JP4706096B2 - Formulation of basic drug with unpleasant taste - Google Patents
Formulation of basic drug with unpleasant taste Download PDFInfo
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- JP4706096B2 JP4706096B2 JP2000322548A JP2000322548A JP4706096B2 JP 4706096 B2 JP4706096 B2 JP 4706096B2 JP 2000322548 A JP2000322548 A JP 2000322548A JP 2000322548 A JP2000322548 A JP 2000322548A JP 4706096 B2 JP4706096 B2 JP 4706096B2
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- JP
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- Prior art keywords
- unpleasant taste
- basic drug
- dissolved
- oral preparation
- aspartame
- 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.)
- Expired - Lifetime
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Description
【０００１】
【発明の属する技術分野】
本発明は、不快な味を呈する塩基性薬物を含有する経口製剤用組成物を水に溶解又は懸濁させたときに、該塩基性薬物に起因する不快な味を簡易にマスキングし、服用性の改善を図った経口製剤に関する。
【０００２】
【従来の技術】
液剤では経時的に力価、効力が低減したり、再分散性が劣化するような薬物について、小児等が服用し易い剤型として、用時溶解又は懸濁して用いるドライシロップ剤が広く普及している。そして、クラリスロマイシン等の不快な味を呈する塩基性薬物についても、これを噴霧凝固造粒等によりワックスマトリックスとし、ドライシロップ剤として提供することが可能となっている（特開平６−１１６１３８号公報）。こうした塩基性薬物を含有するドライシロップ剤を塩基性域から中性域の溶液に溶解又は懸濁させて使用する場合には、該塩基性薬物が液中に溶出して不快な呈味が拡散することはほとんどないといえる。
【０００３】
しかしながら、塩基性薬物を含有するドライシロップ剤をジュース等の酸性液に溶解若しくは懸濁させたとき、又は、酸性薬物とともに水に溶解若しくは懸濁させたとき、すなわち、ドライシロップ剤が酸性液下に溶解又は懸濁されている状態では、塩基性薬物が液中に溶出して該薬物の不快な呈味が拡散し、服用性の悪化を招来することがあった。
【０００４】
【発明が解決しようとする課題】
本発明は、不快な味を呈する塩基性薬物を含有するドライシロップ剤等の経口製剤用組成物を、酸性液中に溶解又は懸濁させたときに生じる不快な呈味を簡易な方法でマスキングし、服用性の悪化を防止した経口製剤を提供することを課題とする。
【０００５】
【課題を解決するための手段】
本発明者らは、かかる課題を解決すべく鋭意検討した結果、不快な味を呈する塩基性薬物を含有するドライシロップ剤とアスパルテームを混合し、これを酸性液中に懸濁させたところ、該塩基性薬物が呈する不快な味を顕著にマスキングしうることを見出し、本発明を完成するに至った。
【０００６】
すなわち，本発明は、不快な味を呈する塩基性薬物を含有する経口製剤用組成物及びアスパルテームを配合したことを特徴とする経口製剤である。
【０００７】
本発明において不快な味とは、苦味、渋味、収斂味等の服用性の悪化を招来する呈味であれば特に限定はない。このような不快な味を呈する塩基性薬物としては、エリスロマイシン、クラリスロマイシン、キタサマイシン、ジョサマイシン、ミデカマイシン、ロキシスタマイシンおよびアジスロマイシン等のマクロライド系抗生物質が挙げられる。
【０００８】
本発明における経口製剤用組成物とは、（ａ）不快な味を呈する塩基性薬物と胃溶性高分子化合物を分散あるいは溶解させた低融点物質からなる複合体、（ｂ）１０質量％から７０質量％の糖アルコールおよび（ｃ）０．１質量％から７質量％の塩基性酸化物からなることを特徴とする経口製剤用組成物であって、その製造方法等は、特開平６−１１６１３８号公報に記載されている。
【０００９】
本発明におけるアスパルテームとは、アスパラギン酸とフェニルアラニンが結合したジペプチドでフェニルアラニンのメチルエステルであるアスパルテーム（α−Ｌ−アスパルチル−Ｌ−フェニルアラニンメチルエステル）であるが、その誘導体であってもよい。
【００１０】
アスパルテームの配合量は、塩基性薬物の呈する不快な味の種類、液中への溶出量等により異なるので一概には言えないが、不快な味を呈する塩基性薬物１質量部に対して通常０．１質量部以上であり、好ましくは０．１〜２質量部である。ただし、２質量部以上を配合しても塩基性薬物の呈する不快な味のマスキング作用を奏していることに何ら変わりはない。
【００１１】
なお、不快な味を呈する塩基性薬物としてクラリスロマイシンを含有する場合のアスパルテームの配合量は、クラリスロマイシン１質量部に対して通常０．１質量部以上であり、好ましくは０．２〜２質量部であり、さらに好ましくは０．６〜１質量部である。ただし、２質量部以上を配合してもクラリスロマイシンの呈する苦味をマスキングしていることに何ら変わりはない。
