JP6700083B2 - Orally fast disintegrating tablets - Google Patents
Orally fast disintegrating tablets Download PDFInfo
- Publication number
- JP6700083B2 JP6700083B2 JP2016066961A JP2016066961A JP6700083B2 JP 6700083 B2 JP6700083 B2 JP 6700083B2 JP 2016066961 A JP2016066961 A JP 2016066961A JP 2016066961 A JP2016066961 A JP 2016066961A JP 6700083 B2 JP6700083 B2 JP 6700083B2
- Authority
- JP
- Japan
- Prior art keywords
- bilberry extract
- tablet
- rapidly disintegrating
- mass
- granules
- 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.)
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
- 239000003232 water-soluble binding agent Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
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- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Description
本発明は、ビルベリーエキスを含む口腔内速崩壊錠に関する。 The present invention relates to an orally rapidly disintegrating tablet containing bilberry extract.
ヨーロッパで長年採取されてきたビルベリーは、アントシアニンを高濃度に含有する健康に良い果実として知られている。特に色素の主成分であるアントシアニンやアントシアニジンの含有量が高いため、健康食品としても広く利用されている。
ビルベリーを水又は水含有エタノールで抽出し、乾燥させたビルベリーエキスは、アントシアニン含量で規格化されて流通している。ビルベリーエキスは、眼精疲労回復、視力回復や血管の透過性改善等に有効であるとして近年その需要が高まっている。
また近年、抗腫瘍作用も確認されており、抗腫瘍剤とすることが特許文献１には記載されている。その他の新たな用途開発も始まっている（特許文献２）。
Bilberries, which have been collected in Europe for many years, are known to be healthy fruits that contain high concentrations of anthocyanins. In particular, it has a high content of anthocyanins and anthocyanidins, which are the main components of the pigment, and is therefore widely used as a health food.
The bilberry extract obtained by extracting bilberries with water or water-containing ethanol and drying the bilberries is standardized and distributed in terms of anthocyanin content. The demand for bilberry extract is increasing in recent years because it is effective for recovery from eye strain, recovery of visual acuity, improvement of blood vessel permeability, and the like.
Further, in recent years, an antitumor effect has been confirmed, and Patent Document 1 describes that the compound is used as an antitumor agent. Development of other new applications has also started (Patent Document 2).
ビルベリーエキスは、タンニンやアントシアニンを高含有するため、非常に渋い味覚を与え、また特有の臭気があるため、そのままでは摂取し難いという欠点を有している。またその色素成分は着色が強いため、口腔中が紫に染まってしまうという欠点をも有している。このため、タブレットや錠菓などの食品では、その配合量は極めて少量となっている。そこで、前記の味覚や臭気、着色という問題を解決するために、ビルベリーエキスを水不溶性物質で被覆する技術が考えられるが、この技術では、ビルベリーエキスに直接水不溶性物質を噴霧し被覆する。このとき、水不溶性物質の噴霧量はビルベリーエキスの重量に対して等量以上必要となるため、ビルベリーエキスをコーティング顆粒とした場合、ビルベリーエキスを７０質量％以上を含むコーティング顆粒は提供されていない。また一般的な造粒技術でビルベリーエキス７０質量％以上を含むコーティング顆粒を製造しても、上記の問題から実用に耐えないものにしかならなかった。 Bilberry extract has a high content of tannin and anthocyanin, and therefore has a very astringent taste, and has a peculiar odor. Further, since the pigment component is strongly colored, it also has a drawback that the oral cavity is dyed purple. For this reason, in foods such as tablets and confectionery, the compounding amount is extremely small. Therefore, in order to solve the above-mentioned problems of taste, odor, and coloration, a technique of coating the bilberry extract with a water-insoluble substance can be considered, but in this technique, the bilberry extract is directly sprayed with the water-insoluble substance and coated. At this time, since the spray amount of the water-insoluble substance is required to be equal to or more than the weight of the bilberry extract, when the bilberry extract is used as the coated granule, the coated granule containing 70% by mass or more of the bilberry extract is not provided. . Further, even if coated granules containing 70% by mass or more of bilberry extract were produced by a general granulation technique, they could not be put into practical use due to the above problems.
本発明者は、ビルベリーエキスの示す作用効果の即効性を高める目的で、口腔内速崩壊錠を検討しているが、前記の味覚や臭気、着色という問題に加えて、口腔内速崩壊錠として製剤化すると、崩壊遅延を引き起こすという新たな問題に直面している。またこれらの問題を解決するためにビルベリーエキスを造粒またはコーティングすることも考えられるが、その際、多量の賦形剤が必要となるため、ビルベリーエキスの配合量が低くなってしまうという問題がある。 The present inventor has investigated an orally rapidly disintegrating tablet for the purpose of enhancing the immediate effect of the action and effect of the bilberry extract, but in addition to the above-mentioned problems of taste and odor, coloring, as an orally rapidly disintegrating tablet. When formulated, they face the new problem of causing delayed disintegration. In addition, granulation or coating of bilberry extract may be considered to solve these problems, but in that case, a large amount of excipient is required, so the problem that the amount of bilberry extract blended becomes low. is there.
口腔内速崩壊錠の従来技術として、エリスリトールやマンニトールを配合した口腔内速崩壊錠に関するもの（特許文献３及び特許文献４）を例示できる。特許文献３は、エリスリトールを配合することで速崩壊性を付与した圧縮組成物に関するものである。同じく特許文献４はマンニトールを配合することで速崩壊性を付与した製剤に関するものである。
また、同じく固形医薬製剤に関する特許がある。特許文献５は医薬成分に、エリスリトール、結晶セルロース、及び崩壊剤を配合することで速崩壊性を付与している。
さらに錠剤を多孔性にすることで速崩壊性を付与する技術がある。特許文献６は、糖アルコールと澱粉を混練して浸潤塊にした後に圧延して成型し、更に減圧乾燥することで多孔性にして速崩壊性を付与した。しかしながら、製造方法が煩雑であり、特殊装置が必要であることから、汎用性に欠ける技術である。
特許文献７は、主薬成分と糖類に水を添加して湿らせ、崩壊剤としての機能を糖類にもたせ、湿潤粉体を打錠した後に乾燥することで速崩壊性を付与するものである
口腔内の崩壊性を高めるために、口腔内で唾液と反応して発泡する成分を含有させ、速崩壊性をより強く付与させた製剤技術がある（特許文献８）。
しかしこれらの技術を適用しても、ビルベリーエキスを配合した口腔内速崩壊錠特有の呈味の問題や口腔内着色性の問題を解決できない。
As a conventional technique of an orally rapidly disintegrating tablet, those relating to an orally rapidly disintegrating tablet containing erythritol or mannitol (Patent Documents 3 and 4) can be exemplified. Patent Document 3 relates to a compression composition imparted with rapid disintegration by blending erythritol. Similarly, Patent Document 4 relates to a preparation having a rapid disintegrating property by incorporating mannitol.
