を第１表に示す。
また安息角を小西式安息角測定機を用いて測定し
た。その結果を第２表に示す。
また前記分級前のIP粒状物について第３表に
示されるごとき一般試験を行なつた。
なお比較のために原料として用いた従来のIP
原末についての見掛比容積および安息角の値をそ
れぞれ第１表および第２表に併記する。なお従来
のIP原末は本発明のIP粒状物のごとく分級によ
り各粒度に分けることは不可能であつた。
The present invention relates to ibuprofen-containing granules and internal preparations containing the same. More specifically, the present invention relates to ibuprofen-containing granules having low bulk and excellent fluidity, and miniaturized internal preparations containing the ibuprofen-containing granules. Ibuprofen [chemical name: 2-(4'-isobutylphenyl)propionic acid] (hereinafter abbreviated as IP) is a drug that is used in a wide range of conditions, from inflammatory pain diseases to febrile diseases. used in the form However, the conventionally used IP bulk powder is bulky, has poor fluidity, and is insoluble in water, so it is not always easy to formulate it for the production of various dosage forms, and it is difficult to handle. There are problems such as inconvenience and poor disintegration of the resulting preparation. Conventionally, in order to solve the above-mentioned problems, the amount of excipients, disintegrants, etc. in the formulation has been increased, but this has inevitably forced the formulation to be larger. Especially in recent years IP
There is a tendency for the dosage of IP to increase (from 600 mg to 900-1200 mg per day), and miniaturization of IP preparations has become an important issue. From this point of view, it is desired to reduce the bulk of the IP bulk powder, improve its fluidity, and improve the disintegration properties of its formulation. In general, methods for reducing the bulk of powder materials and improving fluidity include granulating the powder materials using methods such as dry granulation using slug tableting or wet granulation using water or organic solvents. It is known. However, in the case of powder materials that are bulky and have poor fluidity, such as IP bulk powder, in the dry granulation method described above, not only the IP bulk powder alone but also the addition of a disintegrant to it cannot be used to form slug tablets. This is difficult and requires the use of large amounts of excipients such as binders, resulting in the problem of increased size of the preparation as described above. In addition, wet granulation requires solvents and excipients, making the formulation larger, and the steps include blending, kneading, granulation, and
There are problems in that it requires a lot of drying, is complicated, takes a long time, and increases running costs. However, the present inventors have attempted to reduce the bulk of the IP powder,
As a result of intensive research to improve fluidity and disintegration properties and to miniaturize IP formulations, we have found that when IP bulk powder is heated and melted, cooled and solidified, and then crushed, it has a low bulk, fluidity and disintegration properties. excellent in
We have now completed the present invention by discovering the new fact that IP granules can be obtained and that miniaturization of IP preparations can be achieved very easily when preparing the IP granules. That is, the present invention provides (1) a pulverized product obtained by heating and melting ibuprofen alone or a mixture thereof with at least one of an excipient and a disintegrant in the absence of a medium, and then cooling and solidifying the product, which has an apparent ratio of Volume is 9.3~11.5
ml/5g, angle of repose 40-47°, IP content 78%
(2) An internal preparation characterized by containing the IP-containing granules. The IP-containing granules of the present invention include granules containing IP alone,
It includes granules of IP and an appropriate excipient, granules of IP and an appropriate disintegrant, and further granules of IP, an excipient, and a disintegrant. Furthermore, the term "granular material" as used in the present invention is a concept that also includes powdered material. The IP-containing granules of the present invention have an apparent specific volume of 9.3~
11.5ml/5g, angle of repose 40-47°, IP content 78
% or more. Conventional IP bulk powder has an apparent specific volume of 16ml/5g or more and an angle of repose of 60° or more.
From this, it can be seen that the IP-containing granules of the present invention have low bulk and excellent fluidity. Conventional IP bulk powder cannot be tableted alone;
Although tableting was possible only with the use of a large amount of excipients, in the case of the IP-containing granules of the present invention, granules containing only IP can be tableted by themselves.
