JP6349769B2 - Solid preparation - Google Patents
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- JP6349769B2 JP6349769B2 JP2014029300A JP2014029300A JP6349769B2 JP 6349769 B2 JP6349769 B2 JP 6349769B2 JP 2014029300 A JP2014029300 A JP 2014029300A JP 2014029300 A JP2014029300 A JP 2014029300A JP 6349769 B2 JP6349769 B2 JP 6349769B2
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本発明は、コンドロイチン硫酸ナトリウム含有錠剤に関する。 The present invention relates to a tablet containing sodium chondroitin sulfate.
ムコ多糖類であるコンドロイチン硫酸ナトリウムは高分子多糖類の一種であり、生体内の細胞間に存在し、水分及び栄養の細胞への補給や細胞の水分保持の働きをする。この働きにより、骨と骨をつなぐ細胞組織が潤滑になり、柔軟性が保持されることから、腰痛症や関節痛、肩関節周囲炎（五十肩）等の緩和に汎用されている。
コンドロイチン硫酸ナトリウムは吸湿性が高く、膨張する性質を有するため、コンドロイチン硫酸ナトリウムを含有する錠剤は高湿度化に保存すると、ひび割れが起きるという問題がある。この問題を克服する技術として、コンドロイチン硫酸ナトリウムを含む素錠にフィルムコーティングを行うことにより、割れを抑制する技術が開示されている（特許文献１、２）。しかしながら、これら文献で示されている方法は、フィルムコートに必要な添加剤が多種必要であり、作業時間が長く、コストが高いといった問題があった。
Sodium chondroitin sulfate, which is a mucopolysaccharide, is a kind of high molecular polysaccharide, exists between cells in the body, and functions to supply water and nutrients to cells and to retain water in the cells. Due to this function, the cellular tissue connecting the bones becomes lubricated and the flexibility is maintained, so that it is widely used for the relief of low back pain, joint pain, shoulder periarthritis (fifty shoulders) and the like.
Since chondroitin sulfate sodium is highly hygroscopic and has a swelling property, tablets containing sodium chondroitin sulfate are cracked when stored at high humidity. As a technique for overcoming this problem, a technique for suppressing cracking by performing film coating on uncoated tablets containing sodium chondroitin sulfate has been disclosed (Patent Documents 1 and 2). However, the methods shown in these documents have a problem in that a variety of additives necessary for film coating are required, the working time is long, and the cost is high.
本発明は、フィルムコーティングを施さなくても、ひび割れの生じないコンドロイチン硫酸ナトリウム含有錠剤を提供することを課題とする。 This invention makes it a subject to provide the tablet containing a chondroitin sulfate which does not produce a crack, even if it does not give a film coating.
本発明者らは、コンドロイチン硫酸ナトリウムを含有する素錠について、フィルムコーティングを施すことなく錠剤のひび割れを抑制すべく鋭意検討を行った。その結果、コンドロイチン硫酸ナトリウムに対して特定量のマルトデキストリンを配合した錠剤は、吸湿時のひび割れが抑制されることを見出した。さらに、コンドロイチン硫酸ナトリウムの含量均一性も確保できることを見出し、本発明を完成した。 The present inventors diligently studied to suppress cracking of the tablet without applying film coating to the uncoated tablet containing sodium chondroitin sulfate. As a result, it was found that a tablet containing a specific amount of maltodextrin with respect to sodium chondroitin sulfate is suppressed from cracking during moisture absorption. Furthermore, the present inventors have found that the content uniformity of sodium chondroitin sulfate can be ensured and completed the present invention.