There are also patents relating to solid pharmaceutical formulations. In Patent Document 5, erythritol, crystalline cellulose, and a disintegrant are blended with a pharmaceutical ingredient to impart fast disintegration.
Furthermore, there is a technique for imparting rapid disintegration by making the tablet porous. In Patent Document 6, a sugar alcohol and starch are kneaded to form an infiltrated mass, which is then rolled and molded, and further dried under reduced pressure to make it porous so that rapid disintegration is imparted. However, since the manufacturing method is complicated and a special device is required, the technique lacks versatility.
Patent Literature 7 is to add water to a main ingredient and saccharides to moisten them, to impart a function as a disintegrating agent to saccharides, and to impart a rapid disintegrating property by tableting wet powder and then drying. In order to enhance the disintegration property of the inside, there is a formulation technology in which a component that reacts with saliva in the oral cavity and foams is contained to strongly impart the rapid disintegration property (Patent Document 8).
However, even if these techniques are applied, it is not possible to solve the problem of taste and the problem of colorability in the oral cavity, which are peculiar to the rapidly disintegrating tablet in the oral cavity containing bilberry extract.
本発明者は、ビルベリーエキスの口腔内速崩壊錠を提供するため、種々の加工を施したビルベリーエキス顆粒を含む口腔内速崩壊錠を検討してきた。その過程で、特定の物質とビルベリーエキスの粉末を造粒した造粒物をさらに特定の物質でコーティングすることで、ビルベリーエキスの含量を低下させずに、しかも口腔内速崩壊錠としたときの崩壊遅延を解決できることを見いだし、本発明を完成させた。 The present inventor has studied an orally rapidly disintegrating tablet containing bilberry extract granules which have been subjected to various processes, in order to provide an orally rapidly disintegrating tablet of bilberry extract. In the process, by coating a granulated product obtained by granulating a powder of a specific substance and bilberry extract with a specific substance, the content of the bilberry extract is not reduced, and when rapidly disintegrating tablets in the mouth The present invention has been completed by finding that the delay in collapse can be solved.
すなわち、本発明は、ビルベリーエキスを高含有する口腔内速崩壊錠であって、ビルベリーエキス特有の呈味性が改善され、口腔内の着色がない口腔内速崩壊錠を提供することを課題とする。 That is, the present invention is an orally rapidly disintegrating tablet containing a high content of bilberry extract, the taste peculiar to bilberry extract is improved, and it is an object to provide an orally rapidly disintegrating tablet with no coloration in the oral cavity. To do.
本発明の主な構成は以下の通りである。
１．芯物質と外層からなる顆粒を１〜４５質量％含む口腔内速崩壊錠であって、
顆粒中にビルベリーエキスを７０質量％以上含有し、
顆粒の芯物質が、ビルベリーエキス粉末とケイ酸カルシウムとヒドロキシプロピルセルロースからなる造粒物、
顆粒の外層がシェラック層である、
口腔内速崩壊錠。
２．顆粒中にヒドロキシプロピルセルロースを３〜１０質量％含有する１に記載の口腔内速崩壊錠。
３．顆粒中のヒドロキシプロピルセルロースの分子量が、ゲル浸透クロマトグラフィー法で測定したとき、質量平均分子量が４００００〜１４００００である１または２に記載の口腔内速崩壊錠。
４．口腔内崩壊時間が６０秒以内である１〜３のいずれかに記載の口腔内速崩壊錠。
The main configuration of the present invention is as follows.
1. An orally rapidly disintegrating tablet containing 1 to 45% by mass of granules composed of a core substance and an outer layer,
Contains 70% by mass or more of bilberry extract in granules ,
The core material of the granule is a granulated product composed of bilberry extract powder, calcium silicate and hydroxypropyl cellulose ,
The outer layer of granules is shellac layer ,
Orally fast disintegrating tablet.
2 . Intraorally rapidly disintegrating tablet according to 1 containing 3-10% by weight of hydroxypropyl cellulose in granulocytes.
3. 3. The orally rapidly disintegrating tablet according to 1 or 2 , wherein the hydroxypropyl cellulose in the granule has a mass average molecular weight of 40,000 to 140,000 when measured by gel permeation chromatography.
4. The orally rapidly disintegrating tablet according to any one of 1 to 3 , wherein the orally disintegrating time is 60 seconds or less.
本発明によりビルベリーエキスを高含有する口腔内速崩壊錠であって、ビルベリーエキス特有の呈味性が改善され、口腔内の着色がない口腔内速崩壊錠が提供される。 The present invention provides an orally rapidly disintegrating tablet containing a high content of bilberry extract, in which the taste characteristic of the bilberry extract is improved and the oral cavity is not discolored.
本発明は、ビルベリーエキスを７０質量％以上含有し、ビルベリーエキス粉末とヒドロキシプロピルセルロースからなる造粒物を芯物質とし、外層がシェラック層で形成された顆粒を含有する口腔内速崩壊錠に係る発明である。
本発明の口腔内速崩壊錠は、ビルベリーエキス特有の呈味性を改善し、口腔内の着色を抑えるために、以下のようなコーティング顆粒を用いて口腔内速崩壊錠を製造する。
本発明の錠剤は、ビルベリーエキス粉末とヒドロキシプロピルセルロースからなる造粒物を芯物質とし、外層がシェラック層で形成されたコーティング顆粒を配合する。このようなコーティング顆粒は以下のようにして調製することができる。
ビルベリーエキスは、果実を圧縮粉砕し、圧縮粉砕されたビルベリー砕体より抽出、標準化して２５質量％以上のアントシアニジンを含有する粉体のビルベリーエキスが市販されており、本発明においては、これをビルベリーエキス粉末又はビルベリーエキスの粉末と呼ぶ。本発明には、このビルベリーエキス粉末を上記コーティング顆粒の原料として使用することができる。
ビルベリーエキスの粉末は、単独では粉末としての流動性に欠ける。このため、本発明を実施するにあたっては、ケイ酸カルシウムや二酸化ケイ素、タルクなどの流動化剤をビルベリーエキス１００質量部当たり１〜５質量部添加することで粉末としての好ましい流動性を付与することができる。
The present invention relates to an orally rapidly disintegrating tablet containing bilberry extract in an amount of 70% by mass or more, a granule composed of bilberry extract powder and hydroxypropylcellulose as a core substance, and granules having an outer layer formed of a shellac layer. It is an invention.
The rapidly disintegrating buccal tablets of the present invention are manufactured by using the following coated granules in order to improve the taste peculiar to bilberry extract and suppress coloring in the oral cavity.
The tablet of the present invention comprises a granulated product of bilberry extract powder and hydroxypropylcellulose as a core substance, and coated granules having an outer layer formed of a shellac layer. Such coated granules can be prepared as follows.
