JPS63238015A - Slowly releasing capsule preparation - Google Patents
Slowly releasing capsule preparationInfo
- Publication number
- JPS63238015A JPS63238015A JP6984187A JP6984187A JPS63238015A JP S63238015 A JPS63238015 A JP S63238015A JP 6984187 A JP6984187 A JP 6984187A JP 6984187 A JP6984187 A JP 6984187A JP S63238015 A JPS63238015 A JP S63238015A
- Authority
- JP
- Japan
- Prior art keywords
- capsule
- drug
- stomach
- agar
- film
- 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
- 239000002775 capsule Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 229920001817 Agar Polymers 0.000 claims abstract description 21
- 239000008272 agar Substances 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 21
- 239000000126 substance Substances 0.000 claims abstract description 13
- 238000013268 sustained release Methods 0.000 claims description 9
- 239000012730 sustained-release form Substances 0.000 claims description 9
- 239000007963 capsule composition Substances 0.000 claims description 5
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 3
- 229940088679 drug related substance Drugs 0.000 claims description 3
- 239000004014 plasticizer Substances 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 abstract description 13
- 238000000034 method Methods 0.000 abstract description 8
- 239000011248 coating agent Substances 0.000 abstract description 6
- 238000000576 coating method Methods 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- ARHWPKZXBHOEEE-UHFFFAOYSA-N alclofenac Chemical compound OC(=O)CC1=CC=C(OCC=C)C(Cl)=C1 ARHWPKZXBHOEEE-UHFFFAOYSA-N 0.000 abstract description 4
- 229960005142 alclofenac Drugs 0.000 abstract description 4
- 239000001913 cellulose Substances 0.000 abstract description 4
- 229920002678 cellulose Polymers 0.000 abstract description 3
- 230000005484 gravity Effects 0.000 abstract description 3
- 229960000905 indomethacin Drugs 0.000 abstract description 3
- 229920006243 acrylic copolymer Polymers 0.000 abstract description 2
- 230000006378 damage Effects 0.000 abstract description 2
- 238000013329 compounding Methods 0.000 abstract 1
- 210000000936 intestine Anatomy 0.000 abstract 1
- 210000000056 organ Anatomy 0.000 abstract 1
- 230000000638 stimulation Effects 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 108010010803 Gelatin Proteins 0.000 description 6
- 239000008273 gelatin Substances 0.000 description 6
- 229920000159 gelatin Polymers 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 235000011852 gelatine desserts Nutrition 0.000 description 6
- 238000010828 elution Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 229960004166 diltiazem Drugs 0.000 description 2
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 244000152045 Themeda triandra Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- -1 acetal diethylaminoacetate Chemical class 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 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
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229960004782 chlordiazepoxide Drugs 0.000 description 1
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Abstract
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明は徐放性カプセル製剤に関する。[Detailed description of the invention] (Industrial application field) The present invention relates to sustained release capsule formulations.
（従来の技術およびその問題点）
従来、カプセル製剤は薬剤物質を含む内容物をゼラチン
を主成分とする皮膜により被覆することにより形成され
る。このゼラチンカプセルは強靭である反面、酸に弱く
胃内で容易に溶解し、内容物が一挙に放出される。(Prior Art and its Problems) Conventionally, capsule preparations are formed by coating contents containing a drug substance with a film containing gelatin as a main component. Although gelatin capsules are strong, they are sensitive to acids and easily dissolve in the stomach, allowing the contents to be released all at once.
ところが、ある種の薬剤は、胃内で徐々に放出し、薬効
を持続させることが望まれている。これに必要な徐放性
の製剤は従来製剤中の賦杉剤を改良することにより検討
されてきた。賦形剤によるものらかなり有効であるが、
未だ完全に満足のいくらのは得られていない。However, it is desirable for certain drugs to be released gradually in the stomach to maintain their efficacy. The sustained-release preparations necessary for this have been studied by improving the excipients in conventional preparations. Although those using excipients are quite effective,
I still haven't gotten any amount of complete satisfaction.
（発明の内容）
本発明者等は薬剤のカプセル化による徐放性製剤の研究
開発を進めてきた。種々の皮膜物質の中で寒天が優れた
特性を有していることを見出した。(Contents of the Invention) The present inventors have been conducting research and development of sustained release preparations by encapsulating drugs. It has been found that agar has excellent properties among various coating materials.
即ち、本発明は薬剤物質を含む内容物を寒天皮膜により
カプセル化した徐放性カプセル製剤を提供する。That is, the present invention provides a sustained release capsule formulation in which the contents containing a drug substance are encapsulated with an agar film.
