JPWO2004024138A1 - Dioctyl sodium sulfosuccinate solid formulation - Google Patents

Dioctyl sodium sulfosuccinate solid formulation Download PDF

Info

Publication number
JPWO2004024138A1
JPWO2004024138A1 JP2004535937A JP2004535937A JPWO2004024138A1 JP WO2004024138 A1 JPWO2004024138 A1 JP WO2004024138A1 JP 2004535937 A JP2004535937 A JP 2004535937A JP 2004535937 A JP2004535937 A JP 2004535937A JP WO2004024138 A1 JPWO2004024138 A1 JP WO2004024138A1
Authority
JP
Japan
Prior art keywords
solid preparation
enteric coating
sulfosuccinate
dioctylsodium sulfosuccinate
mass
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
Application number
JP2004535937A
Other languages
Japanese (ja)
Inventor
和田　薫
薫 和田
伊藤　充
充 伊藤
和生 尼野
和生 尼野
細田　敬子
敬子 細田
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Taisho Pharmaceutical Co Ltd
Original Assignee
Taisho Pharmaceutical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Taisho Pharmaceutical Co Ltd filed Critical Taisho Pharmaceutical Co Ltd
Publication of JPWO2004024138A1 publication Critical patent/JPWO2004024138A1/en
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats

Abstract

ロウ状物質であることから、腸溶性被膜などで被覆する一般的な大腸近位放出型の製剤にしにくいジオクチルソジウムスルホサクシネートは、消化管の上部で放出されることから直接作用としては効果的ではなかった。本発明はジオクチルソジウムスルホサクシネートが作用部位の大腸近位で放出され、効果的な瀉下効果を有する固形製剤の提供を目的として完成したものであり、ジオクチルソジウムスルホサクシネートを配合した溶液を用いて、軽質無水ケイ酸を配合した粉体を造粒した顆粒を含む核粒子に、腸溶性被膜が施されていることを特徴とする固形製剤である。Because it is a waxy substance, dioctylsodium sulfosuccinate, which is difficult to make into a general colon proximal-release preparation coated with an enteric coating, etc., is released in the upper part of the digestive tract, so it is effective as a direct action It was not right. The present invention has been completed for the purpose of providing a solid preparation having dioctylsodium sulfosuccinate released in the vicinity of the large intestine at the site of action and having an effective armpit effect, and a solution containing dioctylsodium sulfosuccinate Is a solid preparation characterized in that an enteric coating is applied to core particles containing granules obtained by granulating a powder containing light anhydrous silicic acid.

Description

本発明はジオクチルソジウムスルホサクシネートを配合した製剤に関する。  The present invention relates to a preparation containing dioctylsodium sulfosuccinate.

ジオクチルソジウムスルホサクシネートは瀉下薬として知られている。その作用は腸内で硬便に直接作用して水を浸透させ、便を軟化、膨潤させることにより排泄を促進させるものである。しかし、ジオクチルソジウムスルホサクシネートはロウ状物質であることから、腸溶性被膜などで被覆する一般的な大腸近位放出型の製剤にはしにくいことが知られている。そのため、従来のジオクチルソジウムスルホサクシネートを配合した内服薬剤は、経口投与後、消化管の上部で放出されることから直接作用としては効果的ではなかった。
従来ジオクチルソジウムスルホサクシネートを配合した製剤を製造する技術として、ジオクチルソジウムスルホサクシネートおよび微粉末を特殊な条件で粉末化する技術（日本国特許特開平２−２５５６１３）などが知られているが、ジオクチルソジウムスルホサクシネートを作用部位の大腸近位で放出させる技術は知られていない。
本発明はジオクチルソジウムスルホサクシネートが作用部位の大腸近位で放出され、効果的な瀉下効果を有する固形製剤の提供を目的とする。Dioctylsodium sulfosuccinate is known as a laxative. Its action is to act directly on hard stool in the intestine to permeate water and soften and swell the stool to promote excretion. However, since dioctylsodium sulfosuccinate is a waxy substance, it is known that it is difficult to make a general colon proximal-release preparation coated with an enteric coating or the like. For this reason, conventional drugs containing conventional dioctylsodium sulfosuccinate are not effective as a direct action because they are released in the upper part of the digestive tract after oral administration.
Conventionally, as a technique for producing a preparation containing dioctylsodium sulfosuccinate, a technique for pulverizing dioctylsodium sulfosuccinate and fine powder under special conditions (Japanese Patent Laid-Open No. 2-255613) is known. However, there is no known technique for releasing dioctylsodium sulfosuccinate near the large intestine at the site of action.
An object of the present invention is to provide a solid preparation in which dioctylsodium sulfosuccinate is released in the vicinity of the large intestine at the site of action and has an effective armpit effect.