The bilberry extract is obtained by compressing and crushing fruits, extracting from the crushed bilberry crushed body, and standardizing and powdering bilberry extract containing 25% by mass or more of anthocyanidin is commercially available. It is called bilberry extract powder or bilberry extract powder. In the present invention, this bilberry extract powder can be used as a raw material for the coated granules.
Bilberry extract powder alone lacks fluidity as a powder. Therefore, in practicing the present invention, a fluidizing agent such as calcium silicate, silicon dioxide, or talc should be added in an amount of 1 to 5 parts by mass per 100 parts by mass of bilberry extract so as to impart preferable fluidity as a powder. You can
ヒドロキシプロピルセルロース（以下「ＨＰＣ」）は、セルロースの水酸基を酸化プロピレンでエーテル化することで得られ、多数のヒドロキシプロピル基（−ＯＣＨ２ＣＨ（ＯＨ）ＣＨ３）を持つ。１グルコースあたりの置換された水酸基の平均数は置換度（ｄｅｇｒｅｅ ｏｆ ｓｕｂｓｔｉｔｕｔｉｏｎ，ＤＳ）として表され、これは最大３である。しかしヒドロキシプロピル基にも水酸基が含まれるため、反応途中にここもエーテル化される。そのため、１グルコースあたりのヒドロキシプロピル基の数であるモル置換度（ｍｏｌｅｓ ｏｆ ｓｕｂｓｔｉｔｕｔｉｏｎ，ＭＳ）は３より大きくなる。
セルロースは結晶性が高いため、ＨＰＣを水溶性とするにはＭＳを４以上にする必要がある。疎水基と親水基を持つため、下限臨界溶液温度（ＬＣＳＴ）は約４５℃で、これ以上の温度では不溶性となる。本発明においては水溶性であることが好ましい。
ＨＰＣは、食品添加物として広く利用されており、その安全性も熟知されている。ＨＰＣの分子量は、食品添加物として市販されているものとしては、質量平均分子量が４００００〜９１００００の範囲であるが、必要に応じて分子量の範囲を選択できる。本発明にあっては分子量の小さいものが好ましく、特に好ましくは、質量平均分子量が４００００〜１４００００ものである。なおＨＰＣの分子量は、ゲル浸透クロマトグラフィー法（ＧＰＣ法）で容易に測定可能である。
食品添加物として市販されているＨＰＣとしては、例えば日本曹達株式会社のセルニーＳＳＬ（分子量４００００）、セルニーＳＬ（分子量１０００００）、セルニーＬ（分子量１４００００）、セルニーＭ（分子量６２００００）、セルニーＨ（分子量９１００００）を例示することができる。本発明においてはセルニーＳＳＬまたはＳＬ、Ｌが好ましく、特に好ましくはセルニーＳＳＬを使用することが好ましい。
Hydroxypropyl cellulose (hereinafter “HPC”) is obtained by etherifying a hydroxyl group of cellulose with propylene oxide and has a large number of hydroxypropyl groups (—OCH 2 CH(OH)CH 3 ). The average number of substituted hydroxyl groups per glucose is expressed as the degree of substitution (DS), which is a maximum of 3. However, since the hydroxypropyl group also contains a hydroxyl group, it is etherified during the reaction. Therefore, the molar substitution degree (MS), which is the number of hydroxypropyl groups per glucose, is larger than 3.
Since cellulose has high crystallinity, it is necessary to set MS to 4 or more in order to make HPC water-soluble. Since it has a hydrophobic group and a hydrophilic group, the lower critical solution temperature (LCST) is about 45° C., and it becomes insoluble at a temperature higher than this. In the present invention, it is preferably water-soluble.
HPC is widely used as a food additive, and its safety is well known. The HPC has a mass average molecular weight of 40,000 to 910000 as commercially available as a food additive, but the molecular weight range can be selected as necessary. In the present invention, those having a small molecular weight are preferable, and those having a mass average molecular weight of 40,000 to 140,000 are particularly preferable. The molecular weight of HPC can be easily measured by a gel permeation chromatography method (GPC method).
Examples of HPCs that are commercially available as food additives include, for example, Nippon Soda Co., Ltd.'s CELNY SSL (molecular weight 40,000), CELLNEY SL (molecular weight 100,000), CELLNEY L (molecular weight 140,000), CELLNEY M (molecular weight 620,000), CELLNEY H (molecular weight). 910000). In the present invention, Cerny SSL or SL, L is preferable, and Cernie SSL is particularly preferably used.
シェラックは、ラックカイガラムシおよびその近縁の数種のカイガラムシの分泌する虫体被覆物を精製して得られる樹脂状の物質である。また、セラックともいう。シェラックは水に不溶性であり、チョコレートや錠剤のコーティングに用いられる。
しかし、ビルベリーエキス顆粒をコーティングするためには用いられていない。本発明においては、ビルベリーエキス粉末とヒドロキシプロピルセルロースからなる強固な造粒物を形成させ、これを芯物質とし、外層をシェラック層としたコーティング顆粒を製造する技術を見いだしたものである。
Shellac is a resinous substance obtained by purifying the insect body coat secreted by the scale insect and several scale insects related to it. Also called shellac. Shellac is insoluble in water and is used for coating chocolate and tablets.
However, it has not been used to coat bilberry extract granules. In the present invention, a technique for producing a coated granule in which a strong granulated product composed of bilberry extract powder and hydroxypropyl cellulose is formed, and this is used as a core substance and a shellac layer is used as an outer layer, has been found.
上記のとおり、ビルベリーエキス粉末は、粉末としての流動性にかけるため、本発明では、ケイ酸カルシウムなどの流動化剤をビルベリーエキス１００質量部当たり１〜５質量部添加して混合する。
この粉末を、流動層造粒乾燥機を用いて造粒する。造粒する場合、ビルベリーエキス粉末の結合剤としてＨＰＣを用いる。ＨＰＣは、水又はアルコール溶液として、常法により噴霧しながら造粒する。造粒にあたってはどのような装置であっても使用可能であるが、より強固な造粒物を得るには、側方向から造粒液を噴霧できる機構を有する流動層造粒乾燥機を用いることが好ましい。コーティングにあたっては、前の造粒工程を考慮すると、側方向から造粒液及びコーティング液を噴霧できる機構を有する造粒、乾燥、コーティング機能が一体化した流動層造粒乾燥機を用いることが好ましい。このような装置としてはフロイント産業株式会社製の流動層造粒乾燥機「フローコーター」ＦＬＯ−１、ＦＬＯ−５Ｍを例示できる。なおこのとき、造粒された粒子あたりＨＰＣが１〜５質量％になるように噴霧する造粒液のＨＰＣ濃度を調整する。水溶液とする場合には３〜１０質量％のＨＰＣ濃度とすると好ましい結果を得ることができる。
造粒にあたっては、造粒物の粒子径が１００μｍ〜３００μｍになるように装置の給排気条件、温度条件を設定する。造粒物の粒子径は、服用時のざらつき及びコーティング量を考慮して前記記載の粒子径とすることが望ましい。
As described above, since the bilberry extract powder has poor fluidity as a powder, in the present invention, 1 to 5 parts by mass of a fluidizing agent such as calcium silicate is added and mixed with 100 parts by mass of the bilberry extract.
