JPH0244460B2 - - Google Patents
Info
- Publication number
- JPH0244460B2 JPH0244460B2 JP59036180A JP3618084A JPH0244460B2 JP H0244460 B2 JPH0244460 B2 JP H0244460B2 JP 59036180 A JP59036180 A JP 59036180A JP 3618084 A JP3618084 A JP 3618084A JP H0244460 B2 JPH0244460 B2 JP H0244460B2
- Authority
- JP
- Japan
- Prior art keywords
- isosorbide
- isosorbide nitrate
- weight
- added
- 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.)
- Expired - Lifetime
Links
- YWXYYJSYQOXTPL-JGWLITMVSA-N [(3r,3ar,6s,6as)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-JGWLITMVSA-N 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 10
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 9
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 9
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 9
- 229920000609 methyl cellulose Polymers 0.000 claims description 8
- 239000001923 methylcellulose Substances 0.000 claims description 8
- 235000010981 methylcellulose Nutrition 0.000 claims description 8
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 7
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 7
- 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 description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 7
- -1 isosorbide nitrate ester Chemical class 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 239000008187 granular material Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 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 8
- 239000008101 lactose Substances 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 6
- 229960003827 isosorbide mononitrate Drugs 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- 229920001592 potato starch Polymers 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 239000011812 mixed powder Substances 0.000 description 3
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 2
- 238000004898 kneading 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
- 239000011259 mixed solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229960002479 isosorbide Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は安定なイソソルビド硝酸エステル製剤
及びその製造法に関する。
イソソルビド硝酸エステルとしては、ジニトロ
エステル体である硝酸イソソルビド及びモノニト
ロエステル体である２−又は５−モノ硝酸イソソ
ルビドがあり、これらはいずれも冠血管拡張作用
を有することが知られている。なかでも硝酸イソ
ソルビドは狭心症発作の治療及び予防を目的とし
て、舌下錠、経口錠、徐放錠、注射剤等の形で現
在広く使用されている。
イソソルビド硝酸エステルは、高温で気化し分
解しやすく、急速に加熱するか又は衝撃を与える
と爆発するおそれがあるので、取扱いには十分な
注意を要する。このものは弱いが刺激性の苦味を
呈し、また揮散性を有するため製剤中から徐々に
放出揮散して、製剤中の含有量を低下する傾向が
強く、ときには製剤表面での結晶生成が見られ
る。
本発明者らは、イソソルビド硝酸エステルのこ
れらの欠点を改良するため種々検討した結果、イ
ソソルビド硝酸エステルに特定の成分を配合する
ことにより、刺激性が緩和されかつ揮散性が防止
され、安定で取扱いも容易となり、錠剤、散剤、
坐剤等の固形製剤を調製する上で好適であること
を見出した。
本発明は、イソソルビド硝酸エステルにポリビ
ニルピロリドン、メチルセルロース、ヒドロキシ
