JPH10218761A - Multiple unit type sustained release tablet - Google Patents
Multiple unit type sustained release tabletInfo
- Publication number
- JPH10218761A JPH10218761A JP9024594A JP2459497A JPH10218761A JP H10218761 A JPH10218761 A JP H10218761A JP 9024594 A JP9024594 A JP 9024594A JP 2459497 A JP2459497 A JP 2459497A JP H10218761 A JPH10218761 A JP H10218761A
- Authority
- JP
- Japan
- Prior art keywords
- sustained release
- active ingredient
- unit type
- sustained
- granules
- 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.)
- Granted
Links
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 14
- 238000013268 sustained release Methods 0.000 claims abstract description 53
- 239000012730 sustained-release form Substances 0.000 claims abstract description 53
- 239000008187 granular material Substances 0.000 claims abstract description 45
- 239000004480 active ingredient Substances 0.000 claims abstract description 22
- 239000007771 core particle Substances 0.000 claims abstract description 9
- 239000011159 matrix material Substances 0.000 claims abstract description 9
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 8
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 8
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 8
- 239000000843 powder Substances 0.000 claims abstract description 8
- 239000002245 particle Substances 0.000 claims abstract description 6
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 5
- 239000003826 tablet Substances 0.000 abstract description 30
- 239000000203 mixture Substances 0.000 abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 15
- 229940079593 drug Drugs 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 10
- 239000011248 coating agent Substances 0.000 abstract description 8
- 238000000576 coating method Methods 0.000 abstract description 8
- 235000019441 ethanol Nutrition 0.000 abstract description 7
- 239000010410 layer Substances 0.000 abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002904 solvent Substances 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 238000010828 elution Methods 0.000 abstract description 3
- 238000007906 compression Methods 0.000 abstract description 2
- 230000006835 compression Effects 0.000 abstract description 2
- 238000000748 compression moulding Methods 0.000 abstract description 2
- 230000008021 deposition Effects 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 239000011241 protective layer Substances 0.000 abstract 1
- 230000002459 sustained effect Effects 0.000 abstract 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 12
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 12
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 12
- 238000007922 dissolution test Methods 0.000 description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 8
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 8
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 8
- 239000008108 microcrystalline cellulose Substances 0.000 description 8
- 229940016286 microcrystalline cellulose Drugs 0.000 description 8
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 7
- 235000012239 silicon dioxide Nutrition 0.000 description 7
- 238000000034 method Methods 0.000 description 5
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 229960001985 dextromethorphan Drugs 0.000 description 4
- AKNNEGZIBPJZJG-MSOLQXFVSA-N (-)-noscapine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-MSOLQXFVSA-N 0.000 description 3
- YQSHYGCCYVPRDI-UHFFFAOYSA-N (4-propan-2-ylphenyl)methanamine Chemical compound CC(C)C1=CC=C(CN)C=C1 YQSHYGCCYVPRDI-UHFFFAOYSA-N 0.000 description 3
- DBAKFASWICGISY-DASCVMRKSA-N Dexchlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 DBAKFASWICGISY-DASCVMRKSA-N 0.000 description 3
- 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 3
- 241000593312 Selfia Species 0.000 description 3
- AKNNEGZIBPJZJG-UHFFFAOYSA-N alpha-noscapine Natural products CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-UHFFFAOYSA-N 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229960003782 dextromethorphan hydrobromide Drugs 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 3
- 229960004708 noscapine Drugs 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229960002335 bromhexine hydrochloride Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- YRSGDLIATOURQO-UHFFFAOYSA-N ethyl 4-acetyl-5-oxohexanoate Chemical compound CCOC(=O)CCC(C(C)=O)C(C)=O YRSGDLIATOURQO-UHFFFAOYSA-N 0.000 description 2
- 238000012812 general test Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- KYHQZNGJUGFTGR-LURJTMIESA-N 7-[(2s)-2-hydroxypropyl]-1,3-dimethylpurine-2,6-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C[C@@H](O)C KYHQZNGJUGFTGR-LURJTMIESA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241001106067 Atropa Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 102220590441 Epoxide hydrolase 3_S30D_mutation Human genes 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- DYWNLSQWJMTVGJ-KUSKTZOESA-N Phenylpropanolamine hydrochloride Chemical compound Cl.C[C@H](N)[C@H](O)C1=CC=CC=C1 DYWNLSQWJMTVGJ-KUSKTZOESA-N 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- NTCYWJCEOILKNG-ROLPUNSJSA-N [(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-dimethylazanium;chloride Chemical compound Cl.CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 NTCYWJCEOILKNG-ROLPUNSJSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 229960003556 aminophylline Drugs 0.000 description 1
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 1
- UCDKONUHZNTQPY-UHFFFAOYSA-N bromhexine hydrochloride Chemical compound Cl.C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N UCDKONUHZNTQPY-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000012792 core layer Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940073563 dl- methylephedrine hydrochloride Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 1
- 229960000514 ethenzamide Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 229960002305 phenylpropanolamine hydrochloride Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229960004767 proxyphylline Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は徐放性顆粒と粉末部
からなるマルチプルユニットタイプ徐放性錠剤に関す
る。[0001] The present invention relates to a multiple unit type sustained release tablet comprising a sustained release granule and a powder portion.
