JPH06128147A - Method for improving solubility of sparingly water-soluble medicine and medicine composition obtained thereby - Google Patents
Method for improving solubility of sparingly water-soluble medicine and medicine composition obtained therebyInfo
- Publication number
- JPH06128147A JPH06128147A JP28040292A JP28040292A JPH06128147A JP H06128147 A JPH06128147 A JP H06128147A JP 28040292 A JP28040292 A JP 28040292A JP 28040292 A JP28040292 A JP 28040292A JP H06128147 A JPH06128147 A JP H06128147A
- Authority
- JP
- Japan
- Prior art keywords
- soluble
- water
- poorly water
- solution
- drug
- 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
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、水に難溶性の結晶性薬
品の溶解性を改善する方法およびそれにより得られる溶
解性の改善された薬品組成物に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for improving the solubility of a poorly water-soluble crystalline drug and a drug composition having improved solubility obtained thereby.
【０００２】[0002]
【従来の技術】通常、人（ヒト）が内服する医薬は、消
化器内で溶解され、溶液の状態で体内に吸収されるた
め、溶解度の小さい医薬や溶解速度の遅い医薬（以下、
これらを水難溶性医薬という）は、そのまま内服しても
全量が吸収されることはなく、一部が未溶解のまま体外
に排泄されてしまう。2. Description of the Related Art Usually, a medicine taken by a human (human) is dissolved in the digestive organs and absorbed in the body in a solution state. Therefore, a medicine having a low solubility or a medicine having a slow dissolution rate (hereinafter, referred to as
These are referred to as poorly water-soluble drugs), but even if they are taken orally as they are, the whole amount is not absorbed, and some of them are excreted outside the body while being undissolved.
【０００３】しかし、これでは医薬が無駄になる許りで
なく、医薬の吸収量が各個人によって異なったり、消化
器内の状態によって変動したりするために、適正な内服
量を決めることが出来なくなってしまう。However, this does not allow the medicine to be wasted, and the absorption amount of the medicine varies from individual to individual and varies depending on the condition inside the digestive organs, so that an appropriate oral dose can be determined. It's gone.
【０００４】そこで、従来より、消化器内における水難
溶性医薬の溶解度を大きくしたり、溶解速度を速めたり
する方法が数多く提案されており、そのうち、例えば次
のような幾つかの方法が実用に供されている。Therefore, many methods have been proposed in the past for increasing the solubility or increasing the dissolution rate of poorly water-soluble drugs in the digestive organs. Among them, some of the following methods are practical. Have been served.
【０００５】溶融した尿素やポリエチレングリコール
中に水難溶性医薬を溶解して急冷することにより、非晶
形固溶体とする方法。A method in which a poorly water-soluble drug is dissolved in molten urea or polyethylene glycol and rapidly cooled to obtain an amorphous solid solution.
【０００６】水難溶性医薬をポリビニルピロリドンや
ヒドロキシプロピルメチルセルロースなどと共に有機溶
媒中に溶解し、次いで噴霧乾燥などの方法で溶媒を除去
することにより、上記と同様の固溶体とする方法。A method in which a poorly water-soluble drug is dissolved in an organic solvent together with polyvinylpyrrolidone, hydroxypropylmethylcellulose and the like and then the solvent is removed by a method such as spray drying to obtain a solid solution similar to the above.
【０００７】水難溶性医薬をデンプンなどの担体上に
機械的に融着させ、あるいは溶液として付着させた後、
乾燥することにより、微細な非晶質の付着粒とする方
法。After the poorly water-soluble drug is mechanically fused on a carrier such as starch or attached as a solution,
A method of forming fine amorphous particles by drying.
【０００８】水難溶性医薬をシクロデキストリンまた
はその誘導体などに包接させて溶解性を向上させる方
法。A method for improving solubility by including a poorly water-soluble drug in cyclodextrin or a derivative thereof.