IP alone is also easy to formulate into formulations, and miniaturization of the formulation can be achieved. Furthermore, among the IP-containing granules of the present invention, in the case of granules containing excipients in addition to IP, it is easy to formulate various dosage forms even if the amount of excipients is as small as less than 22%. Miniaturization of the formulation is achieved. For example, in the case of a tablet obtained from the granules of IP and excipient of the present invention (in the case of a tablet with an IP content of 100 mg), the amount of excipient is reduced by 65% compared to a conventional IP tablet. , the diameter of the punch also varies from 8mm to 7mm.
mm, which is smaller than conventional IP tablets. In addition, in the case of the granular product containing a disintegrant in addition to the IP of the present invention alone or a mixture of IP and an excipient, the formulation can be similarly miniaturized, and
The resulting preparation is characterized by excellent disintegration properties despite its miniaturization. In this way, when using the IP-containing granules of the present invention, it is possible to miniaturize the formulation, but at the same time it is possible to prepare high-IP formulations that were not possible with conventional IP bulk powders. be. for example
For the first time, tablets with an IP content of 300 mg to 400 mg/tablet and capsules with an IP content of 300 mg to 400 mg/capsule (No. 2 capsule) have become possible. In the IP-containing granules of the present invention, the formulation can be made smaller as described above, and along with this, the amount of raw materials such as excipients and disintegrants can be reduced, and since the formulation is small, packaging materials can be reduced. The volume is reduced, making transportation and storage easier and reducing their cost. As described above, when using the IP-containing granules of the present invention, it is possible to significantly reduce costs throughout the entire distribution process from the start of formulation to the consumer. However, in order to produce the remarkable effects mentioned above, the apparent specific volume must be 9.3 to 11.5 ml/5 g, especially 10.0 to 11.0 ml/5 g, the angle of repose should be 40 to 47 degrees, especially 43 to 47 degrees, and the IP content should be must be 78% or more. If the apparent specific volume is larger than the above range, the bulk will be high and the intended purpose of the present invention will not be achieved, and if it is smaller than the above range, the particle size of the granules will be too large, which is undesirable in terms of formulation. If the angle of repose is larger than the above range, the fluidity will be poor and formulation will be difficult; if the angle of repose is smaller than the above range, the particle size of the granules will be too large, which is unfavorable for formulation. When the IP content is lower than 78%, it is difficult to achieve miniaturization of the formulation. The IP content is preferably 79% or more when used in tablets, and 93% or more when used in capsules. Excipients that may be used as desired in the present invention include, for example, microcrystalline cellulose (which may contain sodium carboxymethyl cellulose), starch, hydroxypropyl starch,
Examples include calcium stearate, talc, and lactose. Examples of disintegrants that may be used as desired in the present invention include microcrystalline cellulose (which may contain sodium carboxymethyl cellulose), hydroxypropyl starch, and the like. Excipients and disintegrants should have an IP content of at least 78% (preferably 79% if used in tablets).
% or more, preferably when used in capsules
93% or more). of the present invention
IP-containing granules can be easily formulated even with such small amounts of excipients and disintegrants, and the resulting formulations have excellent disintegration properties. The IP-containing granules of the present invention include IP alone, further adding excipients and/or disintegrants if necessary, heating and melting, cooling and solidifying, and then pulverizing.