【０００２】[0002]
【従来の技術】活性薬物の溶出速度を制御する製剤は、
シングルユニットタイプとマルチプルユニットタイプに
分類することができる。シングルユニットタイプは主に
錠剤、マルチプルユニットタイプは主にカプセル剤、顆
粒剤の形態を執ることが多いが、マルチプルユニットタ
イプの製剤はシングルユニットタイプに比べ、(1)有効
成分の吸収の変動が少ない、(2)溶出の再現性がとりや
すい、(3)２種以上の有効成分への応用が可能などの優
れた特徴を有することから、徐放化製剤としてはマルチ
プルユニットタイプが望ましい。また、カプセル剤や顆
粒剤の形態での服薬は困難であるため、錠剤の形態をと
ることが望ましい。しかしながら、従来のマルチプルユ
ニットタイプの徐放化錠剤は、核粒子に薬物層を被覆し
次いでこの表面を徐放化剤により被覆した顆粒を徐放顆
粒とし、これと粉末部を混合し打錠することによって得
られることから、打錠時に徐放顆粒の徐放化膜が破壊さ
れ薬物の溶出制御が困難になることが多い。2. Description of the Related Art Formulations for controlling the dissolution rate of active drugs include
It can be classified into single unit type and multiple unit type. Single unit type often takes the form of tablets, multiple unit type mainly takes the form of capsules and granules, but multiple unit type preparations have (1) less fluctuation in absorption of active ingredients than single unit type, (2 ) Multiple unit type is preferred as a sustained release preparation because it has excellent characteristics that it can be easily applied to two or more kinds of active ingredients, because it has easy reproducibility of dissolution. In addition, it is difficult to take a capsule or granule, so that it is desirable to take a tablet form. However, the conventional multiple unit type sustained release tablet comprises a core layer coated with a drug layer, and then granules whose surface is coated with a sustained release agent to form sustained release granules. Thus, in tableting, the sustained-release film of the sustained-release granules is broken, and it is often difficult to control the dissolution of the drug.
【０００３】このような問題に対して、顆粒を低融点油
脂類及び主薬を含む素顆粒及び放出制御膜からなる不定
形顆粒並びに粉末部からなるマルチプルユニットタイプ
錠剤が提案されている（特開平７−３１６０４２号）。
しかしながら、本技術では、徐放性顆粒が不定形である
ために、均一なコーティング被膜を施すことが困難であ
り、安定した溶出速度の徐放性錠剤が得にくい。また、
ジプロフィリンなどようなの水溶性の薬物については溶
出の制御をすることが困難であった。[0003] In order to solve such problems, there has been proposed a multiple unit type tablet comprising granules comprising a low melting point oil or fat and an active ingredient, irregular granules comprising a controlled release film, and a powder portion (Japanese Patent Laid-Open No. 7-1995). No. 316042).
However, according to the present technology, it is difficult to form a uniform coating film because the sustained-release granules are amorphous, and it is difficult to obtain a sustained-release tablet having a stable dissolution rate. Also,
It has been difficult to control the elution of water-soluble drugs such as diprofylline.
【０００４】[0004]
【発明が解決しようとする課題】本発明の目的は、打錠
工程の圧縮や有効成分の水に対する溶解度に起因する溶
出速度の変化が少なく、かつ成分含有率が均一な優れた
マルチプルユニットタイプの徐放化錠剤を提供すること
にある。SUMMARY OF THE INVENTION An object of the present invention is to provide an excellent multiple unit type which has a small change in the dissolution rate due to the compression in the tableting process and the solubility of the active ingredient in water, and has a uniform component content. It is to provide a release tablet.
【０００５】[0005]
【課題を解決するための手段】本発明者らは、核粒子上
に、ある特定の徐放化基剤と有効成分でマトリックスを
形成させることによって上記課題を解決できることを見
いだし、本発明を完成した。すなわち、本発明は、徐放
性顆粒及び粉末部からなるマルチプルユニットタイプ徐
放性錠剤において、徐放性顆粒が核粒子を被覆する徐放
化基剤と有効成分のマトリックスからなることを特徴と
するマルチプルユニットタイプ徐放性錠剤である。Means for Solving the Problems The present inventors have found that the above problems can be solved by forming a matrix on a core particle with a specific sustained-release base and an active ingredient, and completed the present invention. did. That is, the present invention is characterized in that, in a multiple unit type sustained release tablet comprising a sustained release granule and a powder part, the sustained release granule comprises a sustained release base covering core particles and a matrix of an active ingredient. It is a multiple unit type sustained release tablet.