すなわち、本発明は、
（１）コンドロイチン硫酸ナトリウム、及びコンドロイチン硫酸ナトリウム１質量部に対して０．０５〜０．６質量部のマルトデキストリンを含有する錠剤、
（２）コンドロイチン硫酸ナトリウムの５０％粒子径が１５０μｍ以下である（１）記載の錠剤、
（３）さらに、ヒドロキシプロピルセルロースを含む（１）又は（２）記載の錠剤、
（４）５０％粒子径が１５０μｍ以下のコンドロイチン硫酸ナトリウムをマルトデキストリンとともに造粒し、得られた造粒物にヒドロキシプロピルセルロースを含む成分を加えて混合し、打錠用顆粒とする工程を有する、錠剤の製造方法、
である。
That is, the present invention
(1) A tablet containing 0.05 to 0.6 parts by weight of maltodextrin with respect to 1 part by weight of sodium chondroitin sulfate and sodium chondroitin sulfate,
(2) The tablet according to (1), wherein 50% particle size of sodium chondroitin sulfate is 150 μm or less,
(3) The tablet according to (1) or (2), further comprising hydroxypropylcellulose,
(4) A step of granulating sodium chondroitin sulfate having a 50% particle size of 150 μm or less together with maltodextrin, adding a component containing hydroxypropyl cellulose to the obtained granulated product, and mixing them to form granules for tableting. , Manufacturing method of tablets,
It is.
本発明により、吸湿時のひび割れが抑制されたコンドロイチン硫酸ナトリウム含有錠剤を提供することが可能となった。また、コンドロイチン硫酸ナトリウムを含む打錠用顆粒の流動性が良いため、コンドロイチン硫酸ナトリウムの含量均一性を確保した錠剤の提供が可能となった。 According to the present invention, it is possible to provide a chondroitin sulfate-containing tablet in which cracking during moisture absorption is suppressed. In addition, since the tableting granules containing sodium chondroitin sulfate have good fluidity, it has become possible to provide tablets that ensure the content uniformity of sodium chondroitin sulfate.
本発明のコンドロイチン硫酸ナトリウムの含有量としては、錠剤全量に対して５〜８０質量％、好ましくは２０〜４０質量％である。更に、吸湿時のひび割れの抑制を図るという効果の点から、微細化されていることが好ましい。また、本発明では、微細化されたコンドロイチン硫酸ナトリウムを使用すると、コンドロイチン硫酸ナトリウムを含有する打錠用顆粒の流動性が向上するため、結果として錠剤の質量偏差が小さくなるという利点も有する。そのようなコンドロイチン硫酸ナトリウムの粒子径としては、体積比による５０％粒子径は１５０μｍ以下が好ましく、さらに好ましくは１０μｍ〜１３０μｍである。また、９０％粒子径を求めた場合は、３００μｍ以下が好ましく、好ましくは２０μｍ〜２００μｍが挙げられる。なお、本発明において「５０％粒子径」は、レーザー回析・散乱法により、たとえば、日機装社製のレーザー回折・散乱式粒度径・粒度分布測定装置（マイクロトラックMT３３００EX）等を用いて測定される粒子径の、体積換算として粒径が細かい方から累積して、５０％となった際の粒子径であり、「９０％粒子径」についても同様に９０％となった際の粒子径である。 As content of sodium chondroitin sulfate of this invention, it is 5-80 mass% with respect to the tablet whole quantity, Preferably it is 20-40 mass%. Furthermore, it is preferable that it is refined | miniaturized from the point of suppressing the crack at the time of moisture absorption. Moreover, in this invention, when refined | miniaturized sodium chondroitin sulfate is used, since the fluidity | liquidity of the granule for tableting containing sodium chondroitin sulfate improves, it also has the advantage that the mass deviation of a tablet becomes small as a result. As the particle diameter of such sodium chondroitin sulfate, the 50% particle diameter by volume ratio is preferably 150 μm or less, more preferably 10 μm to 130 μm. Moreover, when calculating | requiring a 90% particle diameter, 300 micrometers or less are preferable, Preferably 20 micrometers-200 micrometers are mentioned. In the present invention, the “50% particle size” is measured by a laser diffraction / scattering method using, for example, a laser diffraction / scattering particle size / particle size distribution measuring device (Microtrac MT3300EX) manufactured by Nikkiso Co., Ltd. The particle diameter is the particle diameter when the particle diameter is accumulated from the finer in terms of volume and becomes 50%, and the “90% particle diameter” is also the particle diameter when it becomes 90%. is there.
