JPH04346919A - Production of sustained release tablet - Google Patents
Production of sustained release tabletInfo
- Publication number
- JPH04346919A JPH04346919A JP15103191A JP15103191A JPH04346919A JP H04346919 A JPH04346919 A JP H04346919A JP 15103191 A JP15103191 A JP 15103191A JP 15103191 A JP15103191 A JP 15103191A JP H04346919 A JPH04346919 A JP H04346919A
- Authority
- JP
- Japan
- Prior art keywords
- tablet
- sustained release
- soluble cellulose
- nonionic water
- cellulose ether
- 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
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 229920003086 cellulose ether Polymers 0.000 claims abstract description 21
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 15
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 15
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000001263 FEMA 3042 Substances 0.000 claims abstract description 14
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims abstract description 14
- 229920002258 tannic acid Polymers 0.000 claims abstract description 14
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 claims abstract description 14
- 229940033123 tannic acid Drugs 0.000 claims abstract description 14
- 235000015523 tannic acid Nutrition 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 3
- 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 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 abstract description 20
- 239000003814 drug Substances 0.000 abstract description 19
- 229940079593 drug Drugs 0.000 abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 9
- 239000011159 matrix material Substances 0.000 abstract description 7
- 238000013268 sustained release Methods 0.000 abstract description 7
- 239000012730 sustained-release form Substances 0.000 abstract description 7
- 229920002678 cellulose Polymers 0.000 abstract description 3
- 239000001913 cellulose Substances 0.000 abstract description 3
- 230000001276 controlling effect Effects 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 10
- 238000010828 elution Methods 0.000 description 10
- 238000000034 method Methods 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 2
- 229960000514 ethenzamide Drugs 0.000 description 2
- 150000002170 ethers Chemical group 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
- 238000006116 polymerization reaction Methods 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical group NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【０００１】0001
【産業上の利用分野】本発明は薬物の錠剤からの放出を
一定の割合で行なうマトリックス型徐放性錠剤の製造方
法、とくにはゲルマトリックス型徐放性錠剤の製造方法
に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing matrix-type sustained-release tablets in which drugs are released from the tablet at a constant rate, and more particularly to a method for producing gel-matrix-type sustained-release tablets.
【０００２】0002
【従来の技術】徐放性錠剤は薬物を持続的に放出するこ
とにより薬効を長時間維持し患者の服用回数を減少させ
たり、また血中濃度が一定値以上になると毒性や副作用
を伴う薬物において、その血中濃度を一定値以下に制御
したりすることを目的に研究されてきた有用な製剤であ
る。従来の徐放性錠剤には薬物を水溶性高分子やワック
スと打錠したマトリックス型や即溶性部分と徐放性部分
とを混合して打錠したスパスタブ型などがある。マトリ
ックス型徐放錠は水の浸透に伴って生ずる薬物の濃度勾
配を駆動力として溶出するもので拡散律速型ともいわれ
ているが、これには水溶性高分子を使ったゲルマトリッ
クス型とワックスを使ったワックスマトリックス型のも
のが多くみられる。ゲルマトリックス型のものはヒドロ
キシプロピルメチルセルロース（以下ＨＰＭＣとする）
単独、またはＨＰＭＣとメチルセルロース（以下ＭＣと
する）、カルボキシメチルセルロースのナトリウム塩（
以下Ｎａ−ＣＭＣとする）などとの混合基剤を主薬とと
もに打錠するもので、特開昭 ５８−１１０５１３号、
特開昭５８−１７４３１１号公報に示されている。また
、ＨＰＭＣをタンニン酸あるいはアクリル酸系ポリマー
と噴霧乾燥して用いる改良方法が「第７回製剤と粒子設
計シンポジウム講演要旨集第１６５ 頁」に示されてい
る。一方、ワックスマトリックス型のものは主薬をワッ
クス処理して得られた打錠末を製錠化するもので、特開
昭５６−１４０９１号公報に示されている。しかし、ゲ
ルマトリックス型において特に水溶性の高い主薬の場合
には、ゲルを形成する基剤を多量に使用しなければ、そ
の溶出を制御することができず、またその改良型では利
点はあるが、工程が長く操作が煩雑となる。さらに、ワ
ックスマトリックス型においては、本来体内の消化液中
ではほとんど溶解も膨潤もしないワックスを使用するた
め、その溶出の制御が難しくわずかな工程の変化で溶出
量が変動し易いという欠点がある。[Prior Art] Sustained-release tablets maintain drug efficacy over a long period of time by continuously releasing drugs, reducing the number of times patients have to take them, and drugs that cause toxicity and side effects when the blood concentration exceeds a certain level. It is a useful preparation that has been studied for the purpose of controlling its blood concentration below a certain value. Conventional sustained-release tablets include matrix-type tablets in which a drug is compressed with a water-soluble polymer or wax, and spasta tab-type tablets in which a rapidly dissolving portion and a sustained-release portion are mixed and compressed. Matrix-type sustained-release tablets elute using the driving force of the concentration gradient of the drug that occurs as water permeates, and are also called diffusion-limited tablets. Many wax matrix types are used. The gel matrix type is hydroxypropyl methylcellulose (hereinafter referred to as HPMC)
Alone, or HPMC and methylcellulose (hereinafter referred to as MC), sodium salt of carboxymethylcellulose (
This is a method in which a mixed base such as Na-CMC (hereinafter referred to as Na-CMC) is compressed together with the main drug.
