JPS6333324A - Composition for filling in soft capsule - Google Patents
Composition for filling in soft capsuleInfo
- Publication number
- JPS6333324A JPS6333324A JP15508786A JP15508786A JPS6333324A JP S6333324 A JPS6333324 A JP S6333324A JP 15508786 A JP15508786 A JP 15508786A JP 15508786 A JP15508786 A JP 15508786A JP S6333324 A JPS6333324 A JP S6333324A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- fatty acid
- acid ester
- sorbitan fatty
- acetaminophen
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 51
- 239000007901 soft capsule Substances 0.000 title claims abstract description 32
- 238000011049 filling Methods 0.000 title claims abstract description 29
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 60
- -1 sorbitan fatty acid ester Chemical class 0.000 claims abstract description 31
- 229960005489 paracetamol Drugs 0.000 claims abstract description 30
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 28
- 229930195729 fatty acid Natural products 0.000 claims abstract description 28
- 239000000194 fatty acid Substances 0.000 claims abstract description 28
- 229920001214 Polysorbate 60 Polymers 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 239000003795 chemical substances by application Substances 0.000 claims abstract 3
- 239000004480 active ingredient Substances 0.000 claims description 30
- 238000002156 mixing Methods 0.000 claims description 8
- 239000001993 wax Substances 0.000 claims description 7
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 5
- 230000000202 analgesic effect Effects 0.000 abstract description 2
- 239000000730 antalgic agent Substances 0.000 abstract description 2
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 2
- 230000001754 anti-pyretic effect Effects 0.000 abstract description 2
- 239000002221 antipyretic Substances 0.000 abstract description 2
- 229920000053 polysorbate 80 Polymers 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 238000013329 compounding Methods 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 abstract 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 abstract 1
- 229940068968 polysorbate 80 Drugs 0.000 abstract 1
- 238000009472 formulation Methods 0.000 description 8
- 229960001948 caffeine Drugs 0.000 description 7
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 235000013871 bee wax Nutrition 0.000 description 5
- 239000012166 beeswax Substances 0.000 description 5
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 5
- 229960000514 ethenzamide Drugs 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 235000019485 Safflower oil Nutrition 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000003813 safflower oil Substances 0.000 description 4
- 235000005713 safflower oil Nutrition 0.000 description 4
- 239000012085 test solution Substances 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 235000013869 carnauba wax Nutrition 0.000 description 3
- 239000004203 carnauba wax Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- NTCYWJCEOILKNG-ROLPUNSJSA-N [(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-dimethylazanium;chloride Chemical compound Cl.CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 NTCYWJCEOILKNG-ROLPUNSJSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 2
- 229960000920 dihydrocodeine Drugs 0.000 description 2
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical group OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229940086241 acetaminophen 400 mg Drugs 0.000 description 1
- KSUUMAWCGDNLFK-UHFFFAOYSA-N apronal Chemical compound C=CCC(C(C)C)C(=O)NC(N)=O KSUUMAWCGDNLFK-UHFFFAOYSA-N 0.000 description 1
- 229960004459 apronal Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000007765 cera alba Substances 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229940073563 dl- methylephedrine hydrochloride Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 229940051020 methylephedrine hydrochloride Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、油性溶剤に難溶性の活性成分を分散した懸濁
液である軟カプセル充填用組成物の流動性及び該活性成
分の利用率の改善に間する。Detailed Description of the Invention [Industrial Application Field] The present invention is directed to improving the fluidity and utilization rate of the active ingredient of a composition for filling soft capsules, which is a suspension of a sparingly soluble active ingredient dispersed in an oily solvent. Take time to improve.