【０００９】[0009]
【発明が解決しようとする課題】ところが、上記した従
来の溶解性改善方法は、いずれも溶解性の改善に付いて
は有効であるが、薬品に対してかなり多量の添加物を使
用しなければ所期の目的を達成することができない。However, all of the above-mentioned conventional methods for improving the solubility are effective in improving the solubility, but unless a considerably large amount of additives is used for the chemicals. Unable to achieve the intended purpose.
【００１０】例えば溶融物中に薬品を溶解して急冷する
方法の場合、溶融媒体は薬品の３〜５倍、デンプン担体
上に薬品を付着させる方法では、担体は薬品の２０〜３
０倍、包接化合物を利用する方法では、シクロデキスト
リンは薬品と略同量を必要とするのが普通である。For example, in the case of a method in which a drug is dissolved in a melt and rapidly cooled, the melting medium is 3 to 5 times that of the drug, and in the method of adhering the drug on a starch carrier, the carrier is 20 to 3 times that of the drug.
In the method using 0 times the clathrate compound, the cyclodextrin usually requires about the same amount as the drug.
【００１１】そのため、従来の溶解性改善方法により得
られる製剤は、必然的に添加物の分だけ製剤の量が増え
てしまうので、１回の服用量が多い医薬には適用し難
い、特定の種類の添加物が賦形剤または結合剤として含
まれるので製剤に望ましい物性を賦与させることが困難
となる、体内に吸収された医薬の動態に添加物が影響を
及ぼすおそれがある、などの問題点を有している。Therefore, the conventional preparations obtained by the method of improving the solubility inevitably increase the amount of the preparations by the amount of the additive, which makes it difficult to apply the preparation to a medicine having a large single dose. Since various kinds of additives are included as excipients or binders, it is difficult to impart desirable physical properties to the preparation, and the additives may affect the dynamics of the drug absorbed in the body. Have a point.
【００１２】また、医薬を担体上に機械的に融着させる
方法の場合は、上記した問題点に加えて、担体への薬品
の付着力が低いために薬品が担体上から次第に剥離して
溶解性改善効果が低下してしまうという問題もある。Further, in the case of the method of mechanically fusing the drug on the carrier, in addition to the above-mentioned problems, the drug is gradually peeled from the carrier and dissolved due to the low adhesion of the drug to the carrier. There is also a problem that the effect of improving sex is reduced.
【００１３】そこで、本発明の目的は、多量の添加物を
使用しなくとも、水難溶性薬品の溶解性を改善すること
のできる技術を提供することにある。Therefore, an object of the present invention is to provide a technique capable of improving the solubility of poorly water-soluble chemicals even without using a large amount of additives.
【００１４】[0014]
【課題を解決するための手段】本発明者らは、水難溶性
の結晶性薬品の溶解性を改善し、しかも上記した従来技
術の問題点を解消すべく鋭意研究を重ねた結果、気中に
分散させた結晶性薬品の粒子に、水溶性高分子を溶解さ
せた溶液を噴霧し、次いでこれを乾燥させることによ
り、所期の目的が達成されることを見出した。また、そ
の際、水溶性高分子を溶解させた溶液中に、この溶液が
付着される薬品と同種の薬品を溶解させておくことによ
り、より一層の好結果が得られることを見出した。The inventors of the present invention have conducted extensive studies to improve the solubility of poorly water-soluble crystalline chemicals and solve the above-mentioned problems of the prior art. It has been found that the intended purpose can be achieved by spraying a solution of a water-soluble polymer on the dispersed particles of the crystalline drug and then drying the solution. Further, at that time, it was found that even better results can be obtained by dissolving in the solution in which the water-soluble polymer is dissolved the same kind of chemical to which this solution is attached.
【００１５】これらの知見は、本発明者らによって初め
て見出されたものであり、当業者の従来の常識からは全
く予想のできなかったものである。従って、本発明方法
の作用機序については未だ明確ではないが、本発明者ら
は、薬品の結晶表面に付着した水溶性高分子の薄膜ない
し微粒子が結晶を可溶化することによるものと推定して
いる。These findings were first discovered by the present inventors and were completely unpredictable from the common general knowledge of those skilled in the art. Therefore, although the mechanism of action of the method of the present invention is still unclear, the present inventors presume that the thin film or fine particles of the water-soluble polymer attached to the surface of the drug crystal solubilizes the crystal. ing.