【００１２】
本発明における経口製剤は、一般的には不快な味を呈する塩基性薬物を含有する経口製剤用組成物とアスパルテームを混合することにより調製することができるが、その他に該塩基性薬物以外の医薬有効成分や種々の製剤原料（賦形剤、結合剤、崩壊剤、流動化剤、香料等）を配合してもよい。
【００１３】
本発明の経口製剤の剤型としては、散剤、顆粒剤等が挙げられるが、用時溶解又は懸濁させて使用するドライシロップ剤について特に有効である。
【００１４】
本発明における経口製剤を溶解又は懸濁させたときの溶液のｐＨは通常４〜７であり、好ましくは５〜７である。塩基性域では、塩基性薬物が溶出せず、不快な味を呈することがないため苦味をマスキングする必要性がなく、また、ｐＨ４未満の強酸性域では、塩基性薬物の溶出が著しく、アスパルテームの配合によっては不快な呈味を充分にマスキングすることができないからである。
【００１５】
さらに、不快な味を呈する塩基性薬物を配合した経口製剤（例えば、ドライシロップ剤）を水に溶解又は懸濁させるときに、所要のアスパルテームを溶解させることによっても該塩基性薬物の呈する不快な味をマスキングすることができる。このときのアスパルテームの使用量は、上述の経口製剤における不快な味を呈する塩基性薬物に対するアスパルテームの配合量と同様である。
【００１６】
【実施例】
以下に、実施例、比較例および試験例を挙げて本発明をより詳細に説明するが、本発明はこれらの実施例等により限定されるものではない。
【００１７】
（実施例１）
経口製剤用組成物の製造
グリセリン脂肪酸エステル（主脂肪酸はステアリン酸で、モノグリセリド含量は９０％以上）２００ｇを約１００℃で融解させ、その中にオイドラギットＥ（（株）樋口商会）３０ｇを分散、溶解させた。さらにその混合液にクラリスロマシン１００ｇを分散させた。この分散液をスプレードライ装置（ＣＬ−１２型 大河原工業（株））を用いて、入口温度８０℃、回転ディスク２００００ｒｐｍの条件で噴霧凝固造粒し、平均粒子径８０μｍの３０％クラリスロマイシンの複合体を約２５０ｇ得た。この複合体１５０ｇにマンニトール２４０ｇ、酸化マグネシウム３ｇ、デンプン１０７ｇを加え、１０％クラリスロマイシン経口製剤用組成物を得た。
【００１８】
（試験例１）［官能評価試験］
実施例１で調製した経口製剤用組成物１ｇと下表１記載の各甘味剤０．０２〜０．１ｇを混合し、各ｐＨの精製水２５ｍＬに懸濁させた。懸濁直後及び５分経過後に５名のパネラーによる苦味の官能評価試験を実施した。各パネラーが試験液を口中に含み、苦味を評価した。その後、液を吐き出し、口中を水ですすいでから３０分以上経過後に他の試験液の苦味を評価した。官能評価は、苦味の強さを以下の基準により数値化して平均値を比較した。その結果を表１に示す。
【００１９】
苦味の評価
全く不快な呈味を感じない ５点
ほとんど不快な呈味を感じない ４点
少し不快な呈味を感じる ３点
不快な呈味をかんじる ２点
非常に不快な呈味を感じる １点
【００２０】
【表１】
【発明の効果】
本発明により、クラリスロマイシン等の塩基性薬物を含有する経口用製剤組成物が弱酸性下に呈する苦味等の不快な味を簡易にマスキングし、服用性良好な経口製剤を提供することが可能となった。[0001]
BACKGROUND OF THE INVENTION
The present invention easily masks the unpleasant taste caused by the basic drug when the composition for oral preparation containing the basic drug exhibiting an unpleasant taste is dissolved or suspended in water, The present invention relates to an oral preparation that is improved.
[0002]
[Prior art]
For drugs that have reduced titer and efficacy over time or whose redispersibility deteriorates, dry syrups that are dissolved or suspended at the time of use have become widespread as dosage forms that children can easily take. Yes. Also, a basic drug having an unpleasant taste, such as clarithromycin, can be provided as a dry syrup by using it as a wax matrix by spray coagulation granulation or the like (Japanese Patent Laid-Open No. 6-116138). ). When a dry syrup containing such a basic drug is used by dissolving or suspending it in a basic to neutral solution, the basic drug elutes in the liquid and unpleasant taste diffuses. There is almost nothing.