プロピルセルロース及びヒドロキシプロピルメチ
ルセルロースよりなる群から選ばれた１種又は２
種以上の成分を配合してなるイソソルビド硝酸エ
ステル組成物である。
本発明の製剤は、好ましくはイソソルビド硝酸
エステル１重量部及びポリビニルピロリドン、メ
チルセルロース、ヒドロキシプロピルセルロース
及びヒドロキシプロピルメチルセルロースよりな
る群から選ばれた１種又は２種以上の成分0.2〜
30重量部を、溶媒に溶解及び／又は分散したのち
溶媒を除去することにより製造される。
本発明に用いられるポリビニルピロリドンとし
ては、日本薬局方外医薬品成分規格（1983）に収
載のポリビニルピロリドンK25、ポリビニルピロ
リドンK30、ポリビニルピロリドンK90があげら
れる。メチルセルロースとしては、第十改正日本
薬局方に収載のメチルセルロースが好ましい。ヒ
ドロキシプロピルセルロースとしては、同薬局方
収載の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としては、同薬局方
収載のヒドロキシプロピルメチルセルロース
2208、ヒドロキシプロピルメチルセルロース
2906、ヒドロキシプロピルメチルセルロース2910
があげられる。
イソソルビド硝酸エステルと前記成分との配合
割合は成分の種類によつて異なるが、イソソルビ
ド硝酸エステル１重量部に対し、前記の成分0.2
〜30重量部、特に好ましくは１〜15重量部の範囲
が好適である。
前記成分の量が多いほど保存安定性が高くな
り、製剤からの薬物放出も遅延化されるが、30重
量％以上加えると製造上の問題が生じる。
本発明の製剤を製造するに際しては、まずイソ
ソルビド硝酸エステルを溶媒に溶解し、次いで前
記の成分を溶解及び／又は分散することが好まし
いが、それぞれを溶液又は懸濁液にしておいて混
合することもできる。
溶媒としては例えばアセトン、メタノール、エ
タノール、イソプロパノール、塩化メチレン、ク
ロロホルム、水など並びにこれらの混合物が用い
られる。溶媒の使用量は、イソソルビド硝酸エス
テル１重量部に対し、２重量部以上好ましくは２
〜20重量部である。
次いでこの混合液に必要に応じ、矯味矯臭剤、
着色剤、増量剤、賦形剤などの添加剤を添加した
のち溶媒を除去する。
溶媒の除去法としては工業的に通常実施されて
いる方法、すなわち常圧又は減圧下に加熱する方
法、噴霧造粒する方法、得られた紛末を最終的に
製剤とすることを考慮してイソソルビド硝酸エス
テルと前記の成分を含む溶液を、目的の製剤とす
るために加える賦形剤に撹拌しながら注加し、造
粒したのち乾燥する方法、流動層造粒機に賦形剤
を入れ、混合溶液を噴霧し乾燥、造粒する方法な
どを用いることができる。
普通は、これらの成分は結合剤として用いられ
るが、主薬と賦形剤等の医薬品添加物との混合粉
末に、結合剤として溶媒に溶解したこれら成分を
添加し、練合したのち造粒する湿式造粒法によつ
て得られた薬剤に比べて、本発明の薬剤は極めて
優れた保存安定性を示した。
こうして得られたイソソルビド硝酸エステル組
成物の粉末あるいは粒剤は、そのままでも用いら
れるが、賦形剤、崩壊剤、徐放化剤、滑沢剤など
の医薬品添加物を加え常法により顆粒剤、細粒
剤、錠剤、バツカル剤、硬カプセル剤、坐剤、軟
膏剤等とすることができる。
実施例 １
５−モノ硝酸イソソルビド2.5ｇをメタノール
20mlに溶解し、これにヒドロキシプロピルメチル
セルロース2910の12.5ｇを加えて撹拌し、この混
合液を45℃で乾燥したのち、破砕して顆粒とす
る。
実施例 ２
実施例１と同様に操作して得た混合液を乳糖25
ｇ及びばれいしよ殿粉10ｇに注加し、練合したの
ち、25メツシユのスクリーンを通して造粒し、45
℃で乾燥して顆粒とする。
実施例 ３
流動層造粒機を用い、５−モノ硝酸イソソルビ
ド10ｇをエタノール200mlに溶解したのち、ヒド
ロキシプロピルセルロース30ｇを加えた混合液を
乳糖100ｇに噴霧し、乾燥して顆粒とする。
実施例 ４
５−モノ硝酸イソソルビド20ｇをエタノール
100mlに溶解し、これにメチルセルロース40ｇを
加えた混合液を、乳糖80ｇ、ばれいしよ殿粉40ｇ
及び結晶セルロース20ｇの混合粉末に注加して練
合したのち、25メツシユのスクリーンを通し、45
℃で乾燥して顆粒とする。
実施例 ５
５−モノ硝酸イソソルビド2.5ｇをエタノール
20mlに溶解し、これにポリビニルピロリドンK30
の7.5ｇを加えて撹拌し、乳糖25ｇ及びばれいし
よ殿粉15ｇに注加して練合したのち、25メツシユ
のスクリーンを通して造粒し、45℃で乾燥して顆
粒とする。
実施例 ６
硝酸イソソルビド2.5ｇをアセトン30mlに溶解
し、これにヒドロキシプロピルセルロース12.5ｇ
を加えた混合液を、乳糖25ｇ及びばれいしよ殿粉
10ｇに注加して練合したのち、25メツシユのスク
リーンを通して造粒し、45℃で乾燥して顆粒とす
る。
実施例 ７
流動層造粒機を用い、硝酸イソソルビド2.5ｇ
を塩化メチレン−メタノール（重量比８：２）
200mlに溶解したのち、メチルセルロース7.5ｇを
加えた混合液を乳糖100ｇに噴霧し、乾燥して顆
粒とする。
試験例
実施例 ８
５−モノ硝酸イソソルビド20ｇをエタノール
100mlに溶解し、これにポリビニルピロリドン
K30の10ｇ及びヒドロキシプロピルメチルセルロ
ース30ｇを加えた混合液を、乳糖80ｇ、ばれいし
よ殿粉40ｇ及び結晶セルロース20ｇの混合粉末に
注加して練合したのち、25メツシユのスクリーン
を通して造粒し、45℃で乾燥して顆粒とする。
実施例 ９
実施例４で得た顆粒100ｇにステアリン酸マグ
ネシウム１ｇを加えて圧縮成形し、１錠あたり５
−モノ硝酸イソソルビド20mgを含有する錠剤を得
た。
本発明の組成物を用い、イソソルビド硝酸エス
テルの揮散性、結晶生成及び刺激性について試験
を行つた。
ａ 試料
実施例２〜６により得られたイソソルビド硝酸
エステル含有顆粒剤及び下記表に示す成分のうち
ヒドロキシプロピルセルロースを除いた成分を混
合し、これにエタノールに溶解したヒドロキシプ