寒天皮膜はゼラチンと異なり、膨潤時に半透膜的作用を
示すことが解った。従って、膨潤時、即ち胃内において
半透膜的作用により、胃内で薬剤が徐々に放出され、徐
放性カプセル製剤の特性を発揮する。また、寒天皮膜は
膨潤してもゼラチンより粘着性か低く、胃壁に付着する
恐れが少なく、カプセルの径や比重を調節すると、胃内
に浮遊する可能性もある。It was found that agar film, unlike gelatin, behaves like a semipermeable membrane when it swells. Therefore, when the drug is swollen, the drug is gradually released in the stomach due to a semipermeable membrane action in the stomach, exhibiting the characteristics of a sustained-release capsule preparation. Furthermore, even when the agar film swells, it is less sticky than gelatin, so there is less risk of it adhering to the stomach wall, and if the diameter and specific gravity of the capsule are adjusted, there is a possibility that it will float in the stomach.
寒天は紅ソウ類中に存在する粘着物で、主成分はアガロ
ースと考えられている。Agar is a sticky substance that exists in red grass, and its main component is thought to be agarose.
カプセルは上記寒天を用いて従来公知の種々の方法で生
産される。寒天はゼラチンに比べて膨潤時の粘着性が少
ないので、二つの半球を形成してこれを接着するという
従来法による継目のあるカー ブセルの製法は困難であ
る。従って、継目なしのカプセル、いわゆるシームレス
カプセルの製法が最適である。シームレスカプセルは一
般に二重円筒オリフィスからカプセル内容物とカプセル
皮膜物質を押出し、これから凝固液中で球形の液滴を形
成するいわゆる滴下法が一般的である。滴下法の具体例
は特公昭５１−８８７５号公報および特公昭５３−１０
６７号公報等が挙げられる。Capsules are produced using the above-mentioned agar by various conventionally known methods. Agar has less stickiness than gelatin when it swells, so it is difficult to make curve cells with a seam using the traditional method of forming two hemispheres and gluing them together. Therefore, a method for producing seamless capsules, so-called seamless capsules, is optimal. Seamless capsules are generally manufactured using the so-called dripping method, in which the capsule contents and capsule coating material are extruded through a double cylindrical orifice to form spherical droplets in a coagulating liquid. Specific examples of the dropping method are given in Japanese Patent Publication No. 51-8875 and Japanese Patent Publication No. 53-10.
Publication No. 67 and the like can be mentioned.
カプセルの寒天皮膜には寒天の他に、可塑剤、高分子物
質、所望により薬剤を含んでもよい。高分子物質の例と
しては天然高分子、例えば、ゼラチン、デンプンおよび
その誘導体（デキストリン、゛スターチ類）、アラビア
ゴム、アルギン酸ナトリウム、トラガント等：合成高分
子、例えば、セルロースおよびその誘導体（エチルセル
ロース、カルボキシメチルセルロース、カルボキシメチ
ルセルロースカルシウム、カルボキシメチルセルロース
ナトリウム、カルボキシメチルエチルセルロース、結晶
セルロース、酢酸セルロース、酢酸フタル酸セルロース
、ヒドロキシプロピルメチルセルロース類、粉末セルロ
ース、ヒドロキシプロピルセルロース、メチルセルロー
ス）、ポリビニルアルコール、ポリビニルピロリドン、
ポリビニルアセタールジエチルアミノアセテート、カル
ボキシビニルポリマー、アクリル系コポリマー類（ポリ
アクリル酸、メタアクリル酸−アクリル酸エチルコポリ
マー、メタアクリル酸−メタアクリル酸メチルコポリマ
ー等）またはこれらの混合物等が挙げられる。高分子物
質は造膜性が良好で膜の物理的強度が大きいので、寒天
皮膜の強度をより一層高め、かつ、水の浸透に対するバ
リアー性にも優れている。従って、持続放出性カプセル
剤としての効果を向上させる。In addition to agar, the agar film of the capsule may contain a plasticizer, a polymeric substance, and, if desired, a drug. Examples of polymeric substances include natural polymers, such as gelatin, starch and its derivatives (dextrin, starches), gum arabic, sodium alginate, tragacanth, etc. Synthetic polymers, such as cellulose and its derivatives (ethyl cellulose, carboxylic acid) Methylcellulose, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carboxymethylethylcellulose, crystalline cellulose, cellulose acetate, cellulose acetate phthalate, hydroxypropylmethylcelluloses, powdered cellulose, hydroxypropylcellulose, methylcellulose), polyvinyl alcohol, polyvinylpyrrolidone,
Examples include polyvinyl acetal diethylaminoacetate, carboxyvinyl polymer, acrylic copolymers (polyacrylic acid, methacrylic acid-ethyl acrylate copolymer, methacrylic acid-methyl methacrylate copolymer, etc.), and mixtures thereof. Since polymeric substances have good film-forming properties and high physical strength of the film, they further increase the strength of the agar film and also have excellent barrier properties against water penetration. Therefore, the effect as a sustained release capsule is improved.