[0003]
However, when a dry syrup containing a basic drug is dissolved or suspended in an acidic liquid such as juice, or dissolved or suspended in water together with an acidic drug, that is, the dry syrup is dissolved under an acidic liquid. Alternatively, in a suspended state, the basic drug is dissolved in the liquid, and the unpleasant taste of the drug is diffused, which may lead to deterioration of the dose.
[0004]
[Problems to be solved by the invention]
The present invention masks an unpleasant taste that occurs when a composition for oral preparations such as a dry syrup containing a basic drug having an unpleasant taste is dissolved or suspended in an acidic solution by a simple method. An object of the present invention is to provide an oral preparation that prevents the deterioration of dosage.
[0005]
[Means for Solving the Problems]
As a result of intensive studies to solve such problems, the present inventors mixed a dry syrup containing a basic drug exhibiting an unpleasant taste and aspartame, and suspended this in an acidic solution. The present inventors have found that the unpleasant taste exhibited by sex drugs can be remarkably masked and have completed the present invention.
[0006]
That is, the present invention is an oral preparation characterized in that the composition for oral preparation containing a basic drug exhibiting an unpleasant taste and aspartame are blended.
[0007]
In the present invention, the unpleasant taste is not particularly limited as long as it is a taste that causes a deterioration in dosage such as bitterness, astringency, and astringency. Examples of basic drugs exhibiting such an unpleasant taste include macrolide antibiotics such as erythromycin, clarithromycin, kitasamycin, josamycin, midecamycin, roxistamycin and azithromycin.
[0008]
The composition for oral preparation in the present invention is (a) a complex composed of a low melting point substance in which a basic drug having an unpleasant taste and a gastric polymer compound are dispersed or dissolved, and (b) 10% by mass to 70%. A composition for oral preparation, characterized by comprising, by weight, sugar alcohol and (c) 0.1 to 7% by weight of basic oxide, and the production method thereof is disclosed in JP-A-6-116138. It is described in the gazette.
[0009]
Aspartame in the present invention is aspartame (α-L-aspartyl-L-phenylalanine methyl ester) which is a dipeptide in which aspartic acid and phenylalanine are bonded and is a methyl ester of phenylalanine (α-L-aspartyl-L-phenylalanine methyl ester), but may be a derivative thereof.
[0010]
The amount of aspartame blended varies depending on the type of unpleasant taste exhibited by the basic drug, the amount of elution into the liquid, etc., but it cannot be generally stated, but it is usually 0 with respect to 1 part by mass of the basic drug exhibiting an unpleasant taste. .1 part by mass or more, preferably 0.1 to 2 parts by mass. However, even if 2 parts by mass or more are blended, there is no change in that the masking action of unpleasant taste exhibited by the basic drug is exhibited.
[0011]
The amount of aspartame in the case of containing clarithromycin as a basic drug exhibiting an unpleasant taste is usually 0.1 parts by mass or more, preferably 0.2 to 1 part by mass with respect to 1 part by mass of clarithromycin. 2 parts by mass, more preferably 0.6-1 part by mass. However, there is no change in masking the bitterness exhibited by clarithromycin even if 2 parts by mass or more are blended.
[0012]
The oral preparation in the present invention can be generally prepared by mixing an aspartame with a composition for oral preparation containing a basic drug that exhibits an unpleasant taste. You may mix | blend an active ingredient and various formulation raw materials (excipient, binder, disintegrant, fluidizing agent, fragrance, etc.).
[0013]
Examples of the dosage form of the oral preparation of the present invention include powders, granules and the like, but it is particularly effective for a dry syrup used by dissolving or suspending at the time of use.
[0014]
The pH of the solution when the oral preparation in the present invention is dissolved or suspended is usually 4 to 7, and preferably 5 to 7. In the basic region, the basic drug does not elute and does not exhibit an unpleasant taste, so there is no need to mask the bitterness. In the strongly acidic region below pH 4, elution of the basic drug is significant, and aspartame This is because unpleasant taste cannot be sufficiently masked depending on the blending of.
[0015]
Furthermore, when an oral preparation (for example, a dry syrup) containing a basic drug that exhibits an unpleasant taste is dissolved or suspended in water, the unpleasant taste exhibited by the basic drug is also obtained by dissolving the required aspartame. Can be masked. The amount of aspartame used at this time is the same as the amount of aspartame added to the basic drug exhibiting an unpleasant taste in the aforementioned oral preparation.
[0016]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples, but the present invention is not limited to these Examples and the like.
