JPH04346930A - Stable aspirin enteric tablet - Google Patents
Stable aspirin enteric tabletInfo
- Publication number
- JPH04346930A JPH04346930A JP14963091A JP14963091A JPH04346930A JP H04346930 A JPH04346930 A JP H04346930A JP 14963091 A JP14963091 A JP 14963091A JP 14963091 A JP14963091 A JP 14963091A JP H04346930 A JPH04346930 A JP H04346930A
- Authority
- JP
- Japan
- Prior art keywords
- aspirin
- enteric
- tablets
- coated
- plasticizer
- 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
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims abstract description 59
- 239000003826 tablet Substances 0.000 claims description 22
- 229930006000 Sucrose Natural products 0.000 claims description 19
- 239000005720 sucrose Substances 0.000 claims description 19
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 18
- 238000009505 enteric coating Methods 0.000 claims description 15
- 239000002702 enteric coating Substances 0.000 claims description 15
- 239000002662 enteric coated tablet Substances 0.000 claims description 12
- 239000011241 protective layer Substances 0.000 claims description 6
- 239000004014 plasticizer Substances 0.000 abstract description 13
- 239000003795 chemical substances by application Substances 0.000 abstract description 12
- 230000007062 hydrolysis Effects 0.000 abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000654 additive Substances 0.000 abstract description 4
- -1 glycerol fatty acid ester Chemical class 0.000 abstract description 4
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 abstract description 4
- 239000000314 lubricant Substances 0.000 abstract description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 abstract description 4
- 230000000202 analgesic effect Effects 0.000 abstract description 3
- 230000001754 anti-pyretic effect Effects 0.000 abstract description 3
- 239000002221 antipyretic Substances 0.000 abstract description 3
- 229920001577 copolymer Polymers 0.000 abstract description 3
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 3
- 239000000194 fatty acid Substances 0.000 abstract description 3
- 229930195729 fatty acid Natural products 0.000 abstract description 3
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 3
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 abstract description 2
- 239000001087 glyceryl triacetate Substances 0.000 abstract description 2
- 235000013773 glyceryl triacetate Nutrition 0.000 abstract description 2
- 229960002622 triacetin Drugs 0.000 abstract description 2
- 230000000996 additive effect Effects 0.000 abstract 1
- 230000007721 medicinal effect Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 description 10
- 239000011248 coating agent Substances 0.000 description 9
- 238000000576 coating method Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000000087 stabilizing effect Effects 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 238000009495 sugar coating Methods 0.000 description 5
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000011247 coating layer Substances 0.000 description 2
- 238000007908 dry granulation Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940100445 wheat starch Drugs 0.000 description 2
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920000084 Gum arabic Polymers 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
- 206010028813 Nausea Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 1
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Abstract
Description
【０００１】0001
【産業上の利用分野】本発明は医療の分野で鎮痛剤及び
解熱剤として広く用いられるアスピリン製剤に関するも
のである。更に詳しくは、アスピリン製剤の望ましくな
い副作用である胃粘膜障害を低減させるため開発された
アスピリン腸溶性製剤の安定化に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an aspirin preparation widely used as an analgesic and antipyretic in the medical field. More specifically, the present invention relates to the stabilization of enteric-coated aspirin formulations, which were developed to reduce gastric mucosal damage, which is an undesirable side effect of aspirin formulations.
【０００２】0002
【従来の技術】アスピリンは鎮痛剤、解熱剤としてリュ
ウマチ性疾患等に広く用いられる。しかし、アスピリン
製剤を経口投与した場合、アスピリンの不溶性粒子が胃
内に滞留し胃粘膜を刺激するため、望ましくない副作用
として食欲不振、胃痛、悪心、嘔吐等の症状が引き起こ
される。かかる点を解決するため、胃液に不溶な腸溶性
皮膜を施し胃内を通過させ吸収部位である小腸にて崩壊
、分散する腸溶性製剤が考案されている。BACKGROUND OF THE INVENTION Aspirin is widely used as an analgesic and antipyretic for rheumatic diseases. However, when an aspirin preparation is orally administered, insoluble particles of aspirin remain in the stomach and irritate the gastric mucosa, causing undesirable side effects such as anorexia, stomach pain, nausea, and vomiting. In order to solve this problem, enteric-coated preparations have been devised, which are coated with an enteric coating that is insoluble in gastric fluid, and which pass through the stomach and disintegrate and disperse in the small intestine, which is the absorption site.