本発明のマルトデキストリンとは、D.E.値が３〜２０の直鎖上のデンプン分解物である。本発明において、マルトデキストリンの含有量は、本発明の効果の点から、コンドロイチン硫酸ナトリウムに対して０．０５〜０．６質量部であることが好ましく、さらに好ましくは０．３〜０．６質量部である。０．０５質量部未満であるとひび割れを生じ、０．６質量部を超えるとコンドロイチン硫酸ナトリウムの含量均一性が保てなくなるからである。 The maltodextrin of the present invention is a starch degradation product on a straight chain having a D.E. value of 3 to 20. In this invention, it is preferable that content of maltodextrin is 0.05-0.6 mass part with respect to the sodium chondroitin sulfate from the point of the effect of this invention, More preferably, it is 0.3-0.6. Part by mass. If the amount is less than 0.05 parts by mass, cracks occur, and if the amount exceeds 0.6 parts by mass, the content uniformity of sodium chondroitin sulfate cannot be maintained.
本発明のヒドロキシプロピルセルロースとは、セルロースエーテルの１つであり、セルロースに酸化プロピレンを反応させ、セルロースの無水グルコース単位当たり３個存在する水酸基の一部を２−ヒドロキシプロポキシル基で置換した部分エーテルである。医薬品及び食品分野において、顆粒剤、錠剤の結合剤、賦形剤として汎用される。ヒドロキシプロピルセルロースの含有量は、吸湿時のひび割れの抑制を図るという点から、錠剤全量に対して１〜２０質量％、好ましくは３〜９質量％である。 The hydroxypropyl cellulose of the present invention is one of the cellulose ethers, a portion obtained by reacting cellulose with propylene oxide and substituting a portion of three hydroxyl groups per anhydroglucose unit of the cellulose with a 2-hydroxypropoxyl group. Ether. In the pharmaceutical and food fields, it is widely used as a granule, a tablet binder, and an excipient. The content of hydroxypropyl cellulose is 1 to 20% by mass, preferably 3 to 9% by mass, based on the total amount of the tablet, from the viewpoint of suppressing cracking during moisture absorption.
本発明の錠剤は、コンドロイチン硫酸ナトリウムとマルトデキストリン及び必要に応じて内服用固形製剤に汎用される公知の添加剤を混合して造粒用粉末を調製し、常法により造粒して顆粒を得た後、打錠することにより得ることができる。また、本発明の効果を損なわない範囲で、他の有効成分及び公知の添加剤を配合することができる。公知の添加剤としては、日本医薬品添加剤協会編「医薬品添加物事典２００７」（２００７年、薬事日報社）に収載されている添加剤等が挙げられる。 The tablet of the present invention is prepared by mixing sodium chondroitin sulfate, maltodextrin and, if necessary, a known additive commonly used in solid preparations for internal use to prepare a granulating powder, and granulating it by a conventional method. After obtaining, it can be obtained by tableting. Further, other active ingredients and known additives can be blended within a range not impairing the effects of the present invention. Known additives include those listed in “Pharmaceutical Additives Encyclopedia 2007” edited by Japan Pharmaceutical Additives Association (2007, Yakuji Nippo).
本発明の錠剤の製造方法は特に限定されないが、例えば以下の方法が挙げられる。
コンドロイチン硫酸ナトリウムとマルトデキストリンを混合し、必要に応じて内服用固形製剤に汎用される公知の添加剤を混合し混合粉体を調製する。コンドロイチン硫酸ナトリウムを微細化する場合は、例えば、ピンミル、ジェットミル、ハンマーミル等の粉砕機などが使用できる。造粒方法は特に制限されず、例えば撹拌造粒、流動層造粒、押し出し造粒、転動流動造粒、乾式造粒などが挙げられるが、特に好ましいのは撹拌造粒である。湿式造粒を行う場合は、例えば水、エタノール、イソプロピルアルコールあるいはそれらの混合溶媒を調製し、前記混合粉体に噴霧して撹拌造粒等の湿式造粒を行ったのち、湿粒を乾燥すればよい。得られた造粒物にヒドロキシプロピルセルロース、及び必要に応じて内服用固形製剤に汎用される公知の添加剤を混合し（後末添加）、打錠用顆粒を調製する。後末添加するヒドロキシプロピルセルロースの添加量は、造粒物１質量部に対して２〜４．５質量％が好ましい。得られた打錠用顆粒を圧縮成形することにより、本発明の錠剤が得られる。
本発明では、直径９．０ｍｍの２段Ｒ面等のＲ型の凸面を有する円形の打錠用杵を使って打錠した。打錠機でＲ型の凸面を有する錠径９．０ｍｍの打錠圧は、錠剤の硬度や打錠用杵の耐圧許容度等を考慮して適宜に設定されるが、通常打錠用杵１本当たり約３００〜５０００ｋｇ／ｃｍ２であり、好ましくは打錠用杵１本当たり約５００〜２０００ｋｇ／ｃｍ２である。なお、本発明の錠剤は、フィルムコーティングを施してもよい。
Although the manufacturing method of the tablet of this invention is not specifically limited, For example, the following method is mentioned.
