JP2004189756A - Offensive taste-masked preparation - Google Patents
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本発明は、不快な薬物の味がマスキングされた服用感のよい製剤に関する。 The present invention relates to a pleasant-to-take formulation in which the unpleasant drug taste is masked.
医薬品が苦味等の不快な味を伴う場合、患者が散剤や粒剤として服用することは著しく困難となる。そこで服用時の口中での不快な味をマスキングするために（１）アスパルテーム等の甘味料や香料等を添加する方法（特許文献１）、（２）包接化合物を添加する方法（特許文献２）及び（３）胃溶性高分子、腸溶性高分子、水不溶性高分子、ワックス類等で被覆を施す方法（特許文献３及び４）がすでに提案されている。
しかし、上記（１）又は（２）の方法では苦味等の不快な味が強い場合は、マスキングは不可能であり、（３）の被覆による方法では、苦味等の強弱に応じて、被覆剤の量を増すことでマスキングすることは可能であるが、被覆剤特有の服用時のザラつき感が生じ、更に被覆剤により薬物の溶出が低下するおそれがあった。
However, masking is not possible when the method (1) or (2) has an unpleasant taste such as bitterness, and the coating method (3) depends on the strength of the bitterness or the like. Although it is possible to mask by increasing the amount of, there is a possibility that a rough feeling at the time of taking, which is peculiar to the coating agent, occurs, and the elution of the drug is further reduced by the coating agent.
従って本発明の目的は、薬物の溶出性が良好で苦味等の不快な味を有するあらゆる薬物に対して有効にマスキングができる製剤を提供することにある。 Accordingly, an object of the present invention is to provide a preparation which has good dissolution of a drug and can effectively mask any drug having an unpleasant taste such as a bitter taste.
斯かる実情に鑑み本発明者らは、鋭意研究を行った結果、薬物に一定量以上の水膨潤性物質を配合した組成物を水又は含水アルコールで湿式造粒すれば、薬物の溶出を低下させずに、不快な味がマスキングされることを見出し本発明を完成した。
すなわち本発明は、薬物及び低置換度ヒドロキシプロピルセルロースを含有する組成物であり、当該低置換度ヒドロキシプロピルセルロースをマスキング剤として組成物中３０重量％以上含有するものを、水又は含水アルコールで湿式造粒して得られる経口用製剤を提供するものである。
In view of such circumstances, the present inventors have conducted intensive studies and as a result, it has been found that if a composition obtained by mixing a drug with a certain amount or more of a water-swellable substance in a wet granulation with water or hydroalcohol, the dissolution of the drug is reduced. Without doing so, they found that unpleasant taste was masked, and completed the present invention.
That is, the present invention relates to a composition containing a drug and a low-substituted hydroxypropylcellulose, wherein the composition containing the low-substituted hydroxypropylcellulose as a masking agent in an amount of 30% by weight or more is wet-coated with water or hydrous alcohol. An oral preparation obtained by granulation is provided.
本発明の製剤は、不快な薬物の味がマスキングされ服用感が良く、薬物の溶出も良好である。 The formulation of the present invention masks the unpleasant drug taste, gives a good feeling of taking, and has good drug elution.
本発明で用いる低置換度ヒドロキシプロピルセルロースは、水を吸収して膨潤する水膨潤性物質であり、１種又は２種以上を混合して用いることができる。使用量は、薬物及び低置換度ヒドロキシプロピルセルロースを含有する組成物中３０重量％以上、特に５０〜９５重量％とすることが好ましい。 The low-substituted hydroxypropylcellulose used in the present invention is a water-swellable substance that absorbs water and swells, and may be used alone or as a mixture of two or more. The amount used is preferably 30% by weight or more, particularly preferably 50 to 95% by weight, in the composition containing the drug and the low-substituted hydroxypropylcellulose.
