JPS58170712A - Indomethacine gradulally releasing tablet - Google Patents
Indomethacine gradulally releasing tabletInfo
- Publication number
- JPS58170712A JPS58170712A JP5431482A JP5431482A JPS58170712A JP S58170712 A JPS58170712 A JP S58170712A JP 5431482 A JP5431482 A JP 5431482A JP 5431482 A JP5431482 A JP 5431482A JP S58170712 A JPS58170712 A JP S58170712A
- Authority
- JP
- Japan
- Prior art keywords
- parts
- indomethacine
- indomethacin
- tablets
- release
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
Description
【発明の詳細な説明】
本発明は消炎、鎮痛剤として繁用されているインドメタ
シンの徐放性錠に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to sustained-release tablets of indomethacin, which is frequently used as an anti-inflammatory and analgesic.
本発明者は先に第九改正日本薬局方の解説欄においても
「錠剤化が困難であるので専らカプセル剤が使用される
」と明記されているインドメタシンの経時的に安定な錠
剤化に成功し、特願昭５７−２５４６４号をもって特許
出願に及んでいたが、本発明はこの発明を更に発展させ
、新たに徐放性をも有する錠剤を提供することに関する
ものである。The present inventor has previously succeeded in making indomethacin into tablets that are stable over time, which is clearly stated in the commentary section of the Ninth Edition of the Japanese Pharmacopoeia that "capsules are exclusively used because it is difficult to make into tablets." , filed a patent application in Japanese Patent Application No. 57-25464, but the present invention further develops this invention and relates to providing a new tablet that also has sustained release properties.
一般に徐放製剤とは一回の投与により長時間薬効を持続
させることを目的とし、このために１日の投与回数が少
なくて済み、特に消炎鎮痛剤の場合は就寝前の投与によ
シ翌朝まで投与を要することがなく、当業界において要
望されること大であるが、インドメタシンについては、
前記したごとく当然のことながら、カプセル製剤につい
てのみ徐放化の研究が行われていたに過ぎない。In general, sustained-release preparations are intended to maintain drug efficacy for a long time with a single administration, and for this reason, the number of administrations per day is small.In particular, in the case of anti-inflammatory analgesics, it is best to administer them before bedtime and then the next morning. Indomethacin does not require administration up to
As mentioned above, as a matter of course, studies on sustained release have only been conducted on capsule formulations.
本発明は主薬インドメタシン粉末に対し水及び有機溶剤
の両者に親和性の強い安定化剤としての高分子フィルム
形成物質とエチルセル口、−スとを有機溶剤の存在下に
表面に被覆させることｋｌなるものである。The present invention involves coating the surface of the main drug indomethacin powder with a polymeric film-forming substance and ethyl cell as a stabilizer having strong affinity for both water and organic solvents in the presence of an organic solvent. It is something.
ここに、水及び有機溶剤の両者に親和性の強い高分子フ
ィルム形成物質とは、ヒドロキシプロピルセルロース（
ＲＰＣ）、ヒドロキシプロピルメチルセルロース（ＨＰ
ＭＯ）、ヒドロキシプロピルメチルセルロース・フタレ
ート（ＨＰＭＣ！−Ｐ）１．ｊ−’ＩＪビニルピロリド
ン（ＰＶＰ）、などが選ばれ、有機溶剤としては、メチ
ルアルコール、エチルアルコール、イソプロピルアルコ
ール、アセトン、塩化メチレンなどの一種又は二種以゛
上が用いられる。Here, the polymeric film-forming substance that has a strong affinity for both water and organic solvents is hydroxypropyl cellulose (
RPC), hydroxypropyl methylcellulose (HP
MO), hydroxypropyl methylcellulose phthalate (HPMC!-P)1. J-'IJ vinylpyrrolidone (PVP), etc. are selected, and as the organic solvent, one or more of methyl alcohol, ethyl alcohol, isopropyl alcohol, acetone, methylene chloride, etc. are used.
ここニ、ヒドロキシプロピルメチルセルロース・フタレ
ートは本発明徐放錠を特に腸溶性化する目的で用いるも
のである。D. Hydroxypropyl methylcellulose phthalate is used especially for the purpose of enteric-coating the sustained-release tablets of the present invention.