【００１６】本発明の適用対象となる水難溶性の結晶性
薬品としては、例えばイブプロフェン、インドメタシ
ン、メフェナム酸、フェニトイン、アジマリン、硝酸イ
ソソルビド、ニフェジピン、ノスカピン、エピネフリ
ン、プレドニゾロン、プロスタグランジンＥ1 およびプ
ロスタグランジンＥ2 などを挙げることができるが、こ
れらに限定されるものではなく、日本薬局方の規定で
「水にほとんど溶けない」または「水に極めて溶けにく
い」もので、かつ結晶または結晶性の薬品であれば、全
てのものが適用対象となる。Examples of the poorly water-soluble crystalline drug to which the present invention is applied include, for example, ibuprofen, indomethacin, mefenamic acid, phenytoin, ajmaline, isosorbide nitrate, nifedipine, noscapine, epinephrine, prednisolone, prostaglandin E 1 and prostaglandin. Examples thereof include, but are not limited to, gin E 2 and the like, which are “poorly insoluble in water” or “extremely insoluble in water” according to Japanese Pharmacopoeia, and crystalline or crystalline. If it is a medicine, all things are applicable.
【００１７】なお、本発明方法を適用して薬品の溶解性
を改善する場合は、粒径５０μｍ以下の結晶粒子を用い
ることが望ましい。When the method of the present invention is applied to improve the solubility of chemicals, it is desirable to use crystalline particles having a particle size of 50 μm or less.
【００１８】本発明で用いる水溶性高分子としては、例
えばヒドロキシエチルセルロース、ヒドロキシプロピル
セルロース、ヒドロキシプロピルメチルセルロース、メ
チルセルロース、カルボキシメチルセルロース、ポリビ
ニルピロリドン、ポリビニルアルコール、ポリアクリル
酸およびその塩、ポリエチレングリコール、プルラン、
デキストリン、アラビアゴム、アルギン酸ナトリウム、
ゼラチンなどを挙げることができるが、これらに限定さ
れるものではなく、薬学的に許容される水溶性高分子で
あれば、いかなるものであってもよい。Examples of the water-soluble polymer used in the present invention include hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, carboxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid and its salts, polyethylene glycol, pullulan,
Dextrin, gum arabic, sodium alginate,
Examples thereof include gelatin, but not limited thereto, and any pharmaceutically acceptable water-soluble polymer may be used.
【００１９】本発明で用いる溶剤としては、例えば水、
あるいはメタノール、イソプロパノール、塩化メチレ
ン、ヘキサン、アセトンなどの有機溶剤、もしくはこれ
らを２種以上含む混合溶剤などを挙げることができる
が、これらに限定されるものではなく、水溶性高分子を
溶解し得るものであればいかなるものであってもよい。
また、対象となる水難溶性の結晶性薬品を溶解し得るか
否かは問わない。Examples of the solvent used in the present invention include water,
Alternatively, examples thereof include organic solvents such as methanol, isopropanol, methylene chloride, hexane, and acetone, or mixed solvents containing two or more of these, but the solvent is not limited to these and can dissolve a water-soluble polymer. Any material may be used.
Further, it does not matter whether or not the target water-insoluble crystalline drug can be dissolved.
【００２０】水難溶性の結晶性薬品と水溶性高分子との
割合は、後者が前者の0.２〜２０重量％程度とする。結
晶性薬品や水溶性高分子の種類にも依るので一概には規
定できないが、通常、この割合は0.３〜１０重量％程度
でよく、最も実用的な割合は0.５〜５重量％程度であ
る。The ratio of the poorly water-soluble crystalline drug and the water-soluble polymer is about 0.2 to 20% by weight of the latter. It cannot be specified unconditionally because it depends on the type of crystalline chemicals and water-soluble polymer, but normally this ratio is about 0.3 to 10% by weight, and the most practical ratio is 0.5 to 5% by weight. It is a degree.