［従来の技術］
軟カプセル剤は、一般に植物油あるいはトリ中鎖脂肪酸
グリセライド等の油性溶剤を基剤とするが、これらの基
剤に溶解しない活性成分を製剤化する場合、活性成分は
分散状態で製剤化せざるを得ない。しかし、その配合量
が多くなると、懸濁液の流動性の低下から、製剤化が困
難となることが知られている。とくにアセトアミノフェ
ンは、解熱、鎮痛消炎剤として単独又は他の活性成分と
の併用で使用され、かかる目的の場合、 １回服用量が
１５０〜３ ０ ０ ｍｇと多く、通常の軟カプセル用
基剤に溶解し難いため、流動性が悪く製剤化が困難であ
ることが知られている。[Prior Art] Soft capsules are generally based on an oily solvent such as vegetable oil or tri-medium chain fatty acid glyceride, but when formulating active ingredients that do not dissolve in these bases, the active ingredients are dispersed. It has no choice but to be formulated. However, it is known that when the amount of the suspension increases, the fluidity of the suspension decreases, making it difficult to formulate a formulation. In particular, acetaminophen is used alone or in combination with other active ingredients as an antipyretic, analgesic and anti-inflammatory agent, and for such purposes, the single dose is as high as 150 to 300 mg, and it can be used in standard soft capsule formulations. It is known that it is difficult to formulate a formulation due to poor fluidity because it is difficult to dissolve in a drug.
このため、特開昭６０−２１８３１８号公報には、アセ
トアミノフェン又は、アセトアミノフェン配合剤につい
て、油性基剤に大豆レシチン、ボリオキシエチレン硬化
ヒマシ油等の界面活性剤の配合により、流動性が改善さ
れ製剤化を容易にする軟カプセル充填用組成物について
記載されている。For this reason, Japanese Patent Application Laid-Open No. 60-218318 discloses that acetaminophen or acetaminophen combination preparations are improved in fluidity by blending a surfactant such as soybean lecithin or polyoxyethylene hydrogenated castor oil into an oily base. A composition for filling soft capsules is described which has improved properties and facilitates formulation.
［発明が解決しようとする問題点コ
上記の従来技術には問題点があり、実用上満足し得るも
のとは言い難い、すなわち、アセトアミノフェンのよう
な非油溶性の活性成分が油性溶剤に懸濁された場合、流
動性の低下と同時に、該活性成分は消化管での溶解性が
低下し易いことが知られる。これは、活性成分粒子の表
面に油性溶剤による被膜が形成され、活性成分の消化管
での溶解速度が低下するものであると推測される。[Problems to be Solved by the Invention] The above-mentioned prior art has problems and cannot be said to be practically satisfactory. It is known that when suspended, the solubility of the active ingredient in the gastrointestinal tract tends to decrease as well as the fluidity decreases. This is presumed to be due to the formation of a film of oil-based solvent on the surface of the active ingredient particles, which reduces the dissolution rate of the active ingredient in the digestive tract.
したがって、理想的には軟カプセル製剤の製剤化に際し
、活性成分を油性溶剤に懸濁状態で調製する必要がある
場合、その充填用組成物の流動性の改善と同時に、消化
管内での活性成分の溶解性、すなわち活性成分の利用率
をも考慮する必要があることは明らかである。Therefore, ideally when formulating a soft capsule formulation, if the active ingredient needs to be prepared in a suspended state in an oily solvent, it is possible to improve the fluidity of the filling composition and at the same time to improve the flow of the active ingredient in the gastrointestinal tract. It is clear that the solubility of the active ingredient, ie the utilization rate of the active ingredient, also needs to be taken into account.
［問題を解決するための手段］
本発明者らは、前記目的を達成する手段を種々検討した
結果、油性基剤にソルビタン脂肪酸エステルと、ポリオ
キシエチレンソルビタン脂肪酸エステルを配合すること
により、懸濁状態でありながら、高濃度に活性成分を配
合した製剤を調製することが可能であることを見出し、
さらに本組成物にワックス類を配合することによって、
その効果が増強され、かつ活性成分の利用率をも低下し
ないことを見出し、本発明を完成した。[Means for Solving the Problem] As a result of various studies on the means for achieving the above object, the present inventors have found that by blending sorbitan fatty acid ester and polyoxyethylene sorbitan fatty acid ester into an oily base, suspension can be achieved. discovered that it is possible to prepare formulations containing active ingredients at high concentrations while
Furthermore, by blending waxes into this composition,
The present invention was completed based on the discovery that the effect is enhanced and the utilization rate of the active ingredient is not reduced.