A mixed powder is prepared by mixing sodium chondroitin sulfate and maltodextrin and, if necessary, mixing known additives commonly used for solid preparations for internal use. When refining chondroitin sodium sulfate, for example, a pulverizer such as a pin mill, a jet mill or a hammer mill can be used. The granulation method is not particularly limited, and examples thereof include stirring granulation, fluidized bed granulation, extrusion granulation, rolling fluidized granulation, and dry granulation. Particularly preferred is stirring granulation. When wet granulation is performed, for example, water, ethanol, isopropyl alcohol or a mixed solvent thereof is prepared, sprayed on the mixed powder, and wet granulation such as stirring granulation is performed, and then the wet granule is dried. That's fine. The resulting granulated product is mixed with hydroxypropylcellulose and, if necessary, known additives commonly used for solid preparations for internal use (late addition) to prepare granules for tableting. The added amount of hydroxypropylcellulose to be added later is preferably 2 to 4.5% by mass with respect to 1 part by mass of the granulated product. The tablet of the present invention is obtained by compression-molding the obtained granules for tableting.
In the present invention, tableting was performed using a circular tableting punch having an R-shaped convex surface such as a two-step R surface having a diameter of 9.0 mm. The tableting pressure of the tablet having a R-shaped convex surface with a tablet diameter of 9.0 mm is appropriately set in consideration of the hardness of the tablet, the pressure tolerance of the tablet punch, and the like. It is about 300 to 5000 kg / cm 2 per one, and preferably about 500 to 2000 kg / cm 2 per one tableting punch. The tablet of the present invention may be subjected to film coating.
以下に、実施例、比較例及び試験例を挙げ、本発明を更に詳細に説明する。 Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples.
実施例１
コンドロイチン硫酸ナトリウム ４８０．０ｇ
（５０％粒子径 ５８．６５μｍ）
（９０％粒子径 １１４．５μｍ）
マルトデキストリン ２８８．０ｇ
結晶セルロース ２１５．０ｇ
ヒドロキシプロピルセルロース ６０．０ｇ
カルメロースカルシウム ５４．０ｇ
コンドロイチン硫酸ナトリウムを常法にて粉砕した後、上記成分を秤量、混合し、撹拌混合造粒装置（商品名：バーチカルグラニュレーター；パウレック社製）に投入、水／エタノール（３：２）混液を噴霧しながら造粒した。得られた造粒物を流動層造粒乾燥機（商品名：ＦＬ−ＭＩＮＩ；フロイント社製）にて乾燥した後、造粒物１０９７．０ｇを得た。この造粒物２１２．０ｇと、結晶セルロース１２８．６ｇ、ヒドロキシプロピルセルロース１１．８ｇ、軽質無水ケイ酸１０．５ｇ、クロスカルメロースナトリウム３５．０ｇ、ステアリン酸マグネシウム２．３ｇとを混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの質量２８６ｍｇとなるように製錠し、錠剤を得た。
Example 1
Sodium chondroitin sulfate 480.0g
(50% particle size 58.65 μm)
(90% particle size 114.5μm)
Maltodextrin 288.0g
215.0 g of crystalline cellulose
Hydroxypropylcellulose 60.0g
Carmellose calcium 54.0g
After pulverizing sodium chondroitin sulfate by a conventional method, the above components are weighed and mixed, and then added to a stirring and mixing granulator (trade name: Vertical Granulator; manufactured by POWREC), and a water / ethanol (3: 2) mixed solution is added. Granulated while spraying. The obtained granulated product was dried with a fluidized bed granulator / dryer (trade name: FL-MINI; manufactured by Freund Corporation) to obtain 1097.0 g of the granulated product. 212.0 g of this granulated product was mixed with 128.6 g of crystalline cellulose, 11.8 g of hydroxypropylcellulose, 10.5 g of light anhydrous silicic acid, 35.0 g of croscarmellose sodium, and 2.3 g of magnesium stearate. Tablet granules were obtained. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the mass per tablet was 286 mg, whereby tablets were obtained.