【００２１】上記の割合が0.２重量％以下になると、充
分な溶解性改善効果が得られなくなる。他方、水溶性高
分子の割合が２０重量％を超えても溶解性改善効果の向
上は期待できず、かつ製剤中に占める添加物の割合が増
加してしまう。また、結晶性薬品の粒子上に一回噴霧し
ただけでは充分な付着量が得られなくなるために噴霧回
数を増やす必要が生じ、噴霧処理時間が長くなってしま
うという不具合も生じる。When the above-mentioned ratio is 0.2% by weight or less, a sufficient solubility improving effect cannot be obtained. On the other hand, even if the proportion of the water-soluble polymer exceeds 20% by weight, improvement of the solubility improving effect cannot be expected, and the proportion of the additive in the formulation increases. In addition, it is necessary to increase the number of times of spraying because a sufficient amount of adhesion cannot be obtained by spraying onto the particles of the crystalline drug only once, which causes a problem that the spraying process time becomes long.
【００２２】水溶性高分子を溶解させた溶液には、界面
活性剤、可塑剤、ｐＨ調節剤などの添加物を少量添加し
てもよい。また、この溶液中に溶解性改善の対象となる
結晶性薬品と同種の薬品を溶解しておいてもよく、これ
によって溶解性改善効果が一層向上する場合が多い。A small amount of additives such as surfactants, plasticizers and pH adjusters may be added to the solution in which the water-soluble polymer is dissolved. Further, the same kind of chemical as the crystalline chemical to be the target of solubility improvement may be dissolved in this solution, and in many cases, the solubility improving effect is further improved.
【００２３】本発明においては、結晶性薬品粒子を気中
に分散させた状態で噴霧処理を行うことが必須の要件で
ある。例えば転動造粒機や攪拌造粒機などを使う場合の
ように、粒子同士が接触した状態で噴霧処理を行うと、
粒子が互いに付着して団塊状になったり、水溶性高分子
の付着が不均一になったりするため、溶解性改善効果が
充分に得られなくなってしまう。In the present invention, it is an essential requirement to carry out the spray treatment in a state in which the crystalline drug particles are dispersed in the air. For example, when using a rolling granulator or a stirring granulator, when performing the spraying process while the particles are in contact with each other,
Since the particles adhere to each other to form a nodule or the water-soluble polymer adheres unevenly, the effect of improving the solubility cannot be sufficiently obtained.
【００２４】結晶性薬品粒子を気中に分散させた状態で
噴霧処理を行うのに好適な装置として、例えば噴霧機構
を備えた流動層や、気流乾燥機型の装置などを挙げるこ
とができる。噴霧機構としては、中央に結晶性薬品粒子
の噴出部、その外側に水溶性高分子溶液の噴出部、さら
にその外側に圧縮空気の噴出部を配置した同心三重構造
のノズル（特願平３−２７０５９８号）などが好適であ
る。As a device suitable for performing the spraying treatment in a state where the crystalline drug particles are dispersed in the air, for example, a fluidized bed having a spraying mechanism, an air flow dryer type device and the like can be mentioned. As the atomizing mechanism, a nozzle having a concentric triple structure in which a crystalline drug particle jetting portion is arranged in the center, a water-soluble polymer solution jetting portion is arranged outside thereof, and a compressed air jetting portion is arranged outside thereof (Japanese Patent Application No. No. 270598) is suitable.
【００２５】以下、実施例を用いて本発明をより具体的
に説明する。Hereinafter, the present invention will be described more specifically with reference to examples.
【００２６】[0026]
〔実施例１〜５〕水難溶性の結晶性薬品粒子としてイン
ドメタシン粒子（平均粒径１０μｍ）を用い、これに表
１に示す各種組成の水溶性高分子の２重量％溶液を噴霧
した。噴霧は、図１に示す構造のジェットコーティング
装置（フロイント産業社製、ＣＭ−ＭＩＮＩ）を使用
し、表２に示す条件で噴霧処理を行った。[Examples 1 to 5] Indomethacin particles (average particle size 10 µm) were used as poorly water-soluble crystalline drug particles, and a 2 wt% solution of a water-soluble polymer having various compositions shown in Table 1 was sprayed onto the particles. For the spraying, a jet coating apparatus (CM-MINI manufactured by Freund Sangyo Co., Ltd.) having the structure shown in FIG.