インドメタシン粉末はそのまま単独で原料として用いて
もよいが、インドメタシンの粉末に対し２００重量％量
までめ、好ましくは５０〜１００重量−量、の微結晶セ
ルロース、メタケイ酸アルミン酸マグネシウムなどの一
種又は二種以上を混合したものを用いることも推奨され
るが、これは本発明の必須条件ではない。Indomethacin powder may be used alone as a raw material, but up to 200% by weight, preferably 50 to 100% by weight, of microcrystalline cellulose, magnesium aluminate metasilicate, etc. Although it is recommended to use a mixture of more than one species, this is not a necessary condition of the invention.
前記いずれの場合にせよ□、インドメタシンの粉末に対
し、高分子フィルム形成物質を１〜５０重量−量、好ま
しくは３〜２０重量％量、そしてエチルセルロースを１
〜５０重量％量、好ましくは３〜２０重量％量、を用い
るが、この場合にエチルセルロースの量と安定化剤の配
合重量比は１：９〜５：５であることが望ましい。In any of the above cases, the polymeric film-forming substance is added in an amount of 1 to 50% by weight, preferably 3 to 20% by weight, and ethyl cellulose is added in an amount of 1 to 50% by weight, based on the powder of indomethacin.
-50% by weight, preferably 3-20% by weight, and in this case, the weight ratio of the amount of ethylcellulose to the stabilizer is preferably 1:9-5:5.
本発明の徐放錠を製造するには、前記した各成分を有機
溶剤の存在下で主薬粉末の表面に被覆したものを基剤と
して、これに製剤学の分野で常用される賦形剤、補助剤
などを用いて常法通りに製錠化するのであるが、この場
合に有機溶剤に対し安定化剤及びエチルセルロースの濃
度は５〜４０重量％、好ましくは５〜２０′重量％、が
用いられる０
なお、本発明の錠剤の徐放性の効果の発揮に主として関
与するのはエチルセルロースであるが、主薬インドメタ
シンの血漿中放出速度を調節するために、■本発明者に
よる特願昭５７−２５４６４号発明のエチルセルロース
を使用していない顆粒又は粉末、■本発明のエチルセル
ロースを使用した顆粒又は粉末及び■本発明の腸溶性錠
剤としてＨＰＭＯ−Ｐを使用した顆粒又は粉末、の三者
又は三者を適宜の割合に混合して錠剤とすることを妨げ
るものではなく、これらも本発明の実施態様の一つとさ
れるものである。In order to produce the sustained-release tablet of the present invention, the above-mentioned components are coated on the surface of the active ingredient powder in the presence of an organic solvent, and then excipients commonly used in the pharmaceutical field are added to the base. Tablets are made in a conventional manner using adjuvants, and in this case, the concentration of the stabilizer and ethyl cellulose is 5 to 40% by weight, preferably 5 to 20% by weight, based on the organic solvent. Although ethylcellulose is mainly involved in exerting the sustained-release effect of the tablet of the present invention, in order to control the plasma release rate of the main drug indomethacin, Granules or powders that do not use ethyl cellulose of the No. 25464 invention; (1) Granules or powders that use ethyl cellulose of the present invention; and (2) Granules or powders that use HPMO-P as enteric-coated tablets of the present invention. This does not preclude the preparation of tablets by mixing them in appropriate proportions, and these are also considered to be one of the embodiments of the present invention.
これら各成分の配合は流動造粒乾燥機、スーパーミキサ
ー、ニーグー、ポニーミキサーなどが適宜利用される。For blending these components, a fluidized granulation dryer, super mixer, Nigoo mixer, pony mixer, etc. are used as appropriate.
以下に実施例をあげて本発明を説明するが、本発明はこ
れに限定されるものではない。The present invention will be explained below with reference to Examples, but the present invention is not limited thereto.
実施例１
ＲＰＣ４０部とエチルセルロース（商品名エトセル：ダ
ウ ケミカル社製）２・０部をエタノール５００部と塩
化メチレン４００部の混液に溶解する。他方、粉砕した
インドメタシン粉末２５０部、微結晶セルロース１５０
部及びメタケイ酸アルミン酸マグネシウム５０部を流動
造粒乾燥機に入れて混合し、前記溶液を噴霧して顆粒化
し乾燥する０
乾燥物を整粒したものに微結晶セルロース２５０部、乳
糖２００部、繊維素ゲルコール酸カルシウム５０部及び
ステアリン酸マグネシウム１０部を加えて直径７ｆｆ、
重量１５０■の錠剤に圧縮成型する。Example 1 40 parts of RPC and 2.0 parts of ethyl cellulose (trade name: Ethocel, manufactured by Dow Chemical Company) are dissolved in a mixed solution of 500 parts of ethanol and 400 parts of methylene chloride. On the other hand, 250 parts of crushed indomethacin powder, 150 parts of microcrystalline cellulose
250 parts of microcrystalline cellulose, 200 parts of lactose, Adding 50 parts of cellulose gelcholate calcium and 10 parts magnesium stearate to a diameter of 7ff,
Compression mold into tablets weighing 150 square meters.