ロピルセルロース溶液を結合剤として加え、造粒
したのち乾燥して得られた顆粒剤Ａを用いた。
ｂ 実験法
シヤーレに顆粒剤を均一な厚さに入れ、40℃の
恒温器内に保存し、各試料の表面の変化を観察し
た。
ｃ 結果
各試料の表面での結晶生成の程度は下記表に示
すとおりで、本発明の組成物を用いた顆粒剤は、
表面での結晶生成が明らかに減少し、口に含んだ
ときの刺激性も緩和された。
The present invention relates to a stable isosorbide nitrate formulation and a method for producing the same. Isosorbide nitrates include dinitroester isosorbide nitrate and mononitroester 2- or 5-monoisosorbide nitrate, both of which are known to have a coronary vasodilator effect. Among them, isosorbide nitrate is currently widely used in the form of sublingual tablets, oral tablets, sustained release tablets, injections, etc. for the purpose of treating and preventing angina attacks. Isosorbide nitrate ester easily vaporizes and decomposes at high temperatures, and may explode if heated rapidly or subjected to impact, so sufficient care must be taken when handling it. This substance has a weak but irritating bitter taste, and because it is volatile, it tends to be gradually released and volatilized from the preparation, reducing the content in the preparation, and sometimes crystal formation is observed on the surface of the preparation. . As a result of various studies to improve these drawbacks of isosorbide nitrate, the present inventors found that by adding specific ingredients to isosorbide nitrate, irritation can be alleviated, volatility can be prevented, and it can be handled stably. tablets, powders,
It has been found that the present invention is suitable for preparing solid preparations such as suppositories. The present invention provides isosorbide nitrate with one or two selected from the group consisting of polyvinylpyrrolidone, methylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose.
This is an isosorbide nitrate composition comprising more than one component. Preferably, the preparation of the present invention contains 1 part by weight of isosorbide nitrate and 0.2 to 0.2 to 0.2 to 2 or more components selected from the group consisting of polyvinylpyrrolidone, methylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose.
It is produced by dissolving and/or dispersing 30 parts by weight in a solvent and then removing the solvent. Examples of polyvinylpyrrolidone used in the present invention include polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, and polyvinylpyrrolidone K90 listed in the Japanese Pharmaceutical Ingredient Standards (1983). As the methylcellulose, methylcellulose listed in the 10th edition of the Japanese Pharmacopoeia is preferred. Hydroxypropyl cellulose is listed in the same pharmacopoeia, and hydroxypropyl methylcellulose is listed in the same pharmacopoeia.