This is disclosed in Japanese Patent Application Laid-Open No. 58-174311. In addition, an improved method of spray-drying HPMC with tannic acid or acrylic acid-based polymers is shown in ``7th Formulation and Particle Design Symposium Abstracts, Page 165.'' On the other hand, the wax matrix type is a tablet made from a tablet powder obtained by treating the main drug with wax, and is disclosed in JP-A-56-14091. However, in the case of a gel matrix type drug with particularly high water solubility, its dissolution cannot be controlled unless a large amount of gel-forming base is used, and although improved versions have advantages, , the process is long and the operation is complicated. Furthermore, the wax matrix type uses wax that hardly dissolves or swells in the body's digestive juices, so it has the disadvantage that it is difficult to control its elution and the amount of elution tends to fluctuate with slight changes in the process.
【０００３】0003
【発明が解決しようとする課題】したがって、本発明の
目的は比較的少量のゲル基剤の添加で薬物の溶出を一定
に制御することのできる徐放性錠剤の製造方法を提供す
るにある。SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a method for producing sustained-release tablets in which the dissolution of a drug can be controlled at a constant level by adding a relatively small amount of gel base.
【０００４】0004
【課題を解決するための手段】本発明者らは上記課題の
解決のため鋭意検討した結果、非イオン性水溶性セルロ
ースエーテルにタンニン酸を添加することにより、比較
的少ない量の非イオン性セルロースエーテルの配合量で
も徐放性の優れた錠剤が得られることを見出し、本発明
を完成させたものである。すなわち、本発明による徐放
性錠剤の製造方法は非イオン性水溶性セルロースエーテ
ル、タンニン酸および主薬を混合し、打錠することを要
旨とするものである。[Means for Solving the Problems] As a result of intensive studies by the present inventors to solve the above problems, the present inventors have found that by adding tannic acid to nonionic water-soluble cellulose ether, a relatively small amount of nonionic cellulose can be reduced. The present invention was completed based on the discovery that tablets with excellent sustained release properties can be obtained even when the amount of ether is added. That is, the gist of the method for producing sustained-release tablets according to the present invention is to mix nonionic water-soluble cellulose ether, tannic acid, and the active ingredient, and then tablet.
【０００５】以下、本発明の詳細について説明すると、
本発明で用いられる非イオン性水溶性セルロースエーテ
ルとしてはＨＰＭＣ、ＭＣまたはヒドロキシプロピルセ
ルロース（以下ＨＰＣとする）が好ましく、これらは単
独または２種以上の組み合わせとして使用される。これ
らの水溶性セルロースエーテルは水に接するとゲルを形
成し、そのゲル層から主薬を拡散によって放出する特性
を持つものである。とくにＨＰＭＣとＨＰＣとはゲルの
形成性に優れているため本発明に適している。さらに、
これらにおいて重合度（水溶液粘度）の高いものは、水
との接触によって形成されるゲル層が重合度の低いもの
に比べて強く、主薬の溶出速度を抑制する性質が大きい
ため、これらを適当に選択することにより目的に応じた
溶出特性の錠剤を得ることができる。[0005] The details of the present invention will be explained below.
The nonionic water-soluble cellulose ether used in the present invention is preferably HPMC, MC or hydroxypropyl cellulose (hereinafter referred to as HPC), and these are used alone or in combination of two or more. These water-soluble cellulose ethers form a gel when they come into contact with water, and have the property of releasing the main drug from the gel layer by diffusion. In particular, HPMC and HPC are suitable for the present invention because they have excellent gel forming properties. moreover,
Among these, those with a high degree of polymerization (aqueous solution viscosity) have a stronger gel layer formed by contact with water than those with a low degree of polymerization, and have a greater ability to suppress the elution rate of the main drug. Depending on the selection, tablets with dissolution characteristics suited to the purpose can be obtained.