【０００６】本発明における徐放化基剤はエチルセルロ
ース又はメタアクリル酸コポリマーである。このうちエ
チルセルロースがより好ましい。メタアクリル酸コポリ
マーとしては、商品名オイドラギットＮＥ３０Ｄ、同Ｒ
Ｓ３０Ｄ、同ＲＬ３０Ｄ等が例示されるが、好ましく
は、オイドラギットＮＥ３０Ｄである。また、これらの
徐放化基剤は単独で用いても、併せ用いても良い。[0006] The sustained release base in the present invention is ethyl cellulose or methacrylic acid copolymer. Of these, ethyl cellulose is more preferred. Examples of the methacrylic acid copolymer include Eudragit NE30D and R
Although S30D and RL30D are exemplified, Eudragit NE30D is preferable. Further, these sustained release bases may be used alone or in combination.
【０００７】また、徐放化基剤の溶剤としては、水及び
低級アルコールの混合物又は低級アルコールが好まし
く、エチルアルコールが最も好ましい。溶剤の使用量は
積層に適した使用量に設定することができる。また、そ
れらの溶剤に徐放化基剤は溶解又は分散されていなけれ
ばならず、更に徐放化基剤溶液に薬物は均一に分散され
ていなければならない。このために撹拌機などの装置を
用い、良く撹拌して用いることが効果的である。As the solvent for the sustained release base, a mixture of water and a lower alcohol or a lower alcohol is preferable, and ethyl alcohol is most preferable. The amount of the solvent used can be set to an amount suitable for lamination. The sustained release base must be dissolved or dispersed in these solvents, and the drug must be uniformly dispersed in the sustained release base solution. For this purpose, it is effective to use a device such as a stirrer and stir well.
【０００８】有効成分の種類は特に限定を受けない。例
えば、ジプロフィリン、臭化水素酸デキストロメトルフ
ァン、塩酸フェニルプロパノールアミン、ベラドンナ
（総）アルカロイド、アセトアミノフェン、テオフィリ
ン、サリチル酸ナトリウム、アスピリン、イブプロフェ
ン、ノスカピン、ｄｌ−塩酸メチルエフェドリン、リン
酸ジヒドロコデイン、エテンザミド、塩酸ブロムヘキシ
ン、ｄ−マレイン酸クロルフェニラミン、アミノフィリ
ン、プロキシフィリン、カフェインなどを挙げることが
できる。これら有効成分は２種以上を混合して用いても
よい。なお、有効成分の粒子径は核粒子への付着率を高
めるために、平均粒子径を20μm以下（好ましくは10μm
以下）とすることが望ましい。[0008] The kind of the active ingredient is not particularly limited. For example, diprofylline, dextromethorphan hydrobromide, phenylpropanolamine hydrochloride, belladonna (total) alkaloid, acetaminophen, theophylline, sodium salicylate, aspirin, ibuprofen, noscapine, dl-methylephedrine hydrochloride, dihydrocodeine phosphate, ethenzamide, Bromohexine hydrochloride, d-chlorpheniramine maleate, aminophylline, proxyphylline, caffeine and the like can be mentioned. These active ingredients may be used as a mixture of two or more kinds. In addition, the particle diameter of the active ingredient is 20 μm or less (preferably 10 μm
The following is desirable.
【０００９】更に有効成分の性質により望まれる溶出速
度は異なるが、本発明では有効成分と徐放化基剤との配
合比を変えることにより、又は徐放化基剤がエチルセル
ロースである場合は、エチルセルロースの分子量を変え
ることにより、自在に制御することが可能である。Further, the desired dissolution rate varies depending on the nature of the active ingredient, but in the present invention, by changing the compounding ratio of the active ingredient and the sustained release base, or when the sustained release base is ethyl cellulose, By changing the molecular weight of ethylcellulose, it can be controlled freely.