一般に、油性基剤に不溶性の活性成分を分散して軟カプ
セル製剤とする場合、ソルビタン脂肪酸エステルあるい
は、ポリオキシエチレンソルビタン脂肪酸エステル単味
、又は他の活面活性剤の配合であってもある程度は、そ
の流動性を改善することは可能であることは知られてい
る。しかし、これら単味の界面活性剤の配合では、充填
用組成物の流動性の改善も不充分であり、かつ活性成分
の消化管への溶解性が低く、利用率が低下するという欠
点があった。Generally, when dispersing an insoluble active ingredient in an oily base to form a soft capsule formulation, even if sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester alone, or other active surfactants are blended, to some extent. It is known that it is possible to improve its flowability. However, the combination of these single surfactants has the disadvantage that the fluidity of the filling composition is not sufficiently improved, and the solubility of the active ingredient in the digestive tract is low, resulting in a lower utilization rate. Ta.
ところが、ソルビタン脂肪酸エステルとポリオキシエチ
レンソルビタン脂肪酸エステルの２種の界面活性剤の配
合により、各々の単味の場合と比較して極めて懸濁液の
流動性が改善され、さらにワックス類を添加することに
よって、その効果が促進されることを見出した。さらに
驚くべきことには、こうして調製された組成物よりなる
製剤は、その活性成分の利用率を低下しないことを見出
した。However, the combination of two types of surfactants, sorbitan fatty acid ester and polyoxyethylene sorbitan fatty acid ester, significantly improves the fluidity of the suspension compared to the case of each surfactant alone, and furthermore, when waxes are added, the fluidity of the suspension is significantly improved. It has been found that this effect can be enhanced by Furthermore, it has surprisingly been found that formulations comprising compositions thus prepared do not reduce the utilization of their active ingredients.
すなわち、本発明は油性基剤にソルビタン脂肪酸エステ
ルと、ポリオキシエチレンソルビタン脂肪酸エステル及
びワックス類を配合することにより、非油溶性の活性成
分を分散した懸濁液の流動性及び該活性成分の利用率を
改善する軟カプセル充填用組成物を供するものである。That is, the present invention improves the fluidity of a suspension in which an oil-insoluble active ingredient is dispersed and the utilization of the active ingredient by blending sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and waxes into an oily base. The present invention provides a soft capsule filling composition that improves the filling rate.
本発明において、ソルビタン脂肪酸エステルとしてはセ
スキオレイン酸ソルビタンエステルが好ましく、その配
合量は軟カプセル充填用組成物の１〜２０重量％が好ま
しい。In the present invention, the sorbitan fatty acid ester is preferably sorbitan sesquioleate, and the amount thereof is preferably 1 to 20% by weight of the composition for filling soft capsules.
ポリオキシエチレンソルビタン脂肪酸エステルとしては
、特にポリソルベー）８０が好ましく、その配合量は、
軟カプセル充填用組成物の０．１〜１０重量％が好まし
い。As the polyoxyethylene sorbitan fatty acid ester, polysorbate) 80 is particularly preferred, and its blending amount is as follows:
It is preferably 0.1 to 10% by weight of the composition for filling soft capsules.
ワックス類としては、経口剤に使用され得るものは何れ
も使用することができ、例えばミツロウ、サラシミツロ
ウ、カルナバロウ、木ロウ、硬化油等が挙げられる。そ
の配合量は、軟カプセル充填用組成物の０．１−１０！
ｉ量％が好ましい。As waxes, any wax that can be used in oral preparations can be used, including beeswax, white beeswax, carnauba wax, wood wax, hydrogenated oil, and the like. The blending amount is 0.1-10! of the composition for filling soft capsules.
The amount i is preferably %.
また、本発明に使用される油性基剤としては１、通常軟
カプセル充填用基剤として使用されるもの〜よ何れでも
良く、例えばサフラワー油、ラッカセイ油、ダイズ油、
トウモロコシ油等の植物油や、トリ中鎖脂肪酸グリセラ
イド等が使用される。The oily base used in the present invention may be any of those commonly used as soft capsule filling bases, such as safflower oil, peanut oil, soybean oil,
Vegetable oils such as corn oil, tri-medium chain fatty acid glycerides, etc. are used.
