JP2936376B2 - Nicorandil tablet manufacturing method - Google Patents
Nicorandil tablet manufacturing methodInfo
- Publication number
- JP2936376B2 JP2936376B2 JP5243720A JP24372093A JP2936376B2 JP 2936376 B2 JP2936376 B2 JP 2936376B2 JP 5243720 A JP5243720 A JP 5243720A JP 24372093 A JP24372093 A JP 24372093A JP 2936376 B2 JP2936376 B2 JP 2936376B2
- Authority
- JP
- Japan
- Prior art keywords
- nicorandil
- mixed
- magnesium stearate
- tablet
- tablets
- 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 - Lifetime
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION
【０００１】[0001]
【産業上の利用分野】本発明はニコランジル錠剤製法の
改良に関するものである。すなわち、本発明は非常に安
定性の良いニコランジル錠剤をつくるように改良したも
のである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improved method for producing nicorandil tablets. That is, the present invention has been improved to produce nicorandil tablets having extremely good stability.
【０００２】[0002]
【従来の技術】ニコランジルは結晶自体は比較的安定で
あるが、通常の打錠法では圧縮により、分解し含量低下
を生じ易く、また、ニコランジルは分子中に硝酸基を有
するため、製剤中に不飽和の炭化水素が多く含まれる天
然油脂類等が存在すると着色し、若干の含量低下が見ら
れることから、得られた錠剤の商品性を著しく損なうこ
とが知られている。2. Description of the Related Art Nicorandil itself is relatively stable in crystals, but it is apt to be decomposed and reduced in content by compression in a usual tableting method, and because nicorandil has a nitrate group in the molecule, it may be contained in a formulation. It is known that the presence of natural fats and oils containing a large amount of unsaturated hydrocarbons causes coloring and a slight decrease in the content, which significantly impairs the commercial properties of the obtained tablets.
【０００３】この対策として、ニコランジルの結晶をス
テアリルアルコール、セタノールおよびステアリン酸か
ら選ばれる１種または２種以上の混合物で被覆した後に
打錠する方法（特開昭５７−１４５６５９号）、ニコラ
ンジルと常温で固体の飽和高級脂肪酸もしくは飽和高級
アルコールの１種または２種以上を混合打錠する方法
（特開昭６２−２５２７２３号）および１種または２種
以上の有機酸ならびに１種または２種以上の飽和高級脂
肪酸もしくは飽和高級アルコールを混合打錠することに
より安定化をはかった方法（特開昭６３−２７０６２４
号）が知られている。[0003] As a countermeasure, a method of coating a nicorandil crystal with one or a mixture of two or more selected from stearyl alcohol, cetanol and stearic acid, followed by tableting (Japanese Patent Application Laid-Open No. 57-145659), a method in which nicorandil and normal temperature And tableting of one or more kinds of solid saturated higher fatty acids or saturated higher alcohols (JP-A-62-252723) with one or more organic acids and one or more solid acids. A method of stabilizing by mixing and compressing a saturated higher fatty acid or a saturated higher alcohol (JP-A-63-270624).
No.) is known.
【０００４】[0004]
【発明が解決しようとする問題点】通常の製剤方法にお
いて圧縮成形時の圧力により、含量低下を生じることか
ら、圧縮成形時における粒子間の摩擦の軽減を目的とし
て、滑沢剤の検討を試みた。数種類の滑沢剤で被覆した
後打錠し検討したが、含量低下、着色は改善されなかっ
た。ところが以外にも不飽和の炭化水素が多く含まれる
天然ワックス類カルナウバロウと滑沢剤ステアリン酸マ
グネシウムをあらかじめ混合し、この混合物（以下、混
合滑沢物と称す）をニコランジルに混合して打錠すると
その安定性が格段に向上するという新知見が得られた。[Problems to be Solved by the Invention] Since the content is reduced due to the pressure during compression molding in a conventional preparation method, an attempt was made to investigate a lubricant for the purpose of reducing friction between particles during compression molding. Was. Tableting after coating with several kinds of lubricants was examined, but the content reduction and coloring were not improved. However, besides, natural waxes Carnauba wax containing a large amount of unsaturated hydrocarbons and a lubricant magnesium stearate are preliminarily mixed, and this mixture (hereinafter, referred to as a mixed lubricant) is mixed with nicorandil and tableted. A new finding was obtained that the stability was significantly improved.