2208, hydroxypropyl methylcellulose
2906, hydroxypropyl methylcellulose 2910
can be given. The blending ratio of isosorbide nitrate and the above components varies depending on the type of component, but 0.2 parts by weight of the above components per 1 part by weight of isosorbide nitrate.
A range of from 1 to 30 parts by weight, particularly preferably from 1 to 15 parts by weight, is suitable. The larger the amount of the component, the higher the storage stability and the delayed release of the drug from the formulation, but if it is added in an amount of 30% by weight or more, manufacturing problems will occur. When producing the preparation of the present invention, it is preferable to first dissolve isosorbide nitrate in a solvent and then dissolve and/or disperse the above components, but it is preferable to form each into a solution or suspension and then mix them. You can also do it. Examples of solvents used include acetone, methanol, ethanol, isopropanol, methylene chloride, chloroform, water, and mixtures thereof. The amount of solvent used is 2 parts by weight or more, preferably 2 parts by weight, per 1 part by weight of isosorbide nitrate.
~20 parts by weight. Next, add flavoring agent, if necessary, to this mixture.
After adding additives such as colorants, fillers, and excipients, the solvent is removed. The method for removing the solvent is one that is commonly used industrially, that is, heating under normal pressure or reduced pressure, spray granulation, and considering that the resulting powder will be used as a final preparation. A method in which a solution containing isosorbide nitrate and the above-mentioned ingredients is poured into the excipients to be added to the desired formulation with stirring, granulated, and then dried; the excipients are placed in a fluidized bed granulator , a method in which a mixed solution is sprayed, dried, and granulated can be used. Normally, these components are used as binders, but these components dissolved in a solvent are added as a binder to a mixed powder of the main drug and pharmaceutical additives such as excipients, kneaded, and then granulated. The drug of the present invention exhibited extremely superior storage stability compared to the drug obtained by wet granulation. The powder or granules of the isosorbide nitrate ester composition obtained in this way can be used as is, but they can be made into granules by adding pharmaceutical additives such as excipients, disintegrants, sustained release agents, and lubricants in a conventional manner. It can be made into fine granules, tablets, capsules, hard capsules, suppositories, ointments, etc. Example 1 2.5 g of isosorbide 5-mononitrate was added to methanol.
12.5 g of hydroxypropyl methyl cellulose 2910 is added to the solution and stirred. The mixture is dried at 45°C and then crushed to form granules. Example 2 A mixture obtained in the same manner as in Example 1 was added to lactose 25
g and 10 g of potato starch, kneaded, and then granulated through a 25 mesh screen.
Dry at ℃ to form granules. Example 3 Using a fluidized bed granulator, 10 g of isosorbide 5-mononitrate was dissolved in 200 ml of ethanol, and then 30 g of hydroxypropylcellulose was added to the mixture, which was then sprayed onto 100 g of lactose and dried to form granules. Example 4 20g of isosorbide 5-mononitrate was added to ethanol
Add 40g of methylcellulose to 100ml of lactose, add 80g of lactose, and 40g of potato starch.
After pouring and kneading into a mixed powder of 20g of crystalline cellulose, pass through a 25 mesh screen to
Dry at ℃ to form granules. Example 5 2.5 g of isosorbide 5-mononitrate was added to ethanol.
Dissolve polyvinylpyrrolidone K30 in 20ml.
Add 7.5 g of the mixture, stir, pour into 25 g of lactose and 15 g of potato starch, knead, then granulate through a 25 mesh screen and dry at 45°C to form granules. Example 6 2.5 g of isosorbide nitrate was dissolved in 30 ml of acetone, and 12.5 g of hydroxypropyl cellulose was added to this.
Add 25g of lactose and potato starch to the mixture.