【０００６】この非イオン性水溶性セルロースエーテル
の添加量は、目的とする徐放性能によって異なるが、通
常は錠剤に対し１０〜４０重量％、とくには１５〜３０
重量％が好ましい。これが１０重量％未満では溶出の初
期に錠剤の崩壊が起きて一度に大量の薬物が放出され、
薬物の血中濃度を一定に制御できなくなって徐放錠とし
ての役割が果せなくなる。またこれが４０重量％を超え
ると溶出後半の溶出速度の低下が著しくなる。なお、こ
れらのマトリックス基剤は上記の様に比較的多量に添加
されるため、Ｎａ−ＣＭＣなどのイオン性セルロースエ
ーテル類は主薬と反応する恐れがあるので、本発明に適
用することができない。[0006] The amount of nonionic water-soluble cellulose ether added varies depending on the desired sustained release performance, but is usually 10 to 40% by weight, particularly 15 to 30% by weight based on the tablet.
Weight percent is preferred. If it is less than 10% by weight, the tablet will disintegrate at the beginning of dissolution and a large amount of drug will be released at once.
It becomes impossible to control the blood concentration of the drug at a constant level, making it impossible to fulfill its role as a sustained-release tablet. Moreover, if this exceeds 40% by weight, the elution rate in the latter half of elution will be significantly reduced. Note that since these matrix bases are added in relatively large amounts as described above, ionic cellulose ethers such as Na-CMC may react with the main drug, and therefore cannot be applied to the present invention.
【０００７】また、本発明で使用されるタンニン酸は市
販のものでよく、その添加量は目的とする徐放性能ある
いは使用される非イオン性水溶性セルロースエーテルに
よって異なるが、通常は非イオン性水溶性セルロースエ
ーテルに対し１〜６０重量％、とくには２〜４０重量％
が好ましい。これが１重量％未満ではその添加効果が十
分でなく、またこれが６０重量％を超えても添加効果が
殆ど変わらず、それ以上に多量に添加する必要はない。[0007] Furthermore, the tannic acid used in the present invention may be commercially available, and the amount added varies depending on the desired sustained release performance or the nonionic water-soluble cellulose ether used. 1 to 60% by weight, especially 2 to 40% by weight based on water-soluble cellulose ether
is preferred. If the amount is less than 1% by weight, the effect of the addition is insufficient, and even if it exceeds 60% by weight, the effect of the addition will hardly change, so there is no need to add more than that.
【０００８】非イオン性水溶性セルロースエーテルにタ
ンニン酸を添加することにより、セルロースエーテル単
独の場合と比べて少量の添加量で徐放性能が得られるが
、その理由は次のように推察される。一般に、セルロー
スエーテル類は多価フェノール類と付加物を形成するが
、多価フェノール類の１種であるタンニン酸も水溶性セ
ルロースエーテルと付加物を形成し、多量に添加すると
水に不溶性となることが知られている。本発明の錠剤を
服用した時、錠剤が水を吸収して水溶性セルロースエー
テルがゲル層を形成するが、予め添加しておいたタンニ
ン酸がセルロースエーテルと付加物を作り、より強固な
ゲル層が形成されるために、主薬の拡散速度が小さくな
るものと考えられる。[0008] By adding tannic acid to nonionic water-soluble cellulose ether, sustained release performance can be obtained with a smaller amount added than when using cellulose ether alone. The reason for this is presumed to be as follows. . Generally, cellulose ethers form adducts with polyhydric phenols, but tannic acid, which is a type of polyhydric phenol, also forms adducts with water-soluble cellulose ethers, and becomes insoluble in water when added in large amounts. It is known. When the tablet of the present invention is taken, the tablet absorbs water and the water-soluble cellulose ether forms a gel layer, but the tannic acid added in advance forms an adduct with the cellulose ether, forming a stronger gel layer. It is thought that the diffusion rate of the main drug decreases due to the formation of .