本発明者らは課題を解決するために種々検討した結果、ジオクチルソジウムスルホサクシネートおよび軽質無水ケイ酸を配合した粉体を造粒し、得られた顆粒、もしくはその顆粒を製錠して得られた錠剤に対して腸溶性被膜を施すことにより、ジオクチルソジウムスルホサクシネートが大腸付近で放出される、優れた製剤が得られることを見出し本発明を完成した。
すなわち本発明は、ジオクチルソジウムスルホサクシネートおよび軽質無水ケイ酸を含む核粒子に、腸溶性被膜が施されていることを特徴とする固形製剤である。
本発明で核粒子とは腸溶性被膜を施す対象物であり、ジオクチルソジウムスルホサクシネートおよび軽質無水ケイ酸を配合した粉体を練合造粒した顆粒、もしくはそれを製錠した錠剤などを用いることができる。
本発明では軽質無水ケイ酸と共にステアリン酸マグネシウムを同時に配合すると打錠時の作業性の点で好ましい。
本発明で腸溶性被膜とはエンテリックコーティングに一般的に用いられるものを使用することができるが、特にメタクリル酸コポリマー（Ｌ、Ｓ、ＬＤ）、ヒドロキシプロピルメチルセルロースフタレート、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、カルボキシメチルエチルセルロースおよび酢酸フタル酸セルロースからなる群から選ばれる成分が好ましい。それらは単独または２種以上を混合させて用いることができる。
腸溶性被膜を直接核粒子に被覆する際の被覆量は、核粒子の質量に対して１〜３０質量％が好ましい。
また、本発明では腸溶性被膜として、腸溶性のカプセルを用いることもできる。その場合は核粒子の顆粒などを腸溶性のカプセルに詰めカプセル剤とする。
本発明では特にジオクチルソジウムスルホサクシネートと他の瀉下作用のある活性成分を同顆粒中、もしくは別顆粒とし、これを混合して配合すると瀉下作用の向上が期待できるので好ましい。他の瀉下作用のある活性成分としては効果の点でビサコジルが好ましく、その配合量は１日投与量で３〜１５ｍｇが好ましい。
ここで、ビサコジルは難溶性のため、製剤に配合しても十分な効果が得られないことがあったが、本発明でビサコジルをジオクチルソジウムスルホサクシネートと同時配合することにより溶解度が向上することも見出した。したがって、本発明でビサコジルとジオクチルソジウムスルホサクシネートを同時配合することにより、それぞれ単独に投与する場合に比べて相乗効果が期待できる。そのため、本発明では核粒子にビサコジルを同時配合した処方がより好ましい。
本発明では、ジオクチルソジウムスルホサクシネートを溶解させる溶媒に水溶性高分子を配合すると、得られる顆粒の性状の点で好ましい。
ここで配合する水溶性高分子は、結合剤として通常用いられるものを使用することができるが、好ましいものとしてヒドロキシプロピルセルロース、ポリビニルピロリドンおよびヒドロキシプロピルメチルセルロースをあげることができる。水溶性高分子の配合量は、ジオクチルソジウムスルホサクシネート１質量部に対し０．１〜０．３質量部が好ましい。
本発明において、軽質無水ケイ酸はジオクチルソジウムスルホサクシネート１質量部に対して０．５〜１．５質量部の配合が好ましく、０．６〜１．３質量部の配合がさらに好ましい。１．５質量部を超えて配合すると、余剰の軽質無水ケイ酸などに起因する微粉末により、打錠時に障害が発生することがあるからである。
本発明においてステアリン酸マグネシウムはジオクチルソジウムスルホサクシネート１質量部に対して０．０５〜０．５質量部が好ましく、０．１〜０．３質量部の配合がより好ましい。
本発明の核粒子は以下のように製造される。
ジオクチルソジウムスルホサクシネートを水、エタノールなどの溶媒に溶解して溶液とする。その溶液を噴霧しながらもしくは一括に添加し、軽質無水ケイ酸および必要があればステアリン酸マグネシウムを混合した粉体を造粒して粉体を得る。
得られた粉体に、必要があれば通常の医薬品製造に使用される他の薬効成分、添加剤などを加え、常法により、混合、粉砕、造粒等の工程を経て、顆粒剤、錠剤などの形態の核粒子を得ることができる。
本発明の核粒子は錠剤とすることもできるが、一般的に錠剤を製造する際に滑沢剤であるステアリン酸マグネシウムを高濃度で配合すると、得られた錠剤は物性が低いことが知られている。しかし、本発明ではステアリン酸マグネシウムを粉体中に練り込むことにより、造粒後に打錠した際にもその錠剤物性、特に崩壊性や錠剤硬度が低下すること無く配合することができる。したがって腸溶性被膜を施したフィルム錠剤も優れた物性のものを得ることができる。As a result of various studies to solve the problems, the present inventors granulated a powder containing dioctylsodium sulfosuccinate and light silicic acid anhydride, and tableted the obtained granule or the granule. The present invention was completed by finding that an excellent preparation in which dioctyl sodium sulfosuccinate is released in the vicinity of the large intestine can be obtained by applying an enteric coating to the obtained tablet.
That is, the present invention is a solid preparation characterized in that an enteric coating is applied to core particles containing dioctylsodium sulfosuccinate and light anhydrous silicic acid.
In the present invention, the core particle is an object to which an enteric coating is applied, such as granules obtained by kneading and granulating a powder containing dioctyl sodium sulfosuccinate and light anhydrous silicic acid, or tablets obtained by tableting the same. Can be used.
In the present invention, it is preferable to blend magnesium stearate together with light anhydrous silicic acid from the viewpoint of workability during tableting.
In the present invention, an enteric coating generally used for enteric coating can be used, and in particular, methacrylic acid copolymer (L, S, LD), hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, A component selected from the group consisting of carboxymethyl ethyl cellulose and cellulose acetate phthalate is preferred. They can be used alone or in admixture of two or more.
The coating amount when directly coating the enteric coating onto the core particles is preferably 1 to 30% by mass with respect to the mass of the core particles.