本発明に適用される活性成分としては、油性溶剤に不溶
で、懸濁状態で軟カプセル充填用組成物となし得るもの
であれば何れでも良いが、特にアセトアミノフェン又は
アセトアミノフェン配合剤に適用が好ましい。このとき
、アセトアミノフェン配合剤に配合される他の活性成分
としては、例えばマレイン酸クロルフェニラミン、リン
酸ジヒドロコデイン、ヒヘンズ酸チペビジン、臭化水素
デキストロメトルファン、塩酸メチルエフェドリン、ア
リルイソプロピルアセチル尿素、エテンザミド、無水カ
フェイン等が挙げられる。The active ingredient applicable to the present invention may be any active ingredient as long as it is insoluble in an oily solvent and can be made into a composition for filling soft capsules in a suspended state, but especially acetaminophen or acetaminophen combination preparations. Application is preferred. At this time, other active ingredients incorporated into the acetaminophen combination drug include, for example, chlorpheniramine maleate, dihydrocodeine phosphate, tipevidine henzate, dextromethorphan hydrogen bromide, methylephedrine hydrochloride, allylisopropylacetylurea, Examples include ethenzamide, anhydrous caffeine, and the like.
本発明の軟カプセル用組成物を得るには、予め微粉砕し
た活性成分を当該基剤に分散させるか、あるいは当該基
剤に活性成分を加えたのち、微細化する方法によって調
製される。The composition for soft capsules of the present invention can be prepared by dispersing a previously finely ground active ingredient in the base, or by adding the active ingredient to the base and then pulverizing the mixture.
［作用］
本発明で得られる軟カプセル充填用組成物は、活性成分
の配合量が多く、かつ懸濁状態で調製する必要がある場
合でも、その流動性が改善され、さらに、本発明により
得られた組成物を充填してなる軟カプセル剤が経口投与
された場合、活性成分の消化管での溶解性は低下するこ
となく、したがって、利用率も低下することはない。[Function] The composition for filling soft capsules obtained by the present invention has improved fluidity even when the active ingredient is contained in a large amount and needs to be prepared in a suspended state. When a soft capsule prepared by filling the composition is orally administered, the solubility of the active ingredient in the gastrointestinal tract does not decrease, and therefore, the utilization rate does not decrease either.
［実施例コ
以下、本発明の具体的な実施例を示すが、本発明はこれ
らに何ら限定されるものではない。[Examples] Specific examples of the present invention will be shown below, but the present invention is not limited to these in any way.
（実施例１）
アセトアミノフェン ２５．０ ｇソルビタ
ン脂肪酸エステル ２．５ポリオキシエチレンソ
ルビタン
脂肪酸エステル ０．５サフラワー油
２２．０上記組成中の基剤にアセトア
ミノフェンを均一に分散し、軟カプセル充填用組成物を
調製した。(Example 1) Acetaminophen 25.0 g Sorbitan fatty acid ester 2.5 Polyoxyethylene sorbitan fatty acid ester 0.5 Safflower oil
22.0 Acetaminophen was uniformly dispersed in the base in the above composition to prepare a composition for filling soft capsules.
（実施例２）
アセトアミノフェン ２５．０ ｇソルビタ
ン脂肪酸エステル ２．５ポリオキシエチレンソ
ルビタン
脂肪酸エステル ０．５ミツロウ
０．５サフラワー油
２１．５上記組成中の基剤をあらかじめ加温し、ミ
ツロウを溶解したのち、アセトアミノフェンを均一に分
散し、軟カプセル充填用組成物をＷｉｌｕた。(Example 2) Acetaminophen 25.0 g Sorbitan fatty acid ester 2.5 Polyoxyethylene sorbitan fatty acid ester 0.5 Beeswax
0.5 safflower oil
21.5 The base in the above composition was heated in advance to dissolve beeswax, and then acetaminophen was uniformly dispersed to form a composition for filling soft capsules.