It can be obtained by classifying it to an appropriate particle size, if desired. The method of the present invention consists of extremely simple steps of heating and melting, cooling and solidifying, and pulverization, and the melter and pulverizer used may also be ordinary ones. In the method of the present invention, by using such a simple method, IP granules, which could not be obtained without the use of excipients using conventional dry granulation methods, can be obtained from IP alone or by adding only a disintegrant to it. It has characteristics. Furthermore, since the method of the present invention does not use water or organic solvents, it does not require equipment and time for drying as in conventional wet granulation methods, and there is no variation in moisture content, making process control easy. It has been confirmed that the method of the present invention has no effect on the chemical properties of IP. In the method of the present invention, the IP may be heated to a temperature higher than the melting point of the IP (approximately 76° C.). There is no particular upper limit on the heating temperature as long as the raw materials such as IP do not decompose or change in quality, but usually
The temperature is around 100℃. When using excipients and disintegrants that do not dissolve in the IP melt, these are well dispersed in the IP melt. Although the molten material can be cooled and solidified by natural cooling or forced cooling (including rapid cooling and slow cooling), natural cooling is preferable because it requires no special equipment and is inexpensive. The solidified material may be pulverized using a conventional pulverizer, such as a roll crusher, hammer mill, screen mill, or the like. The degree of pulverization is determined by the apparent specific volume of the specified range,
From the viewpoint of obtaining a granular material having an angle of repose, it is preferable to use 12 to 120 meshes (inch meshes, hereinafter the same), particularly 20 to 80 meshes. Traditional
IP bulk powder is fine and has poor fluidity, so it has been impossible to classify it to obtain particles of appropriate particle size. However, when using the method of the present invention, it is possible to obtain particles with an appropriate particle size by classification. Furthermore, the particle size can be made uniform. The IP-containing granules of the present invention are formulated into an appropriate dosage form and used as an internally administered nonsteroidal anti-inflammatory analgesic and antipyretic agent. Dosage forms include tablets, capsules,
Examples include powders and granules, and these preparations can be manufactured by conventional methods with or without using commonly used carriers. In particular, when used as tablets and capsules, the features of the present invention, such as miniaturization of the IP formulation and high IP content, are clearly exhibited. Examples of carriers other than the above-mentioned excipients and disintegrants include light anhydrous silicic acid. The IP preparation of the present invention may contain other drugs such as anti-inflammatory agents, analgesics, antipyretics, analgesic hypnotics, central stimulants, antihistamines, and vitamins. Although the IP preparation of the present invention is smaller in size or has a higher content, it exhibits the same pharmacological effects as conventional IP preparations. Next, the present invention will be explained with reference to Examples. Example 1 Three different lots A, B and C of IP bulk powder were placed in a stainless steel container and heated in a boiling water bath. The melting point of IP is around 76°C, so when the temperature exceeds that, the IP bulk powder in the stainless steel container begins to melt, and eventually becomes a complete molten liquid. This melt was poured onto parchment paper and left to cool naturally for a while (about 10 to 20 minutes) to solidify. This solidified material was ground with a screen mill to obtain 24 to 120 mesh granules. The apparent specific volume of the resulting granules was 11.0 ml/5 g, and the angle of repose was 45°. The IP granules were classified to obtain IP granules of different particle sizes shown in Table 1, and the apparent specific volumes of these were measured. The results are shown in Table 1.