本発明に適用する薬物は苦味等を有する薬物であれば特に限定されず、例えばイブプロフェン、ジクロフェナクナトリウム、フルフェナム酸、スルピリン、アスピリン、ケトプロフェン等の解熱鎮痛消炎剤；カフェイン等の利尿剤；テオフィリン等の気管支拡張剤；マレイン酸クロルフェニラミン、塩酸ジフェンヒドラミン、塩酸プロメタジン等の抗ヒスタミン剤；塩酸ノスカピン、クエン酸カルベタペンタン、臭化水素デキストロメトルファン、クエン酸イソアミニル、リン酸ジメモルファン等の鎮咳去痰剤；塩酸タランピシリン、塩酸バカンピシリン、セファクロル、エリスロマイシン等の各種抗生物質；シメチジン、塩酸ピレンゼピン等の抗潰瘍剤；リン酸ジヒドロコデイン、dl−塩酸メチルエフェドリン等の交感神経興奮剤；塩酸デラプリル、塩酸メクロフェノキサート、塩酸ジルチアゼム等の循環器官用剤；ビンポセチン等の脳循環改善剤；クロルジアゼポキシド、ジアゼパム等の抗不安剤；フルスルチアミン、塩酸チアミン、パントテン酸カルシウム、アスコルビン酸、トラネキサム酸等のビタミン剤；塩酸キニーネ等の抗マラリア剤；塩酸エチレフリン、ジギトキシン等の強心剤；塩酸プロプラノロール、塩酸アルプレノロール等の抗不整脈剤；塩酸ロペラミド等の止瀉剤；クロルプロマジン等の向精神剤等を挙げることができる。 The drug applied to the present invention is not particularly limited as long as it has a bitter taste and the like, and examples thereof include antipyretic analgesic and anti-inflammatory agents such as ibuprofen, diclofenac sodium, flufenamic acid, sulpyrine, aspirin, ketoprofen; diuretics such as caffeine; Bronchodilators; antihistamines such as chlorpheniramine maleate, diphenhydramine hydrochloride, and promethazine hydrochloride; antitussive expectorants such as noscapine hydrochloride, carbetapentane citrate, dextromethorphan hydrogen bromide, isoaminyl citrate, dimemorphan phosphate; Antibiotics such as tarampicillin, bacampicillin hydrochloride, cefaclor, erythromycin; antiulcer agents such as cimetidine and pirenzepine hydrochloride; sympathomimetics such as dihydrocodeine phosphate and dl-methylephedrine hydrochloride; dehydrochloride Cardiovascular agents such as prill, meclofenoxate hydrochloride and diltiazem hydrochloride; cerebral circulation improving agents such as vinpocetine; anxiolytics such as chlordiazepoxide and diazepam; fursultiamine, thiamine hydrochloride, calcium pantothenate, ascorbic acid, tranexamic acid Antimalarial agents such as quinine hydrochloride; cardiotonic agents such as ethylephrine hydrochloride and digitoxin; antiarrhythmic agents such as propranolol hydrochloride and alprenolol hydrochloride; antidiarrheal agents such as loperamide hydrochloride; psychotropic agents such as chlorpromazine; be able to.
薬物の配合量は、目的に応じて適宜決定すればよいが、低置換度ヒドロキシプロピルセルロースの配合量の関係から、薬物及び低置換度ヒドロキシプロピルセルロースを含有する組成物中７０重量％以下、５０重量％以下とすることが好ましい。 The compounding amount of the drug may be appropriately determined according to the purpose. However, from the relation of the compounding amount of the low-substituted hydroxypropylcellulose, 70% by weight or less, 50% or less, in the composition containing the drug and the low-substituted hydroxypropylcellulose. % By weight or less.
本発明で用いる含水アルコール中のアルコールとしては、エチルアルコール、メチルアルコール、イソプロピルアルコール等の医薬品又はその製造に用いることができるアルコールが挙げられ、含水アルコールとしては、アルコールが５０重量％以下のもの、特に３０重量％以下のものが好ましい。水又は含水アルコールは湿式造粒の練合溶媒として使用し、低置換度ヒドロキシプロピルセルロースを膨潤状態とするためのものであり、その使用量は低置換度ヒドロキシプロピルセルロースに対して２〜５重量倍とすることが好ましい。
水又は含水アルコールの練合溶媒には、目的により甘味料、精製白糖等の糖類、Ｄ−マンニトール等の糖アルコール、水に溶解又は分散した高分子等の医薬品で通常使用することのできる添加物を加えてもよい。
Examples of the alcohol in the hydrated alcohol used in the present invention include pharmaceuticals such as ethyl alcohol, methyl alcohol, and isopropyl alcohol or alcohols that can be used in the production thereof. Examples of the hydrated alcohol include those containing 50% by weight or less of alcohol, Particularly, those having a content of 30% by weight or less are preferable. Water or hydrous alcohol is used as a kneading solvent for wet granulation, and is used to make the low-substituted hydroxypropylcellulose into a swollen state, and the amount used is 2 to 5% by weight based on the low-substituted hydroxypropylcellulose. Preferably, it is doubled.
Additives that can be used in pharmaceuticals such as sweeteners, sugars such as purified sucrose, sugar alcohols such as D-mannitol, and polymers dissolved or dispersed in water depending on the purpose are used as the kneading solvent for water or aqueous alcohol. May be added.
本発明における「薬物及び低置換度ヒドロキシプロピルセルロースを含有する組成物」とは、造粒の適用対象でこれらを含む粉体処方物をいい、薬物及び低置換度ヒドロキシプロピルセルロースのみであってもよいが、一般にはこれらと添加剤とからなるものをいう。ここで用いられる添加剤としては、医薬品として添加できるものであれば特に限定されないが、例えば、賦形剤（希釈剤）、結合剤、崩壊剤、甘味料、着香料、色素等が挙げられる。ここで、賦形剤（希釈剤）としては、例えば糖類（乳糖、精製白糖、ブドウ糖等）、糖アルコール（Ｄ−マンニトール、ソルビトール、キシリトール、エリスリトール等）等が挙げられる。結合剤としては、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、ポリビニルピロリドン、デキストリン、アルファー化デンプン等が挙げられる。崩壊剤としては、トウモロコシデンプン等のデンプン類等が挙げられる。甘味料としては、サッカリンナトリウムやアスパルテーム等が挙げられる。香料としては、オレンジやレモン等の柑橘系香料やメントールやハッカ油等が挙げられる。色素としては、天然色素や合成色素等が挙げられる。 The `` composition containing the drug and the low-substituted hydroxypropylcellulose '' in the present invention refers to a powder formulation containing these in the application of granulation, even if only the drug and the low-substituted hydroxypropylcellulose Good, but generally refers to those composed of these and additives. The additives used here are not particularly limited as long as they can be added as pharmaceuticals, and include, for example, excipients (diluents), binders, disintegrants, sweeteners, flavors, pigments, and the like. Here, examples of the excipient (diluent) include sugars (lactose, purified sucrose, glucose, etc.), sugar alcohols (D-mannitol, sorbitol, xylitol, erythritol, etc.). Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinylpyrrolidone, dextrin, pregelatinized starch and the like. Disintegrators include starches such as corn starch. Sweeteners include saccharin sodium and aspartame. Examples of the flavor include citrus flavors such as orange and lemon, menthol, peppermint oil and the like. Examples of the dye include natural dyes and synthetic dyes.