実施例２
コンドロイチン硫酸ナトリウム ４８０．０ｇ
（５０％粒子径 ５８．６５μｍ）
（９０％粒子径 １１４．５μｍ）
マルトデキストリン １４４．０ｇ
結晶セルロース ３６３．３ｇ
ヒドロキシプロピルセルロース ６０．０ｇ
カルメロースカルシウム ５４．０ｇ
コンドロイチン硫酸ナトリウムを常法にて粉砕した後、上記成分を秤量、混合し、撹拌混合造粒装置（商品名：バーチカルグラニュレーター；パウレック社製）に投入、水／エタノール（３：２）混液を噴霧しながら造粒した。得られた造粒物を流動層造粒乾燥機（商品名：ＦＬ−ＭＩＮＩ；フロイント社製）にて乾燥した後、造粒物１１０１．３ｇを得た。この造粒物２７２．６ｇと、ヒドロキシプロピルセルロース１５．０ｇ、軽質無水ケイ酸１３．５ｇ、クロスカルメロースナトリウム４５．０ｇ、ステアリン酸マグネシウム３．０ｇと混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの質量２９０ｍｇとなるように製錠し、錠剤を得た。
Example 2
Sodium chondroitin sulfate 480.0g
(50% particle size 58.65 μm)
(90% particle size 114.5μm)
Maltodextrin 144.0g
Crystalline cellulose 363.3g
Hydroxypropylcellulose 60.0g
Carmellose calcium 54.0g
After pulverizing sodium chondroitin sulfate by a conventional method, the above components are weighed and mixed, and then added to a stirring and mixing granulator (trade name: Vertical Granulator; manufactured by POWREC), and a water / ethanol (3: 2) mixed solution is added. Granulated while spraying. The obtained granulated product was dried with a fluidized bed granulation dryer (trade name: FL-MINI; manufactured by Freund Corporation) to obtain 1101.3 g of the granulated product. This granulated product (272.6 g) was mixed with hydroxypropylcellulose (15.0 g), light anhydrous silicic acid (13.5 g), croscarmellose sodium (45.0 g) and magnesium stearate (3.0 g) to obtain granules for tableting. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the mass per tablet was 290 mg, whereby tablets were obtained.
実施例３
実施例２の造粒物３６３．５ｇ、結晶セルロース２２０．４ｇ、ヒドロキシプロピルセルロース２０．０ｇ、軽質無水ケイ酸１８．０ｇ、クロスカルメロースナトリウム６０．０ｇ、ステアリン酸マグネシウム４．０ｇと混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの質量２８６ｍｇとなるように製錠し、錠剤を得た。
Example 3
363.5 g of the granulated product of Example 2, 220.4 g of crystalline cellulose, 20.0 g of hydroxypropyl cellulose, 18.0 g of light anhydrous silicic acid, 60.0 g of croscarmellose sodium, 4.0 g of magnesium stearate, Granules for tableting were obtained. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the mass per tablet was 286 mg, whereby tablets were obtained.