In the present invention, an enteric capsule can also be used as the enteric coating. In that case, the core particle granules are packed in an enteric capsule to form a capsule.
In the present invention, it is particularly preferable to add dioctyl sodium sulfosuccinate and another active ingredient having an axillary action in the same granule or in a separate granule, which can be mixed and blended, since an improvement in the axillary action can be expected. The other active ingredient having an armpit action is preferably bisacodyl in view of the effect, and the compounding amount thereof is preferably 3 to 15 mg as a daily dose.
Here, because bisacodyl is poorly soluble, there were cases where sufficient effects could not be obtained even if blended in the preparation, but the solubility is improved by blending bisacodyl with dioctylsodium sulfosuccinate in the present invention. I also found out. Therefore, a synergistic effect can be expected by simultaneously blending bisacodyl and dioctylsodium sulfosuccinate in the present invention as compared with the case where each is administered alone. Therefore, in this invention, the prescription | regulation which mix | blended bisacodyl with the core particle simultaneously is more preferable.
In the present invention, when a water-soluble polymer is blended in a solvent in which dioctylsodium sulfosuccinate is dissolved, it is preferable in terms of the properties of the resulting granules.
As the water-soluble polymer to be blended here, those usually used as a binder can be used, and preferred examples thereof include hydroxypropylcellulose, polyvinylpyrrolidone and hydroxypropylmethylcellulose. As for the compounding quantity of water-soluble polymer, 0.1-0.3 mass part is preferable with respect to 1 mass part of dioctylsodium sulfosuccinate.
In the present invention, the light anhydrous silicic acid is preferably blended in an amount of 0.5 to 1.5 parts by weight, more preferably 0.6 to 1.3 parts by weight with respect to 1 part by weight of dioctylsodium sulfosuccinate. This is because when the blending exceeds 1.5 parts by mass, trouble may occur during tableting due to fine powder caused by excess light silicic anhydride and the like.
In this invention, 0.05-0.5 mass part is preferable with respect to 1 mass part of dioctylsodium sulfosuccinates, and the mixing | blending of 0.1-0.3 mass part is more preferable for magnesium stearate.
The core particle of the present invention is produced as follows.
Dioctyl sodium sulfosuccinate is dissolved in a solvent such as water or ethanol to obtain a solution. The solution is sprayed or added all at once, and a powder obtained by mixing light anhydrous silicic acid and, if necessary, magnesium stearate is granulated to obtain a powder.
If necessary, other medicinal ingredients and additives used in normal pharmaceutical production are added to the obtained powder, followed by mixing, pulverization, granulation, etc. in the usual manner, granules, tablets And so on.
Although the core particles of the present invention can be made into tablets, it is generally known that when a tablet is produced, when the magnesium stearate, which is a lubricant, is blended at a high concentration, the obtained tablets have low physical properties. ing. However, in the present invention, magnesium stearate is kneaded into the powder, so that even when tableting is performed after granulation, the tablet physical properties, in particular, disintegration and tablet hardness can be blended. Accordingly, film tablets with an enteric coating can also be obtained with excellent physical properties.