【０００５】本発明は、これらの新知見に基づき完成さ
れたもので、製剤中にその混合滑沢物を少なくとも０．
５重量％を含有させることによって安定なニコランジル
の錠剤を得ることができる。[0005] The present invention has been completed based on these new findings.
By containing 5% by weight, stable nicorandil tablets can be obtained.
【０００６】さらに、本発明によれば天然ワックス類カ
ルナウバロウおよび硬化ヒマシ油が使用でき、ニコラン
ジル結晶を被覆するための装置や設備等も不要である。Further, according to the present invention, natural waxes such as carnauba wax and hydrogenated castor oil can be used, and no apparatus or equipment for coating nicorandil crystals is required.
【０００７】[0007]
【課題を解決するための手段】賦形剤、崩壊剤、滑沢
剤、結合剤等の医薬担体を配合して成る粗成物に対し、
ニコランジルの結晶とカルナウバロウおよび硬化ヒマシ
油より選ばれる１種または２種ならびにステアリン酸マ
グネシウム、ステアリン酸カルシウム、酸化マグネシウ
ムおよびタルクより選ばれる１種または２種以上を混合
する混合滑沢物を、０．５重量％以上配合し、通常の製
剤方法より錠剤とすることができる。Means for Solving the Problems For a crude product comprising a pharmaceutical carrier such as an excipient, a disintegrant, a lubricant, a binder, etc.,
A mixed lubricant in which nicorandil crystals are mixed with one or two selected from carnauba wax and hydrogenated castor oil and one or two or more selected from magnesium stearate, calcium stearate, magnesium oxide and talc, % By weight or more, and can be made into tablets by a usual preparation method.
【０００８】また、上記の医薬担体としては、例えば、
乳糖、トウモロコシデンプン、マンニトール、ブドウ
糖、デキストリン、白糖、結晶セルロース、カルボキシ
メチルセルロースカルシウム、ヒドロキシプロピルセル
ロース、エチルセルロース、ステアリン酸マグネシウ
ム、ステアリン酸カルシウム、酸化マグネシウム、タル
ク等が用いられる。The above-mentioned pharmaceutical carriers include, for example,
Lactose, corn starch, mannitol, glucose, dextrin, sucrose, crystalline cellulose, carboxymethylcellulose calcium, hydroxypropylcellulose, ethylcellulose, magnesium stearate, calcium stearate, magnesium oxide, talc and the like are used.
【０００９】[0009]
【作用】本発明によって得られた錠剤は、温度、湿度に
対する安定性および圧縮成形時の安定性に優れている。
これは不飽和の炭化水素が多く含まれるカルナウバロウ
等をあらかじめステアリン酸マグネシウム等で混合被覆
することにより直接ニコランジルとカルナウバロウ等の
接触を防ぎ、着色を抑え、また、この操作により防湿お
よび滑沢効果も増大するため、吸湿度および圧縮成形時
の圧力による含量低下も抑えられるものと推測した。以
下、実施例をあげて説明するが、本発明はこれらに限定
されるものではない。The tablet obtained by the present invention is excellent in stability against temperature and humidity and stability during compression molding.
This is because carnauba wax containing a large amount of unsaturated hydrocarbons is mixed and coated in advance with magnesium stearate to prevent direct contact between nicorandil and carnauba wax, etc., suppress coloring, and this operation also provides moisture-proof and lubricating effects. It is presumed that the decrease in the content due to the moisture absorption and the pressure during the compression molding can be suppressed. Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited thereto.