実施例４
コンドロイチン硫酸ナトリウム ４８０．０ｇ
（５０％粒子径 １２８．２μｍ）
（９０％粒子径 １７８．０μｍ）
マルトデキストリン ２８８．０ｇ
結晶セルロース ２１５．０ｇ
ヒドロキシプロピルセルロース ６０．０ｇ
カルメロースカルシウム ５４．０ｇ
上記成分を秤量、混合し、撹拌混合造粒装置（商品名：バーチカルグラニュレーター；パウレック社製）に投入、水／エタノール（３：２）混液を噴霧しながら造粒した。得られた造粒物を流動層造粒乾燥機（商品名：ＦＬ−ＭＩＮＩ；フロイント社製）にて乾燥した後、造粒物１０９７．２ｇを得た。この造粒物２２７．２ｇと、結晶セルロース１３９．０ｇ、ヒドロキシプロピルセルロース１２．５ｇ、軽質無水ケイ酸１１．２５ｇ、クロスカルメロースナトリウム３７．５ｇ、ステアリン酸マグネシウム２．５ｇとを混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの重量２８７ｍｇとなるように製錠し、錠剤を得た。
Example 4
Sodium chondroitin sulfate 480.0g
(50% particle size 128.2 μm)
(90% particle size 178.0 μm)
Maltodextrin 288.0g
215.0 g of crystalline cellulose
Hydroxypropylcellulose 60.0g
Carmellose calcium 54.0g
The above components were weighed and mixed, put into a stirring and mixing granulator (trade name: Vertical Granulator; manufactured by POWREC), and granulated while spraying a water / ethanol (3: 2) mixture. After the obtained granulated product was dried with a fluidized bed granulator / dryer (trade name: FL-MINI; manufactured by Freund Corporation), 1097.2 g of the granulated product was obtained. 227.2 g of this granulated product was mixed with 139.0 g of crystalline cellulose, 12.5 g of hydroxypropyl cellulose, 11.25 g of light anhydrous silicic acid, 37.5 g of croscarmellose sodium, and 2.5 g of magnesium stearate. Tablet granules were obtained. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the weight per tablet was 287 mg, to obtain tablets.
実施例５
コンドロイチン硫酸ナトリウム ４８０．０ｇ
（５０％粒子径 ５３．２１μｍ）
（９０％粒子径 １８０．５μｍ）
マルトデキストリン ２８８．０ｇ
結晶セルロース ２１５．２ｇ
ヒドロキシプロピルセルロース ６０．０ｇ
カルメロースカルシウム ５４．０ｇ
コンドロイチン硫酸ナトリウムを常法にて粉砕した後、上記成分を秤量、混合し、撹拌混合造粒装置（商品名：バーチカルグラニュレーター；パウレック社製）に投入、水／エタノール（３：２）混液を噴霧しながら造粒した。得られた造粒物を流動層造粒乾燥機（商品名：ＦＬ−ＭＩＮＩ；フロイント社製）にて乾燥した後、造粒物１０９７．２ｇを得た。この造粒物２２７．２ｇと、結晶セルロース１５１．５ｇ、軽質無水ケイ酸１１．２５ｇ、クロスカルメロースナトリウム３７．５ｇ、ステアリン酸マグネシウム２．５ｇとを混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの重量２８７ｍｇとなるように製錠し、錠剤を得た。
Example 5
Sodium chondroitin sulfate 480.0g
(50% particle size 53.21 μm)
(90% particle size 180.5μm)
Maltodextrin 288.0g
215.2 g of crystalline cellulose
Hydroxypropylcellulose 60.0g
Carmellose calcium 54.0g
After pulverizing sodium chondroitin sulfate by a conventional method, the above components are weighed and mixed, and then added to a stirring and mixing granulator (trade name: Vertical Granulator; manufactured by POWREC), and a water / ethanol (3: 2) mixed solution is added. Granulated while spraying. After the obtained granulated product was dried with a fluidized bed granulator / dryer (trade name: FL-MINI; manufactured by Freund Corporation), 1097.2 g of the granulated product was obtained. 227.2 g of this granulated product was mixed with 151.5 g of crystalline cellulose, 11.25 g of light anhydrous silicic acid, 37.5 g of croscarmellose sodium, and 2.5 g of magnesium stearate to obtain granules for tableting. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the weight per tablet was 287 mg, to obtain tablets.