After pouring into 10 g and kneading, the mixture is granulated through a 25-mesh screen and dried at 45°C to form granules. Example 7 Using a fluidized bed granulator, 2.5 g of isosorbide nitrate
methylene chloride-methanol (weight ratio 8:2)
After dissolving in 200 ml, 7.5 g of methyl cellulose was added and the mixture was sprayed onto 100 g of lactose and dried to form granules. Test Example Example 8 20g of isosorbide 5-mononitrate was added to ethanol.
Dissolve polyvinylpyrrolidone in 100ml
A mixed solution of 10 g of K30 and 30 g of hydroxypropyl methyl cellulose was poured into a mixed powder of 80 g of lactose, 40 g of potato starch, and 20 g of crystalline cellulose, kneaded, and then granulated through a 25-mesh screen. Dry at ℃ to form granules. Example 9 1 g of magnesium stearate was added to 100 g of the granules obtained in Example 4, and the mixture was compression molded to yield 5 granules per tablet.
- Tablets containing 20 mg of isosorbide mononitrate were obtained. The composition of the present invention was used to test the volatility, crystal formation, and irritation of isosorbide nitrate. a Sample The isosorbide nitrate-containing granules obtained in Examples 2 to 6 and the components shown in the table below excluding hydroxypropylcellulose were mixed, and a hydroxypropylcellulose solution dissolved in ethanol was added as a binder. In addition, granules A obtained by granulating and drying were used. b Experimental method Granules were placed in a shear dish to a uniform thickness and stored in a thermostat at 40°C, and changes in the surface of each sample were observed. c Results The degree of crystal formation on the surface of each sample is as shown in the table below, and the granules using the composition of the present invention were
Crystal formation on the surface was clearly reduced, and the irritation when placed in the mouth was also alleviated.
【表】【table】
Claims (1)
ロリドン、メチルセルロース、ヒドロキシプロピ
ルセルロース及びヒドロキシプロピルメチルセル
ロースよりなる群から選ばれた１種又は２種以上
の成分を配合することを特徴とする、安定なイソ
ソルビド硝酸エステル組成物。 ２ イソソルビド硝酸エステル１重量部とポリビ
ニルピロリドン、メチルセルロース、ヒドロキシ
プロピルセルロース及びヒドロキシプロピルメチ
ルセルロースよりなる群から選ばれた１種又は２
種以上の成分0.2〜30重量部とを、溶媒に溶解及
び／又は分散したのち溶媒を除去することを特徴
とする、安定なイソソルビド硝酸エステル組成物
の製造法。[Scope of Claims] 1. A stable method characterized by blending isosorbide nitrate with one or more components selected from the group consisting of polyvinylpyrrolidone, methylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose. Isosorbide nitrate composition. 2 1 part by weight of isosorbide nitrate and one or two selected from the group consisting of polyvinylpyrrolidone, methylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose
1. A method for producing a stable isosorbide nitrate ester composition, which comprises dissolving and/or dispersing 0.2 to 30 parts by weight of one or more components in a solvent, and then removing the solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3618084A JPS60181052A (en) | 1984-02-29 | 1984-02-29 | Stable isosorbide nitrate composition and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3618084A JPS60181052A (en) | 1984-02-29 | 1984-02-29 | Stable isosorbide nitrate composition and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60181052A JPS60181052A (en) | 1985-09-14 |
| JPH0244460B2 true JPH0244460B2 (en) | 1990-10-04 |
Family
ID=12462533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3618084A Granted JPS60181052A (en) | 1984-02-29 | 1984-02-29 | Stable isosorbide nitrate composition and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60181052A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1187750B (en) * | 1985-10-15 | 1987-12-23 | Eurand Spa | PROCEDURE FOR THE PREPARATION OF TABLETS, EVEN OF PROLONGED RELEASE, OF ISCSORBIDE-5-MONONITRATE STABILIZED AND FORMULATIONS SO OBTAINED |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5593235A (en) * | 1979-01-05 | 1980-07-15 | Nec Corp | Integrated circuit |
-
1984
- 1984-02-29 JP JP3618084A patent/JPS60181052A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5593235A (en) * | 1979-01-05 | 1980-07-15 | Nec Corp | Integrated circuit |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60181052A (en) | 1985-09-14 |
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| EXPY | Cancellation because of completion of term |