実施例２
ＨＰ Ｍ ０３０ 部、エトセル３０部をエタノール５
００部と塩化メチレン４００部の混液に溶解し、以下実
施例１と同様に処理して圧縮錠剤を製する。Example 2 30 parts of HP M0 and 30 parts of Ethocel were mixed with 5 parts of ethanol.
00 parts of methylene chloride and 400 parts of methylene chloride, and then treated in the same manner as in Example 1 to prepare compressed tablets.
実施例５
（１）ＲＰＣ４０部、エトセル２０部をエタノール５０
０部と塩化メチレン４００部の混液に溶解する。他方、
粉砕したインドメタシン粉末２５０部、微結晶セルロー
ス１５０部及びメタケイ酸アルミン酸マグネシウム５０
部を流動造粒乾燥機に入れて混合′シ、前記溶液を噴霧
して顆粒化し乾燥するＯ
（２）ＨＰＭＣ−Ｐ２Ｏ部、エトセル２０部をエタノー
ル５００部と塩化メチレフ４００部の混液に溶解し、以
下（１）と同様にして顆粒化して乾燥する。Example 5 (1) 40 parts of RPC, 20 parts of Ethocel and 50 parts of ethanol
0 parts and 400 parts of methylene chloride. On the other hand,
250 parts of ground indomethacin powder, 150 parts of microcrystalline cellulose and 50 parts of magnesium aluminate metasilicate
(2) Dissolve part of HPMC-P2O and 20 parts of Ethocel in a mixture of 500 parts of ethanol and 400 parts of methylene chloride. , and then granulated and dried in the same manner as in (1) below.
上記（１）及び（２）で製した顆粒を合し、これと微結
晶セルロース５００部、乳糖４００部、繊維素グリコー
ル酸カルシウム６０部及びステアリン酸マグネシウム２
０部を加えて直径７ｆｆ、重量１５０ダの錠剤に圧縮成
型する。The granules produced in (1) and (2) above are combined, and this is combined with 500 parts of microcrystalline cellulose, 400 parts of lactose, 60 parts of cellulose calcium glycolate, and 2 parts of magnesium stearate.
0 parts and compression molded into tablets with a diameter of 7 ff and a weight of 150 Da.
本発明腕の徐放性の効果は下記の実験成績により証明さ
れる：
〔実験方法〕
５羽の家兎・に１羽あたり１錠ずつを強制的に経口投与
し、投与後１．２．４．６．８及び１２時間ごとに採血
し、ガスクロマトグラフィーにより下記条件下で血漿中
濃度を定量した。The sustained release effect of the arm of the present invention is proven by the following experimental results: [Experimental method] One tablet per rabbit was forcibly administered orally to five rabbits, and after administration 1.2. Blood was collected every 4.6.8 and 12 hours, and the plasma concentration was determined by gas chromatography under the following conditions.
日立ガスクロマトグラフ装置０７３型
検出器；水素炎イオン化ディテクター
カラム；直径５ＭＭ、長さ２ｍのガラス管に１．５ ％
ＯＶ−Ｉ Ｑｒａｓｃｋｒｏｍ Ｑを充填測定温度；
カラム２４０°Ｃ１検出器２９０°Ｃ＊ヤ！Ｊ Ｔ−カ
ス； ９１素（９０１Ｉｖ′１Ａ−）感度、 ５ｔｎｓ
Ｉ Ｄ２、Ｒａｎｇｅ ｉ ６検体としては、■前記
実施例１によシ製造直後本
の本発明腕、＠同上ら発明錠を１９８１年版医薬品製造
指針に従い、４０°Ｃ１相対湿度７５チの環境下で１２
ケ月間保存加速したもの、θ市販Ａ社製徐放カプセル剤
、Ｏ市販Ｂ社製徐放カプセル及び■本発明者の特願昭５
７−２５４６４号明細書の実施例１の非徐放性錠剤をそ
れぞれ用いた。Hitachi gas chromatograph instrument type 073 detector; flame ionization detector column; 1.5% in a glass tube with a diameter of 5 mm and a length of 2 m.