【００１０】核粒子上に徐放化基剤と有効成分の混合物
でマトリックスを形成させる方法としては、複合型コー
ティング機、転動流動コーティング機及び流動層コーテ
ィング機等を利用することができる。また、必要に応じ
キュアリングを行うことも効果的である。キュアリング
は徐放化基剤の軟化点以上で行うことが良い。この核粒
子には、結晶セルロース球形顆粒（商品名：セルフィ
ア）、乳糖・結晶セルロース球形顆粒（商品名：ノンパ
レル）などを用いることができる。なお、核粒子の大き
さとしては、平均粒子径１００〜１０００μｍの範囲が
好ましい。As a method of forming a matrix on the core particles with a mixture of the sustained-release base and the active ingredient, a composite coating machine, a tumbling fluid coating machine, a fluidized bed coating machine and the like can be used. It is also effective to perform curing as needed. The curing is preferably performed at a temperature equal to or higher than the softening point of the sustained-release base. As the core particles, crystalline cellulose spherical granules (trade name: Selfia), lactose / crystalline cellulose spherical granules (trade name: nonpareil) and the like can be used. The size of the core particles is preferably in the range of an average particle diameter of 100 to 1000 μm.
【００１１】粉末部としては、微結晶セルロース、軽質
無水ケイ酸、低置換度ヒドロキシプロピルセルロース、
ヒドロキシプロピルセルロース、乳糖、コーンスターチ
などを混合して用いる。As the powder part, microcrystalline cellulose, light anhydrous silicic acid, low-substituted hydroxypropylcellulose,
Hydroxypropyl cellulose, lactose, corn starch and the like are mixed and used.
【００１２】本発明においては、圧縮成型による溶出速
度の変化をより少なくするために、徐放性顆粒の外層を
更に水溶性高分子の保護皮膜で被覆することが本発明の
効果を高める。この場合用いられる水溶性高分子として
は、ヒドロキシプロピルメチルセルロース、ヒドロキシ
プロピルセルロースなどを挙げることができる。この水
溶性高分子は徐放性顆粒に対して１５重量％以下とする
ことが好ましい。In the present invention, the effect of the present invention is enhanced by further coating the outer layer of the sustained-release granules with a protective film of a water-soluble polymer in order to further reduce the change in the dissolution rate due to compression molding. Examples of the water-soluble polymer used in this case include hydroxypropylmethylcellulose, hydroxypropylcellulose and the like. The content of the water-soluble polymer is preferably 15% by weight or less based on the sustained-release granules.
【００１３】[0013]
【発明の効果】本発明における徐放化顆粒は、従来の薬
物層を被覆し次いでこの表面を徐放化剤により被覆した
顆粒とは異なり、徐放化基剤と有効成分（薬物）の混合
物でマトリックスを形成させているので、粉末部を混合
し打錠するにあたってマトリックス層が破壊され難く、
錠剤の硬度を挙げることが可能である。また、本発明の
マルチプルユニットタイプの徐放化錠剤は、有効成分の
水に対する溶解度に起因する溶出速度の変化が少なく、
また有効成分含有率は均一である。The sustained-release granules according to the present invention are different from granules in which a conventional drug layer is coated and the surface thereof is coated with a sustained-release agent, and a mixture of a sustained-release base and an active ingredient (drug). Since the matrix is formed by mixing, the matrix layer is hard to be broken when mixing the powder part and tableting,
It is possible to mention the hardness of the tablet. Further, the multiple unit type sustained release tablet of the present invention has a small change in the dissolution rate due to the solubility of the active ingredient in water,
The active ingredient content is uniform.
【００１４】[0014]
【実施例】以下には実施例を挙げて具体的に本発明を説
明する。 （実施例１）95%エタノールにジプロフィリンを分散さ
せ、コロイドミルを用いて粉砕し、平均粒子径を20μm
以下に調製した。次いでエチルセルロースを溶解させ
た。ボトムスプレー型流動層コーティング機（パウレッ
ク社製、ＧＰＣＧ−１）を用いてこの分散液を核粒子
（セルフィアCP-305）に積層させ、徐放性顆粒とした。
この徐放性顆粒４０部に、微結晶セルロース３０部、軽
質無水ケイ酸２部、低置換度ヒドロキシプロピルセルロ
ース２部及びヒドロキシプロピルセルロース３部を混合
し、ロータリー打錠機にて打錠（打錠圧１.５ｔ）を行
い、１錠２９０ｍｇの錠剤を製造した。EXAMPLES The present invention will be specifically described below with reference to examples. (Example 1) Diprofylline was dispersed in 95% ethanol and pulverized using a colloid mill, and the average particle size was 20 µm.
It was prepared as follows. Then the ethyl cellulose was dissolved. This dispersion was laminated on core particles (Selfia CP-305) using a bottom spray type fluidized bed coating machine (GPCG-1 manufactured by Powrex) to obtain sustained release granules.