This powder is granulated using a fluidized bed granulation dryer. When granulating, HPC is used as a binder for bilberry extract powder. HPC is granulated as a water or alcohol solution while spraying by a conventional method. Any device can be used for granulation, but to obtain a stronger granulated product, use a fluidized bed granulation dryer having a mechanism capable of spraying the granulation liquid from the lateral direction. Is preferred. When coating, considering the previous granulation step, it is preferable to use a fluidized bed granulation dryer having an integrated granulation, drying and coating function, which has a mechanism capable of spraying the granulation liquid and the coating liquid from the lateral direction. .. Examples of such an apparatus include a fluidized bed granulation dryer “Flow Coater” FLO-1 and FLO-5M manufactured by Freund Sangyo Co., Ltd. At this time, the HPC concentration of the granulating liquid to be sprayed is adjusted so that HPC is 1 to 5 mass% per granulated particle. When used as an aqueous solution, a preferable result can be obtained by setting the HPC concentration to 3 to 10% by mass.
In granulating, the supply/exhaust conditions and temperature conditions of the apparatus are set so that the particle size of the granulated product is 100 μm to 300 μm. The particle size of the granulated product is preferably the above-described particle size in consideration of the roughness during administration and the coating amount.
得られた造粒物にシェラックを噴霧液としてコーティングをおこなう。シェラックは、しばしば、乾燥した固体シェラックから調製された適切な分散剤を使用して、中性もしくは僅かに酸性の水中に分散させた塩基性物質水溶液中に溶解された物や、食品グレードの有機溶媒（例えば、アルコールなど（特に、エタノール））中に溶解された物が市販されている。具体的には、フロイント産業株式会社製「ＡＱ Ｓｈｅｌａｘ（１０％濃度シェラック水溶液）」、日本シェラック工業株式会社製「ラックグレーズ１０Ｅ（１０％濃度シェラック溶液）」や「ラックグレーズ２０Ｅ、２５Ｅ、３２Ｅ、２０ＥＮ、２５ＥＮ、３２ＥＮ」などを例示できる。造粒物へのコーティングに当たっては、同様に側方からシェラック溶液を噴霧して、乾燥させることにより本発明のビルベリーエキスを７０質量％以上含有し、ビルベリーエキス粉末とヒドロキシプロピルセルロースからなる造粒物を芯物質とし、外層がシェラック層で形成されたコーティング顆粒を得ることができる。
このコーティング顆粒は、水に溶解せず、またビルベリーエキス由来の色素を放出しない。またコーティング顆粒を口腔内に含んでもビルベリーエキス独特の渋みや臭味をほとんど感じない。
The obtained granules are coated with shellac as a spray liquid. Shellac is often dissolved in an aqueous solution of a basic substance dispersed in neutral or slightly acidic water using a suitable dispersant prepared from dry solid shellac, or food grade organics. Those dissolved in a solvent (eg, alcohol (especially ethanol)) are commercially available. Specifically, "AQ Shelax (10% concentration shellac aqueous solution)" manufactured by Freund Sangyo Co., Ltd., "Rack glaze 10E (10% concentration shellac solution)" manufactured by Japan Shellac Co., Ltd. and "Rack glaze 20E, 25E, 32E," 20EN, 25EN, 32EN" and the like. When coating a granulated product, a shellac solution is sprayed from the side in the same manner and dried to contain 70% by mass or more of the bilberry extract of the present invention, and the granulated product is composed of bilberry extract powder and hydroxypropyl cellulose. It is possible to obtain coated granules in which the core material is and the outer layer is a shellac layer.
The coated granules do not dissolve in water and do not release the pigment derived from bilberry extract. Moreover, even if the coated granules are contained in the oral cavity, the astringency and odor characteristic of bilberry extract are hardly felt.
ビルベリーエキスを７０質量％以上含有し、ビルベリーエキス粉末とヒドロキシプロピルセルロースからなる造粒物を芯物質とし、外層がシェラック層で形成されたコーティング顆粒は、口腔内速崩壊錠の従来技術にしたがって口腔内速崩壊錠とすることができる。
ビルベリーエキスを７０質量％以上含有し、ビルベリーエキス粉末とヒドロキシプロピルセルロースからなる造粒物を芯物質とし、外層がシェラック層で形成されたコーティング顆粒を本発明の口腔内速崩壊錠に用いる場合は、錠剤あたり１〜４５質量％とすることが好ましい。これ以上の含有量とする場合、硬度低下や崩壊遅延などの問題が発生する場合がある。
通常は、１０〜３５質量％配合することが好ましい配合量である。
Coated granules containing 70% by mass or more of bilberry extract, a granulated product of bilberry extract powder and hydroxypropylcellulose as a core substance, and an outer layer of shellac layer are prepared according to the conventional technique of rapidly disintegrating buccal tablets in the oral cavity. It can be used as a rapidly disintegrating tablet.
When the coated granules containing bilberry extract in an amount of 70% by mass or more, a granule composed of bilberry extract powder and hydroxypropyl cellulose as a core substance, and an outer layer formed of a shellac layer are used for the orally rapidly disintegrating tablet of the present invention, It is preferable that the amount is 1 to 45 mass% per tablet. When the content is more than the above range, problems such as hardness decrease and disintegration delay may occur.
Usually, the blending amount is preferably 10 to 35% by mass.
本発明において、主賦形剤として使用する糖類は、医薬、食品製剤の技術分野で使用されうる単糖及び二糖、並びにそれらの糖アルコールである。これらの具体的なものとしては、マンニトール、エリスリトール、キシリトール、乳糖及びグルコース、更に、マルトース、ソルビトース、トレハロース、ショ糖及び果糖などを挙げることができる。これらは単独でも２種以上組み合わせても用いることができる。特にエリスリトールは崩壊性を付与する上で好ましい。エリスリトールは錠剤に３０〜６０質量％、特に好ましくは４４０〜５０質量％を含有させることで適切な成型しやすさ、ならびに好ましい口腔内崩壊特性を本発明の錠剤にもたせることができる。 In the present invention, the saccharides used as the main excipient are monosaccharides and disaccharides that can be used in the technical fields of medicines and food preparations, and sugar alcohols thereof. Specific examples thereof include mannitol, erythritol, xylitol, lactose and glucose, as well as maltose, sorbitol, trehalose, sucrose and fructose. These can be used alone or in combination of two or more. In particular, erythritol is preferable for imparting disintegration. When erythritol is contained in the tablet in an amount of 30 to 60% by mass, particularly preferably 440 to 50% by mass, the tablet of the present invention can have proper moldability and favorable orally disintegrating properties.