第１図は、実施例および比較例の溶出性試験の結果を示した図であり、縦軸に溶出率、横軸に時間およびｐＨを示した。FIG. 1 is a graph showing the results of dissolution tests of Examples and Comparative Examples, where the vertical axis indicates the dissolution rate, and the horizontal axis indicates time and pH.

以下、実施例、比較例および試験例により本発明をさらに詳細に説明する。  Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples.

［内核錠の製造］
ビサコジル６００ｇ、乳糖１２４８ｇ、ヒドロキシプロピルセルロース６３２ｇ、低置換度ヒドロキシプロピルセルロース９３２ｇおよび軽質無水ケイ酸１２０ｇを混合して得られた粉体に、精製水を造粒溶媒として攪拌造粒し乾燥し顆粒Ａとした。
次にジオクチルソジウムスルホサクシネート９６０ｇおよびヒドロキシプロピルセルロース２００ｇをアルコールに溶解し、軽質無水ケイ酸９６０ｇステアリン酸マグネシウム２８８ｇの混合粉体と共に練合造粒を行い、乾燥、整粒後、顆粒Ｂを得た。顆粒Ａ、顆粒Ｂ、ステアリン酸マグネシウム３０ｇおよび軽質無水ケイ酸３０ｇを添加して混合した。得られた顆粒を打錠して、錠径５ｍｍ、１錠重量５０ｍｇの錠剤を得た。これを核粒子とした。
［腸溶性被膜の製造］
タルク１６７ｇ、クエン酸トリエチル３１ｇ、メタクリル酸コポリマー（Ｓ、Ｌ混合物）３３５ｇおよびヒドロキシプロピルセルロース６７ｇをアルコールに分散溶解させた。コーティング装置に内核錠を入れ、腸溶性被膜液をスプレーコーティングし、１錠当たり約１０ｍｇまで腸溶性被膜層を施し本発明の固形製剤を得た。
比較例
実施例１と同様にして製造した核粒子の錠剤を比較例として用いた。
試験例１
実施例および比較例で得られた製剤を、日局溶出試験法第３法フロースルーセル法にて、溶出試験液のｐＨを１．２、６．５５、７．２１、６．７１に変化させ、経時的にサンプリングし、ＨＰＬＣにてジオクチルソジウムスルホサクシネートを定量し、溶出率を求めた。その結果を図１に示した。
図１から明らかなように、実施例１より、ジオクチルソジウムスルホサクシネートは胃内を想定した低いｐＨでは溶出せず、ｐＨ７．２１の小腸下部で溶出を開始し、比較例に比べて、より作用部位に近いところで放出させることができることが判った。
試験例２
以下の方法により、ビサコジルとジオクチルソジウムスルホサクシネートを同時配合した際の溶解性を測定した。
ビサコジルを精製水に分散させ、一定条件下で５時間振とうさせた液を３０００ｍｉｎ−１，５ｍｉｎの条件にて遠心分離した。その後、上澄液を採取しＨＰＬＣにてビサコジル含量を定量した。
同様にして、濃度が０．０７％、０．１４％、０．３５％となるようにジオクチルソジウムスルホサクシネートを添加した溶液にビサコジルを分散させ、５時間振とうさせた液を３０００ｍｉｎ−１，５ｍｉｎの条件にて遠心分離した。その後、上澄液を採取しＨＰＬＣにてビサコジル含量を定量した。結果を表１に示した。