高分子物質の配合量は１０〜５０重量％、好ましくは１
０〜３０重量％である。寒天皮膜に配合する薬剤の例と
しては持続放出性をもたせることが望ましい循環器用薬
にフエジビン、ジルチアゼム、ベラパミル、ジビリダモ
ール等）や非ステロイド系抗炎症薬（インドメタシン、
ケトプロフェン、イブプロフェン等）や胃潰瘍治療薬（
シメチジン、ラニチジン、ファモチジン等）や精神神経
用薬（メブロバメート、クロルジアゼポキシド、ジアゼ
パム等）などが挙げられ、水溶性・水難溶性のいかんを
問わずほとんどの薬剤を用いることが可能である。The blending amount of the polymeric substance is 10 to 50% by weight, preferably 1
It is 0 to 30% by weight. Examples of drugs to be added to the agar film include cardiovascular drugs that are preferably sustained-release, such as fuedibine, diltiazem, verapamil, and diviridamol, and non-steroidal anti-inflammatory drugs (indomethacin, etc.).
ketoprofen, ibuprofen, etc.) and gastric ulcer treatment drugs (
cimetidine, ranitidine, famotidine, etc.) and psychiatric and neurological drugs (mebrobamate, chlordiazepoxide, diazepam, etc.), and most drugs can be used regardless of whether they are water-soluble or poorly water-soluble.
カプセル内容物は種々の薬剤と油状物質を含む。The contents of the capsule include various drugs and oily substances.
好適な薬剤の例としては水溶性であり、かつ、ある程度
の脂溶性も持つ薬剤（ジルチアゼム、アルクロフェナッ
ク、インドメタシン等）が最適であるが、油状物質中に
薬剤を懸濁させて用いる場合にはほとんどの薬剤を用い
る事が可能である。Examples of suitable drugs include those that are water-soluble and have some degree of fat-solubility (diltiazem, alclofenac, indomethacin, etc.); It is possible to use most drugs.
油状物質は通常カプセル内容物に用いるものであり、水
に不溶の揮発性または不揮発性液体、例えば、製剤用添
加物に指定されている植物油、芳香族および脂肪族炭化
水素、エーテル類、エステル類、アルコール類、有機酸
等：水に可溶の不揮発性液体、例えば、ポリエチレング
リコール等；水に可溶の比較的不揮発性化合物、例えば
、プロピレングリコール、イソプロピルアルコール等が
挙げられる。これらはいずれも安定性、安全性や製剤化
の面において最適である。薬剤が親水性物質の場合は、
油状物質はワックス、所望によりレシチンの組合せ、ま
たは油と油ゲル化剤の組合せか使用される。Oily substances are those normally used in capsule contents and include volatile or non-volatile liquids that are insoluble in water, such as vegetable oils, aromatic and aliphatic hydrocarbons, ethers and esters, which are specified as additives for formulations. , alcohols, organic acids, etc.: nonvolatile liquids soluble in water, such as polyethylene glycol; and relatively nonvolatile compounds soluble in water, such as propylene glycol, isopropyl alcohol, etc. All of these are optimal in terms of stability, safety, and formulation. If the drug is a hydrophilic substance,
The oily substance used may be a wax, optionally a combination of lecithin, or a combination of oil and an oil gelling agent.
（発明の効果）
寒天皮膜のカプセルは膨潤時の半透膜的作用により、内
容物が徐々に放出される。カプセルの比重を１．１以下
、粒径２Ｊ！１以上に調節すれば胃内で浮遊する。胃内
で浮遊した場合、胃内で直接作用のある薬物の効果が持
続する。特に、薬物の吸収部位が小腸上部に限定されて
いる場合に持続的吸収が期待できる。また、小腸下部と
大腸の消化管内で分解される薬物の持続性を望むために
消化管上部での持続放出が期待できる。本発明のカブセ
ル製剤は膨潤時の粘着性が低く、胃または腸壁への接着
が少なく、刺激と傷害が少ない。本発明のカプセル製剤
は親水性物質の複合体も使用できる。(Effects of the Invention) The content of the agar-film capsule is gradually released due to its semipermeable membrane action when it swells. The specific gravity of the capsule is less than 1.1 and the particle size is 2J! If adjusted to 1 or more, it will float in the stomach. When suspended in the stomach, the effects of drugs that act directly in the stomach persist. In particular, sustained absorption can be expected when the absorption site of the drug is limited to the upper small intestine. In addition, since the drug is degraded in the lower small intestine and large intestine, it is expected that the drug will be released sustainably in the upper gastrointestinal tract. The capsule formulation of the present invention has low stickiness when swollen, less adhesion to the stomach or intestinal wall, and less irritation and injury. A complex of hydrophilic substances can also be used in the capsule formulation of the present invention.