【０００９】この非イオン性水溶性セルロースエーテル
とタンニン酸は打錠する前に粉末同士で混合すればよい
。本徐放剤の製造を実際の処方に即して説明すると、非
イオン性水溶性セルロースエーテル、タンニン酸および
主薬を、Ｖ型混合機などを使用してよく混合した後、常
法により直接打錠することにより目的の錠剤を得ること
ができる。なお、この打錠末には、必要に応じてデンプ
ン、乳糖などの賦形剤またはステアリン酸マグネシウム
などの滑沢剤を適量添加してもよい。[0009] The nonionic water-soluble cellulose ether and tannic acid may be mixed together in powder form before tabletting. To explain the production of this sustained-release agent in accordance with the actual formulation, nonionic water-soluble cellulose ether, tannic acid, and the active ingredient are thoroughly mixed using a V-type mixer, and then directly injected using a conventional method. The desired tablet can be obtained by tabletting. In addition, an appropriate amount of excipients such as starch and lactose or a lubricant such as magnesium stearate may be added to this tablet powder as necessary.
【００１０】0010
【実施例】以下、本発明の具体的態様を実施例および比
較例により説明するが、本発明はこの実施例の記載のみ
に限定されるものではない。
実施例１〜３および比較例１〜２
ＨＰＭＣ（信越化学工業社製、９０ＳＨ−１００）、エ
テンザミドおよびタンニン酸を、表１に示す割合でＶ型
ブレンダーを用いて１０分間混合し、さらにステアリン
酸マグネシウム（以下 Ｍｇ−Ｓｔとする）を混合後、
岡田精工製単発打錠機ＫＴ−２型を用いて０．８ｔ／ｃ
ｍ２で打錠し、１０ｍｍ径の平型の徐放性錠剤とした。
得られた各錠剤について下記の条件で溶出試験を行った
ところ、表２に示す結果が得られた。
方 法：日本薬局方１１のパドル法（回転数：１００
ｒｐｍ）試験液：日局第１液（ｐＨ：１．２ ）EXAMPLES Specific embodiments of the present invention will be explained below with reference to Examples and Comparative Examples, but the present invention is not limited to the description of these Examples. Examples 1 to 3 and Comparative Examples 1 to 2 HPMC (manufactured by Shin-Etsu Chemical Co., Ltd., 90SH-100), ethenzamide and tannic acid were mixed for 10 minutes using a V-type blender in the proportions shown in Table 1, and then stearic acid After mixing magnesium (hereinafter referred to as Mg-St),
0.8t/c using Okada Seiko's single-shot tablet press KT-2 type
The mixture was compressed into flat sustained-release tablets with a diameter of 10 mm. A dissolution test was conducted on each of the obtained tablets under the following conditions, and the results shown in Table 2 were obtained. Method: Japanese Pharmacopoeia 11 paddle method (number of revolutions: 100
rpm) Test solution: Japanese Pharmacopoeia No. 1 solution (pH: 1.2)
【００
１１】00
11]
【表１】[Table 1]
【００１２】0012
【表２】[Table 2]
【００１３】これより、実施例１〜３ではＨＰＭＣの添
加量が同一の比較例１と比較して溶出が非常に抑制され
ていること、またほぼ同様の溶出速度が得られた実施例
１と比較例２のＨＰＭＣ添加量を比較すると比較例は実
施例の２．５ 倍であることが判った。From this, it can be seen that in Examples 1 to 3, elution was extremely suppressed compared to Comparative Example 1 in which the amount of HPMC added was the same, and that in Examples 1 to 3, the elution rate was almost the same as in Example 1. Comparing the amount of HPMC added in Comparative Example 2, it was found that the amount in Comparative Example was 2.5 times that in Example.
【００１４】実施例４〜６および比較例３〜４実施例１
〜３および比較例１〜２において、ＨＰＭＣを ６０Ｓ
Ｈ−４０００に、エテンザミドをサリチルアミドにそれ
ぞれ変えて表３に示す処方としたほかは、同様の操作を
行った。得られた錠剤について溶出試験を行ったところ
、表４に示す結果が得られた。Examples 4 to 6 and Comparative Examples 3 to 4 Example 1
-3 and Comparative Examples 1-2, HPMC was 60S
The same operation was carried out as H-4000 except that ethenzamide was replaced with salicylamide and the formulations shown in Table 3 were obtained. When the obtained tablets were subjected to a dissolution test, the results shown in Table 4 were obtained.
【００１５】[0015]
【表３】[Table 3]
【００１６】[0016]
【表４】[Table 4]
【００１７】これより、実施例４〜６ではＨＰＭＣの添
加量が同一の比較例３と比べて、溶出が非常に抑制され
ていること、またほぼ同様の溶出速度が得られた実施例
６と比較例４のＨＰＭＣ添加量を比較すると、比較例は
実施例に比べて３倍であることが判った。[0017] From this, it can be seen that in Examples 4 to 6, the elution was extremely suppressed compared to Comparative Example 3, in which the amount of HPMC added was the same, and that in Example 6, almost the same elution rate was obtained. Comparing the amount of HPMC added in Comparative Example 4, it was found that the amount in Comparative Example was three times that in Example.