本発明において湿式造粒に使用される方法は、攪拌造粒や流動層造粒そして押し出し造粒法等の通常医薬品等に利用される湿式造粒法であれば特に限定されないが、好ましくは押し出し造粒法である。 The method used for wet granulation in the present invention is not particularly limited as long as it is a wet granulation method used for ordinary pharmaceuticals and the like such as stirring granulation, fluidized bed granulation and extrusion granulation, but is preferably extruded. It is a granulation method.
本発明の経口用製剤は、例えば次の如くして製造することができる。
まず、薬物と低置換度ヒドロキシプロピルセルロースそして必要に応じて他の添加物を加え、攪拌型混合機、例えばバーチカルグラニュレーター（パウレック（株）製）等の混合機で混合後、精製水又は１０〜３０重量％含水アルコールを低置換度ヒドロキシプロピルセルロースの２倍から５倍程度加え練合し低置換度ヒドロキシプロピルセルロースを膨潤状態とする。この練合物を押し出し造粒機、例えばファインリューザー（不二パウダル（株）製）押し出し造粒機にて造粒し、箱形乾燥機又は流動層造粒乾燥機にて乾燥する。この乾燥によって低置換度ヒドロキシプロピルセルロースが収縮する際に不快な味を有する薬物を中に取り込みマスキングされると考えられる。そして、最後に篩を用いて目的の粒度の顆粒を得る。
The oral preparation of the present invention can be produced, for example, as follows.
First, a drug, a low-substituted hydroxypropylcellulose, and other additives as necessary are added, and mixed with a stirring-type mixer, for example, a mixer such as a vertical granulator (manufactured by Powrex Co., Ltd.). About 30% by weight of hydroalcoholic alcohol is added about 2 to 5 times the low-substituted hydroxypropylcellulose and kneaded to make the low-substituted hydroxypropylcellulose into a swollen state. The kneaded product is granulated by an extrusion granulator, for example, a fine-luzer (manufactured by Fuji Paudal Co., Ltd.) extrusion granulator, and dried by a box dryer or a fluidized bed granulator / dryer. It is considered that the low-substituted hydroxypropylcellulose shrinks and incorporates a drug having an unpleasant taste into the mask when the shrinkage occurs. Finally, a granule having a desired particle size is obtained using a sieve.
一方、押し出し造粒後、マルメライザー（不二パウダル（株）製）にて球形処理を施したのち、箱形乾燥機又は流動層乾燥機にて乾燥し、最後に篩を用いて目的の粒度の球形顆粒を製造することもできる。
また、上記練合物を、直ちに箱形乾燥機又は流動層造粒乾燥機にて乾燥し、最後に篩を用いて目的の粒度の顆粒とすることもできる。
目的とする顆粒の粒度は、水又は含水アルコールの量を調節するか、押し出し造粒時のスクリーン径を０．３〜１．２mmの範囲で変えることにより散剤や細粒剤そして顆粒剤を得ることができる。
得られた顆粒剤に、更に服用感や薬物の安定性等を考慮して糖類や高分子等でコーティングを行うこともできる。
更に得られた顆粒に、賦形剤（希釈剤）、崩壊剤、滑沢剤等を添加して錠剤にすることもできる。
On the other hand, after extrusion granulation, the particles were subjected to spherical treatment with a marmellaizer (manufactured by Fuji Paudal Co., Ltd.), dried with a box drier or a fluidized bed drier, and finally with a sieve using a sieve. Can also be produced.
Further, the kneaded product can be immediately dried in a box-shaped dryer or a fluidized-bed granulator and finally, granules having a desired particle size can be obtained by using a sieve.
The particle size of the target granules is obtained by adjusting the amount of water or hydroalcohol or changing the screen diameter during extrusion granulation in the range of 0.3 to 1.2 mm to obtain powders, fine granules and granules. be able to.
The obtained granules can be further coated with a saccharide, a polymer, or the like in consideration of the feeling of taking and stability of the drug.
Further, excipients (diluents), disintegrants, lubricants and the like can be added to the obtained granules to make tablets.
以下に本発明を実施例により詳細に説明する。 Hereinafter, the present invention will be described in detail with reference to Examples.