Figure 2004024138
表から明らかなようにジオクチルソジウムスルホサクシネートが共存することによりビサコジルの溶解度が大幅に向上することがわかった。[Manufacture of inner core tablets]
The powder obtained by mixing 600 g of bisacodyl, 1248 g of lactose, 632 g of hydroxypropyl cellulose, 932 g of low-substituted hydroxypropyl cellulose and 120 g of light anhydrous silicic acid is stirred and granulated with purified water as a granulating solvent, dried and granulated A It was.
Next, 960 g of dioctylsodium sulfosuccinate and 200 g of hydroxypropyl cellulose are dissolved in alcohol, kneaded and granulated with a mixed powder of 960 g of light anhydrous silicic acid 288 g of magnesium stearate, dried, sized, and then granulated B. Obtained. Granule A, Granule B, 30 g of magnesium stearate and 30 g of light anhydrous silicic acid were added and mixed. The obtained granules were tableted to obtain tablets with a tablet diameter of 5 mm and a tablet weight of 50 mg. This was used as a core particle.
[Manufacture of enteric coating]
167 g of talc, 31 g of triethyl citrate, 335 g of methacrylic acid copolymer (S, L mixture) and 67 g of hydroxypropyl cellulose were dispersed and dissolved in alcohol. The inner core tablet was placed in a coating apparatus, and an enteric coating solution was spray coated, and an enteric coating layer was applied to about 10 mg per tablet to obtain a solid preparation of the present invention.
Comparative Example A core particle tablet produced in the same manner as in Example 1 was used as a comparative example.
Test example 1
The preparations obtained in Examples and Comparative Examples were changed to pH 1.2, 6.55, 7.21, and 6.71 by JP 3 dissolution method third flow-through cell method. And sampled over time, and dioctylsodium sulfosuccinate was quantified by HPLC to determine the elution rate. The results are shown in FIG.
As is clear from FIG. 1, from Example 1, dioctylsodium sulfosuccinate does not elute at a low pH assumed in the stomach and starts to elute at the lower intestine at pH 7.21, compared to the comparative example, It was found that it can be released closer to the site of action.
Test example 2
The solubility when bisacodyl and dioctyl sodium sulfosuccinate were blended simultaneously was measured by the following method.
Bisacodyl was dispersed in purified water, and a solution shaken for 5 hours under a fixed condition was centrifuged under conditions of 3000 min −1 and 5 min. Thereafter, the supernatant was collected and bisacodyl content was quantified by HPLC.
Similarly, bisacodyl was dispersed in a solution to which dioctylsodium sulfosuccinate was added so that the concentration would be 0.07%, 0.14%, and 0.35%, and a solution that was shaken for 5 hours was 3000 min −. Centrifugation was performed for 1 and 5 min. Thereafter, the supernatant was collected and bisacodyl content was quantified by HPLC. The results are shown in Table 1.
Figure 2004024138
As is apparent from the table, it was found that the solubility of bisacodyl was greatly improved by the coexistence of dioctylsodium sulfosuccinate.