一般に、錠剤硬度を高めるには、水溶性結合剤として、例えば、ポリビニルピロリドン、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、ポリビニルアルコールなどが使用されている。しかし、通常の圧縮成型過程で得られる錠剤は速やかな崩壊性を示さない。本発明では、このような結合剤を使用せずに、結晶セルロースを選択することが好ましい。さらに崩壊剤として加工デンプンや、市販されている配合剤、例えば富士化学工業株式会社製「エフメルトＦ１」を適量添加すると好ましい速崩壊性を示す。
賦形剤は、あらかじめ、ケイ酸カルシウムや二酸化ケイ素、タルクなどの流動化剤と混合し、造粒しておくことで好ましい効果を得ることができる。また、造粒工程を必要としない簡便な直接打錠法によっても製造することができる。
結晶セルロースは錠剤中に１０〜２０質量％を配合する。崩壊促進の目的で配合する配合剤は錠剤中に１〜５質量％含有させることで好ましい結果を得ることができる。
Generally, in order to increase tablet hardness, for example, polyvinylpyrrolidone, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, etc. are used as a water-soluble binder. However, tablets obtained by a normal compression molding process do not show rapid disintegration. In the present invention, it is preferable to select crystalline cellulose without using such a binder. Further, when a suitable amount of modified starch as a disintegrating agent or a commercially available compounding agent such as "F-melt F1" manufactured by Fuji Chemical Industry Co., Ltd. is added, a preferable rapid disintegrating property is exhibited.
The excipient can be mixed with a fluidizing agent such as calcium silicate, silicon dioxide, or talc in advance and granulated to obtain a desired effect. It can also be produced by a simple direct compression method that does not require a granulation step.
Crystalline cellulose is compounded in the tablet in an amount of 10 to 20% by mass. A desirable result can be obtained by incorporating 1 to 5% by mass of a compounding agent to be incorporated for the purpose of promoting disintegration in a tablet.
また、場合によっては特開２０１４−１８１２２１号公報に開示された、酸源と１種類又は複数の発泡源を唾液中の水分を介して反応させて糖類及び崩壊剤を含有する製剤とすることもできる。このような製剤とする場合は、酸源としてクエン酸、発泡源としてアルカリ金属、アルカリ土類金属の炭酸塩及び重炭酸塩よりなる群から選ばれる少なくとも１種とを配合し、必要に応じて矯味あるいは微発泡の補助として１錠中に少量の他の有機酸を配合することができる。
特に発泡源としては重炭酸ナトリウムと炭酸カルシウムの併用が好ましい。本発明においては、炭酸カルシウムは多孔性炭酸カルシウム又は多孔質炭酸カルシウムが特に好ましい。
Further, in some cases, a preparation containing a saccharide and a disintegrant may be prepared by reacting an acid source with one or more foaming sources through water in saliva, which is disclosed in JP-A-2014-181221. it can. In the case of such a preparation, citric acid is used as the acid source, and at least one selected from the group consisting of alkali metal, alkaline earth metal carbonates and bicarbonates as the foaming source, and if necessary, A small amount of other organic acid can be added to one tablet as an aid for taste masking or fine foaming.
A combination of sodium bicarbonate and calcium carbonate is particularly preferable as the foaming source. In the present invention, the calcium carbonate is particularly preferably porous calcium carbonate or porous calcium carbonate.
本発明の錠剤は、口腔内での崩壊の際に好ましい香味を付与するために、粉末香料を配合することができる。粉末香料は香味成分として精油を含有し、デキストリン、澱粉類、アラビアガム、ゼラチン、カゼインなどを含有し、粉末化されたものであって、粉末香料の粒子径が３００μｍ以上に整粒されたものを用いなければならない。この粒子径よりも小さな粒子径の粉末香料が混入する場合は、速崩壊性を阻害する。特に精油を香料成分として含有する粉末香料を使用する場合は注意を要する。
このような粉末香料は、市販されている粉末香料を篩別して得ることができる。
また粉末香料を調製する工程において、造粒操作を行い、粒子径を３００μｍ以上になるように造粒しても良い。造粒は噴霧乾燥法によって粉末香料を調製した後、湿式造粒や乾式造粒など公知の技術に基づき調製することができる。
The tablet of the present invention can be mixed with a powdered flavor in order to impart a preferable flavor upon disintegration in the oral cavity. The powdered fragrance contains essential oil as a flavor component, contains dextrin, starches, gum arabic, gelatin, casein, etc. and is powdered, and the particle size of the powdered fragrance is regulated to 300 μm or more. Must be used. When a powdered fragrance having a particle size smaller than this particle size is mixed, the rapid disintegration property is hindered. In particular, caution is required when using a powdered flavor containing essential oil as a flavor component.
Such a powdered fragrance can be obtained by sieving a commercially available powdered fragrance.
Further, in the step of preparing the powdered fragrance, a granulation operation may be performed to granulate the particle diameter to 300 μm or more. Granulation can be carried out by a known technique such as wet granulation or dry granulation after the powder flavor is prepared by the spray drying method.
本発明の錠剤は、上記以外の材料として、打錠に際し必要な滑沢剤や流動化剤を配合することができる。 The tablet of the present invention may contain, as a material other than the above, a lubricant and a fluidizing agent necessary for tableting.
打錠用末は、本発明の効果に悪影響を及ぼさない限り、錠剤の製造に一般に用いられる種々の添加剤を含むことができる。結合剤以外の添加剤としては、例えば、クエン酸、酒石酸、リンゴ酸などの酸味料、例えば、アスパルテーム、サッカリンナトリウム、ステビアなどの人工甘味料、例えば、ステアリン酸マグネシウム、ショ糖脂肪酸エステル、タルクなどの滑沢剤、例えば、食用黄色５号、食用赤色２号及び食用青色２号などの食用色素、食用レーキ色素、酸化鉄などの着色剤を挙げることができる。これらの添加剤は、単独でも２種以上を組み合わせて使用することができる。 The tableting powder can contain various additives generally used in the production of tablets, as long as the effects of the present invention are not adversely affected. Examples of the additives other than the binder include acidulants such as citric acid, tartaric acid, and malic acid, for example, artificial sweeteners such as aspartame, sodium saccharin, and stevia, such as magnesium stearate, sucrose fatty acid ester, and talc. Lubricants, for example, food dyes such as Food Yellow No. 5, Food Red No. 2 and Food Blue No. 2, food lake dyes, and coloring agents such as iron oxide can be mentioned. These additives may be used alone or in combination of two or more.