Filling OV-I Qrasckrom Q measurement temperature;
Column 240°C1 Detector 290°C *Ya! J T-cass; 91 elements (901Iv'1A-) sensitivity, 5tns
I D2, Range i 6 The specimens were: ■ The arm of the present invention immediately after manufacture according to Example 1, and the tablet of the invention by @same et al., in an environment of 40° C. and relative humidity of 75° C. according to the 1981 Pharmaceutical Manufacturing Guidelines. 12
Accelerated storage for 1 month, θ commercially available sustained release capsules made by company A, O commercially available sustained release capsules made by company B, and ■ patent application of the present inventor in 1973
The non-sustained release tablets of Example 1 of Specification No. 7-25464 were used in each case.
上記■〜■の各検体による血漿中インドメタシン濃度（
単位：μｔ／ｍｌ ）をそれぞれ表１〜５に示す：
表１
表２
表３
表４
表５
上記動物実験により得られた数値は添付図面でグラフ化
して示されるが、本発明によるインドメタシン徐放錠は
製造後１２ケ月間の加速試験を経た後も製造直後のもの
と＃１とんど同等の血漿中濃度の推移を示し、本発明者
による非徐放錠に比して投与約２時間後の最高値は若干
低いが、投与８時間目以降においても有意の高血漿濃度
を維持していることが証明された。なお、市販の徐放カ
プセル剤に比しても同等以上の持続値を示していること
が判明する。Plasma indomethacin concentration (
Units: μt/ml) are shown in Tables 1 to 5, respectively: Table 1 Table 2 Table 3 Table 4 Table 5 The numerical values obtained from the above animal experiments are shown graphically in the attached drawings, and the sustained release of indomethacin according to the present invention Even after undergoing an accelerated test for 12 months after manufacture, the tablets showed a change in plasma concentration that was almost the same as that immediately after manufacture, and the time after administration was approximately 2 hours compared to the non-extended release tablet developed by the present inventors. Although the maximum value after administration was slightly lower, it was proven that a significantly high plasma concentration was maintained even after 8 hours of administration. Furthermore, it has been found that the sustained release value is equivalent to or higher than that of commercially available sustained release capsules.
【図面の簡単な説明】
図面は各検体１錠ずつを投与後１２時間までの家兎血漿
中の生薬濃度（μｆ／ｍｌ）を示す。第１図において一
シー、十及び→−はそれぞれ本発明の実施例１の錠剤の
製造直後のもの、同１２ケ月間の加速試験を施したもの
及び特願昭５７−２５４６４号発明の実施例１の非徐放
性錠についてのものである。第２図において÷ 及び
→−はそれぞれＡ社製及びＢ社製のインドメタシン徐放
性カプセル剤についてのものである。
（特許出願人 チョダ薬品株式会社）
（代理人 弁理士 糟谷 安）
手続補正書（方式）
％式％
／事件の表示
昭和５７年特許願第５４５１４号
２発明の名称
インドメタシン徐放錠
３補正をする者
事件との関係：特許出願人
昭和５７年７月９日
昭和５７年７月２７日（発送日）
乙補正の対象
明細書の図面の簡単な説明の欄
Ｚ補正の内容
明細書第１２頁の第２行０冒頭より第３行目の［−ｍ−
を示す。ｊまでを抹消し、代シに下記文章を挿入する。
記
図面（第１．２図）は各検体１錠ずつを投与後１２時間
までの家兎血漿中の主薬濃度（μｔ／ｍｌ’）を示す全
面図である。
（代理人 弁理士 糟谷 安）[Brief Description of the Drawings] The drawings show the concentration of crude drug (μf/ml) in rabbit plasma up to 12 hours after administration of one tablet of each sample. In FIG. 1, 1, 10, and →- are respectively tablets immediately after production of Example 1 of the present invention, tablets subjected to accelerated testing for 12 months, and Example of the invention of Japanese Patent Application No. 57-25464. This is about the non-extended release tablet of No. 1. In Figure 2, ÷ and
→- refers to indomethacin sustained release capsules manufactured by Company A and Company B, respectively. (Patent applicant: Choda Pharmaceutical Co., Ltd.) (Agent: Patent attorney: Yasu Kasuya) Procedural amendment (method) % formula % / Indication of case 1982 Patent Application No. 54514 2 Name of the invention Indomethacin extended-release tablets 3 Make amendments Relationship with the patent applicant's case: July 9, 1980 July 27, 1982 (Shipping date) Column for a brief explanation of the drawings in the specification subject to amendment B Page 12 of the description of the contents of the Z amendment From the beginning of the second line 0 to the third line [-m-