本発明によりジオクチルソジウムスルホサクシネートを作用部位である大腸近位に効率的に放出させることが可能になったので、効果的な瀉下薬として有用である。  The present invention makes it possible to efficiently release dioctylsodium sulfosuccinate to the proximal part of the large intestine, which is the site of action, and is therefore useful as an effective laxative.

Claims (10)

ジオクチルソジウムスルホサクシネートおよび軽質無水ケイ酸を含む核粒子に、腸溶性被膜が施されていることを特徴とする固形製剤。A solid preparation characterized in that an enteric coating is applied to core particles containing dioctylsodium sulfosuccinate and light silicic anhydride. 核粒子中に、さらにビサコジルを含むことを特徴とする１記載の固形製剤。2. The solid preparation according to 1, wherein bisacodyl is further contained in the core particle. 核粒子中に、さらにステアリン酸マグネシウムを含む１または２に記載の固形製剤。3. The solid preparation according to 1 or 2, further comprising magnesium stearate in the core particle. 腸溶性被膜の被覆量が、核粒子の質量に対して１〜３０質量％である１〜３のいずれかに記載の固形製剤。The solid preparation according to any one of 1 to 3, wherein the coating amount of the enteric coating is 1 to 30% by mass with respect to the mass of the core particles. 腸溶性被膜が、メタクリル酸コポリマーＬ、メタクリル酸コポリマーＳ、メタクリル酸コポリマーＬＤ、ヒドロキシプロピルメチルセルロースフタレート、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、カルボキシメチルエチルセルロースおよび酢酸フタル酸セルロースから選ばれる少なくとも１種である１〜４のいずれかに記載の固形製剤。The enteric coating is at least one selected from methacrylic acid copolymer L, methacrylic acid copolymer S, methacrylic acid copolymer LD, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose and cellulose acetate phthalate. 4. The solid preparation according to any one of 4 above. ジオクチルソジウムスルホサクシネート１質量部に対する軽質無水ケイ酸の配合量が０．５〜１．５質量部である１〜５のいずれかに記載の固形製剤。The solid formulation in any one of 1-5 whose compounding quantity of a light silicic acid anhydride with respect to 1 mass part of dioctyl sodium sulfosuccinate is 0.5-1.5 mass part. ジオクチルソジウムスルホサクシネート１質量部に対するステアリン酸マグネシウムの配合量が０．０５〜０．５質量部である１〜６のいずれかに記載の固形製剤。The solid formulation in any one of 1-6 whose compounding quantity of magnesium stearate with respect to 1 mass part of dioctylsodium sulfosuccinate is 0.05-0.5 mass part. ジオクチルソジウムスルホサクシネートを製剤全体の１０質量％以上配合したことを特徴とする１〜７のいずれかに記載の固形製剤。The solid preparation according to any one of 1 to 7, wherein 10% by mass or more of dioctylsodium sulfosuccinate is added to the whole preparation. ジオクチルソジウムスルホサクシネートを配合した溶液を用いて、軽質無水ケイ酸を配合した粉体を造粒した顆粒を含む核粒子に、腸溶性被膜が施されていることを特徴とする固形製剤。A solid preparation characterized in that an enteric coating is applied to core particles containing granules obtained by granulating a powder containing light anhydrous silicic acid using a solution containing dioctyl sodium sulfosuccinate. ジオクチルソジウムスルホサクシネートを配合した溶液を用いて、軽質無水ケイ酸を配合した粉体を造粒し、得られた顆粒を含む核粒子に対して、腸溶性被膜を施すことを特徴とする固形製剤の製造方法。A solution containing dioctyl sodium sulfosuccinate is used to granulate a powder containing light anhydrous silicic acid, and an enteric coating is applied to the core particles containing the resulting granules. A method for producing a solid preparation.
JP2004535937A 2002-09-10 2003-09-10 Dioctyl sodium sulfosuccinate solid formulation Pending JPWO2004024138A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2002264688 2002-09-10
JP2002264688 2002-09-10
PCT/JP2003/011585 WO2004024138A1 (en) 2002-09-10 2003-09-10 Solid preparation containing dioctyl sodium sulfosuccinate