実施例１
イブプロフェン１００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）９００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２９００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Example 1
100 g of ibuprofen and 900 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 2900 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Malmerizer Q400 (Fuji Paudal Co., Ltd.) After the spheroidizing treatment, a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) is used, dried with a 30- and 42-mesh sieve, and fine granules of 30-42 mesh are prepared. Manufactured.
実施例２
イブプロフェン３００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）７００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２２００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Example 2
300 g of ibuprofen and 700 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). To this, 2200 g of 10% ethanol aqueous solution was added and kneaded, and granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and a Malmerizer Q400 (Fuji Paudal Co., Ltd.) After the spheroidizing treatment, a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) is used, dried with a 30- and 42-mesh sieve, and fine granules of 30-42 mesh are prepared. Manufactured.
実施例３
イブプロフェン５００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）５００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液１６００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Example 3
500 g of ibuprofen and 500 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 1600 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Malmerizer Q400 (Fuji Powdal Co., Ltd.) After the spheroidizing treatment, a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) is used, dried with a 30- and 42-mesh sieve, and fine granules of 30-42 mesh are prepared. Manufactured.
実施例４
イブプロフェン７００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）３００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液９５０ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Example 4
700 g of ibuprofen and 300 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 950 g of a 10% aqueous ethanol solution was added thereto, kneaded, and granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). After the spheroidizing treatment, a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) is used, dried with a 30- and 42-mesh sieve, and fine granules of 30-42 mesh are prepared. Manufactured.
比較例１
イブプロフェン９００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）１００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２５０ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．４５mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Comparative Example 1
900 g of ibuprofen and 100 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 250 g of a 10% ethanol aqueous solution is added to the mixture, and the mixture is kneaded, and granulated with a Fine Luzer EXR-60 (0.45 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). After the spheroidizing treatment, a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) is used, dried with a 30- and 42-mesh sieve, and fine granules of 30-42 mesh are prepared. Manufactured.
比較例２
イブプロフェン１００ｇ、低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）１００ｇ及び乳糖８００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液１２０ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．４５mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Comparative Example 2
100 g of ibuprofen, 100 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 800 g of lactose were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 120 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.45 mm screen, manufactured by Fuji Paudal Co., Ltd.), and Malmerizer Q400 (Fuji Paudal Co., Ltd.) After the spheroidizing treatment, a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) is used, dried with a 30- and 42-mesh sieve, and fine granules of 30-42 mesh are prepared. Manufactured.
試験例１
実施例１〜４及び比較例１〜２で得られた細粒剤について、下記の試験方法により苦味試験及び溶出試験を実施した。その結果を表１に示した。
試験方法
苦味試験：イブプロフェン１５０mg相当量を口み含みイブプロフェンの刺激的な苦味を感じる時間を測定した。
溶出試験：パドル法 １００rpm 試験液：日局第２液（pH６．８）
Test example 1
The fine granules obtained in Examples 1 to 4 and Comparative Examples 1 and 2 were subjected to a bitterness test and a dissolution test by the following test methods. The results are shown in Table 1.
Test Method Bitterness test: The time required to feel the irritating bitterness of ibuprofen while eating 150 mg equivalent of ibuprofen was measured.
Dissolution test: Paddle method 100 rpm Test solution: JP 2nd solution (pH 6.8)
表１より、本発明の実施例１〜４は、比較例１〜２よりもイブプロフェンの刺激的な苦味が明らかに抑制されていることが苦味試験結果よりわかる（苦味を感じる時間が３０秒以上の時マスキングされたと評価した）。そして、溶出性をみると２分ではイブプロフェンの溶出は実施例では比較例に比較して低いが、１０〜２０分で良好に溶出し、溶出性には問題ないことが溶出試験の結果からわかる（１０分で５０％以上、２０分で８０％以上の場合、薬物の放出は速溶性であると評価した）。 From Table 1, it can be seen from the results of the bitterness test that Examples 1 to 4 of the present invention clearly suppress the irritating bitterness of ibuprofen as compared with Comparative Examples 1 and 2 (the time to feel bitterness is 30 seconds or more). At that time was evaluated as masked). When the dissolution property is examined, the dissolution of ibuprofen is lower in the example in 2 minutes than in the comparative example in the example, but the dissolution is good in 10 to 20 minutes, and the dissolution property shows no problem from the result of the dissolution test. (If 50% or more at 10 minutes and 80% or more at 20 minutes, the release of the drug was assessed as fast dissolving).
実施例５
無水カフェイン１００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）９００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２８００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．８mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２４と３０メッシュの篩で整粒し２４−３０メッシュの顆粒剤を製造した。
Example 5
100 g of anhydrous caffeine and 900 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed using a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 2800 g of a 10% aqueous ethanol solution was added thereto, kneaded, and granulated with a Fine Luzer EXR-60 (0.8 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and a Malmerizer Q400 (Fuji Paudal Co., Ltd.) ) And then dried with a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sieved with 24 and 30 mesh sieves to produce 24-30 mesh granules. did.
実施例６
無水カフェイン３００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）７００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２１００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．８mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２４と３０メッシュの篩で整粒し２４−３０メッシュの顆粒剤を製造した。
Example 6
300 g of anhydrous caffeine and 700 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 2100 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.8 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Malmerizer Q400 (Fuji Paudal Co., Ltd.) ) And then dried with a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sieved with 24 and 30 mesh sieves to produce 24-30 mesh granules. did.