【００２７】図１において、１は処理室、２はサイクロ
ン、３は空気導入部、４はフィルタ、５はヒータ、６は
ブロアである。処理室１内の底部に設置された三流体ノ
ズル７には、外部から薬品粒子８、水溶性高分子９およ
び圧縮空気１０がそれぞれ供給される。図２に拡大して
示すように、三流体ノズル７には、粒子導入路８ａ、溶
液導入路９ａおよび２系統の空気導入路１０ａ、１０ｂ
が設けられ、この三流体ノズル７から上方に向かってス
プレーされる薬品粒子８と水溶性高分子溶液９とがジェ
ット気流によって接触されるようになっている。In FIG. 1, 1 is a processing chamber, 2 is a cyclone, 3 is an air inlet, 4 is a filter, 5 is a heater, and 6 is a blower. Chemical particles 8, water-soluble polymer 9 and compressed air 10 are supplied to the three-fluid nozzle 7 installed at the bottom of the processing chamber 1 from the outside. As shown in an enlarged scale in FIG. 2, the three-fluid nozzle 7 has a particle introduction passage 8a, a solution introduction passage 9a, and two air introduction passages 10a and 10b.
The chemical particles 8 sprayed upward from the three-fluid nozzle 7 and the water-soluble polymer solution 9 are brought into contact with each other by a jet stream.
【００２８】[0028]
【表１】 [Table 1]
【００２９】[0029]
【表２】 [Table 2]
【００３０】表１に示す比較例１は、２重量％のインド
メタシンを溶解させたエタノールをインドメタシン粒子
に噴霧した例であり、比較例２は、水不溶性高分子であ
るエチルセルロースを２重量％溶解させたエタノールを
噴霧した例であり、比較例３は、エタノールのみを噴霧
した例である。噴霧は、いずれも図１に示すジェットコ
ーティング装置を使用し、表２に示す条件で行った。Comparative Example 1 shown in Table 1 is an example in which ethanol in which 2% by weight of indomethacin is dissolved is sprayed on indomethacin particles, and Comparative Example 2 dissolves 2% by weight of ethylcellulose, which is a water-insoluble polymer. Comparative Example 3 is an example in which only ethanol is sprayed. The spraying was performed under the conditions shown in Table 2 using the jet coating device shown in FIG.
【００３１】上記の方法で得られた実施例１〜５および
比較例１〜３の薬品組成物各６mgを溶出試験に付し、図
３に示す溶出曲線を得た。本溶出試験において、各薬品
組成物中のインドメタシンの溶出性は、日局１２溶出試
験法第２法（パドル法）に準拠し、ｐＨ4.７の酢酸緩衝
液（９００ml) を用いて自動溶出試験器（日本分光工業
社製、ＤＴ−６００）にて評価した。6 mg of each of the chemical compositions of Examples 1 to 5 and Comparative Examples 1 to 3 obtained by the above method was subjected to a dissolution test to obtain a dissolution curve shown in FIG. In this dissolution test, the dissolution property of indomethacin in each drug composition was based on the Japanese Pharmacopoeia 12 dissolution test method 2 (paddle method), and an automatic dissolution test was performed using an acetate buffer solution (900 ml) with a pH of 4.7. Evaluation was performed with a container (DT-600, manufactured by JASCO Corporation).
【００３２】〔実施例６〕水難溶性の結晶性薬品粒子と
してメフェナム酸粒子（平均粒径２７μｍ）を用い、Ｈ
ＰＣ−Ｌ（日本曹達社製、ヒドロキシプロピルセルロー
ス）の５％エタノール溶液を噴霧した。噴霧は、図１に
示すジェットコーティング装置を使用し、表２に示す条
件で噴霧処理を行った。Example 6 Mefenamic acid particles (average particle size 27 μm) were used as the poorly water-soluble crystalline drug particles, and H
A 5% ethanol solution of PC-L (manufactured by Nippon Soda Co., Ltd., hydroxypropyl cellulose) was sprayed. For the spraying, the jet coating apparatus shown in FIG. 1 was used, and the spraying treatment was performed under the conditions shown in Table 2.