【０００３】一方、アスピリンは高温で保存したり、水
分が存在していると容易に加水分解しサリチル酸と酢酸
を生成するという問題がある。更に、アスピリンの加水
分解は種々の添加剤、例えば滑沢剤、崩壊剤の配合によ
り促進されることもよく知られている（Ｍ．Ｒ．Ｎａｚ
ａｒｅｔｈ，ｅｔ．ａｌ：Ｊ．Ｐｈａｒｍ．Ｓｃｉ．，
５０，６２０（１９６１） 等）。 従って、アスピ
リン腸溶性製剤を製造するためには、皮膜剤、可塑剤と
アスピリンとの相互作用、或はコーティング時の残留溶
媒の影響によりアスピリンの安定性が低下しないように
工夫することが必要である。[0003] On the other hand, aspirin has the problem of being easily hydrolyzed to produce salicylic acid and acetic acid when stored at high temperatures or in the presence of moisture. Furthermore, it is well known that the hydrolysis of aspirin is promoted by the addition of various additives, such as lubricants and disintegrants (M.R. Naz
areth, et. al:J. Pharm. Sci. ，
50, 620 (1961), etc.). Therefore, in order to manufacture enteric-coated aspirin preparations, it is necessary to take measures to prevent the stability of aspirin from decreasing due to the interaction between coating agents, plasticizers and aspirin, or the effects of residual solvent during coating. be.
【０００４】米国薬局方によれば、アスピリン錠の遊離
サリチル酸（以下ＦＳＡと略す）の含量規格は０．３％
以下であるのに対し、アスピリン腸溶錠のＦＳＡ含量規
格は３．０％以下で設定されており、アスピリン腸溶錠
の安定化の困難さを裏付けるものである。According to the US Pharmacopoeia, the standard content of free salicylic acid (hereinafter abbreviated as FSA) in aspirin tablets is 0.3%.
In contrast, the FSA content standard for aspirin enteric-coated tablets is set at 3.0% or less, which confirms the difficulty in stabilizing aspirin enteric-coated tablets.
【０００５】日本工業技術連盟出版「医薬品のコーティ
ング」５６〜５７頁にはアスピリンの加水分解を促進さ
せる物質を別層にする方法、又は更に非反応性の中間層
を置くという方法（米国特許明細書２，７６８，１１５
）が示されており、一例として蔗糖に種々の添加物を加
えた中間層が例示されている。一方、特開昭５６−７７
２２３号公報、或は特開昭６１−１４０２５０号公報に
同様の技術を利用したアスピリンの安定化法が報告され
ているが、いずれもその処方において日本薬局方に示さ
れるＦＳＡ含量規格（０．１５％以下）を室温で長期に
亙り満足する効果のある中間層の配合成分は何ら開示さ
れていない。つまり、アスピリン製剤に関して従来技術
においては、効果的な腸溶性製剤の安定化方法は未だ確
立していない状況にある。``Pharmaceutical Coating'' published by the Japan Federation of Industrial Science and Technology, pp. 56-57 describes a method of forming a separate layer of a substance that promotes the hydrolysis of aspirin, or a method of further placing a non-reactive intermediate layer (US patent specification). Book 2,768,115
) is shown, and an example of the intermediate layer is sucrose with various additives added. On the other hand, JP-A-56-77
A method for stabilizing aspirin using a similar technique has been reported in JP-A No. 223 and JP-A-61-140250, but in both cases, the FSA content standards (0. 15% or less) at room temperature for a long period of time. In other words, in the prior art regarding aspirin preparations, an effective method for stabilizing enteric-coated preparations has not yet been established.
【０００６】[0006]
【発明が解決しようとする課題】従って、本発明は上記
状況に鑑みなされたもので、治療上有用であり、かつ安
定性の優れたアスピリン腸溶性製剤を提供することを目
的とするものである。[Problems to be Solved by the Invention] Therefore, the present invention was made in view of the above circumstances, and an object of the present invention is to provide an enteric-coated aspirin preparation that is therapeutically useful and has excellent stability. .