また滑沢剤は組成中に添加するのではなく、外部滑沢剤として使用しても良い。
本発明の構成は、簡単な混合と打錠による極めて簡便な方法で、目的とする香味を付与された口腔内速崩壊錠の錠剤を製造できる優れたものである。打錠工程では、一般に粉末の圧縮成型に常用されている打錠機、例えば、単発打錠機或いはロータリー式打錠機を使用することができる。打錠圧は、例えば、打錠用末２００ｍｇを、直径（φ）８ｍｍの杵及び単発打錠機を用いて打錠する場合、通常、２００〜１５００ｋｇ、好ましくは５００〜１０００ｋｇ程度に設定する。打錠時の温度は、通常室温（２０〜３０℃程度）でよく、特に調整する必要はない。本発明の口腔内速崩壊錠は適度な硬度を有しているため、円形、楕円形などの所望される形状に加工することができる。このような錠剤の直径或いは長径は、通常６〜１５ｍｍであり、その重量は、通常８０ｍｇから１０００ｍｇとなるが、これに限定されるものではない。また、錠剤に分割するための割線を刻んだ分割錠とすることも可能である。
本発明による錠剤は口腔内での速崩壊性を備えながら、直径１５ｍｍの錠剤硬度が１０ｋｇｆを超えており、製造・流通・保管に耐え得る錠剤硬度を有している。
Further, the lubricant may be used as an external lubricant instead of being added to the composition.
The constitution of the present invention is excellent in that it is possible to produce a desired intraorally rapidly disintegrating tablet with a flavor by a very simple method by simple mixing and tableting. In the tableting process, a tableting machine commonly used for powder compression molding, for example, a single shot tableting machine or a rotary tableting machine can be used. The tableting pressure is usually set to 200 to 1500 kg, preferably about 500 to 1000 kg when tableting powder 200 mg is tableted using a punch having a diameter (φ) of 8 mm and a single tableting machine. The temperature at the time of tableting may be usually room temperature (about 20 to 30° C.), and it is not particularly necessary to adjust it. Since the orally rapidly disintegrating tablet of the present invention has an appropriate hardness, it can be processed into a desired shape such as a circle or an ellipse. The diameter or major axis of such tablets is usually 6 to 15 mm, and the weight thereof is usually 80 mg to 1000 mg, but is not limited thereto. Further, it is also possible to make a split tablet in which a dividing line for dividing the tablet is cut.
The tablet according to the present invention has a tablet hardness with a diameter of 15 mm of more than 10 kgf while having a rapid disintegration property in the oral cavity, and has a tablet hardness capable of withstanding production, distribution and storage.
本発明の口腔内速崩壊錠は、口腔内での速やかな崩壊性を有しているため、飲み易くかつ取り扱いが容易である。また賦香することにより小児なども飲用しやすくなるとともに、市販の粉末香料を配合した場合の崩壊性の阻害も発生しない。
また、ビルベリーエキスに由来する異味や異臭が多少感じられる様な場合、香料によってマスキングできるため小児患者の予防や治療にも用いることができる。さらに唾液量の少ないシェーグレン症候群の患者や高齢者などに服用させる場合には、最小限の水で速やかに崩壊するため利便である。また、水摂取の制限されている患者や小児にも適している。
The rapidly disintegrating buccal tablet of the present invention has a rapid disintegrating property in the oral cavity, and thus is easy to drink and easy to handle. In addition, the perfume makes it easier for children and the like to drink, and does not inhibit the disintegration when a commercially available powdered fragrance is added.
Further, when a slight taste or odor derived from bilberry extract is felt, it can be masked with a fragrance, so that it can be used for prevention or treatment of pediatric patients. Furthermore, when it is taken by patients with Sjogren's syndrome and the elderly who have a small amount of saliva, it is convenient because it quickly disintegrates with a minimum amount of water. It is also suitable for patients and children with limited water intake.
本発明の製剤は、汎用の粉砕機、混合機、打錠機を使用できるため従来の製造装置がそのまま利用できる。更に、煩雑な工程を経ることなく製造工程が極めて簡便であり、製造コスト、製造時間などの面から、従来の口腔内速崩壊錠の製造方法に比較して有利である。また、医薬品だけでなく健康食品や錠菓としても有用な製品となる。 Since the formulation of the present invention can use a general-purpose pulverizer, mixer or tableting machine, conventional manufacturing equipment can be used as it is. Further, the manufacturing process is extremely simple without complicated processes, and is advantageous in comparison with the conventional method for manufacturing an orally rapidly disintegrating tablet in terms of manufacturing cost, manufacturing time, and the like. Further, it is a useful product not only as a medicine but also as a health food or a tablet confection.
以下に実施例を示し、本発明を説明する。
１．ビルベリーエキスを７０質量％以上含有するコーティング顆粒の製造例
１）造粒工程
流動層造粒乾燥機（フロイント産業株式会社製、ＦＬＯ−５Ｍ）に、ビルベリー抽出エキス粉末（ｉｎｄｅｎａ社製）２５００ｇとケイ酸カルシウム（富田製薬株式会社製）３０ｇを入れ混合した。次いで、造粒液として１０質量％ヒドロキシプロピルセルロース水溶液１０００ｇを側方より噴霧を行い、乾燥後、造粒物（９５質量％ビルベリーエキス含有）を得た。
Hereinafter, the present invention will be described with reference to examples.
1. Production example of coated granules containing 70% by mass or more of bilberry extract 1) Granulation step
In a fluidized bed granulation dryer (FLO-5M, manufactured by Freund Sangyo Co., Ltd.), 2500 g of bilberry extract powder (manufactured by indena) and 30 g of calcium silicate (manufactured by Tomita Pharmaceutical Co., Ltd.) were mixed. Next, 1000 g of a 10 mass% hydroxypropylcellulose aqueous solution was sprayed from the side as a granulation liquid, and after drying, a granulated product (containing 95 mass% bilberry extract) was obtained.
２）コーティング工程
造粒物１８００ｇに、コーティング液として１０質量％セラック水溶液（フロイント産業株式会社製）５５００ｇを側方より噴霧しながらコーティングを行った。乾燥後、コーティング顆粒を得た。配合量から計算するとこの粒子はビルベリーエキスを７３質量％含有している。
2) Coating step 1800 g of the granulated product was coated while laterally spraying 5500 g of a 10 mass% shellac aqueous solution (manufactured by Freund Sangyo Co., Ltd.) as a coating liquid. After drying, coated granules were obtained. This particle contains 73% by mass of bilberry extract when calculated from the blending amount.