To 40 parts of the sustained-release granules, 30 parts of microcrystalline cellulose, 2 parts of light silicic anhydride, 2 parts of low-substituted hydroxypropylcellulose and 3 parts of hydroxypropylcellulose were mixed, and the mixture was compressed with a rotary tableting machine. A tablet pressure of 1.5 t) was performed to produce a tablet of 290 mg per tablet.
【００１５】（実施例２）実施例１と同様にして、表１
に示した組成にて徐放性顆粒を調製した。この徐放性顆
粒４０部に対し、微結晶セルロース３０部、軽質無水ケ
イ酸２部、低置換度ヒドロキシプロピルセルロース２部
及びヒドロキシプロピルセルロース３部を混合し、ロー
タリー打錠機にて打錠（打錠圧１.５ｔ）を行い、１錠
２９０ｍｇの錠剤を製造した。Example 2 In the same manner as in Example 1, Table 1
The sustained release granules were prepared according to the composition shown in Table 1. To 40 parts of these sustained-release granules, 30 parts of microcrystalline cellulose, 2 parts of light anhydrous silicic acid, 2 parts of low-substituted hydroxypropylcellulose and 3 parts of hydroxypropylcellulose were mixed, and tableted with a rotary tableting machine ( A tableting pressure of 1.5 t) was performed to produce a tablet of 290 mg per tablet.
【００１６】（実施例３）実施例１と同様にして、表１
に示した組成にて徐放性顆粒を調製した。この徐放性顆
粒４０部に対し、微結晶セルロース３０部、軽質無水ケ
イ酸２部、低置換度ヒドロキシプロピルセルロース２部
及びヒドロキシプロピルセルロース３部を混合し、ロー
タリー打錠機にて打錠（打錠圧１.５ｔ）を行い、１錠
２９０ｍｇの錠剤を製造した。Example 3 In the same manner as in Example 1, Table 1
The sustained release granules were prepared according to the composition shown in Table 1. To 40 parts of these sustained-release granules, 30 parts of microcrystalline cellulose, 2 parts of light anhydrous silicic acid, 2 parts of low-substituted hydroxypropylcellulose and 3 parts of hydroxypropylcellulose were mixed, and tableted with a rotary tableting machine ( A tableting pressure of 1.5 t) was performed to produce a tablet of 290 mg per tablet.
【００１７】（実施例４）実施例１と同様にして、表１
に示した組成にて徐放性顆粒を調製した。この徐放性顆
粒４０部に対し、微結晶セルロース３０部、軽質無水ケ
イ酸２部、低置換度ヒドロキシプロピルセルロース２部
及びヒドロキシプロピルセルロース３部を混合し、ロー
タリー打錠機にて打錠（打錠圧１.５ｔ）を行い、１錠
２９０ｍｇの錠剤を製造した。(Example 4) In the same manner as in Example 1, Table 1
The sustained release granules were prepared according to the composition shown in Table 1. To 40 parts of these sustained-release granules, 30 parts of microcrystalline cellulose, 2 parts of light anhydrous silicic acid, 2 parts of low-substituted hydroxypropylcellulose and 3 parts of hydroxypropylcellulose were mixed, and tableted with a rotary tableting machine ( A tableting pressure of 1.5 t) was performed to produce a tablet of 290 mg per tablet.
【００１８】[0018]
【表１】 [Table 1]
【００１９】（実施例５）活性薬物としてデキストロメ
トルファンを用いた他は、実施例１と同様にして徐放性
顆粒を調製した（表２参照）。但し、デキストロメトル
ファンは95%エタノールに溶解することから、コロイド
ミルは用いなかった。その徐放性顆粒に対し微結晶セル
ロース３０部、軽質無水ケイ酸２部、低置換度ヒドロキ
シプロピルセルロース２部及びヒドロキシプロピルセル
ロース３部を混合し、ロータリー打錠機にて打錠（打錠
圧１.５ｔ）を行い、１錠２９０ｍｇの錠剤を製造し
た。Example 5 Controlled release granules were prepared in the same manner as in Example 1 except that dextromethorphan was used as the active drug (see Table 2). However, since dextromethorphan was dissolved in 95% ethanol, a colloid mill was not used. 30 parts of microcrystalline cellulose, 2 parts of light anhydrous silicic acid, 2 parts of low-substituted hydroxypropylcellulose and 3 parts of hydroxypropylcellulose are mixed with the sustained-release granules, and the mixture is compressed with a rotary tableting machine (tablet pressure). 1.5t) was performed to produce a tablet of 290 mg per tablet.