【０００７】[0007]
【課題を解決するための手段】本発明者らは前記問題点
を解決するため鋭意検討を行った結果、アスピリンを含
有する裸錠と腸溶性皮膜との間に、庶糖のみからなる保
護層が存在することを特徴とするアスピリン腸溶錠を見
い出し、本発明を完成するに至った。[Means for Solving the Problems] The present inventors have conducted intensive studies to solve the above-mentioned problems, and have found that a protective layer consisting only of sucrose is provided between the aspirin-containing plain tablet and the enteric coating. The present inventors have discovered an enteric-coated aspirin tablet characterized by the presence of aspirin, and have completed the present invention.
【０００８】即ち、本発明はアスピリンと腸溶性皮膜剤
及び腸溶性皮膜剤に添加する可塑剤との相互作用による
アスピリンの加水分解を抑制するため、裸錠と腸溶性皮
膜との間に保護層として庶糖の単独成分をコーティング
することを特徴とするアスピリン腸溶錠に関するもので
ある。That is, the present invention provides a protective layer between the plain tablet and the enteric coating in order to suppress the hydrolysis of aspirin due to the interaction between aspirin and the enteric coating agent and the plasticizer added to the enteric coating agent. The present invention relates to an aspirin enteric-coated tablet characterized in that it is coated with a single component of sucrose.
【０００９】本発明において、アスピリン裸錠とは、ア
スピリンと適当な医療用添加物、例えば賦形剤、滑沢剤
を加え常法により造粒、打錠を行なって得たものをいう
。[0009] In the present invention, aspirin plain tablets refer to those obtained by adding aspirin and appropriate medical additives, such as excipients and lubricants, and granulating and tableting in a conventional manner.
【００１０】賦形剤としては、例えばコムギデンプン、
バレイショデンプン、トウモロコシデンプン、乳糖、結
晶セルロースまたは無水リン酸水素カルシウム等が挙げ
られ、特に好ましくはコムギデンプン、バレイショデン
プン、トウモロコシデンプンが挙げられる。Examples of excipients include wheat starch,
Examples include potato starch, corn starch, lactose, crystalline cellulose, and anhydrous calcium hydrogen phosphate, and particularly preferred are wheat starch, potato starch, and corn starch.
【００１１】滑沢剤としては、例えばタルク、硬化油、
ステアリン酸等が挙げられ、特に好ましくはステアリン
酸が挙げられる。[0011] As the lubricant, for example, talc, hydrogenated oil,
Examples include stearic acid, and particularly preferred is stearic acid.
【００１２】庶糖としては医薬品用に通常用いられる等
級のものが単独で使用され、又、その配合量はアスピリ
ン裸錠に対して５重量％以上あればよく、通常１５〜３
０重量％とすることが好ましい。[0012] As the sucrose, a grade commonly used for pharmaceuticals is used alone, and the amount of sucrose to be added is 5% by weight or more relative to the aspirin plain tablet, and is usually 15 to 3% by weight.
The content is preferably 0% by weight.
【００１３】腸溶性皮膜剤としては、例えばフタル酸セ
ルロースアセテート、ヒドロキシプロピルメチルセルロ
ースフタレート（以下ＨＰＭＣＰと略す）、メタアクリ
ル酸アクリル酸メチルコポリマー、ヒドロキシプロピル
メチルセルロースアセテートサクシネートまたは酢酸サ
クシネート等が挙げられ、特に好ましくは、ヒドロキシ
プロピルメチルセルロースフタレートまたはメタアクリ
ル酸アクリル酸メチルコポリマーが挙げられる。Examples of enteric coating agents include cellulose phthalate acetate, hydroxypropyl methyl cellulose phthalate (hereinafter abbreviated as HPMCP), methacrylic acid methyl acrylate copolymer, hydroxypropyl methyl cellulose acetate succinate, and acetic acid succinate. Preferably, hydroxypropyl methyl cellulose phthalate or methacrylic acid methyl acrylate copolymer is used.
【００１４】腸溶性皮膜剤に添加する可塑剤としては、
例えばグリセリン脂肪酸エステル、トリアセチンまたは
クエン酸トリエチル等が挙げられる。[0014] Plasticizers added to the enteric coating agent include:
Examples include glycerin fatty acid ester, triacetin, triethyl citrate, and the like.