実施例７
無水カフェイン５００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）５００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液１５５０ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．８mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２４と３０メッシュの篩で整粒し２４−３０メッシュの顆粒剤を製造した。
Example 7
500 g of anhydrous caffeine and 500 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 1550 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.8 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Malmerizer Q400 (Fuji Paudal Co., Ltd.) ) And then dried with a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sieved with 24 and 30 mesh sieves to produce 24-30 mesh granules. did.
実施例８
無水カフェイン７００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）３００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液８５０ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．８mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２４と３０メッシュの篩で整粒し２４−３０メッシュの顆粒剤を製造した。
Example 8
700 g of anhydrous caffeine and 300 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 850 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.8 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Malmerizer Q400 (Fuji Paudal Co., Ltd.) ) And then dried with a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sieved with 24 and 30 mesh sieves to produce 24-30 mesh granules. did.
比較例３
無水カフェイン９００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）１００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２４と３０メッシュの篩で整粒し２４−３０メッシュの顆粒剤を製造した。
Comparative Example 3
900 g of anhydrous caffeine and 100 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 200 g of a 10% aqueous ethanol solution was added thereto, kneaded, and granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). ) And then dried with a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sieved with 24 and 30 mesh sieves to produce 24-30 mesh granules. did.
比較例４
無水カフェイン１００ｇ、低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）１００ｇ及び乳糖８００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液１００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２４と３０メッシュの篩で整粒し２４−３０メッシュの顆粒剤を製造した。
Comparative Example 4
100 g of anhydrous caffeine, 100 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 800 g of lactose were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 100 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and a Malmerizer Q400 (Fuji Paudal Co., Ltd.) ) And then dried with a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sieved with 24 and 30 mesh sieves to produce 24-30 mesh granules. did.
試験例２
実施例５〜８及び比較例３〜４で得られた顆粒剤について、下記の試験方法により苦味試験及び溶出試験を実施した。その結果を表２に示した。
試験方法
苦味試験：無水カフェイン８０mg相当量を口み含み無水カフェインの苦味を感じる時間を測定した。
溶出試験：パドル法 １００rpm 試験液：水
Test example 2
For the granules obtained in Examples 5 to 8 and Comparative Examples 3 and 4, a bitterness test and a dissolution test were performed by the following test methods. The results are shown in Table 2.
Test Method Bitterness test: The amount of anhydrous caffeine equivalent to 80 mg was perfumed and the time for which the bitterness of anhydrous caffeine was felt was measured.
Dissolution test: Paddle method 100 rpm Test solution: water
表２より、無水カフェインの場合もイブプロフェンの場合と同様に実施例５〜８は比較例３〜４よりも無水カフェインの苦味が抑制されていることがわかる。 From Table 2, it can be seen that in the case of anhydrous caffeine, as in the case of ibuprofen, the bitterness of anhydrous caffeine was suppressed in Examples 5 to 8 more than in Comparative Examples 3 and 4.
実施例９
マレイン酸クロルフェニラミン１００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）９００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２９００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（１．０mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２０と２４メッシュの篩で整粒し２０−２４メッシュの顆粒剤を製造した。
実施例１０
Example 9
100 g of chlorpheniramine maleate and 900 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 2900 g of a 10% aqueous ethanol solution was added thereto, kneaded, and granulated with a Fine Luzer EXR-60 (1.0 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and a Malmerizer Q400 (Fuji Paudal Co., Ltd.) ) And then dried with a fluid bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), and sized with a 20 and 24 mesh sieve to produce 20-24 mesh granules. did.
Example 10
ジクロフェナクナトリウム１００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）９００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２９００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．８mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２４と３０メッシュの篩で整粒し２４−３０メッシュの顆粒剤を製造した。 100 g of diclofenac sodium and 900 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). To this, 2900 g of a 10% aqueous ethanol solution was added and kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.8 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Malmerizer Q400 (Fuji Paudal Co., Ltd.) ) And then dried with a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sieved with 24 and 30 mesh sieves to produce 24-30 mesh granules. did.
実施例１１
イブプロフェン１００ｇとカルメロースカルシウム（ＥＣＧ−５０５、五徳薬品（株）製）９００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２９００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Example 11
100 g of ibuprofen and 900 g of carmellose calcium (ECG-505, manufactured by Gotoku Pharmaceutical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 2900 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Malmerizer Q400 (Fuji Paudal Co., Ltd.) After the spheroidizing treatment, a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) is used, dried with a 30- and 42-mesh sieve, and fine granules of 30-42 mesh are prepared. Manufactured.
実施例１２
イブプロフェン１００ｇとクロスカルメロースナトリウム（Ａｃ−ｄｉ−ｓｏｌ、旭化成工業（株）製）９００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液３０００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの棒状細粒剤を製造した。
Example 12
100 g of ibuprofen and 900 g of croscarmellose sodium (Ac-di-sol, manufactured by Asahi Kasei Kogyo Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 3000 g of a 10% aqueous ethanol solution was added thereto, and the mixture was kneaded and granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). ) And then dried with a fluid bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), sized with a 30 and 42 mesh sieve, and a 30-42 mesh rod-shaped fine granule. Was manufactured.