The angle of repose was also measured using a Konishi angle of repose measuring device. The results are shown in Table 2. Further, general tests as shown in Table 3 were conducted on the IP granules before classification. For comparison, conventional IP used as raw material
The apparent specific volume and angle of repose values for the bulk powder are also listed in Tables 1 and 2, respectively. In addition, it was impossible to separate the conventional IP bulk powder into various particle sizes by classification like the IP granules of the present invention.
【表】【table】
【表】【table】
【表】【table】
【表】
第１表から、本発明のIP粒状物は従来のIP原
末にくらべて嵩が小さくなつていることがわか
る。第２表から、本発明のIP粒状物は従来のIP
原末にくらべて流動性がすぐれていることがわか
る。また第３表から、本発明のIP粒状物は従来
のIP原末と化学的性質がかわらないことがわか
る。このことから、本発明の方法がIP粒状物の
化学的性質に何らの影響も及ぼさないことがわか
る。
実施例 ２
従来のIP原末300ｇ、アビセルRC591（旭化成工
業(株)製微結晶セルロース、アビセル：登録商標）
15ｇおよびステアリン酸カルシウム２ｇを実施例
１と同様にして加熱溶融した。アビセルRC591お
よびステアリン酸カルシウムは溶融しないので
IPの溶融液に充分分散させた。えられた溶融混
合物を硫酸紙上に流し込み、自然放冷により固化
させた。この固化物を実施例１と同じ粉砕機で粉
砕して24〜120メツシユの粒状物をえた。えられ
た粒状物の見掛比容積は10.8ml／５ｇ、安息角は
44.5゜であつた。
前記粒状物317ｇにアエロジル（日本アエロジ
ル(株)製軽質無水ケイ酸）１ｇを加えて混合し、え
られた混合物のうち318mg（IPを300mg含有する）
を２号硬カプセルに通常の方法で充填した。えら
れたカプセル剤は第９改正日本薬局方の製剤総則
に記載されているカプセル剤の試験のすべてに合
格した。
なお従来のIP原末300mgを通常の方法でカプセ
ルに充填するためには前記で用いたカプセルより
も大きい０〜00号以上の硬カプセルを使用しなけ
ればならなかつた。
実施例 ３
従来のIP原末400ｇ、アビセルRC591の16ｇお
よびステアリン酸カルシウム１ｇを実施例１と同
様に加熱溶融したアビセルRC591およびステアリ
ン酸カルシウムは溶融しないのでIPの溶融液に
充分分散させた。えられた溶融混合物を硫酸紙上
に流し込み、自然放冷により固化させた。この固
化物を実施例１と同じ粉砕機で粉砕して28〜120
メツシユの粒状物をえた。えられた粒状物の見掛
比容積は11.0ml／ｇ、安息角は44.5゜であつた。
前記粒状物417ｇにアエロジル１ｇを加えて混
合し、えられた混合物のうち418mg（IPを400mg
含有する）を１号硬カプセルに通常の方法で充填
した。えられたカプセル剤は前記カプセル剤の試
験のすべてに合格した。
なお従来のIP原末400mgを通常の方法でカプセ
ルに充填するためには前記で用いたカプセルより
も大きい00号以上の硬カプセルを使用しなければ
ならなかつた。
実施例 ４
従来のIP原末100ｇ、アビセルRC591の10ｇ、
ヒドキシプロピルスターチ15ｇおよびステアリン
酸カルシウム１ｇを実施例１と同様に加熱溶融し
た。アビセルRC591、ヒドキシプロピルスターチ
およびステアリン酸カルシウムは溶融しないので
IPの溶融液に充分分散させた。えられた溶融混
合物を硫酸紙上に流し込み、自然放冷により固化
させた。この固化物を実施例１と同じ粉砕機で粉
砕して20〜120メツシユの粒状物をえた。えられ
た粒状物の見掛比容積は10.5ml／５ｇ、安息角は
46゜であつた。
前記粒状物を通常の直打式打錠法により打錠し
て第４表に示す重量、寸法の錠剤（IP含有量100
mg）を調製した。比較のためにIP含有量が100mg
の従来の錠剤についての重量、寸法を第４表に併
記する。なお前記錠剤は第９改正日本薬局方の製
剤総則に記載されている錠剤の試験にすべて合格
した。Table 1 shows that the IP granules of the present invention have a smaller bulk than the conventional IP bulk powder. From Table 2, it can be seen that the IP granules of the present invention are different from the conventional IP granules.
It can be seen that the fluidity is superior to that of bulk powder. Furthermore, Table 3 shows that the chemical properties of the IP granules of the present invention are the same as those of conventional IP bulk powder. This shows that the method of the invention has no effect on the chemical properties of the IP granules. Example 2 300 g of conventional IP bulk powder, Avicel RC591 (microcrystalline cellulose manufactured by Asahi Kasei Corporation, Avicel: registered trademark)
15 g and 2 g of calcium stearate were heated and melted in the same manner as in Example 1. Since Avicel RC591 and calcium stearate do not melt
It was sufficiently dispersed in the IP melt. The resulting molten mixture was poured onto parchment paper and allowed to cool naturally to solidify. This solidified product was pulverized using the same pulverizer as in Example 1 to obtain 24 to 120 mesh granules. The apparent specific volume of the obtained granules is 10.8ml/5g, and the angle of repose is
It was 44.5°. 1 g of Aerosil (light anhydrous silicic acid manufactured by Nippon Aerosil Co., Ltd.) was added to 317 g of the granules and mixed, and 318 mg of the resulting mixture (containing 300 mg of IP) was obtained.