【００１５】本発明のアスピリン腸溶錠は例えば次の方
法により製造することができる。アスピリン裸錠の常法
による造粒法としては、湿式造粒法、乾式造粒法が挙げ
られるが、アスピリンの加水分解を引き起こさないよう
乾式造粒法を用いる方が望ましい。庶糖のコーティング
法としては、アスピリン裸錠に庶糖がコーティングされ
れば特に限定されないが、一般的に裸錠に例えば単シロ
ップなどの庶糖水溶液を適当な糖衣パンを用いて添加す
る方法が用いられる。腸溶性皮膜剤及び可塑剤のコーテ
ィング法としては固形物表面を高分子皮膜でコーティン
グする場合に行われる通常の技術方法によってコーティ
ングすれば良いが、例えばハイコーターを用いてコーテ
ィングする、あるいは糖衣パン内でコーティング液をス
プレーガンで添加する方法などが挙げられる。The aspirin enteric-coated tablet of the present invention can be produced, for example, by the following method. Conventional granulation methods for aspirin naked tablets include wet granulation and dry granulation, but it is preferable to use dry granulation to avoid causing hydrolysis of aspirin. The coating method for sucrose is not particularly limited as long as the aspirin tablets are coated with sucrose, but generally a method is used in which a sucrose aqueous solution such as simple syrup is added to the tablets using an appropriate sugar coating pan. The enteric coating agent and plasticizer may be coated by the usual technical methods used when coating the surface of a solid material with a polymer film. An example of this method is to add the coating liquid using a spray gun.
【００１６】[0016]
【発明の効果】このようにして得られるアスピリン裸錠
と、腸溶性皮膜剤及び可塑剤からなる腸溶性皮膜の間に
、保護層として庶糖を施したアスピリン腸溶錠は、高温
条件下、例えば５０℃に長期間放置してもアスピリンの
加水分解が抑制される。従って、アスピリンが長期間に
亙って安定に保存され、その結果、薬効を良好に発揮す
ることが出来る。Effects of the Invention: Aspirin enteric-coated tablets in which sucrose is applied as a protective layer between the aspirin plain tablets obtained in this way and the enteric coating consisting of an enteric coating agent and a plasticizer can be prepared under high temperature conditions, e.g. Hydrolysis of aspirin is suppressed even if left at 50°C for a long period of time. Therefore, aspirin can be stored stably for a long period of time, and as a result, it can exhibit its medicinal efficacy well.
【００１７】[0017]
【実施例】以下に実施例及び実験例を示し、本発明を更
に具体的に説明するが、これらにより本発明はなんら限
定されるものではない。
実施例１
アスピリン ９７５０ｇ、トウモロコシデンプン１９
５０ｇを共に乾式造粒し、得られた顆粒にステアリン酸
３００ｇを加え常法により打錠し、１錠４００ｍｇ
のアスピリン裸錠を得た。これに庶糖水溶液（重量比
庶糖：精製水＝２：１）を糖衣パンを用いて添加し、
１錠当り１５０ｍｇの均一な糖衣層を施し、更にその表
面に、表１に示す腸溶性皮膜剤と可塑剤を塩化メチレン
：エタノール＝１：１（重量比）に溶かした溶液（重量
比、腸溶性皮膜剤：可塑剤：塩化メチレン：エタノール
＝２３．７５：２．５：１１２．５：１１２．５）を１
錠当りの皮膜量が２６．２５ｍｇとなるように、糖衣パ
ンを用いてコーティングし、アスピリン腸溶錠を得た。
実施例２〜５
実施例１と同様の方法で製したアスピリン裸錠に対し、
表２に示すように蔗糖量を変化させて実施例１と同様の
方法でコーティングを行い、更に実施例１と同様の方法
で表２に示す腸溶性皮膜及び可塑剤をコーティングし、
実施例２、３、４及び５のアスピリン腸溶錠を得た。[Examples] The present invention will be explained in more detail with reference to Examples and Experimental Examples, but the present invention is not limited by these in any way. Example 1 Aspirin 9750g, corn starch 19
Dry granulate 50g of the granules, add 300g of stearic acid to the resulting granules, and tablet by a conventional method, each tablet weighing 400mg.
I got aspirin tablets. Add to this a sucrose aqueous solution (weight ratio
Add sucrose: purified water = 2:1) using sugar-coated bread,
A uniform sugar coating layer of 150 mg per tablet is applied, and a solution of the enteric coating agent and plasticizer shown in Table 1 dissolved in methylene chloride:ethanol = 1:1 (weight ratio, Soluble coating agent: plasticizer: methylene chloride: ethanol = 23.75: 2.5: 112.5: 112.5) at 1
Aspirin enteric-coated tablets were obtained by coating using sugar-coated bread so that the amount of coating per tablet was 26.25 mg. Examples 2 to 5 For aspirin plain tablets produced in the same manner as in Example 1,
Coating was performed in the same manner as in Example 1 by varying the amount of sucrose as shown in Table 2, and further coated with the enteric coating and plasticizer shown in Table 2 in the same manner as in Example 1,
Aspirin enteric-coated tablets of Examples 2, 3, 4 and 5 were obtained.