【００３３】上記の方法で得られた薬品組成物各２０mg
を前記の試験法に準拠し、日局１２崩壊試験法第２液溶
出試験に付し、図４に示す溶出曲線を得た。20 mg each of the pharmaceutical composition obtained by the above method
According to the above-mentioned test method, was subjected to the Japanese Pharmacopoeia 12 disintegration test method second liquid dissolution test, and the dissolution curve shown in FIG. 4 was obtained.
【００３４】[0034]
【発明の効果】前記実施例１〜６の結果から明らかなよ
うに、本発明の溶解性改善方法によれば、多量の添加物
を使用しなくとも、水難溶性薬品の溶解性を改善するこ
とができるという優れた効果が得られる。As is clear from the results of Examples 1 to 6, according to the solubility improving method of the present invention, the solubility of poorly water-soluble chemicals can be improved without using a large amount of additives. The excellent effect of being able to do is obtained.
【図１】実施例で用いたジェットコーティング装置の全
体構成図である。FIG. 1 is an overall configuration diagram of a jet coating apparatus used in an example.
【図２】図１に示すジェットコーティング装置の三流体
ノズルを拡大して示す断面図である。2 is an enlarged sectional view showing a three-fluid nozzle of the jet coating apparatus shown in FIG.
【図３】実施例１〜５および比較例１〜３の薬品組成物
の溶出曲線を示す図である。FIG. 3 is a diagram showing elution curves of the chemical compositions of Examples 1 to 5 and Comparative Examples 1 to 3.
【図４】実施例６の薬品組成物の溶出曲線を示す図であ
る。FIG. 4 is a diagram showing an elution curve of the drug composition of Example 6.
１ 処理室 ２ サイクロン ３ 空気導入部 ４ フィルタ ５ ヒータ ６ ブロア ７ 三流体ノズル７ ８ 薬品粒子 ８ａ 粒子導入路 ９ 水溶性高分子溶液 ９ａ 溶液導入路 １０ 圧縮空気 １０ａ 空気導入路 １０ｂ 空気導入路 1 Processing chamber 2 Cyclone 3 Air introduction part 4 Filter 5 Heater 6 Blower 7 Three-fluid nozzle 7 8 Chemical particles 8a Particle introduction path 9 Water-soluble polymer solution 9a Solution introduction path 10 Compressed air 10a Air introduction path 10b Air introduction path
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 47/34 Ｄ 7433−4Ｃ Ｇ 7433−4Ｃ 47/36 Ｄ 7433−4Ｃ Ｇ 7433−4Ｃ 47/38 Ｄ 7433−4Ｃ Ｇ 7433−4Ｃ 47/42 Ｄ 7433−4Ｃ Ｇ 7433−4Ｃ (72)発明者 杉原 正泰 東京都新宿区河田町８−１ 東京女子医科 大学病院 薬剤部内 (72)発明者 仲田 遣功 東京都新宿区河田町８−１ 東京女子医科 大学病院 薬剤部内 (72)発明者 武井 成通 東京都新宿区高田馬場２丁目14番２号 フ ロイント産業株式会社内 (72)発明者 鵜野沢 一臣 東京都新宿区高田馬場２丁目14番２号 フ ロイント産業株式会社内 (72)発明者 山中 邦昭 東京都新宿区高田馬場２丁目14番２号 フ ロイント産業株式会社内 (72)発明者 杉山 守 東京都新宿区高田馬場２丁目14番２号 フ ロイント産業株式会社内─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification number Reference number within the agency FI Technical display area A61K 47/34 D 7433-4C G 7433-4C 47/36 D 7433-4C G 7433-4C 47 / 38 D 7433-4C G 7433-4C 47/42 D 7433-4C G 7433-4C (72) Inventor Masayasu Sugihara 8-1 Kawatamachi, Shinjuku-ku, Tokyo Tokyo Women's Medical University Hospital Pharmacy (72) Inventor Nakata Achievement 8-1 Kawata-cho, Shinjuku-ku, Tokyo Within the Department of Pharmacy, Tokyo Women's Medical University Hospital (72) Inventor Narimichi Takei 2-14-2 Takadanobaba, Shinjuku-ku, Tokyo Inside Freud Sangyo Co., Ltd. Ichiomi 2-14-2 Takadanobaba, Shinjuku-ku, Tokyo Inside Freud Sangyo Co., Ltd. (72) Inventor Kuniaki Yamanaka 2-14-2 Takadanobaba, Shinjuku-ku, Tokyo Inside Freund Sangyo Co., Ltd. (72) Inventor Mamoru Sugiyama 2-14-2 Takadanobaba, Shinjuku-ku, Tokyo Inside Freund Sangyo Co., Ltd.