３）得られたコーティング顆粒の特性
＜粒子径評価＞
コーティング顆粒の粒子径を５０％粒子径Ｄ５０（メジアン径）及び１０％粒子径Ｄ１０、９０％粒子径Ｄ９０により評価した。測定は画像処理式粒子径分布測定装置（マイクロトラック・ベル株式会社製）を使用した。コーティング顆粒の５０％粒子径Ｄ５０（メジアン径）及び１０％粒子径Ｄ１０、９０％粒子径Ｄ９０を図１に示す。コーティング前後でＤ５０及びＤ１０、Ｄ９０にほとんど差が見られなかったことから、造粒が生じることなく、コーティングを行えたことがわかる。また、コーティング後では、コーティング前に比べ、Ｄ５０及びＤ１０、Ｄ９０が均等に増大していることから、均一なコーティングが行えたことがわかる。
3) Characteristics of the obtained coated granules <particle size evaluation>
The particle size of the coated granules was evaluated by 50% particle size D50 (median size), 10% particle size D10, and 90% particle size D90. For the measurement, an image processing type particle size distribution measuring device (manufactured by Microtrac Bell Co., Ltd.) was used. The 50% particle diameter D50 (median diameter), the 10% particle diameter D10, and the 90% particle diameter D90 of the coated granules are shown in FIG. Since there was almost no difference in D50, D10, and D90 before and after coating, it can be seen that the coating could be performed without granulation. Further, after coating, D50, D10, and D90 were increased more uniformly than before coating, which indicates that uniform coating was performed.
＜形状評価＞
走査型電子顕微鏡（株式会社日立ハイテクノロジーズ製）により、ビルベリーエキス粉末（原末）及び造粒物、コーティング顆粒の形状評価を行った。走査型電子顕微鏡により得られた観察画像を図２に示す。コーティング顆粒の表面は平滑化しており、緻密な粒子であることがわかる。
<Shape evaluation>
Using a scanning electron microscope (manufactured by Hitachi High-Technologies Corporation), the shape evaluation of the bilberry extract powder (bulk powder), granules, and coated granules was performed. The observed image obtained by the scanning electron microscope is shown in FIG. The surface of the coated granules is smooth, and it can be seen that the particles are dense particles.
＜マスキング評価＞
得られたコーティング顆粒を、５人の被験者に服用してもらい、コーティング顆粒の渋み及び臭味を評価した。服用方法は薬用匙に１スプーンを採り、これを口腔内に１分間含んだ後吐き出した。渋み、臭味の評価結果を下記表１、２にそれぞれ示す。
<Masking evaluation>
The obtained coated granules were taken by 5 subjects, and the astringency and odor of the coated granules were evaluated. As a method of taking, one spoon was taken in a medicinal spoon, contained in the oral cavity for 1 minute, and then exhaled. The evaluation results of astringency and odor are shown in Tables 1 and 2 below.
コーティング顆粒はわずかに苦味を感じる程度であり、臭味に関しては全く感じない結果であった。 The coated granules had a slightly bitter taste and no odor.
＜着色評価＞
溶出試験によりコーティング顆粒の着色評価を行った。着色は試験液の色素による着色を目視により評価した。試料は下記表３の組成になるように混合後、単発打錠機（岡田精工株式会社製）を使用して成型した錠剤を用いた。錠剤の質量は３４０ｍｇ、形状は直径９ｍｍ１２Ｒ、硬度は崩壊時間が１０秒以内となるように２ｋｇｆ以下とした。比較として、ビルベリーエキス粉末（原末）及び造粒物を同様に試験した。
<Coloring evaluation>
The elution test evaluated the color of the coated granules. The color was evaluated by visually observing the coloration of the test liquid due to the dye. The sample used was a tablet formed by mixing so as to have the composition shown in Table 3 below and molding using a single-shot tableting machine (made by Okada Seiko Co., Ltd.). The mass of the tablet was 340 mg, the shape was 9 mm12R in diameter, and the hardness was 2 kgf or less so that the disintegration time was within 10 seconds. For comparison, bilberry extract powder (bulk powder) and granules were similarly tested.
ビルベリーエキス粉末（原末）及び造粒物は開始１０秒後で、色素による着色が認められたが、コーティング顆粒は着色が認められなかった。 The bilberry extract powder (bulk powder) and the granulated product were colored by the pigment 10 seconds after the start, but the coated granules were not colored.
２．口腔内速崩壊錠の製造
（１）賦形剤成分の造粒
下記の表４の組成で賦形剤の造粒物を調製した。
2. Production of Orally Rapidly Disintegrating Tablet (1) Granulation of Excipient Components Excipient granules having the composition shown in Table 4 below were prepared.
造粒は流動層造粒装置（株式会社パウレック製）を用い、エリスリトール水溶液を造粒液として用いた。 For the granulation, a fluidized bed granulator (manufactured by Paulec Co., Ltd.) was used, and an erythritol aqueous solution was used as the granulating liquid.
（２）混合
製造例１．で得たビルベリーエキスのコーティング顆粒、賦形剤の造粒物（表４）、崩壊剤（エフメルトＦ１）（富士化学工業株式会社製）、軽質無水ケイ酸、ステアリン酸カルシウム含む表５の組成をＶ型混合機（筒井理化学器械株式会社製）で混合した。
(2) Mixing Production Example 1. The composition of Table 5 including the coated granules of the bilberry extract obtained in the above, granules of excipient (Table 4), disintegrant (F-melt F1) (manufactured by Fuji Chemical Industry Co., Ltd.), light anhydrous silicic acid and calcium stearate is V They were mixed with a mold mixer (manufactured by Tsutsui Rikagaku Kikai Co., Ltd.).
（３）錠剤成型
混合後、単発打錠機（岡田精工株式会社社製）を使用して、錠剤硬度が７ｋｇｆになるよう打圧の調整を行い、錠剤質量３４０ｍｇ、錠剤形状９ｍｍ１２Ｒの口腔内速崩壊錠を成型した。
(3) Tablet molding After mixing, the tableting pressure was adjusted using a single-shot tableting machine (made by Okada Seiko Co., Ltd.) so that the tablet hardness was 7 kgf, and the oral mass velocity of tablet weight 340 mg and tablet shape 9 mm12R. Molded disintegrating tablets.
３．口腔内速崩壊錠の評価
口腔内速崩壊錠について、錠剤硬度、打錠時における打圧、摩損度、口腔内崩壊時間、トリコープテスタを用いた崩壊時間を測定した。結果を表６に示す。また、日本薬局方溶出試験「パドル法」に従い溶出試験を実施した。
3. Evaluation of Orally Rapidly Disintegrating Tablets With respect to the orally rapidly disintegrating tablets, tablet hardness, tableting pressure during tableting, friability, oral disintegration time, and disintegration time using a Tricorp tester were measured. The results are shown in Table 6. Further, the dissolution test was carried out according to the Japanese Pharmacopoeia dissolution test “paddle method”.
＜錠剤硬度＞
得られた錠剤の硬度は、デジタル錠剤硬度計（岡田精工株式会社製）を用いて測定した。
<Tablet hardness>
The hardness of the obtained tablets was measured using a digital tablet hardness meter (made by Okada Seiko Co., Ltd.).
＜摩損度試験＞
日本薬局方に基づく錠剤摩損度試験器（ＰＨＡＲＭＡ ＴＥＳＴ製）を使用し、錠剤２０粒について摩損試験を行った。試験条件は次のとおり設定した。
回転速度：２５回転／分
回転時間：１０分
実施例１〜３、比較例１は特に問題のない摩損度であった。
<friability test>
A tablet friability tester (manufactured by PHARMA TEST) based on the Japanese Pharmacopoeia was used to perform a friability test on 20 tablets. The test conditions were set as follows.