（実施例３）
アセトアミノフェン １２．０ｇエテンザミ
ド １４．４無水カフエイン
３．６ソルビタン脂肪酸エステル ２
．０ポリオキシエチレンソルビタン
脂肪酸エステル ０・５トリ中鎖脂肪酸
グリセリン １７．６上記組成中の基剤に、アセト
アミノフェン、エテンザミド、無水カフェインを順次均
一に分散せしめ、軟カプセル充填用組成物とした。(Example 3) Acetaminophen 12.0g Ethenzamide 14.4 Anhydrous Caffeine
3.6 Sorbitan fatty acid ester 2
．． 0 polyoxyethylene sorbitan fatty acid ester 0.5 tri medium chain fatty acid glycerin 17.6 Acetaminophen, ethenzamide, and anhydrous caffeine were uniformly dispersed in the base in the above composition in order to prepare a composition for filling soft capsules. .
（実施例４）
アセトアミノフェン １２．０ｇエテンザミ
ド １４．４無水カフエイン
３．６ソルビタン脂肪酸エステル ２
．０ポリオキシエチレンソルビタン
脂肪酸エステル ０・５ミツロウ
０．５サフラワー油
１７．０上記組成中の基剤をあらかじめ加温し、ミ
ツロウを溶解したのち、アセトアミノフェン、エテンザ
ミド、無水カフェインを順次均一に分散せしめ、軟カプ
セル充填用組成物をｓ＋ｉ＊ｂた。(Example 4) Acetaminophen 12.0g Ethenzamide 14.4 Anhydrous Caffeine
3.6 Sorbitan fatty acid ester 2
．． 0 polyoxyethylene sorbitan fatty acid ester 0.5 beeswax
0.5 safflower oil
17.0 The base in the above composition was heated in advance to dissolve beeswax, and then acetaminophen, ethenzamide, and anhydrous caffeine were uniformly dispersed in this order to prepare a composition for filling soft capsules.
（実施例５）
アセトアミノフェン ２０．０ｇマレイン酸
クロルフェニラミン ０．２リン酸ジヒドロコデイン
０．３ｄｌ−塩酸メチルエフェドリン
０．６無水カフエイン ０．７ソル
ビタン脂肪酸エステル ２．２ポリオキシエチレ
ンソルビタン
脂肪酸エステル ０．５
カルナウバロウ ０．８トリ中鎖脂肪
酸グリセリン ２４．７上記朝成中の基剤をあらか
じめ加温し、カルナウバロウを溶解したのち、順次アセ
トアミノフェン以下無水カフェインまで均一に分散せし
め、軟カプセル充填用組成物を調製した。(Example 5) Acetaminophen 20.0g Chlorpheniramine maleate 0.2 Dihydrocodeine phosphate 0.3 dl-Methylephedrine hydrochloride
0.6 Anhydrous caffeine 0.7 Sorbitan fatty acid ester 2.2 Polyoxyethylene sorbitan fatty acid ester 0.5 Carnauba wax 0.8 Tri-medium chain fatty acid glycerin 24.7 Preheat the base in the above morning preparation and add carnauba wax. After dissolving, acetaminophen and anhydrous caffeine were uniformly dispersed in order to prepare a composition for filling soft capsules.
［発明の効果コ
比較例
本発明の組成物の比較例として、第１表にアセトアミノ
フェン配合の充填用組成物をＳｌｉ製した。[Effects of the Invention - Comparative Example As a comparative example of the composition of the present invention, filling compositions containing acetaminophen as shown in Table 1 were manufactured using SLI.
第１表
（試験例１）
比較例の検体１及び２と、本発明の実施例１及び２の軟
カプセル充填用組成物の流動性を評価し、その結果を第
２表に示した。流動性は、良好（０）、一応流動性有り
（Δ）、流動性なしくＸ）の３段階で評価した。Table 1 (Test Example 1) The fluidity of Comparative Samples 1 and 2 and the soft capsule filling compositions of Examples 1 and 2 of the present invention was evaluated, and the results are shown in Table 2. The fluidity was evaluated in three stages: good (0), some fluidity (Δ), and no fluidity (X).