Claims (5)
せ、これに水溶性高分子を溶解させた溶液を噴霧して付
着させた後、乾燥させることを特徴とする水難溶性薬品
の溶解性改善方法。1. Dissolution of a poorly water-soluble drug, characterized in that crystal particles of a poorly water-soluble drug are dispersed in the air, a solution in which a water-soluble polymer is dissolved is sprayed onto the solution, and then dried. Sex improvement method.
に、この溶液が付着される水難溶性薬品と同種の水難溶
性薬品を溶解させておくことを特徴とする請求項１記載
の水難溶性薬品の溶解性改善方法。2. The poorly water-soluble chemical according to claim 1, wherein a poorly water-soluble chemical of the same kind as the poorly water-soluble chemical to which the solution is attached is dissolved in the solution in which the water-soluble polymer is dissolved. Method of improving solubility of chemicals.
対して、0.２〜２０重量部の水溶性高分子を付着させる
ことを特徴とする請求項１記載の水難溶性薬品の溶解性
改善方法。3. The improved solubility of a poorly water-soluble drug according to claim 1, wherein 0.2 to 20 parts by weight of a water-soluble polymer is attached to 100 parts by weight of crystal particles of the poorly water-soluble drug. Method.
いることを特徴とする請求項１記載の水難溶性薬品の溶
解性改善方法。4. The method for improving the solubility of a poorly water-soluble chemical according to claim 1, wherein a poorly water-soluble chemical having a particle size of 50 μm or less is used.
に、水溶性高分子を溶解させた溶液を噴霧して付着させ
た後、乾燥させることにより得られる溶解性の改善され
た薬品組成物。5. A chemical composition with improved solubility obtained by spraying and adhering a solution of a water-soluble polymer on particles of a poorly water-soluble chemical dispersed in air, and adhering the solution. object.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28040292A JPH06128147A (en) | 1992-10-20 | 1992-10-20 | Method for improving solubility of sparingly water-soluble medicine and medicine composition obtained thereby |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28040292A JPH06128147A (en) | 1992-10-20 | 1992-10-20 | Method for improving solubility of sparingly water-soluble medicine and medicine composition obtained thereby |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06128147A true JPH06128147A (en) | 1994-05-10 |
Family
ID=17624535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28040292A Pending JPH06128147A (en) | 1992-10-20 | 1992-10-20 | Method for improving solubility of sparingly water-soluble medicine and medicine composition obtained thereby |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06128147A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5547683A (en) * | 1992-10-09 | 1996-08-20 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Method for producing microgranulated particle |
| WO2001047495A1 (en) * | 1999-12-23 | 2001-07-05 | Pfizer Products Inc. | Pharmaceutical compositions providing enhanced drug concentrations |
| JP2003073261A (en) * | 2001-09-05 | 2003-03-12 | Shin Etsu Chem Co Ltd | Method for producing pharmaceutical solid preparation including sparingly soluble medicament |
| WO2004110448A1 (en) * | 2003-06-17 | 2004-12-23 | Kyowa Hakko Kogyo Co., Ltd. | Medicinal composition containing benidipine hydrochloride |
-
1992
- 1992-10-20 JP JP28040292A patent/JPH06128147A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5547683A (en) * | 1992-10-09 | 1996-08-20 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Method for producing microgranulated particle |
| WO2001047495A1 (en) * | 1999-12-23 | 2001-07-05 | Pfizer Products Inc. | Pharmaceutical compositions providing enhanced drug concentrations |