[0017]
Example 1
Production of Composition for Oral Formulation 200 g of glycerin fatty acid ester (main fatty acid is stearic acid, monoglyceride content is 90% or more) is melted at about 100 ° C., and 30 g of Eudragit E (Higuchi Shokai) is dispersed therein. Dissolved. Further, 100 g of Clarislo machine was dispersed in the mixture. This dispersion was spray-coagulated and granulated using a spray drying apparatus (CL-12 type Okawara Kogyo Co., Ltd.) under the conditions of an inlet temperature of 80 ° C. and a rotating disk of 20000 rpm, and 30% clarithromycin having an average particle diameter of 80 μm About 250 g of the complex was obtained. To 150 g of this composite, 240 g of mannitol, 3 g of magnesium oxide and 107 g of starch were added to obtain a composition for 10% clarithromycin oral preparation.
[0018]
(Test Example 1) [Sensory evaluation test]
1 g of the composition for oral preparation prepared in Example 1 and 0.02 to 0.1 g of each sweetener listed in Table 1 below were mixed and suspended in 25 mL of purified water at each pH. A sensory evaluation test of bitterness was conducted by 5 panelists immediately after suspension and after 5 minutes. Each panelist contained the test solution in the mouth and evaluated the bitterness. Thereafter, the liquid was discharged, and the bitterness of other test liquids was evaluated after 30 minutes or more after rinsing the mouth with water. In sensory evaluation, the intensity of bitterness was digitized according to the following criteria and the average values were compared. The results are shown in Table 1.
[0019]
Bitterness evaluation No unpleasant taste 5 points Almost unpleasant taste 4 points Uncomfortable taste 3 points Uncomfortable taste 2 points Unpleasant taste 1 point Very unpleasant taste 1 point [0020]
[Table 1]
【The invention's effect】
According to the present invention, an oral preparation composition containing a basic drug such as clarithromycin can easily mask an unpleasant taste such as a bitter taste exhibited under weak acidity and provide an oral preparation with good dosage. It became.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000322548A JP4706096B2 (en) | 2000-10-23 | 2000-10-23 | Formulation of basic drug with unpleasant taste |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000322548A JP4706096B2 (en) | 2000-10-23 | 2000-10-23 | Formulation of basic drug with unpleasant taste |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002128705A JP2002128705A (en) | 2002-05-09 |
| JP4706096B2 true JP4706096B2 (en) | 2011-06-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000322548A Expired - Lifetime JP4706096B2 (en) | 2000-10-23 | 2000-10-23 | Formulation of basic drug with unpleasant taste |
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| Country | Link |
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| JP (1) | JP4706096B2 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999016470A1 (en) * | 1997-09-30 | 1999-04-08 | Daiichi Pharmaceutical Co., Ltd. | Oral preparation |
| WO1999049842A1 (en) * | 1998-03-31 | 1999-10-07 | Asta Medica Aktiengesellschaft | Fizzy formulations |
| WO1999055320A1 (en) * | 1998-04-29 | 1999-11-04 | Sumitomo Pharmaceuticals Co., Ltd. | Oral formulation comprising biguanide and an organic acid |
| JP2000273051A (en) * | 1999-03-19 | 2000-10-03 | Kobayashi Pharmaceut Co Ltd | Liquid preparation whose bitter taste is masked |
| JP2001226293A (en) * | 2000-02-17 | 2001-08-21 | Kotaro Kanpo Seiyaku Kk | Taking assisting agent |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0256416A (en) * | 1988-08-19 | 1990-02-26 | Daikyo Yakuhin Kogyo Kk | Granule with suppressed bitterness |
| JP3265680B2 (en) * | 1992-03-12 | 2002-03-11 | 大正製薬株式会社 | Oral pharmaceutical composition |
| JP3247511B2 (en) * | 1993-09-07 | 2002-01-15 | 山之内製薬株式会社 | Pharmaceutical composition |
| FR2730163B1 (en) * | 1995-02-03 | 1997-04-04 | Jouveinal Lab | NOVEL PHARMACEUTICAL COMPOSITION CONTAINING TRIMEBUTINE AND PROCESS FOR THE PREPARATION THEREOF |
-
2000
- 2000-10-23 JP JP2000322548A patent/JP4706096B2/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999016470A1 (en) * | 1997-09-30 | 1999-04-08 | Daiichi Pharmaceutical Co., Ltd. | Oral preparation |
| WO1999049842A1 (en) * | 1998-03-31 | 1999-10-07 | Asta Medica Aktiengesellschaft | Fizzy formulations |
| WO1999055320A1 (en) * | 1998-04-29 | 1999-11-04 | Sumitomo Pharmaceuticals Co., Ltd. | Oral formulation comprising biguanide and an organic acid |
| JP2000273051A (en) * | 1999-03-19 | 2000-10-03 | Kobayashi Pharmaceut Co Ltd | Liquid preparation whose bitter taste is masked |
| JP2001226293A (en) * | 2000-02-17 | 2001-08-21 | Kotaro Kanpo Seiyaku Kk | Taking assisting agent |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002128705A (en) | 2002-05-09 |
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