比較例１
コンドロイチン硫酸ナトリウム ５３３．３ｇ
（５０％粒子径 ８４．９８μｍ）
（９０％粒子径 ２５７．７μｍ）
結晶セルロース ５６８．９ｇ
ヒドロキシプロピルセルロース ６６．７ｇ
カルメロースカルシウム ６０．０ｇ
上記成分を秤量後、混合し、撹拌混合造粒装置（商品名：バーチカルグラニュレーター；パウレック社製）に投入、水／エタノール（３：２）混液を噴霧しながら造粒した。得られた造粒物を流動層造粒乾燥機（商品名：ＦＬ−ＭＩＮＩ；フロイント社製）にて乾燥した後、造粒物１２２８．９ｇを得た。この造粒物３６３．６ｇと、軽質無水ケイ酸１０．８ｇ、クロスカルメロースナトリウム３６．０ｇ、ステアリン酸マグネシウム１．２ｇとを混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの質量３４３ｍｇとなるように製錠し、錠剤を得た。
Comparative Example 1
Chondroitin sulfate sodium 533.3g
(50% particle size 84.98 μm)
(90% particle size 257.7 μm)
Crystalline cellulose 568.9g
Hydroxypropylcellulose 66.7g
Carmellose calcium 60.0g
The above components were weighed and mixed, and put into a stirring and mixing granulator (trade name: Vertical Granulator; manufactured by POWREC), and granulated while spraying a water / ethanol (3: 2) mixture. After the obtained granulated product was dried with a fluidized bed granulator / dryer (trade name: FL-MINI; manufactured by Freund Corporation), 1228.9 g of the granulated product was obtained. 363.6 g of this granulated product was mixed with 10.8 g of light anhydrous silicic acid, 36.0 g of croscarmellose sodium, and 1.2 g of magnesium stearate to obtain granules for tableting. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the mass per tablet was 343 mg, whereby tablets were obtained.
比較例２
コンドロイチン硫酸ナトリウム ５３３．３ｇ
（５０％粒子径 ５８．６５μｍ）
（９０％粒子径 １１４．５μｍ）
結晶セルロース ５６８．９ｇ
ヒドロキシプロピルセルロース ６６．７ｇ
カルメロースカルシウム ６０．０ｇ
コンドロイチン硫酸ナトリウムを常法にて粉砕した後、上記成分を秤量後、混合し、撹拌混合造粒装置（商品名：バーチカルグラニュレーター；パウレック社製）に投入、水／エタノール（３：２）混液を噴霧しながら造粒した。得られた造粒物を流動層造粒乾燥機（商品名：ＦＬ−ＭＩＮＩ；フロイント社製）にて乾燥した後、造粒物１１０６．０ｇを得た。この造粒物３６３．６ｇと、軽質無水ケイ酸１０．８ｇ、クロスカルメロースナトリウム３６．０ｇ、ステアリン酸マグネシウム１．２ｇとを混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの質量３４３ｍｇとなるように製錠し、錠剤を得た。
Comparative Example 2
Chondroitin sulfate sodium 533.3g
(50% particle size 58.65 μm)
(90% particle size 114.5μm)
Crystalline cellulose 568.9g
Hydroxypropylcellulose 66.7g
Carmellose calcium 60.0g
After pulverizing sodium chondroitin sulfate by a conventional method, the above components are weighed and mixed, and then added to a stirring and mixing granulator (trade name: Vertical Granulator; manufactured by POWREC), water / ethanol (3: 2) mixed solution Granulated while spraying. After the obtained granulated product was dried with a fluidized bed granulator / dryer (trade name: FL-MINI; manufactured by Freund Corporation), 1106.0 g of the granulated product was obtained. 363.6 g of this granulated product was mixed with 10.8 g of light anhydrous silicic acid, 36.0 g of croscarmellose sodium, and 1.2 g of magnesium stearate to obtain granules for tableting. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the mass per tablet was 343 mg, whereby tablets were obtained.
比較例３
比較例２の造粒物１９７．５ｇとヒドロキシプロピルセルロース９．６ｇ、結晶セルロース１０６．８ｇ、軽質無水ケイ酸１１．５ｇ、クロスカルメロースナトリウム３．５ｇ、ステアリン酸マグネシウム０．４ｇとを混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの質量３４３ｍｇとなるように製錠し、錠剤を得た。
Comparative Example 3
197.5 g of the granulated product of Comparative Example 2 was mixed with 9.6 g of hydroxypropyl cellulose, 106.8 g of crystalline cellulose, 11.5 g of light anhydrous silicic acid, 3.5 g of croscarmellose sodium, and 0.4 g of magnesium stearate. Granules for tableting were obtained. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the mass per tablet was 343 mg, whereby tablets were obtained.