was filled into No. 2 hard capsules in the usual manner. The obtained capsules passed all of the tests for capsules listed in the General Rules for Preparations of the Ninth Edition of the Japanese Pharmacopoeia. In addition, in order to fill 300 mg of the conventional IP bulk powder into capsules by the usual method, it was necessary to use hard capsules of size 0 to 00 or larger, which are larger than the capsules used above. Example 3 400 g of conventional IP bulk powder, 16 g of Avicel RC591, and 1 g of calcium stearate were heated and melted in the same manner as in Example 1. Since Avicel RC591 and calcium stearate did not melt, they were sufficiently dispersed in the IP melt. The resulting molten mixture was poured onto parchment paper and allowed to cool naturally to solidify. This solidified product was crushed with the same crusher as in Example 1 to give a powder of 28 to 120
I got mesh granules. The apparent specific volume of the resulting granules was 11.0 ml/g, and the angle of repose was 44.5°. 1 g of Aerosil was added to 417 g of the granules and mixed, and 418 mg of the resulting mixture (400 mg of IP
) was filled into No. 1 hard capsules in a conventional manner. The resulting capsules passed all of the capsule tests described above. In order to fill 400 mg of the conventional IP bulk powder into capsules by the usual method, it was necessary to use hard capsules of No. 00 or larger, which are larger than the capsules used above. Example 4 100g of conventional IP bulk powder, 10g of Avicel RC591,
15 g of hydroxypropyl starch and 1 g of calcium stearate were heated and melted in the same manner as in Example 1. Avicel RC591, hydroxypropyl starch and calcium stearate do not melt
It was sufficiently dispersed in the IP melt. The resulting molten mixture was poured onto parchment paper and allowed to cool naturally to solidify. This solidified product was pulverized using the same pulverizer as in Example 1 to obtain 20 to 120 mesh granules. The apparent specific volume of the obtained granules is 10.5ml/5g, and the angle of repose is
It was 46 degrees. The granules were compressed using a normal direct compression method to form tablets with the weight and dimensions shown in Table 4 (IP content: 100
mg) was prepared. IP content is 100mg for comparison
The weight and dimensions of the conventional tablets are also listed in Table 4. The tablets passed all tests for tablets listed in the General Rules for Preparations of the Ninth Edition of the Japanese Pharmacopoeia.
【表】
第４表から、本発明の錠剤は従来品にくらべて
小型化が達成されていることがわかる。
実施例 ５
実施例４でえられた見掛比容積10.5ml／５ｇ、
安息角46゜のIP含有粒状物を通常の直打式打錠法
により打錠して第５表に示す重量、寸法の錠剤
（IP含有量200mg）を調製した。比較のためにIP
含有量が200mgの従来の錠剤についての重量、寸
法を第５表に併記する。なお前記錠剤は前述の錠
剤の試験にすべて合格した。[Table] Table 4 shows that the tablets of the present invention are more compact than conventional products. Example 5 Apparent specific volume obtained in Example 4: 10.5ml/5g,
The IP-containing granules having an angle of repose of 46° were compressed using a conventional direct compression method to prepare tablets (IP content: 200 mg) having the weights and dimensions shown in Table 5. IP for comparison
The weight and dimensions of conventional tablets containing 200 mg are also listed in Table 5. Note that the tablet passed all of the tablet tests described above.
【表】
第５表から、本発明の錠剤は従来品にくらべて
小型化が達成されていることがわかる。
実施例 ６
実施例４でえられた見掛比容積10.5ml／５ｇ、
安息角46゜のIP含有粒状物を通常の直打式打錠法
により打錠して第６表に示す重量、寸法の錠剤
（IP含有量300mg）を調製した。比較のためにIP
含有量が300mgの従来の錠剤についての重量、寸
法を第６表に併記する。なお前記錠剤は前述の錠
剤の試験にすべて合格した。Table 5 shows that the tablets of the present invention are more compact than conventional products. Example 6 Apparent specific volume obtained in Example 4: 10.5 ml/5 g,
IP-containing granules having an angle of repose of 46° were compressed using a conventional direct compression method to prepare tablets (IP content: 300 mg) having the weights and dimensions shown in Table 6. IP for comparison
The weight and dimensions of conventional tablets with a content of 300 mg are also listed in Table 6. Note that the tablet passed all of the tablet tests described above.