【００１８】比較例
実施例１と同様の方法で、アスピリン裸錠に表１に示す
ような糖衣層成分から得られた糖衣液、腸溶性皮膜剤及
び可塑剤をコーティングし比較例１と２のアスピリン腸
溶錠を得た。また比較例３として、アスピリン裸錠に蔗
糖コーティングを施さず、直接腸溶性皮膜剤及び可塑剤
をコーティングしたアスピリン腸溶錠も製した。比較例
３の配合成分及び１錠当りの分量を表２に示す。Comparative Example In the same manner as in Example 1, aspirin plain tablets were coated with a sugar coating solution, an enteric coating agent, and a plasticizer obtained from the sugar coating layer components shown in Table 1. Aspirin enteric-coated tablets were obtained. In addition, as Comparative Example 3, aspirin enteric-coated tablets were also produced in which aspirin plain tablets were not coated with sucrose and were directly coated with an enteric coating agent and a plasticizer. Table 2 shows the ingredients of Comparative Example 3 and the amount per tablet.
【表１】[Table 1]
【表２】
なお、表１及び表２中で可塑剤として使用したグリセリ
ン脂肪酸エステルはイーストマンコダック社製のマイバ
セット９−４０Ｔ（登録商標）である。[Table 2] The glycerin fatty acid ester used as a plasticizer in Tables 1 and 2 is Myvaset 9-40T (registered trademark) manufactured by Eastman Kodak.
【００１９】実験例１
次に実施例１及び比較例１及び２で得たアスピリン腸溶
錠をガラス瓶に詰め密栓し、温度５０℃の条件下に１カ
月間保存し、経時的なＦＳＡ生成量を調べた。表３にそ
の結果を示す。表３に示される様に庶糖に通常用いられ
る糖衣成分すなわち、硫酸カルシウム、タルク、アラビ
アゴム末及びポリビニルアルコールを添加した場合安定
化効果は見られず、保護層の安定化効果は本発明のよう
な庶糖単独に限って特異的なものであることが判明した
。Experimental Example 1 Next, the aspirin enteric-coated tablets obtained in Example 1 and Comparative Examples 1 and 2 were packed in a glass bottle, tightly stoppered, and stored at a temperature of 50°C for one month, and the amount of FSA produced over time was measured. I looked into it. Table 3 shows the results. As shown in Table 3, no stabilizing effect was observed when sugar coating components commonly used for sucrose, such as calcium sulfate, talc, gum arabic powder, and polyvinyl alcohol, were added, and the stabilizing effect of the protective layer was similar to that of the present invention. It was found that this effect is specific only to sucrose alone.
【表３】[Table 3]
【００２０】実験例２
アスピリン裸錠に対する庶糖量と保護効果の関係を次の
実験により明らかにした。実施例２、３、４、５及び比
較例３で得られたアスピリン腸溶錠をガラス瓶に詰め密
栓し、５０℃の条件下に１カ月間保存し、経時的なＦＳ
Ａ生成量を調べた。表４にその結果を示す。Experimental Example 2 The relationship between the amount of sucrose and the protective effect on aspirin naked tablets was clarified by the following experiment. The aspirin enteric-coated tablets obtained in Examples 2, 3, 4, and 5 and Comparative Example 3 were packed in glass bottles, tightly stoppered, and stored at 50°C for 1 month.
The amount of A produced was investigated. Table 4 shows the results.
【表４】
表４に示す様に、蔗糖の保護層によりアスピリンが安定
化し、さらにアスピリン裸錠に対して庶糖量を増やすほ
ど安定化効果が見られるが１８．８％以上であればその
効果は変わらないことが明らかとなった。[Table 4] As shown in Table 4, aspirin is stabilized by the protective layer of sucrose, and the stabilizing effect is seen as the amount of sucrose is increased for aspirin naked tablets, but if it is 18.8% or more, the effect is greater. It became clear that there was no change.