| US8026286B2 (en) | 1999-12-23 | 2011-09-27 | Bend Research, Inc. | Pharmaceutical compositions providing enhanced drug concentrations |
| US8501231B2 (en) | 1999-12-23 | 2013-08-06 | Bend Research, Inc. | Pharmaceutical compositions providing enhanced drug concentrations |
| US8796341B2 (en) | 1999-12-23 | 2014-08-05 | Bend Research, Inc. | Pharmaceutical compositions providing enhanced drug concentrations |
| US8980321B2 (en) | 1999-12-23 | 2015-03-17 | Bend Research, Inc. | Pharmaceutical compositions providing enhanced drug concentrations |
| US9457095B2 (en) | 1999-12-23 | 2016-10-04 | Bend Research, Inc. | Pharmaceutical compositions providing enhanced drug concentrations |
| JP2003073261A (en) * | 2001-09-05 | 2003-03-12 | Shin Etsu Chem Co Ltd | Method for producing pharmaceutical solid preparation including sparingly soluble medicament |
| JP4644397B2 (en) * | 2001-09-05 | 2011-03-02 | 信越化学工業株式会社 | Method for producing pharmaceutical solid preparation containing poorly soluble drug |
| WO2004110448A1 (en) * | 2003-06-17 | 2004-12-23 | Kyowa Hakko Kogyo Co., Ltd. | Medicinal composition containing benidipine hydrochloride |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2334991T3 (en) | FARMACO MICROPARTICLES. | |
| Hari et al. | Chitosan/calcium alginate microcapsules for intestinal delivery of nitrofurantoin | |
| JP3265680B2 (en) | Oral pharmaceutical composition | |
| JP3460538B2 (en) | Fast dissolving film preparation | |
| RU2163803C2 (en) | Dariphenacin-containing pharmaceutical compositions | |
| JP4825385B2 (en) | Thin film formulation for two-phase release of pharmacologically active substances or other substances | |
| JP2784184B2 (en) | Spheroid | |
| TWI422375B (en) | Medicinal preparation having a superior light stability | |
| JP4644397B2 (en) | Method for producing pharmaceutical solid preparation containing poorly soluble drug | |
| CN103301070A (en) | Formulations for a tight junction effector | |
| JP2001172201A (en) | Use of film coating for masking the taste for oral administration, oral administration form and production thereof | |
| UA79578C2 (en) | Controlled release composition containing galantamine, process for the preparation thereof, dosage form and packaging | |
| IE69042B1 (en) | Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets | |
| JP2001511443A (en) | Oral pharmaceutical preparation containing anti-ulcer active compound and method for producing the same | |
| EP0616802B1 (en) | Oral preparation for release in lower digestive tracts | |
| JPH11506432A (en) | Bisacodyl dosage form for colon delivery | |
| JP3221891B2 (en) | Rotary granulation and taste-masking coating for the preparation of chewable pharmaceutical tablets | |
| BR112014023278B1 (en) | METHOD FOR THE PRODUCTION OF ENTERIC CALCIUM ALGINATE MICROCAPSULAS AND PHARMACEUTICAL COMPOSITION IN ORAL MULTIPARTICULA | |
| JP2008174511A (en) | Bitter taste-masking composition | |
| JP2000053563A (en) | Rapid releasable fine granule having masked bitterness | |
| JPH06128147A (en) | Method for improving solubility of sparingly water-soluble medicine and medicine composition obtained thereby | |
| JPH05339151A (en) | Sustained release oxybutynin hydrochloride preparation | |
| JPH06227969A (en) | Method for improving enteric property of medicine and medicine composition obtained thereby | |
| JP5466379B2 (en) | Film-form preparation and method for producing film-form preparation | |
| JP4716063B2 (en) | Unpleasant taste masking particles and oral preparations containing the same |