【表】
第６表から、本発明の錠剤は従来品にくらべて
小型化が達成されていることがわかる。
実施例 ７
実施例４でえられた見掛比容積10.5ml／５ｇ、
安息角46゜のIP含有粒状物を通常の直打式打錠法
により打錠して第７表に示す重量、寸法の錠剤
（IP含有量400mg）を調製した。比較のためにIP
含有量が400mgの従来の錠剤についての重量、寸
法を第７表に併記する。なお前記錠剤は前述の錠
剤の試験にすべて合格した。[Table] Table 6 shows that the tablets of the present invention are more compact than conventional products. Example 7 Apparent specific volume obtained in Example 4: 10.5ml/5g,
The IP-containing granules having an angle of repose of 46° were compressed using a conventional direct compression method to prepare tablets (IP content: 400 mg) having the weights and dimensions shown in Table 7. IP for comparison
The weight and dimensions of conventional tablets with a content of 400 mg are also listed in Table 7. Note that the tablet passed all of the tablet tests described above.
【表】
第７表から、本発明の錠剤は従来品にくらべて
小型化が達成されていることがわかる。
実施例 ８
実施例２でえられたIP含有量300mgのカプセル
剤と従来のIP含有量100mgの錠剤とをそれぞれビ
ーグル犬５匹に経口投与し、投与後１時間、２時
間、３時間、６時間、10時間、24時間後における
IPの血中濃度を測定した。投与量はIP基準量で
30mg／Kgとした。１週間休薬後、実施例２のカプ
セル剤を投与した犬５匹（群）には従来の錠剤
を、従来の錠剤を投与した犬５匹（群）には実
施例２のカプセル剤を投与し、前記と同様にして
IPの血中濃度を測定した。結果を第８〜９表に
示す。[Table] Table 7 shows that the tablets of the present invention are more compact than conventional products. Example 8 Capsules with an IP content of 300 mg obtained in Example 2 and conventional tablets with an IP content of 100 mg were each orally administered to five beagle dogs, and 1 hour, 2 hours, 3 hours, and 6 hours after administration. hours, 10 hours, 24 hours later
The blood concentration of IP was measured. Dosage is IP standard dose.
The amount was set at 30mg/Kg. After one week of drug withdrawal, the 5 dogs (group) that received the capsules of Example 2 received the conventional tablets, and the 5 dogs (groups) that received the conventional tablets received the capsules of Example 2. and do the same as above
The blood concentration of IP was measured. The results are shown in Tables 8-9.
【表】【table】
【表】【table】
【表】
第８〜９表から明らかなごとく、本発明のIP
カプセル剤と従来のIP錠剤とでは血中濃度推移
において有意の差が認められなかつた。したがつ
て本発明のIPカプセル剤は現在医薬品として販
売されているIP錠剤と同様な薬理効果を奏しう
るものである。
実施例６でえられたIP含有量300mgの錠剤に
TC―５（ヒドロキシプロピルメチルセルロース）
コーテングを20％施した錠剤と従来のIP含有量
100mgの錠剤とをそれぞれビーグル犬５匹に経口
投与し、投与後１時間、２時間、３時間、６時
間、10時間、24時間後におけるIPの血中濃度を
測定した。投与量はIP基準で30mg／Kgとした。
１週間休薬後、実施例６の錠剤を投与した犬５匹
（群）には従来の錠剤を、従来の錠剤を投与し
た犬５匹（群）には実施例６の錠剤を投与し、
前記と同様にしてIPの血中濃度を測定した。結
果を第10〜11表に示す。[Table] As is clear from Tables 8 and 9, the IP of the present invention
No significant difference was observed in blood concentration over time between capsules and conventional IP tablets. Therefore, the IP capsule of the present invention can exhibit the same pharmacological effects as IP tablets currently sold as pharmaceuticals. The tablets with an IP content of 300 mg obtained in Example 6
TC-5 (Hydroxypropyl methylcellulose)
Tablets with 20% coating and conventional IP content
A 100 mg tablet was orally administered to five beagle dogs, and blood concentrations of IP were measured 1 hour, 2 hours, 3 hours, 6 hours, 10 hours, and 24 hours after administration. The dose was 30 mg/Kg based on IP.
After one week of drug withdrawal, the 5 dogs (group) that had been administered the tablets of Example 6 were administered the conventional tablets, and the 5 dogs (group) that had been administered the conventional tablets were administered the tablets of Example 6.