【００２０】（実施例６）実施例５と同様にして、表２
の組成にて徐放性顆粒を調製した。この徐放性顆粒４０
部に対し、微結晶セルロース３０部、軽質無水ケイ酸２
部、低置換度ヒドロキシプロピルセルロース２部及びヒ
ドロキシプロピルセルロース３部を混合し、ロータリー
打錠機にて打錠（打錠圧１.５ｔ）を行い、１錠２９０
ｍｇの錠剤を製造した。(Embodiment 6) As in Embodiment 5, Table 2
The sustained-release granules were prepared with the following composition. These sustained release granules 40
Parts, microcrystalline cellulose 30 parts, light anhydrous silicic acid 2
Parts, 2 parts of low-substituted hydroxypropylcellulose and 3 parts of hydroxypropylcellulose, and tableting (tablet pressure: 1.5 t) with a rotary tableting machine.
mg tablets were produced.
【００２１】[0021]
【表２】 [Table 2]
【００２２】（実施例７）実施例４で得られた徐放性顆
粒３部と、実施例５で得られた徐放性顆粒１部に対し、
下記組成の粉末部を流動層造粒機（フロイント産業 Ｆ
ＬＯ−１型）を用いて、５％ヒドロキシプロピルセルロ
ース／精製水１０００ｇを噴霧して造粒した速放性顆粒
４部を混合し、ステアリン酸マグネシウムを混合物に対
して０.０５％加えてロータリー打錠機にて、打錠（打
錠圧１.５ｔ）を行い、１錠２９０ｍｇの錠剤を製造し
た。Example 7 3 parts of the sustained release granules obtained in Example 4 and 1 part of the sustained release granules obtained in Example 5
A powder part having the following composition is mixed with a fluidized bed granulator (Freund Sangyo F.
Using LO-1 type), 4 parts of quick-release granules granulated by spraying 5 g of hydroxypropylcellulose / 1000 g of purified water were mixed, and 0.05% of magnesium stearate was added to the mixture, and the mixture was rotary-dried. Tableting (tablet pressure: 1.5 t) was performed with a tableting machine to produce one tablet of 290 mg.
【００２３】 成分 （ｇ） ジプロフイリン １００ ノスカピン ４０ 臭化水素酸デキストロメトルファン １８ ｄ−マレイン酸クロルフェニラミン ４ 塩酸ブロムヘキシン ８ 乳糖 １７５ 結晶セルロース ５０ 軽質無水ケイ酸 １２ 低置換度ヒドロキシプロピルセルロース １０８ （比較例）精製水（１０００g）にジプロフィリン（５
００g）とヒドロキシプロピルセルロース（３０g）を溶
解し、ボトムスプレー型流動層コーティング機（ＧＰＣ
Ｇ−１）を用いてセルフィアCP-305（１０００g）に噴
霧造粒して素顆粒を作製した。次いで、エチルセルロー
ス（７センチホ゜アス゛）（１５０g）を９５％エタノール溶液
（１３５０g）に溶解させ、素顆粒にコーティングし、
徐放性顆粒を作製した。この徐放性顆粒４０部に対し、
微結晶セルロース３０部、軽質無水ケイ酸２部、低置換
度ヒドロキシプロピルセルロース２部及びヒドロキシプ
ロピルセルロース３部を混合し、ロータリー打錠機にて
打錠（打錠圧１.５ｔ）を行い、１錠２９０ｍｇの錠剤
を作製した。Ingredients (g) Diprofyrin 100 Noscapine 40 Dextromethorphan hydrobromide 18 d-Chlorpheniramine maleate 4 Bromhexine hydrochloride 8 Lactose 175 Crystalline cellulose 50 Light silicic anhydride 12 Lightly substituted hydroxypropylcellulose 108 (Comparative example) ) Purified water (1000g)
00g) and hydroxypropylcellulose (30g) were dissolved in a bottom spray type fluidized bed coating machine (GPC
Using G-1), spray granulation was performed on Selfia CP-305 (1000 g) to prepare elementary granules. Next, ethyl cellulose (7 centipores) (150 g) was dissolved in a 95% ethanol solution (1350 g), and coated on elementary granules.
Sustained-release granules were produced. For 40 parts of the sustained release granules,
30 parts of microcrystalline cellulose, 2 parts of light anhydrous silicic acid, 2 parts of low-substituted hydroxypropylcellulose and 3 parts of hydroxypropylcellulose were mixed, and the mixture was compressed with a rotary tableting machine (tablet pressure: 1.5 t). One tablet of 290 mg was prepared.
【００２４】試験例１ 実施例４、５及び比較例で製造した錠剤について溶出試
験を行った。溶出試験は日本薬局方一般試験法の溶出試
験法第２法に準じて行った。Test Example 1 Dissolution tests were performed on the tablets produced in Examples 4 and 5 and Comparative Example. The dissolution test was performed according to the dissolution test method 2 of the Japanese Pharmacopoeia General Test Method.