（実施例） 本発明を実施例により更に詳細に説明する。(Example) The present invention will be explained in more detail with reference to Examples.
実施例１
皮膜処方として、ゼラチン：寒天＝Ｄ−ソルビトールを
重量比で９：Ｏ：１１５：４：ｌおよび３：６：ｌの３
種類を用意し、カプセル内容物としてアルクロフェナッ
クを中鎖脂肪酸トリグリセライド（ＭＣＴ）に６％ｗ／
ｗで溶解した溶液を用いた。それぞれの皮膜処方につい
て膜厚を４段階（１１６〜２３６μだ）に変え、二重ノ
ズル法により約６１のシームレスソフトカプセルを調整
し、試料とした。Example 1 As a film formulation, gelatin:agar=D-sorbitol was prepared in a weight ratio of 9:O:115:4:l and 3:6:l.
As capsule contents, Alclofenac is added to medium chain fatty acid triglyceride (MCT) at 6% w/
A solution dissolved in w was used. For each film formulation, the film thickness was changed to four levels (116 to 236 μm), and about 61 seamless soft capsules were prepared by the double nozzle method and used as samples.
上記の試料について日本薬局方の回転バスケット法を利
用し、溶出実験を行った。結果を第１図に示す。第１図
は皮膜処方５：４：１のカプセルに。An elution experiment was conducted on the above sample using the Japanese Pharmacopoeia's rotating basket method. The results are shown in Figure 1. Figure 1 shows a capsule with a film formulation of 5:4:1.
ついての放出曲線を膜厚をパラメーターとして示し、図
中０印線は寒天無添加で膜厚２０３μズの場合、また・
、ム、■、◆印線は皮膜処方が５：４：ｌで膜厚がそれ
ぞれ＋２９．１６５．２０２．２２７μｍのカプセルの
溶出曲線を示す。すなわち、寒天無添加のカプセルにお
いては溶出実験開始後直ちに崩壊してほぼ３０分で放出
を完了してしまうのに対して、寒天を含む処方のカプセ
ルでは放出終了後においても原形を保ち、崩壊は全く認
められなかった。また、５０％溶出時間は約２〜４時間
まで延長され、良好な徐放性を示すことが確認された。The release curve for the film is shown using the film thickness as a parameter.
, M, ■, and ◆ lines indicate the dissolution curves of capsules with a film formulation of 5:4:l and a film thickness of +29.165.202.227 μm, respectively. In other words, capsules without agar disintegrate immediately after the start of the dissolution experiment and release is completed in approximately 30 minutes, whereas capsules formulated with agar retain their original shape even after release and do not disintegrate. It was not recognized at all. Furthermore, the 50% elution time was extended to approximately 2 to 4 hours, confirming that good sustained release properties were exhibited.
さらにその効果は膜厚に依存することも示された。Furthermore, it was also shown that the effect depends on the film thickness.
実施例２
実施例１の試料のうち皮膜処方３：６：Ｉ、膜１′１１
３３μｍのカプセルを試料とした。溶出実験は実施例１
に記載の方法を用い、溶出のｐＨを４．０．５．０．６
．０．６，８の４段階に変えて実験を行った。結果を第
２図に示す。第２図において◆、■、ム、・印線はそれ
ぞれｐ４．０．５．０．６．０．６゜８の溶出液を用い
た場合の溶出実験結果である。Example 2 Among the samples of Example 1, film formulation 3:6:I, film 1'11
A 33 μm capsule was used as a sample. Elution experiment is Example 1
Using the method described in
．． The experiment was conducted with four levels of 0.6 and 8. The results are shown in Figure 2. In FIG. 2, the lines marked ♦, ■, mm, and .are the results of an elution experiment using an eluent of p4.0.5.0.6.0.6°8, respectively.