The blood concentration of IP was measured in the same manner as above. The results are shown in Tables 10-11.
【表】【table】
【表】
第10〜11表から明らかなごとく、本発明のIP
錠剤と従来のIP錠剤とでは血中濃度推移におい
て有意の差が認められなかつた。したがつて本発
明のIP錠剤は現在医薬品として販売されている
IP錠剤と同等な薬理効果を奏しうるものである。[Table] As is clear from Tables 10 and 11, the IP of the present invention
No significant difference was observed in blood concentration over time between the tablet and the conventional IP tablet. Therefore, the IP tablet of the present invention is currently being sold as a pharmaceutical product.
It has the same pharmacological effect as IP tablets.
Claims (1)
び崩壊剤の少なくとも１種との混合物を媒体の不
存在下で加熱溶融したのち冷却固化したものの粉
砕物であつて、見掛比容積が9.3〜11.5ml／５ｇ、
安息角が40〜47゜、イブプロフエン含有率が78重
量％以上である粒状物からなることを特徴とする
イブプロフエン含有粒状物。 ２ 見掛比容積が10.0〜11.0ml／５ｇ、安息角が
43〜47゜である特許請求の範囲第１項記載のイブ
プロフエン含有粒状物。 ３ 前記粒状物がイブプロフエン単独の粒状物で
ある特許請求の範囲第１項または第２項記載のイ
ブプロフエン含有粒状物。 ４ 前記粒状物がイブプロフエンと賦形剤および
崩壊剤の少なくとも１種との混合物の粒状物であ
る特許請求の範囲第１項または第２項記載のイブ
プロフエン含有粒状物。 ５ イブプロフエン含有率が79重量％以上であつ
て、錠剤の製造に用いられる特許請求の範囲第１
項または第２項記載のイブプロフエン含有粒状
物。 ６ イブプロフエン含有率が93重量％以上であつ
て、カプセル剤の製造に用いられる特許請求の範
囲第１項または第２項記載のイブプロフエン含有
粒状物。 ７ イブプロフエン単独またはこれと賦形剤およ
び崩壊剤の少なくとも１種との混合物を媒体の不
存在下で加熱溶融したのち冷却固化したものの粉
砕物であつて、見掛比容積が9.3〜11.5ml／５ｇ、
安息角が40〜47゜、イブプロフエン含有率が78重
量％以上であるイブプロフエン含有粒状物を含有
してなることを特徴とする内服剤。 ８ イブプロフエン含有粒状物の見掛比容積が
10.0〜11.0ml／５ｇ、安息角が43〜47゜である特許
請求の範囲第７項記載の内服剤。 ９ イブプロフエン含有粒状物がイブプロフエン
単独の粒状物である特許請求の範囲第７項または
第８項記載の内服剤。 １０ イブプロフエン含有粒状物がイブプロフエ
ンと賦形剤および崩壊剤の少なくとも１種との混
合物の粒状物である特許請求の範囲第７項または
第８項記載の内服剤。 １１ イブプロフエン含有粒状物におけるイブプ
ロフエン含有率が79重量％以上であり、錠剤の形
態である特許請求の範囲第７項または第８項記載
の内服剤。 １２ イブプロフエン含有粒状物におけるイブプ
ロフエン含有率が93重量％以上であり、カプセル
剤の形態である特許請求の範囲第７項または第８
項記載の内服剤。[Scope of Claims] 1. A pulverized product obtained by heating and melting ibuprofen alone or a mixture of it and at least one of an excipient and a disintegrant in the absence of a medium, cooling and solidifying the product, which has an apparent specific volume. is 9.3-11.5ml/5g,
An ibuprofen-containing granule comprising a granule having an angle of repose of 40 to 47° and an ibuprofen content of 78% by weight or more. 2 The apparent specific volume is 10.0 to 11.0ml/5g, and the angle of repose is
Ibuprofen-containing granules according to claim 1, which have an angle of 43 to 47°. 3. The ibuprofen-containing granular material according to claim 1 or 2, wherein the granular material is a granular material containing ibuprofen alone. 4. The ibuprofen-containing granule according to claim 1 or 2, wherein the granule is a granule of a mixture of ibuprofen and at least one of an excipient and a disintegrant. 5 Ibuprofen content rate is 79% by weight or more and Claim 1 is used for manufacturing tablets
The ibuprofen-containing granular material according to item 1 or 2. 6. The ibuprofen-containing granules according to claim 1 or 2, which have an ibuprofen content of 93% by weight or more and are used for manufacturing capsules. 7 Ibuprofen alone or a mixture of it and at least one of an excipient and a disintegrant is heated and melted in the absence of a medium, then cooled and solidified, and the resulting product has an apparent specific volume of 9.3 to 11.5 ml/ 5g,
An internal medicine characterized by containing ibuprofen-containing granules having an angle of repose of 40 to 47 degrees and an ibuprofen content of 78% by weight or more. 8 The apparent specific volume of the ibuprofen-containing granules is