【００１０】[0010]
【実施例１】 錠剤処方（１錠中） ニコランジル ５（ｍｇ） カルナウバロウ ０．７５ ステアリン酸マグネシウム ０．２５ マンニトール ４０．２ 低置換度ヒドロキシプロピルセルロース ０．８ カルボキシメチルセルロースカルシウム ２．５ ステアリン酸マグネシウム ０．５ ─────────────────────────── 計 ５０ｍｇExample 1 Tablet formulation (in one tablet) Nicorandil 5 (mg) Carnauba wax 0.75 Magnesium stearate 0.25 Mannitol 40.2 Low substituted hydroxypropylcellulose 0.8 Carboxymethylcellulose calcium 2.5 Magnesium stearate 0 ─────────────────────────── Total 50mg
【００１１】マンニトール４０．２ｇ、低置換度ヒドロ
キシプロピルセルロース０．８ｇおよびカルボキシメチ
ルセルロースカルシウム２．５ｇを乳鉢中で混合した
後、水を加えて練合した。練合物を４８メッシュの篩で
造粒した後、４０℃で６時間乾燥した。乾燥物を４８メ
ッシュの篩で整粒し、造粒物を得た。[0011] 40.2 g of mannitol, 0.8 g of low-substituted hydroxypropylcellulose and 2.5 g of calcium carboxymethylcellulose were mixed in a mortar and kneaded with water. The kneaded product was granulated with a 48-mesh sieve and then dried at 40 ° C. for 6 hours. The dried product was sized with a 48-mesh sieve to obtain a granulated product.
【００１２】カルナウバロウ０．７５ｇとその１／３の
量に相当するステアリン酸マグネシウム０．２５ｇを乳
鉢中で混合し、混合滑沢物を得た。0.75 g of Carnauba wax and 0.25 g of magnesium stearate corresponding to one third of the amount were mixed in a mortar to obtain a mixed lubricant.
【００１３】ニコランジル５ｇ、造粒物４３．５ｇ、混
合滑沢物１ｇおよびステアリン酸マグネシウム０．５ｇ
をポリ袋中で混合した。Nicorandil 5 g, granulated product 43.5 g, mixed lubricant 1 g and magnesium stearate 0.5 g
Was mixed in a plastic bag.
【００１４】上記混合末を直径５ｍｍの臼および平型杵
をセットした単発打錠機で１錠５０ｍｇとなるように圧
縮成形した。The above-mentioned mixed powder was compression-molded to 50 mg per tablet using a single-shot tableting machine in which a die having a diameter of 5 mm and a flat punch were set.
【００１５】比較のために、実施例処方中の混合滑沢物
の替わりに同量のマンニトールでおき換えた錠剤（以
下、対照１と称す）および特開昭５７−１４５６５９号
に従いステアリルアルコールを用いた錠剤を製造した
（以下、対照２と称す）。For comparison, tablets prepared by substituting the same amount of mannitol in place of the mixed lubricant in the formulation of the Examples (hereinafter referred to as Control 1) and using stearyl alcohol in accordance with JP-A-57-144569 were used. The tablets were manufactured (hereinafter referred to as Control 2).
【００１６】各錠剤をガラスビンに入れ、密栓状態で４
０℃−３カ月間および開放状態で４０℃、７５％ＲＨ−
３カ月間それぞれ加速し、安定性を比較した。加速前を
１００％とした残存率で示すと第１表のとおりである。Each tablet is placed in a glass bottle, and 4
0 ° C. for 3 months and at 40 ° C., 75% RH-
Each accelerated for three months and compared for stability. Table 1 shows the residual rates with the pre-acceleration as 100%.