比較例５
マレイン酸クロルフェニラミン１００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）１００ｇ及び乳糖８００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液３００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．８mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２０と２４メッシュの篩で整粒し２０−２４メッシュの顆粒剤を製造した。
Comparative Example 5
100 g of chlorpheniramine maleate, 100 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 800 g of lactose were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex). . 300 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded and granulated with a Fine Luzer EXR-60 (0.8 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). ) And then dried with a fluid bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), and sized with a 20 and 24 mesh sieve to produce 20-24 mesh granules. did.
比較例６
ジクロフェナクナトリウム１００ｇと低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）１００ｇ及び乳糖８００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液３００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、２４と３０メッシュの篩で整粒し２４−３０メッシュの顆粒剤を製造した。
Comparative Example 6
100 g of diclofenac sodium, 100 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 800 g of lactose were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 300 g of a 10% aqueous ethanol solution was added to the mixture, and the mixture was kneaded. The mixture was granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and the Malmerizer Q400 (Fuji Paudal Co., Ltd.) ) And then dried with a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sieved with 24 and 30 mesh sieves to produce 24-30 mesh granules. did.
比較例７
イブプロフェン１００ｇとカルメロースカルシウム（ＥＣＧ−５０５、五徳薬品（株）製）１００ｇ及び乳糖８００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液２５０ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．４５mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Comparative Example 7
100 g of ibuprofen, 100 g of carmellose calcium (ECG-505, manufactured by Gotoku Pharmaceutical Co., Ltd.) and 800 g of lactose were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 250 g of a 10% ethanol aqueous solution is added to the mixture, and the mixture is kneaded, and granulated with a Fine Luzer EXR-60 (0.45 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). After the spheroidizing treatment, a fluidized-bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) is used, dried with a 30- and 42-mesh sieve, and fine granules of 30-42 mesh are prepared. Manufactured.
比較例８
イブプロフェン１００ｇとクロスカルメロースナトリウム（Ａｃ−ｄｉ−ｓｏｌ、旭化成工業（株）製）１００ｇ及び乳糖８００ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これに１０％エタノール水溶液３２０ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．４５mm径スクリーン、不二パウダル（株）製）で造粒し、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの棒状細粒剤を製造した。
Comparative Example 8
100 g of ibuprofen, 100 g of croscarmellose sodium (Ac-di-sol, manufactured by Asahi Kasei Kogyo Co., Ltd.) and 800 g of lactose were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). 320 g of a 10% ethanol aqueous solution is added to the mixture, and the mixture is kneaded, granulated with a Fine Luzer EXR-60 (0.45 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and a fluidized bed dryer WSG-5 (Okawara) The product was dried at a manufacturing company, and sized with a 30- and 42-mesh sieve to produce a 30-42 mesh rod-shaped fine granule.
試験例３
実施例９〜１２及び比較例５〜８で得られた細粒剤や顆粒剤について、下記の試験方法で苦味試験及び溶出試験を実施した。この結果を表３に示す。
試験方法
苦味試験：マレイン酸クロルフェニラミン２０mg、ジクロフェナクナトリウム２５mg、イブプロフェン１５０mg相当量を口に含みそれぞれの薬物の苦味を感じる時間を測定した。
溶出試験：パドル法 １００rpm
試験液：水（マレイン酸クロルフェニラミン、ジクロフェナクナトリウム）、日局第２液pH６．８（イブプロフェン）
Test example 3
The fine granules and granules obtained in Examples 9 to 12 and Comparative Examples 5 to 8 were subjected to a bitterness test and a dissolution test by the following test methods. Table 3 shows the results.
Test Method Bitterness test: Chlorpheniramine maleate 20 mg, diclofenac sodium 25 mg, ibuprofen equivalent to 150 mg were contained in the mouth, and the time to feel the bitterness of each drug was measured.
Dissolution test: paddle method 100 rpm
Test solution: water (chlorpheniramine maleate, diclofenac sodium), Japanese Pharmacopoeia second solution pH 6.8 (ibuprofen)
表３より実施例９〜１２では、マレイン酸クロルフェニラミン、ジクロフェナクナトリウム及びイブプロフェン等の薬物は、ＥＣＧ−５０５、Ａｃ−ｄｉ−ｓｏｌ等の水膨潤性物質を用いても比較例よりも薬物の苦味が抑制されていることがわかる。 From Table 3, in Examples 9 to 12, in Examples 9 to 12, drugs such as chlorpheniramine maleate, diclofenac sodium and ibuprofen were more effective than the Comparative Examples even when water swelling substances such as ECG-505 and Ac-di-sol were used. It turns out that bitterness is suppressed.
実施例１３
イブプロフェン１５０ｇ、アリルイソプロピルアセチル尿素６０ｇ、無水カフェイン８０ｇ及び低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）９９７ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これにアスパルテーム１３ｇを含む１０％エタノール水溶液２９００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Example 13
150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine and 997 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). ). To this, 2900 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added, kneaded, and granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). After performing spheronization treatment with Powdal Co., Ltd.), it is dried with a fluid bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), sized with a 30- and 42-mesh sieve, and sized with a 30-42 mesh. Fine granules were produced.