なお横軸は時間の平方根で示す。すなわち、アルクロフ
ェナックのｐＫａ値（４，０７）に近接したｐＨ４以下
では全く溶出しなかったのに対して、アルカリ性側へ移
行するにつれて放出は次第に速やかになることが示され
た。Note that the horizontal axis is expressed as the square root of time. In other words, it was shown that while there was no elution at pH 4 or below, which is close to the pKa value of alclofenac (4,07), the release gradually became more rapid as the pH shifted to the alkaline side.
第１図は実施例１の実験データを示す図であり、縦軸は
放出率、横軸は時間を示すグラフである。
第２図は実施例２の実験データを示す図であり、縦軸は
放出率、横軸は時間を示すグラフである。FIG. 1 is a graph showing experimental data of Example 1, with the vertical axis showing the release rate and the horizontal axis showing time. FIG. 2 is a graph showing experimental data of Example 2, with the vertical axis showing the release rate and the horizontal axis showing time.
Claims (1)
した徐放性カプセル製剤。 ２、寒天皮膜が寒天ベース、可塑剤および高分子物質か
らなる第１項記載の徐放性カプセル製剤。 ３、寒天皮膜が更に薬剤を含む第２項記載の徐放性カプ
セル製剤。[Scope of Claims] 1. A sustained-release capsule preparation in which a drug substance-containing content is encapsulated with an agar film. 2. The sustained-release capsule preparation according to item 1, wherein the agar film comprises an agar base, a plasticizer, and a polymeric substance. 3. The sustained release capsule formulation according to item 2, wherein the agar film further contains a drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6984187A JPS63238015A (en) | 1987-03-24 | 1987-03-24 | Slowly releasing capsule preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6984187A JPS63238015A (en) | 1987-03-24 | 1987-03-24 | Slowly releasing capsule preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63238015A true JPS63238015A (en) | 1988-10-04 |
Family
ID=13414431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6984187A Pending JPS63238015A (en) | 1987-03-24 | 1987-03-24 | Slowly releasing capsule preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63238015A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01193216A (en) * | 1988-01-29 | 1989-08-03 | Fuji Kapuseru Kk | Soft capsule and globular article |
| EP0882449A1 (en) * | 1997-06-03 | 1998-12-09 | Uni Colloid Kabushiki Kaisha | Sustained release capsule and method for preparing the same |
| JP2001247453A (en) * | 2000-03-09 | 2001-09-11 | Marin Pharm:Kk | Film for soft capsule and soft capsule formulation |
| JP2005523346A (en) * | 2001-10-18 | 2005-08-04 | フイルメニツヒ ソシエテ アノニム | Spray-dried composition and method for producing the same |
| WO2009087938A1 (en) * | 2008-01-10 | 2009-07-16 | Takeda Pharmaceutical Company Limited | Capsule formulation |
| WO2018225770A1 (en) * | 2017-06-09 | 2018-12-13 | 富士カプセル株式会社 | Seamless capsule coating composition and seamless capsule |
-
1987
- 1987-03-24 JP JP6984187A patent/JPS63238015A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01193216A (en) * | 1988-01-29 | 1989-08-03 | Fuji Kapuseru Kk | Soft capsule and globular article |
| EP0882449A1 (en) * | 1997-06-03 | 1998-12-09 | Uni Colloid Kabushiki Kaisha | Sustained release capsule and method for preparing the same |
| US6030641A (en) * | 1997-06-03 | 2000-02-29 | Uni Colloid Kabushiki Kaisha | Sustained release capsule and method for preparing the same |
| JP2001247453A (en) * | 2000-03-09 | 2001-09-11 | Marin Pharm:Kk | Film for soft capsule and soft capsule formulation |
| JP2005523346A (en) * | 2001-10-18 | 2005-08-04 | フイルメニツヒ ソシエテ アノニム | Spray-dried composition and method for producing the same |
| WO2009087938A1 (en) * | 2008-01-10 | 2009-07-16 | Takeda Pharmaceutical Company Limited | Capsule formulation |
| JP5421126B2 (en) * | 2008-01-10 | 2014-02-19 | 武田薬品工業株式会社 | Capsule formulation |
| WO2018225770A1 (en) * | 2017-06-09 | 2018-12-13 | 富士カプセル株式会社 | Seamless capsule coating composition and seamless capsule |
| JPWO2018225770A1 (en) * | 2017-06-09 | 2020-04-09 | 富士カプセル株式会社 | Composition for seamless capsule film and seamless capsule |
| US11364206B2 (en) | 2017-06-09 | 2022-06-21 | Fuji Capsule Co., Ltd. | Seamless capsule shell composition and seamless capsule |
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