The internal medicine according to claim 7, which has a dosage of 10.0 to 11.0 ml/5 g and an angle of repose of 43 to 47°. 9. The internal medicine according to claim 7 or 8, wherein the ibuprofen-containing granules are granules containing ibuprofen alone. 10. The internal preparation according to claim 7 or 8, wherein the ibuprofen-containing granules are granules of a mixture of ibuprofen and at least one of an excipient and a disintegrant. 11. The internal medicine according to claim 7 or 8, wherein the ibuprofen content in the ibuprofen-containing granules is 79% by weight or more and is in the form of a tablet. 12 The ibuprofen content of the ibuprofen-containing granules is 93% by weight or more and is in the form of a capsule, claim 7 or 8.
Oral medications listed in section.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2434480A JPS56120616A (en) | 1980-02-27 | 1980-02-27 | Ibuprofen-containing granule, its preparation, and internal medicine comprising it |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2434480A JPS56120616A (en) | 1980-02-27 | 1980-02-27 | Ibuprofen-containing granule, its preparation, and internal medicine comprising it |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56120616A JPS56120616A (en) | 1981-09-22 |
| JPS6346726B2 true JPS6346726B2 (en) | 1988-09-19 |
Family
ID=12135561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2434480A Granted JPS56120616A (en) | 1980-02-27 | 1980-02-27 | Ibuprofen-containing granule, its preparation, and internal medicine comprising it |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS56120616A (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8716975D0 (en) * | 1987-07-17 | 1987-08-26 | Boots Co Plc | Therapeutic agents |
| US5240712A (en) * | 1987-07-17 | 1993-08-31 | The Boots Company Plc | Therapeutic agents |
| DE3833446A1 (en) * | 1988-10-01 | 1990-04-05 | Hoechst Ag | METHOD FOR THE PRODUCTION OF MEDICAMENT PARTICLES WITH IMPROVED FLUID, STORAGE AND FORMULATION PROPERTIES AND MEDICAMENTS CONTAINING SUCH MEDICAMENT PARTICLES |
| DE3833448A1 (en) * | 1988-10-01 | 1990-04-12 | Hoechst Ag | METHOD OF OBTAINING IBUPROFEN FOR DIRECT TESTING |
| PT1235558E (en) * | 1999-12-09 | 2006-09-29 | Boots Co Plc | THERAPEUTIC AGENTS |
| RU2403013C2 (en) * | 2005-12-16 | 2010-11-10 | Ханми Фарм. Ко., Лтд. | Solid dispersion containing active component with low fusion temperature, and oral tablet containing it |
| WO2013143688A1 (en) | 2012-03-26 | 2013-10-03 | Glatt Ag | Taste-masked ibuprofen granules |
| CN105816434B (en) * | 2016-04-19 | 2019-09-17 | 山东新华制药股份有限公司 | Ibuprofen granule and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS52111533A (en) * | 1976-03-12 | 1977-09-19 | Kanebo Ltd | Preparation of fine powder of ibuprophene |
-
1980
- 1980-02-27 JP JP2434480A patent/JPS56120616A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS52111533A (en) * | 1976-03-12 | 1977-09-19 | Kanebo Ltd | Preparation of fine powder of ibuprophene |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56120616A (en) | 1981-09-22 |
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