Claims (1)
の間に、庶糖のみからなる保護層が存在することを特徴
とするアスピリン腸溶錠。1. An aspirin enteric-coated tablet, characterized in that a protective layer consisting only of sucrose is present between the aspirin-containing plain tablet and the enteric coating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14963091A JPH04346930A (en) | 1991-05-25 | 1991-05-25 | Stable aspirin enteric tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14963091A JPH04346930A (en) | 1991-05-25 | 1991-05-25 | Stable aspirin enteric tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04346930A true JPH04346930A (en) | 1992-12-02 |
Family
ID=15479429
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14963091A Pending JPH04346930A (en) | 1991-05-25 | 1991-05-25 | Stable aspirin enteric tablet |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04346930A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH072648A (en) * | 1993-04-23 | 1995-01-06 | Ciba Geigy Ag | Slowly releasable drug delivery device |
| EP0693282A3 (en) * | 1994-07-18 | 1996-12-18 | Lilly Co Eli | Duloxetine enteric pellets |
| US6268355B1 (en) | 1997-06-25 | 2001-07-31 | Teikoku Seiyaku Co., Ltd. | Stable aspirin-containing preparations for external use |
| GB2374343A (en) * | 2001-04-11 | 2002-10-16 | Bioprogress Tech Int Inc | Modified cellulose films plasticised with fruit acids or salts thereof |
| JP2006083162A (en) * | 2004-08-18 | 2006-03-30 | Nippon Shinyaku Co Ltd | Double-coated tablet |
| US7029663B1 (en) | 1997-06-25 | 2006-04-18 | Teikoku Seiyaku Co., Ltd. | Stable ointment containing acetylsalicylic acid |
| JP2010059119A (en) * | 2008-09-05 | 2010-03-18 | Towa Yakuhin Kk | Enteric coated aspirin tablet |
| JP2015517994A (en) * | 2012-03-29 | 2015-06-25 | ヘイロー セラピューティックス， エルエルシー | Halofuginone dosage form and use thereof |
| JP2015526498A (en) * | 2013-08-02 | 2015-09-10 | サノフイ | Pharmaceutical tablets containing acetylsalicylic acid and clopidogrel |
| US9433632B2 (en) | 2011-11-30 | 2016-09-06 | Takeda Pharmaceutical Company Limited | Dry coated tablet |
-
1991
- 1991-05-25 JP JP14963091A patent/JPH04346930A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH072648A (en) * | 1993-04-23 | 1995-01-06 | Ciba Geigy Ag | Slowly releasable drug delivery device |
| JP2006342187A (en) * | 1993-04-23 | 2006-12-21 | Novartis Ag | Controlled release drug delivery device |
| EP0693282A3 (en) * | 1994-07-18 | 1996-12-18 | Lilly Co Eli | Duloxetine enteric pellets |
| CN1106191C (en) * | 1994-07-18 | 2003-04-23 | 伊莱利利公司 | Duloxetine enteric pellets |
| US7029663B1 (en) | 1997-06-25 | 2006-04-18 | Teikoku Seiyaku Co., Ltd. | Stable ointment containing acetylsalicylic acid |
| US6268355B1 (en) | 1997-06-25 | 2001-07-31 | Teikoku Seiyaku Co., Ltd. | Stable aspirin-containing preparations for external use |
| GB2374343A (en) * | 2001-04-11 | 2002-10-16 | Bioprogress Tech Int Inc | Modified cellulose films plasticised with fruit acids or salts thereof |
| JP2006083162A (en) * | 2004-08-18 | 2006-03-30 | Nippon Shinyaku Co Ltd | Double-coated tablet |
| JP2010059119A (en) * | 2008-09-05 | 2010-03-18 | Towa Yakuhin Kk | Enteric coated aspirin tablet |
| US9433632B2 (en) | 2011-11-30 | 2016-09-06 | Takeda Pharmaceutical Company Limited | Dry coated tablet |
| US10238605B2 (en) | 2011-11-30 | 2019-03-26 | Takeda Pharmaceutical Company Limited | Dry coated tablet |
| JP2015517994A (en) * | 2012-03-29 | 2015-06-25 | ヘイロー セラピューティックス， エルエルシー | Halofuginone dosage form and use thereof |
| JP2015526498A (en) * | 2013-08-02 | 2015-09-10 | サノフイ | Pharmaceutical tablets containing acetylsalicylic acid and clopidogrel |
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