【００１７】[0017]
【表１】 [Table 1]
【００１８】[0018]
【実施例２】 錠剤処方（１錠中） ニコランジル ５（ｍｇ） 硬化ヒマシ油 ０．７５ ステアリン酸マグネシウム ０．２５ マンニトール ４０．２ 低置換度ヒドロキシプロピルセルロース ０．８ カルボキシメチルセルロースカルシウム ２．５ ステアリン酸マグネシウム ０．５ ─────────────────────────── 計 ５０ｍｇExample 2 Tablet formulation (in one tablet) Nicorandil 5 (mg) Hardened castor oil 0.75 Magnesium stearate 0.25 Mannitol 40.2 Low substituted hydroxypropylcellulose 0.8 Carboxymethylcellulose calcium 2.5 Stearic acid Magnesium 0.5 ─────────────────────────── Total 50mg
【００１９】マンニトール４０．２ｇ、低置換度ヒドロ
キシプロピルセルロース０．８ｇおよびカルボキシメチ
ルセルロースカルシウム２．５ｇを乳鉢中で混合した
後、水を加えて練合した。練合物を４８メッシュの篩で
造粒した後、４０℃で６時間乾燥した。乾燥物を４８メ
ッシュの篩で整粒し、造粒物を得た。40.2 g of mannitol, 0.8 g of low-substituted hydroxypropylcellulose and 2.5 g of calcium carboxymethylcellulose were mixed in a mortar and kneaded with water. The kneaded product was granulated with a 48-mesh sieve and then dried at 40 ° C. for 6 hours. The dried product was sized with a 48-mesh sieve to obtain a granulated product.
【００２０】硬化ヒマシ油０．７５ｇとその１／３の量
に相当するステアリン酸マグネシウム０．２５ｇを乳鉢
中で混合し、混合滑沢物を得た。[0027] 0.75 g of hydrogenated castor oil and 0.25 g of magnesium stearate corresponding to 1/3 thereof were mixed in a mortar to obtain a mixed lubricant.
【００２１】ニコランジル５ｇ、造粒物４３．５ｇ、混
合滑沢物１ｇおよびステアリン酸マグネシウム０．５ｇ
をポリ袋中で混合した。5 g of Nicorandil, 43.5 g of granules, 1 g of mixed lubricant and 0.5 g of magnesium stearate
Was mixed in a plastic bag.
【００２２】上記混合末を直径５ｍｍの臼および平型杵
をセットした単発打錠機で１錠５０ｍｇとなるように圧
縮成形した。The mixed powder was compression-molded to 50 mg per tablet using a single-shot tableting machine in which a die having a diameter of 5 mm and a flat punch were set.
【００２３】比較のために、実施例処方中の混合滑沢物
の替わりに同量のマンニトールでおき換えた錠剤を同条
件で製造した。For comparison, tablets were prepared under the same conditions by replacing the mixed lubricant in the formulation of the example with the same amount of mannitol.
【００２４】両錠剤をガラスビンに入れ、密栓状態で４
０℃−３カ月間および開放状態で４０℃、７５％ＲＨ−
３カ月間それぞれ加速し、安定性を比較した。加速前を
１００％とした残存率で示すと第２表のとおりである。Put both tablets in a glass bottle and seal 4
0 ° C. for 3 months and at 40 ° C., 75% RH-
Each accelerated for three months and compared for stability. Table 2 shows the residual rate with the value before acceleration set to 100%.
【００２５】[0025]
【表２】 [Table 2]
【００２６】実施例１および２の結果より、本発明は明
らかに対照群以上にニコランジル含量低下を抑え、ま
た、錠剤の着色も認められなかった。From the results of Examples 1 and 2, the present invention clearly suppressed the decrease in nicorandil content more than the control group, and no coloring of the tablet was observed.
【００２７】カルナウバロウおよび硬化ヒマシ油は天然
ワックス類であり入手し易く、また、ニコランジルを被
覆するための装置や設備等も不要であり、通常の製剤方
法により低コストで錠剤を製することができた。Carnauba wax and hydrogenated castor oil are natural waxes, are easily available, and do not require equipment or equipment for coating nicorandil. Tablets can be manufactured at low cost by a conventional preparation method. Was.