第２表
第２表より、明らかに本発明の組成物の流動性は改善さ
れており、製剤化が容易である。From Table 2, it is clear that the composition of the present invention has improved fluidity and is easy to formulate.
（試験例２）
比較例検体２と、本発明の実施例２の軟カプセル充填用
組成物からのアセトアミノフェンの試験液（日局第１液
：ｐＨ１，２）への溶出を、坐剤放出試験器（ＴＭＳ−
１０３： 富山産業）を用いて比較した。(Test Example 2) The elution of acetaminophen from Comparative Example Sample 2 and the soft capsule filling composition of Example 2 of the present invention into a test solution (Japanese Pharmacopoeia No. 1 solution: pH 1, 2) was measured using a suppository. Release tester (TMS-
103: Toyama Sangyo).
フラスコ内に４００１の試験液（＋）Ｈｌ、２）を入れ
、１００ｒｐ■で攪拌し、３７℃に加温する０次いでセ
ルを組み立てミリポアフィルタ−を密着し、軟カプセル
内容物１ｇを入れ液に浸し、さらに５■１の試験液（ｐ
Ｈ１，２）を加える。内相と放出量の液面を一致せしめ
、直ちにフィルターから１〜２ｍｍの位置に５ Ｏｒｐ
ｍの回転をセル内に加える。Pour 4001 test solution (+) Hl, 2) into the flask, stir at 100 rpm, and warm to 37°C. Next, assemble the cell, attach a Millipore filter, and add 1 g of the contents of the soft capsule to the liquid. immerse, and then add 5×1 test solution (p
Add H1, 2). Align the liquid levels of the internal phase and the discharge amount, and immediately place a 5-orp at a position 1 to 2 mm from the filter.
Add m rotations into the cell.
放出量より試験液をサンプリングし、適当に希釈したの
ち分光光度計により、アセトアミノフェンの放出量を時
閉を追って求めた。その結果を第１図に示す。A test solution was sampled based on the amount released, and after diluting it appropriately, the amount of acetaminophen released was determined over time using a spectrophotometer. The results are shown in FIG.
第１図より、明らかに本発明の組成物からの７セトアミ
ノフエンの溶出性は改善されている。From FIG. 1, it is clear that the dissolution of 7cetaminophene from the composition of the present invention is improved.
試験例３
比較例検体２と、本発明の実施例２より得られた充填用
組成物を、ｌカプセル当り４００１ｇを含有する軟カプ
セル剤とした。Test Example 3 Comparative Example Sample 2 and the filling composition obtained from Example 2 of the present invention were made into soft capsules containing 4001 g per 1 capsule.
この軟カプセル剤を各々２カプセル（アセトアミノフェ
ン４００ ｍｇ）ずつピーグル犬に経口投与し、その利
用率を比較した。Two capsules (acetaminophen 400 mg) of each of these soft capsules were orally administered to Peagle dogs, and the utilization rates were compared.
ピーグル犬は、１群２頭、２群のクロスオーバーとし、
採血は、０，０．５，１，１．５．２，３゜４．６．９
，１２．２４時閏で行い、液体クロマトグラフィー（島
津製作所）を用いて血中アセトアミノフェン濃度を測定
した。これらの結果を平均値で第３表に示す。Peagle dogs are 2 dogs per group, a crossover between the 2 groups,
Blood collection is 0, 0.5, 1, 1.5.2, 3°4.6.9
, 12.24 hours, and the blood acetaminophen concentration was measured using liquid chromatography (Shimadzu Corporation). These results are shown in Table 3 as average values.
第３表
第３表の結果、明らかに本発明の組成物は、アセトアミ
ノフェンの利用率の低下を防止しており、本発明は有用
である。As shown in Table 3, the composition of the present invention clearly prevents a decrease in the utilization rate of acetaminophen, and the present invention is useful.