実施例１４
イブプロフェン１５０ｇ、アリルイソプロピルアセチル尿素６０ｇ、無水カフェイン８０ｇ及び低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）６５０ｇ、エリスリトール（日研化学（株）製）３４７ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これにアスパルテーム１３ｇを含む１０％エタノール水溶液２１００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Example 14
150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine, 650 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.), and 347 g of erythritol (manufactured by Niken Kagaku Co., Ltd.) Mixer FM-VG-25 (manufactured by Powrex Corporation). To this, 2100 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added, kneaded, and granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). After performing spheronization treatment with Powdal Co., Ltd.), it is dried with a fluid bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), sized with a 30- and 42-mesh sieve, and sized with a 30-42 mesh. Fine granules were produced.
実施例１５
イブプロフェン１５０ｇ、アリルイソプロピルアセチル尿素６０ｇ、無水カフェイン８０ｇ及び低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）３９０ｇ、エリスリトール（日研化学（株）製）６０７ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これにアスパルテーム１３ｇを含む１０％エタノール水溶液１１００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．６mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Example 15
150 g of ibuprofen, 60 g of allylisopropylacetyl urea, 80 g of anhydrous caffeine, 390 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 607 g of erythritol (manufactured by Niken Kagaku Co., Ltd.) Mixer FM-VG-25 (manufactured by Powrex Corporation). To this, 1100 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added, kneaded, and granulated with a Fine Luzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). After performing spheronization treatment with Powdal Co., Ltd.), it is dried with a fluid bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), sized with a 30- and 42-mesh sieve, and sized with a 30-42 mesh. Fine granules were produced.
実施例１６
イブプロフェン１５０ｇ、アリルイソプロピルアセチル尿素６０ｇ、無水カフェイン８０ｇ及び低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）９９７ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これにアスパルテーム１３ｇを含む１０％エタノール水溶液２１００ｇを加えて練合し、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と１５０メッシュの篩で整粒し３０−１５０メッシュの細粒剤を製造した。
Example 16
150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine and 997 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed with a vertical granulator FM-VG-25 (manufactured by Powrex Corporation). ). To this, 2100 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added, kneaded, dried with a fluid bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), and sized with a 30 and 150 mesh sieve. A 150 mesh fine granule was produced.
比較例９
イブプロフェン１５０ｇ、アリルイソプロピルアセチル尿素６０ｇ、無水カフェイン８０ｇ及び低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）２６０ｇ、エリスリトール（日研化学（株）製）７３７ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これにアスパルテーム１３ｇを含む１０％エタノール水溶液７００ｇを加えて練合し、ファインリュザーＥＸＲ−６０（０．４５mm径スクリーン、不二パウダル（株）製）で造粒し、マルメライザーＱ４００（不二パウダル（株）製）で球形化処理を施した後、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と４２メッシュの篩で整粒し３０−４２メッシュの細粒剤を製造した。
Comparative Example 9
150 g of ibuprofen, 60 g of allylisopropylacetyl urea, 80 g of anhydrous caffeine, 260 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.), and 737 g of erythritol (Nikken Chemical Co., Ltd.) Mixer FM-VG-25 (manufactured by Powrex Corporation). To this, 700 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added, kneaded, and granulated with a Fine Luzer EXR-60 (0.45 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.). After performing spheronization treatment with Powdal Co., Ltd.), it is dried with a fluid bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), sized with a 30- and 42-mesh sieve, and sized with a 30-42 mesh. Fine granules were produced.
比較例１０
イブプロフェン１５０ｇ、アリルイソプロピルアセチル尿素６０ｇ、無水カフェイン８０ｇ及び低置換度ヒドロキシプロピルセルロース（Ｌ−ＨＰＣ ＬＨ３１、信越化学工業（株）製）２６０ｇ、エリスリトール（日研化学（株）製）７３７ｇをバーチカルグラニュレーターＦＭ−ＶＧ−２５（パウレック（株）製）で混合した。これにアスパルテーム１３ｇを含む１０％エタノール水溶液５００ｇを加えて練合し、流動層乾燥機ＷＳＧ−５型（大川原製作所（株）製）で乾燥し、３０と１５０メッシュの篩で整粒し３０−１５０メッシュの細粒剤を製造した。
Comparative Example 10
150 g of ibuprofen, 60 g of allylisopropylacetyl urea, 80 g of anhydrous caffeine, 260 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.), and 737 g of erythritol (Nikken Chemical Co., Ltd.) Mixer FM-VG-25 (manufactured by Powrex Corporation). To this, 500 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added, kneaded, dried with a fluid bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), and sized with a 30 and 150 mesh sieve. A 150 mesh fine granule was produced.
試験例４
実施例１３〜１６及び比較例９〜１０で得られた細粒剤や顆粒剤について、下記試験方法によりイブプロフェンについて苦味試験及び溶出試験を実施した。その結果を表４に示した。
試験方法
苦味試験：イブプロフェン１５０mg相当量を口に含みイブプロフェンの刺激的な苦味を感じる時間を測定した。
溶出試験：パドル法 １００rpm 試験液：日局２液（pH６．８）
Test example 4
For the fine granules and granules obtained in Examples 13 to 16 and Comparative Examples 9 to 10, a bitterness test and a dissolution test were performed on ibuprofen by the following test method. Table 4 shows the results.