【００２５】打錠前後の徐放性顆粒成分であるジプロフ
ィリンの溶出試験結果を図１に示した。打錠前後の徐放
性顆粒成分であるデキストロメトルファンの溶出試験結
果を図２に示した。また、比較例で製造した錠剤につい
て打錠前後の徐放性顆粒成分であるジプロフィリンの溶
出試験結果を図３に示した。FIG. 1 shows the results of the dissolution test of the sustained release granule component diprofylline before and after tableting. FIG. 2 shows the dissolution test results of dextromethorphan, which is a sustained release granule component before and after tableting. FIG. 3 shows the dissolution test results of diprofilin, which is a sustained-release granule component, before and after tableting of the tablets produced in Comparative Examples.
【００２６】試験例２ 実施例７で製造した錠剤について重量変動及び含量均一
性試験を行った。試験法は日本薬局方一般試験法に準じ
て行った。結果を以下に示した。Test Example 2 The tablets prepared in Example 7 were subjected to a weight variation and content uniformity test. The test method was performed according to the Japanese Pharmacopoeia general test method. The results are shown below.
【００２７】 重量変動 ｃｖ １.２５％ 含量均一性 ジプロフィリン ２.４３ ノスカピン ２.１９ 臭化水素酸デキストロメトルファン ２.６０ ｄ−マレイン酸クロルフェニラミン ２.６２ 塩酸ブロムヘキシン ３.０２。Weight variation cv 1.25% content uniformity diprofylline 2.43 noscapine 2.19 dextromethorphan hydrobromide 2.60 d-chlorpheniramine maleate 2.62 bromhexine hydrochloride 3.02.
【図１】 実施例４で製造した錠剤の打錠前後のジプロ
フィリンの溶出試験結果を示す。FIG. 1 shows the results of a diprofilin dissolution test before and after tableting of a tablet produced in Example 4.
【図２】 実施例５で製造した錠剤の打錠前後のデキス
トロメトルファンの溶出試験結果を示す。FIG. 2 shows the results of a dissolution test of dextromethorphan before and after tableting of the tablet produced in Example 5.
【図３】 比較例で製造した錠剤の打錠前後のジプロフ
ィリンの溶出試験結果を示す。FIG. 3 shows the dissolution test results of diprofylline before and after tableting of the tablets produced in Comparative Examples.
Claims (5)
ルユニットタイプ徐放性錠剤において、徐放性顆粒が核
粒子を被覆する徐放化基剤と有効成分のマトリックスか
らなることを特徴とするマルチプルユニットタイプ徐放
性錠剤。1. A multiple unit type sustained release tablet comprising a sustained release granule and a powder part, wherein the sustained release granule comprises a sustained release base covering core particles and a matrix of an active ingredient. Unit type sustained release tablet.
れていることを特徴とする請求項１記載のマルチプルユ
ニットタイプ徐放性錠剤。2. The multiple unit type sustained release tablet according to claim 1, wherein the sustained release granules are further coated with a water-soluble polymer.
請求項１又は２記載のマルチプルユニットタイプ徐放性
錠剤。3. The multiple unit type sustained release tablet according to claim 1, wherein the sustained release base is ethyl cellulose.
求項１〜３のいずれかに記載のマルチプルユニットタイ
プ徐放性錠剤。4. The multiple unit type sustained release tablet according to claim 1, wherein the particle size of the active ingredient is 20 μm or less.