shows. Delete up to J and insert the following sentence in place of C. The drawing (Figure 1.2) is a full-scale view showing the concentration of the active drug (μt/ml') in rabbit plasma up to 12 hours after administration of one tablet of each sample. (Representative Patent Attorney Yasu Kasuya)
Claims (1)
ィルム形成物質を１〜５０重量％及びエチルセルロース
を１〜５ｏ重量％の割合で被覆したものを製錠基剤とし
てなるインドメタシン徐放錠。 ２、親水性高分子フィルム形成物質がヒドロキシプロピ
ルセルロース、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メチルセルロース・フタレート及び
ポリビニルピロリドンよりなる群よシ選ばれた一種もし
くは二種以上のものである特許請求の範囲第１項記載の
インドメタシン徐放錠。 ３、親水性高分子フィルム形成物質がヒドロキシプロピ
ルメチルセルロース・フタレートである特許請求の範囲
第１項記載のインドメタシン徐放錠。[Scope of Claims] 1. Indomethacin powder, which is an active ingredient indomethacin powder, is coated with a hydrophilic polymeric film-forming substance in a proportion of 1 to 50% by weight and ethyl cellulose in a proportion of 1 to 50% by weight as a tableting base. Release the tablet. 2. The hydrophilic polymer film-forming substance is hydroxypropylcellulose, hydroxypropylmethylcellulose,
The sustained-release indomethacin tablet according to claim 1, which is one or more selected from the group consisting of hydroxypropyl methylcellulose phthalate and polyvinylpyrrolidone. 3. The indomethacin extended-release tablet according to claim 1, wherein the hydrophilic polymeric film-forming substance is hydroxypropylmethylcellulose phthalate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5431482A JPS58170712A (en) | 1982-03-31 | 1982-03-31 | Indomethacine gradulally releasing tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5431482A JPS58170712A (en) | 1982-03-31 | 1982-03-31 | Indomethacine gradulally releasing tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS58170712A true JPS58170712A (en) | 1983-10-07 |
Family
ID=12967116
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5431482A Pending JPS58170712A (en) | 1982-03-31 | 1982-03-31 | Indomethacine gradulally releasing tablet |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58170712A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4525345A (en) * | 1981-12-24 | 1985-06-25 | Verex Laboratories, Inc. | Constant order release, solid dosage indomethacin formulation and method of treating arthritis and other inflammatory conditions |
| US4652442A (en) * | 1983-07-05 | 1987-03-24 | Arcana Chem. Pharm. Fabrik Gesellschaft M.B.H. | Process of producing a sustained release preparation containing indomethacin or niomethacin |
| US4927640A (en) * | 1985-10-11 | 1990-05-22 | Aktiebolaget Hassle | Controlled release beads having glass or silicon dioxide core |
| US4942040A (en) * | 1987-10-08 | 1990-07-17 | Aktiebolaget Hassle | Pharmaceutical preparation and a process for its preparation |
-
1982
- 1982-03-31 JP JP5431482A patent/JPS58170712A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4525345A (en) * | 1981-12-24 | 1985-06-25 | Verex Laboratories, Inc. | Constant order release, solid dosage indomethacin formulation and method of treating arthritis and other inflammatory conditions |
| US4652442A (en) * | 1983-07-05 | 1987-03-24 | Arcana Chem. Pharm. Fabrik Gesellschaft M.B.H. | Process of producing a sustained release preparation containing indomethacin or niomethacin |
| US4927640A (en) * | 1985-10-11 | 1990-05-22 | Aktiebolaget Hassle | Controlled release beads having glass or silicon dioxide core |
| US4942040A (en) * | 1987-10-08 | 1990-07-17 | Aktiebolaget Hassle | Pharmaceutical preparation and a process for its preparation |
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