第１図は、軟カプセル充填用組成物からのアセトアミノ
フェンの溶出率を示したものであり、図中線ｌは本発明
の実施例２により得られた組成物からのアセトアミノフ
ェンの溶出率を示す。
図中線２は、比較例検体２により得られた組成物からの
アセトアミノフェンの溶出率を示す。FIG. 1 shows the dissolution rate of acetaminophen from the composition for filling soft capsules, and the line l in the figure indicates the dissolution rate of acetaminophen from the composition obtained in Example 2 of the present invention. Show rate. Line 2 in the figure indicates the elution rate of acetaminophen from the composition obtained from Comparative Example Sample 2.
Claims (1)
シエチレンソルビタン脂肪酸エステルを配合してなる基
剤に、活性成分を均一に分散してなる軟カプセル充填用
組成物。 ２）油性溶剤に、ソルビタン脂肪酸エステルと、ポリオ
キシエチレンソルビタン脂肪酸エステル及びワックス類
を配合してなる基剤に活性成分を均一に分散してなる軟
カプセル充填用組成物。 ３）活性成分が、アセトアミノフェン又はアセトアミノ
フェン配合剤である特許請求の範囲第１項記載の軟カプ
セル充填用組成物。 ４）活性成分が、アセトアミノフェン又はアセトアミノ
フェン配合剤である特許請求の範囲第２項記載の軟カプ
セル充填用組成物。[Scope of Claims] 1) A composition for filling soft capsules, comprising an active ingredient uniformly dispersed in a base prepared by blending sorbitan fatty acid ester and polyoxyethylene sorbitan fatty acid ester in an oily solvent. 2) A soft capsule filling composition comprising an active ingredient uniformly dispersed in a base prepared by blending sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and waxes in an oily solvent. 3) The composition for filling soft capsules according to claim 1, wherein the active ingredient is acetaminophen or an acetaminophen combination agent. 4) The composition for filling soft capsules according to claim 2, wherein the active ingredient is acetaminophen or an acetaminophen combination agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61155087A JPH07549B2 (en) | 1986-07-03 | 1986-07-03 | Composition for filling soft capsules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61155087A JPH07549B2 (en) | 1986-07-03 | 1986-07-03 | Composition for filling soft capsules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6333324A true JPS6333324A (en) | 1988-02-13 |
| JPH07549B2 JPH07549B2 (en) | 1995-01-11 |
Family
ID=15598366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61155087A Expired - Fee Related JPH07549B2 (en) | 1986-07-03 | 1986-07-03 | Composition for filling soft capsules |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07549B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59134902A (en) * | 1983-01-24 | 1984-08-02 | Fujitsu Ltd | Fitting device of dielectric resonator |
| JPH03200728A (en) * | 1989-02-23 | 1991-09-02 | Glaxo Canada Inc | Pharmaceutical composition |
| JP2010024234A (en) * | 2009-10-09 | 2010-02-04 | Fuji Capsule Kk | Composition for filling soft capsule agent |
| JP2013528439A (en) * | 2010-06-03 | 2013-07-11 | アキュキャップス・インダストリーズ・リミテッド | Multi-phase soft gel capsule, apparatus and method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6289617A (en) * | 1985-08-12 | 1987-04-24 | ウイリアム ガウフ タツカ− | Drug composition and preparation |
-
1986
- 1986-07-03 JP JP61155087A patent/JPH07549B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6289617A (en) * | 1985-08-12 | 1987-04-24 | ウイリアム ガウフ タツカ− | Drug composition and preparation |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59134902A (en) * | 1983-01-24 | 1984-08-02 | Fujitsu Ltd | Fitting device of dielectric resonator |
| JPH03200728A (en) * | 1989-02-23 | 1991-09-02 | Glaxo Canada Inc | Pharmaceutical composition |
| JP2010024234A (en) * | 2009-10-09 | 2010-02-04 | Fuji Capsule Kk | Composition for filling soft capsule agent |
| JP2013528439A (en) * | 2010-06-03 | 2013-07-11 | アキュキャップス・インダストリーズ・リミテッド | Multi-phase soft gel capsule, apparatus and method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07549B2 (en) | 1995-01-11 |
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