求項１〜３のいずれかに記載のマルチプルユニットタイ
プ徐放性錠剤。5. The multiple unit type sustained release tablet according to claim 1, wherein the particle size of the active ingredient is 10 μm or less.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP02459497A JP3870470B2 (en) | 1997-02-07 | 1997-02-07 | Multiple unit type sustained release tablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP02459497A JP3870470B2 (en) | 1997-02-07 | 1997-02-07 | Multiple unit type sustained release tablets |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH10218761A true JPH10218761A (en) | 1998-08-18 |
| JP3870470B2 JP3870470B2 (en) | 2007-01-17 |
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ID=12142491
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
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| Country | Link |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999053905A1 (en) * | 1998-04-17 | 1999-10-28 | Taisho Pharmaceutical Co., Ltd. | Multiple-unit sustained release tablets |
| WO2002087549A1 (en) * | 2001-04-25 | 2002-11-07 | Taisho Pharmaceutical Co., Ltd. | Multiple unit type sustained-release tablets |
| JP2002370968A (en) * | 2001-06-12 | 2002-12-24 | Towa Yakuhin Kk | Medicament-containing sustained-release granule and tablet containing the same |
| JP2003511403A (en) * | 1999-10-13 | 2003-03-25 | アクゾ・ノベル・エヌ・ベー | A new formulation of mirtazapine |
| WO2005023222A1 (en) * | 2003-09-05 | 2005-03-17 | Ssp Co., Ltd. | Pharmaceutical composition with improved solubility and fluidity |
| JP2011184461A (en) * | 2000-02-28 | 2011-09-22 | Takeda Chem Ind Ltd | Compressed solid preparation |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4367722B2 (en) * | 1998-04-17 | 2009-11-18 | 大正製薬株式会社 | Multiple unit type sustained release tablets |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6130534A (en) * | 1984-07-23 | 1986-02-12 | Tooa Eiyoo Kk | Hydrogenated ergot-alkaloid preparation and its preparation |
| JPH01249718A (en) * | 1988-03-30 | 1989-10-05 | Tomoaki Fukuda | Production of microcapsule |
| JPH02174931A (en) * | 1988-09-27 | 1990-07-06 | Takeda Chem Ind Ltd | Nucleate granule and its preparation |
| JPH0592918A (en) * | 1991-03-07 | 1993-04-16 | Takeda Chem Ind Ltd | Nucleated powder and its production |
| JPH06293635A (en) * | 1993-04-08 | 1994-10-21 | Amano Pharmaceut Co Ltd | Impact-resistant enteric granule and tablet containing the same |
| WO1995010264A1 (en) * | 1993-10-12 | 1995-04-20 | Tokyo Tanabe Company Limited | Tablet containing enteric granules |
| JPH07126153A (en) * | 1993-11-04 | 1995-05-16 | Ota Seiyaku Kk | Granule for intracolic release type phamaceutical preparation |
| JPH07165568A (en) * | 1993-09-21 | 1995-06-27 | Takeda Chem Ind Ltd | Idebenone granule and its production |
| JPH07330585A (en) * | 1994-06-01 | 1995-12-19 | Nippon Roussel Kk | Granules for sustained release disopyramide preparation and production thereof |
-
1997
- 1997-02-07 JP JP02459497A patent/JP3870470B2/en not_active Expired - Fee Related
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6130534A (en) * | 1984-07-23 | 1986-02-12 | Tooa Eiyoo Kk | Hydrogenated ergot-alkaloid preparation and its preparation |
| JPH01249718A (en) * | 1988-03-30 | 1989-10-05 | Tomoaki Fukuda | Production of microcapsule |
| JPH02174931A (en) * | 1988-09-27 | 1990-07-06 | Takeda Chem Ind Ltd | Nucleate granule and its preparation |
| JPH0592918A (en) * | 1991-03-07 | 1993-04-16 | Takeda Chem Ind Ltd | Nucleated powder and its production |
| JPH06293635A (en) * | 1993-04-08 | 1994-10-21 | Amano Pharmaceut Co Ltd | Impact-resistant enteric granule and tablet containing the same |
| JPH07165568A (en) * | 1993-09-21 | 1995-06-27 | Takeda Chem Ind Ltd | Idebenone granule and its production |
| WO1995010264A1 (en) * | 1993-10-12 | 1995-04-20 | Tokyo Tanabe Company Limited | Tablet containing enteric granules |
| JPH07126153A (en) * | 1993-11-04 | 1995-05-16 | Ota Seiyaku Kk | Granule for intracolic release type phamaceutical preparation |
| JPH07330585A (en) * | 1994-06-01 | 1995-12-19 | Nippon Roussel Kk | Granules for sustained release disopyramide preparation and production thereof |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999053905A1 (en) * | 1998-04-17 | 1999-10-28 | Taisho Pharmaceutical Co., Ltd. | Multiple-unit sustained release tablets |
| US6558700B1 (en) | 1998-04-17 | 2003-05-06 | Taisho Pharmaceutical Co., Ltd. | Multiple-unit sustained release tablets |
| JP2003511403A (en) * | 1999-10-13 | 2003-03-25 | アクゾ・ノベル・エヌ・ベー | A new formulation of mirtazapine |
| JP2011184461A (en) * | 2000-02-28 | 2011-09-22 | Takeda Chem Ind Ltd | Compressed solid preparation |
| WO2002087549A1 (en) * | 2001-04-25 | 2002-11-07 | Taisho Pharmaceutical Co., Ltd. | Multiple unit type sustained-release tablets |
| JP2002370968A (en) * | 2001-06-12 | 2002-12-24 | Towa Yakuhin Kk | Medicament-containing sustained-release granule and tablet containing the same |
| WO2005023222A1 (en) * | 2003-09-05 | 2005-03-17 | Ssp Co., Ltd. | Pharmaceutical composition with improved solubility and fluidity |
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| Publication number | Publication date |
|---|---|
| JP3870470B2 (en) | 2007-01-17 |
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