フロントページの続き (72)発明者 東 ゆかり 福井県坂井郡金津町六日６号35番地 小 林化工株式会社内 審査官 上條 のぶよ (58)調査した分野(Int.Cl.6，ＤＢ名) A61K 31/455 A61K 9/20 A61K 47/02 A61K 47/12 A61K 47/44 ＣＡ（ＳＴＮ)Continuing from the front page (72) Yukari Higashi, No. 6 , Kobayashi Chemicals Co., Ltd. No. 6, No. 6, Kanatsu-cho, Sakai-gun, Fukui Pref. A61K 31/455 A61K 9/20 A61K 47/02 A61K 47/12 A61K 47/44 CA (STN)
Claims (2)
範囲で混合した後にこの混合物を用いてニコランジルを
混合し打錠することを特徴とする安定なニコランジル錠
剤の製法。 群（Ａ）：カルナウバロウおよび硬化ヒマシ油より選ば
れる１種または２種の混合物 群（Ｂ）：ステアリン酸マグネシウム、ステアリン酸カ
ルシウム、酸化マグネシウムおよびタルクより選ばれる
１種または２種以上の混合物1. A stable nicorandil tablet comprising the steps of mixing groups (A) and (B) in a ratio of 1: 5 to 3: 1, and then mixing and tableting nicorandil using this mixture. Recipe. Group (A): One or two kinds of mixtures selected from carnauba wax and hydrogenated castor oil Group (B): One or more kinds of mixtures selected from magnesium stearate, calcium stearate, magnesium oxide and talc
ジル製剤総重量の少なくとも０．５重量％含ませる特許
請求の範囲第１項に記載の安定なニコランジル錠剤の製
法。2. A stable nicorandil tablet according to claim 1, wherein the mixture of groups (A) and (B) comprises at least 0.5% by weight of the total weight of the nicorandil preparation .
Law .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5243720A JP2936376B2 (en) | 1993-09-03 | 1993-09-03 | Nicorandil tablet manufacturing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5243720A JP2936376B2 (en) | 1993-09-03 | 1993-09-03 | Nicorandil tablet manufacturing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0769889A JPH0769889A (en) | 1995-03-14 |
| JP2936376B2 true JP2936376B2 (en) | 1999-08-23 |
Family
ID=17107992
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5243720A Expired - Lifetime JP2936376B2 (en) | 1993-09-03 | 1993-09-03 | Nicorandil tablet manufacturing method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2936376B2 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8071128B2 (en) | 1996-06-14 | 2011-12-06 | Kyowa Hakko Kirin Co., Ltd. | Intrabuccally rapidly disintegrating tablet and a production method of the tablets |
| US9358214B2 (en) | 2001-10-04 | 2016-06-07 | Adare Pharmaceuticals, Inc. | Timed, sustained release systems for propranolol |
| FR2872705B1 (en) * | 2004-07-08 | 2008-07-18 | Aventis Pharma Sa | COMPOSITIONS CONTAINING NICORANDIL, PROCESS FOR PREPARATION AND USE |
| US9884014B2 (en) | 2004-10-12 | 2018-02-06 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| NZ709754A (en) | 2004-10-21 | 2017-02-24 | Adare Pharmaceuticals Inc | Taste-masked pharmaceutical compositions with gastrosoluble pore-formers |
| US9161918B2 (en) | 2005-05-02 | 2015-10-20 | Adare Pharmaceuticals, Inc. | Timed, pulsatile release systems |
| JP2011241148A (en) * | 2008-09-08 | 2011-12-01 | Nippon Chemiphar Co Ltd | Solid preparation for medical use |
| MX2012006240A (en) | 2009-12-02 | 2012-10-03 | Aptalis Pharma Ltd | Fexofenadine microcapsules and compositions containing them. |
-
1993
- 1993-09-03 JP JP5243720A patent/JP2936376B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0769889A (en) | 1995-03-14 |
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