Test method Bitterness test: The amount of ibuprofen 150 mg equivalent in the mouth was measured, and the time during which the irritating bitterness of ibuprofen was felt was measured.
Dissolution test: Paddle method 100 rpm Test solution: 2 JP (pH 6.8)
表４より、本発明の実施例１３〜１６は、比較例９〜１０よりもイブプロフェンの不快な味が明らかに抑制されていることがわかる。 Table 4 shows that Examples 13 to 16 of the present invention clearly suppress the unpleasant taste of ibuprofen as compared with Comparative Examples 9 to 10.
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| JP2008127350A (en) * | 2006-11-22 | 2008-06-05 | Ss Pharmaceut Co Ltd | Deodorizing solid composition |
| JP2008133234A (en) * | 2006-11-29 | 2008-06-12 | Ss Pharmaceut Co Ltd | Oral solid state composition reducing irritating property to digestive tract |
| JP2010154769A (en) * | 2008-12-26 | 2010-07-15 | Asahi Breweries Ltd | Polyphenol-containing granule or polyphenol-containing chewable tablet, and method for producing the tablet or the granule |
| JP2012207038A (en) * | 2012-07-20 | 2012-10-25 | Ssp Co Ltd | Oral solid composition reduced in irritation to digestive tract |
| JP2014055187A (en) * | 2013-12-25 | 2014-03-27 | Ss Pharmaceut Co Ltd | Oral solid composition reduced in irritation to digestive tract |
| JP2014114310A (en) * | 2007-06-08 | 2014-06-26 | Bayer Intellectual Property Gmbh | Extrudate with improved taste masking |
| KR20210053887A (en) | 2018-08-31 | 2021-05-12 | 하우스 웰니스 푸드 코퍼레이션 | Composition for oral intake that is chewed in the oral cavity and/or dissolved in the oral cavity, comprising a component derived from turmeric |
| CN113453563A (en) * | 2019-02-20 | 2021-09-28 | 三得利控股株式会社 | Oral composition containing protein and method for improving flavor of oral composition containing protein |
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| JPH0383922A (en) * | 1989-08-28 | 1991-04-09 | Takeda Chem Ind Ltd | Ibuprofen-containing composition for oral administration |
| JPH03130214A (en) * | 1989-07-20 | 1991-06-04 | Dainippon Pharmaceut Co Ltd | Quick release pharmaceutical with offensive taste masked |
| JPH07188058A (en) * | 1993-12-24 | 1995-07-25 | Shionogi & Co Ltd | Granule improved in taste and its production |
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2004
- 2004-03-26 JP JP2004093003A patent/JP4210615B2/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03130214A (en) * | 1989-07-20 | 1991-06-04 | Dainippon Pharmaceut Co Ltd | Quick release pharmaceutical with offensive taste masked |
| JPH0383922A (en) * | 1989-08-28 | 1991-04-09 | Takeda Chem Ind Ltd | Ibuprofen-containing composition for oral administration |
| JPH07188058A (en) * | 1993-12-24 | 1995-07-25 | Shionogi & Co Ltd | Granule improved in taste and its production |
| JPH09208495A (en) * | 1996-01-26 | 1997-08-12 | Kyorin Pharmaceut Co Ltd | Granular formulation diminished bitter taste of drug and its production |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008127350A (en) * | 2006-11-22 | 2008-06-05 | Ss Pharmaceut Co Ltd | Deodorizing solid composition |
| JP2008133234A (en) * | 2006-11-29 | 2008-06-12 | Ss Pharmaceut Co Ltd | Oral solid state composition reducing irritating property to digestive tract |
| JP2014114310A (en) * | 2007-06-08 | 2014-06-26 | Bayer Intellectual Property Gmbh | Extrudate with improved taste masking |
| JP2010154769A (en) * | 2008-12-26 | 2010-07-15 | Asahi Breweries Ltd | Polyphenol-containing granule or polyphenol-containing chewable tablet, and method for producing the tablet or the granule |
| JP4565219B2 (en) * | 2008-12-26 | 2010-10-20 | アサヒビール株式会社 | Polyphenol-containing granule or polyphenol-containing chewable tablet and method for producing the same |
| JP2012207038A (en) * | 2012-07-20 | 2012-10-25 | Ssp Co Ltd | Oral solid composition reduced in irritation to digestive tract |
| JP2014055187A (en) * | 2013-12-25 | 2014-03-27 | Ss Pharmaceut Co Ltd | Oral solid composition reduced in irritation to digestive tract |
| KR20210053887A (en) | 2018-08-31 | 2021-05-12 | 하우스 웰니스 푸드 코퍼레이션 | Composition for oral intake that is chewed in the oral cavity and/or dissolved in the oral cavity, comprising a component derived from turmeric |
| CN113453563A (en) * | 2019-02-20 | 2021-09-28 | 三得利控股株式会社 | Oral composition containing protein and method for improving flavor of oral composition containing protein |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4210615B2 (en) | 2009-01-21 |
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