Rotation speed: 25 rotations/minute Rotation time: 10 minutes Examples 1 to 3 and Comparative Example 1 were friability with no particular problem.
＜口腔内崩壊試験＞
３名の官能評価員に１錠を口中に含んだときの崩壊時間を測定した。実施例１〜３は口中に含んだとき６０秒以内の崩壊が認められたが、比較例１は崩壊を認められなかった。
<Oral disintegration test>
Disintegration time when one tablet was included in the mouth was measured by three sensory assessors. In Examples 1 to 3, disintegration within 60 seconds was observed when contained in the mouth, but Comparative Example 1 was not disintegrated.
＜崩壊試験（トリコープテスタ）＞
岡田精工株式会社製崩壊試験機「トリコープテスタ」を用いた崩壊試験をおこなった。試験条件は、つぎのとおり設定した。トリコープテスタは口中に含んだとき、速やかな崩壊を示す口腔内速崩壊錠の崩壊性を評価する目的で開発された崩壊試験機である。表６の 崩壊時間（トリコープテスタ）はｎ３の平均値を示す。
試験液：水
試験液温度：３７℃
荷重：２０ｇ
滴下間隔：１．２７秒
滴下速度：３．０ｍＬ／ｍｉｎ
滴下高さ：７ｃｍ
実施例１〜３は６０秒以内に崩壊が認められたが、比較例１は、その崩壊時間は１４１秒であり、崩壊遅延が認められた。
<Disintegration test (Tricorp Tester)>
A disintegration test was performed using a disintegration tester “Tricorp Tester” manufactured by Okada Seiko Co., Ltd. The test conditions were set as follows. The Tricorp Tester is a disintegration tester developed for the purpose of evaluating the disintegration properties of an orally rapidly disintegrating tablet that exhibits rapid disintegration when contained in the mouth. The disintegration time (Tricorp tester) in Table 6 shows the average value of n3.
Test solution: water Test solution temperature: 37°C
Load: 20g
Drop interval: 1.27 seconds Drop speed: 3.0 mL/min
Dropping height: 7 cm
In Examples 1 to 3, disintegration was observed within 60 seconds, but in Comparative Example 1, the disintegration time was 141 seconds, and disintegration delay was observed.
実施例１〜３における口腔内崩壊時間及びトリコープテスタを用いた崩壊時間はそれぞれ６０秒以内であり、崩壊遅延は認めず、優れた崩壊性を示した。 The disintegration time in the oral cavity and the disintegration time using the Tricorp tester in Examples 1 to 3 were each within 60 seconds, no delay in disintegration was observed, and excellent disintegration was exhibited.
＜錠剤の溶出試験＞
実施例１の口腔内速崩壊錠について、溶出試験を行った。試験条件は、つぎのとおり設定した。
試験液：試験液に水及び日本薬局方溶出試験第１液、日本薬局方溶出試験第２液
試験液容量：９００ｍＬ
温度：３７℃
パドル回転数：５０ｒｐｍ
検出器：紫外可視分光光度計（波長５１５ｎｍ）
<Tablet dissolution test>
A dissolution test was performed on the orally rapidly disintegrating tablet of Example 1. The test conditions were set as follows.
Test liquid: water as a test liquid and Japanese Pharmacopoeia dissolution test No. 1 liquid, Japanese Pharmacopoeia dissolution test No. 2 liquid Test liquid capacity: 900 mL
Temperature: 37°C
Paddle rotation speed: 50 rpm
Detector: UV-visible spectrophotometer (wavelength 515nm)
水の溶出試験については、口腔内でのビルベリーエキスの放出を評価する目的で試験を行った。測定結果を図４（水）に示す。測定結果より、３０秒後の溶出率は１％以下であったことから、口腔内速崩壊錠とした服用した際に、ビルベリーエキスが放出されないため、ビルベリーエキス由来の渋みや臭味、着色がないことがわかる。 The water dissolution test was conducted for the purpose of evaluating the release of bilberry extract in the oral cavity. The measurement result is shown in FIG. 4 (water). From the measurement results, the dissolution rate after 30 seconds was 1% or less, so that when taken as an orally rapidly disintegrating tablet, the bilberry extract was not released, so the astringency, odor, and coloration derived from the bilberry extract I know there isn't.
溶出試験第１液、溶出試験第２液の溶出試験は、本発明の口腔内速崩壊錠に加えて市販されているブルーベリーエキス含有錠剤を参考として試験を行った。測定結果を図５（溶出試験第１液）、図６（溶出試験第２液）に示す。
測定結果より、本発明の口腔内速崩壊錠は、ビルベリーエキスを水不溶性物質でコーティングした顆粒を含むが、その溶出性は市販されているブルーベリーエキス含有錠剤と比較しても、優れた溶出性を示した。
The dissolution tests of the first liquid and the second liquid of the dissolution test were conducted with reference to commercially available tablets containing blueberry extract in addition to the orally rapidly disintegrating tablet of the present invention. The measurement results are shown in FIG. 5 (dissolution test first liquid) and FIG. 6 (dissolution test second liquid).
From the measurement results, the orally rapidly disintegrating tablet of the present invention contains granules coated with a bilberry extract with a water-insoluble substance, but its dissolution is superior to that of commercially available blueberry extract-containing tablets. showed that.
従って、本発明によれば、ビルベリーエキスを７０質量％以上含むコーティング顆粒を錠剤中に配合することにより、１錠あたりビルベリーエキスを最大で３０質量％含有し、ビルベリーエキス特有の呈味性が改善され、口腔内の着色がない口腔内速崩壊錠を提供することができる。 Therefore, according to the present invention, by incorporating the coated granules containing bilberry extract in an amount of 70% by mass or more into a tablet, the bilberry extract is contained in a maximum amount of 30% by mass per tablet, and the taste peculiar to bilberry extract is improved. Thus, it is possible to provide an orally rapidly disintegrating tablet with no coloration in the oral cavity.
Claims (4)
顆粒中にビルベリーエキスを７０質量％以上含有し、
顆粒の芯物質が、ビルベリーエキス粉末とケイ酸カルシウムとヒドロキシプロピルセルロースからなる造粒物、
顆粒の外層がシェラック層である、
口腔内速崩壊錠。 An orally rapidly disintegrating tablet containing 1 to 45% by mass of granules composed of a core substance and an outer layer,
Contains 70% by mass or more of bilberry extract in granules ,
The core material of the granule is a granulated product composed of bilberry extract powder, calcium silicate and hydroxypropyl cellulose ,
The outer layer of granules is shellac layer ,
Orally fast disintegrating tablet.
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| JP2000327701A (en) * | 1999-05-18 | 2000-11-28 | Shin Etsu Chem Co Ltd | Hydroxypropyl cellulose having low degree of substitution and solid formulation |
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