【００１８】[0018]
【発明の効果】本発明の徐放性錠剤によれば、比較的少
量のゲル基剤の添加で薬物の溶出を一定に制御すること
ができる。According to the sustained release tablet of the present invention, the elution of the drug can be controlled to a constant level by adding a relatively small amount of gel base.
Claims (3)
ンニン酸および主薬を混合し、打錠することを特徴とす
る徐放性錠剤の製造方法。1. A method for producing sustained-release tablets, which comprises mixing nonionic water-soluble cellulose ether, tannic acid, and an active ingredient and compressing the mixture.
ヒドロキシプロピルメチルセルロース、ヒドロキシプロ
ピルセルロースまたはメチルセルロースから選択される
１種または２種以上の組み合わせである請求項１記載の
徐放性錠剤の製造方法。Claim 2: The nonionic water-soluble cellulose ether is
2. The method for producing sustained-release tablets according to claim 1, which is one or a combination of two or more selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, and methylcellulose.
スエーテルに対し、１〜６０重量％の割合で添加される
請求項１記載の徐放性錠剤の製造方法。3. The method for producing sustained-release tablets according to claim 1, wherein tannic acid is added in a proportion of 1 to 60% by weight based on the nonionic water-soluble cellulose ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15103191A JPH04346919A (en) | 1991-05-27 | 1991-05-27 | Production of sustained release tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15103191A JPH04346919A (en) | 1991-05-27 | 1991-05-27 | Production of sustained release tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04346919A true JPH04346919A (en) | 1992-12-02 |
Family
ID=15509791
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15103191A Pending JPH04346919A (en) | 1991-05-27 | 1991-05-27 | Production of sustained release tablet |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04346919A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6476006B2 (en) | 2000-06-23 | 2002-11-05 | Teva Pharmaceutical Industries, Ltd. | Composition and dosage form for delayed gastric release of alendronate and/or other bis-phosphonates |
| US6881420B2 (en) | 2000-06-23 | 2005-04-19 | Teva Pharmaceutical Industries Ltd. | Compositions and dosage forms for gastric delivery of irinotecan and methods of treatment that use it to inhibit cancer cell proliferation |
| US7674480B2 (en) | 2000-06-23 | 2010-03-09 | Teva Pharmaceutical Industries Ltd. | Rapidly expanding composition for gastric retention and controlled release of therapeutic agents, and dosage forms including the composition |
| US20140109798A1 (en) * | 2012-10-18 | 2014-04-24 | Shin-Etsu Chemical Co., Ltd. | Preparation of cellulose ether powder |
-
1991
- 1991-05-27 JP JP15103191A patent/JPH04346919A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6476006B2 (en) | 2000-06-23 | 2002-11-05 | Teva Pharmaceutical Industries, Ltd. | Composition and dosage form for delayed gastric release of alendronate and/or other bis-phosphonates |
| US6881420B2 (en) | 2000-06-23 | 2005-04-19 | Teva Pharmaceutical Industries Ltd. | Compositions and dosage forms for gastric delivery of irinotecan and methods of treatment that use it to inhibit cancer cell proliferation |
| US7674480B2 (en) | 2000-06-23 | 2010-03-09 | Teva Pharmaceutical Industries Ltd. | Rapidly expanding composition for gastric retention and controlled release of therapeutic agents, and dosage forms including the composition |
| US20140109798A1 (en) * | 2012-10-18 | 2014-04-24 | Shin-Etsu Chemical Co., Ltd. | Preparation of cellulose ether powder |
| KR20140049942A (en) * | 2012-10-18 | 2014-04-28 | 신에쓰 가가꾸 고교 가부시끼가이샤 | Preparation of cellulose ether powder |
| CN103772719A (en) * | 2012-10-18 | 2014-05-07 | 信越化学工业株式会社 | Preparation of cellulose ether powder |
| US9611379B2 (en) * | 2012-10-18 | 2017-04-04 | Shin-Etsu Chemical Co., Ltd. | Preparation of cellulose ether powder |
| CN103772719B (en) * | 2012-10-18 | 2018-01-02 | 信越化学工业株式会社 | The preparation of cellulose ether powder |
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