Publications (1)

Publication Number Publication Date
JPWO2004024138A1 true JPWO2004024138A1 (en) 2006-01-05

Family

ID=31986541

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2004535937A Pending JPWO2004024138A1 (en) 2002-09-10 2003-09-10 Dioctyl sodium sulfosuccinate solid formulation

Country Status (3)

Country Link
JP (1) JPWO2004024138A1 (en)
AU (1) AU2003262060A1 (en)
WO (1) WO2004024138A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007055969A (en) * 2005-08-26 2007-03-08 Taisho Pharmaceut Co Ltd Bisacodyl dissolution-improving agent
SI2379063T2 (en) 2009-01-09 2021-09-30 Fwp Ip Aps Pharmaceutical formulation comprising one or more fumaric acid esters in an erosion matrix

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5799521A (en) * 1980-12-11 1982-06-21 Eisai Co Ltd Solid composition containing bisacodyl
JPH02255613A (en) * 1989-03-27 1990-10-16 Lion Corp Pharmaceutical containing dioctyl sodium sulfosuccinate blended therein
US5843479A (en) * 1993-02-26 1998-12-01 The Procter & Gamble Company Bisacodyl dosage form with multiple enteric polymer coatings for colonic delivery

Also Published As

Publication number Publication date
AU2003262060A1 (en) 2004-04-30
WO2004024138A1 (en) 2004-03-25

Similar Documents

Publication Publication Date Title
JP3611456B2 (en) Theophylline sustained release tablets
EP2448406B1 (en) Extended release oral pharmaceutical compositions of 3-hydroxy-n-methylmorphinan and method of use
KR930007245B1 (en) Process for preparing controlled-release preparation
DE60319252T2 (en) FORMULATION OF ACETAMINOPHES AND TRAMADOL WITH DELAYED RELEASE
JP4572300B2 (en) Pimobendan oral dosage formulation
US6048547A (en) Process for manufacturing solid compositions containing polyethylene oxide and an active ingredient
TWI325318B (en) Capsule and method of manufacturing the same
CN105682648A (en) Pharmaceutical composition containing dimethyl fumarate for administration at low daily dose
JPH0122245B2 (en)
NZ201008A (en) Oral preparations containing dipyridamole and at least 5 molar equivalents of orally acceptable acidic excipient
KR20070115918A (en) Multiple unit oral sustained release preparation and process for production of the same
JPH0733330B2 (en) Stable solid preparation having elastic coating and method for producing the same
KR20100099113A (en) Zibotentan composition containing mannitol and/or microcrystalline cellulose
KR100429694B1 (en) Slow release of valproate metal salt
WO1999053905A1 (en) Multiple-unit sustained release tablets
WO2006103551A1 (en) Controlled release formulations of oxycodone
JP2019524683A (en) Oral pharmaceutical formulation comprising tamsulosin hydrochloride-containing sustained release pellets with improved content uniformity
HU229569B1 (en) Multiparticulate controlled release selective serotonin reuptake inhibitor formulations
KR101680925B1 (en) Unpleasant taste-masking particles and an oral preparation containing same
JPWO2004024138A1 (en) Dioctyl sodium sulfosuccinate solid formulation
WO2018165781A1 (en) Composition of dosage form containing guaifenesin and use thereof
KR102104507B1 (en) Pharmaceutical formulations comprising sodium palmitoyl-l-prolyl-l-prolyl-glycyl-l-tyrosinate and methods for preparing the same
JP2002068964A (en) Sustained release tablet for oral administration
JPS63267720A (en) Sustained release preparation of emorfazone
JPH08325142A (en) Isopropamide iodide-containing formulation

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20060831

RD07 Notification of extinguishment of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7427

Effective date: 20090605

RD07 Notification of extinguishment of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7427

Effective date: 20090624

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20090630

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20090824

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20091027