比較例４
コンドロイチン硫酸ナトリウム ４８０．０ｇ
（５０％粒子径 ５３．２１μｍ）
（９０％粒子径 １８０．５μｍ）
マルトデキストリン １４．４ｇ
結晶セルロース ４９７．４ｇ
ヒドロキシプロピルセルロース ６０．０ｇ
カルメロースカルシウム ５４．０ｇ
コンドロイチン硫酸ナトリウムを常法にて粉砕した後、上記成分を秤量後、混合し、撹拌混合造粒装置（商品名：バーチカルグラニュレーター；パウレック社製）に投入、水／エタノール（３：２）混液を噴霧しながら造粒した。得られた造粒物を流動層造粒乾燥機（商品名：ＦＬ−ＭＩＮＩ；フロイント社製）にて乾燥した後、造粒物１０９０．０ｇを得た。この造粒物２２７．５ｇと、結晶セルロース１３９．０ｇ、ヒドロキシプロピルセルロース１２．５ｇ、軽質無水ケイ酸１１．２ｇ、クロスカルメロースナトリウム３７．６ｇ、ステアリン酸マグネシウム２．５ｇとを混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの質量２８７ｍｇとなるように製錠し、錠剤を得た。
Comparative Example 4
Sodium chondroitin sulfate 480.0g
(50% particle size 53.21 μm)
(90% particle size 180.5μm)
Maltodextrin 14.4g
497.4 g of crystalline cellulose
Hydroxypropylcellulose 60.0g
Carmellose calcium 54.0g
After pulverizing sodium chondroitin sulfate by a conventional method, the above components are weighed and mixed, and then added to a stirring and mixing granulator (trade name: Vertical Granulator; manufactured by POWREC), water / ethanol (3: 2) mixed solution Granulated while spraying. The obtained granulated product was dried with a fluidized bed granulation dryer (trade name: FL-MINI; manufactured by Freund Corporation), and 1090.0 g of the granulated product was obtained. 227.5 g of this granulated product was mixed with 139.0 g of crystalline cellulose, 12.5 g of hydroxypropyl cellulose, 11.2 g of light anhydrous silicic acid, 37.6 g of croscarmellose sodium, and 2.5 g of magnesium stearate. Tablet granules were obtained. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the mass per tablet was 287 mg, to obtain tablets.
比較例５
コンドロイチン硫酸ナトリウム ４８０．０ｇ
（５０％粒子径 ５３．２１μｍ）
（９０％粒子径 １８０．５μｍ）
マルトデキストリン ４９６．８ｇ
ヒドロキシプロピルセルロース ６０．１ｇ
カルメロースカルシウム ５４．０ｇ
コンドロイチン硫酸ナトリウムを常法にて粉砕した後、上記成分を秤量後、混合し、撹拌混合造粒装置（商品名：バーチカルグラニュレーター；パウレック社製）に投入、水／エタノール（３：２）混液を噴霧しながら造粒した。得られた造粒物を流動層造粒乾燥機（商品名：ＦＬ−ＭＩＮＩ；フロイント社製）にて乾燥した後、造粒物１０７０．３ｇを得た。この造粒物２２７．５ｇと、結晶セルロース１３９．０ｇ、ヒドロキシプロピルセルロース１２．５ｇ、軽質無水ケイ酸１１．２ｇ、クロスカルメロースナトリウム３７．６ｇ、ステアリン酸マグネシウム２．５ｇとを混合し、打錠用顆粒を得た。得られた打錠用顆粒をロータリー式打錠機で直径９．０ｍｍ、１錠当たりの質量２８７ｍｇとなるように製錠し、錠剤を得た。
Comparative Example 5
Sodium chondroitin sulfate 480.0g
(50% particle size 53.21 μm)
(90% particle size 180.5μm)
496.8 g of maltodextrin
Hydroxypropylcellulose 60.1g
Carmellose calcium 54.0g
After pulverizing sodium chondroitin sulfate by a conventional method, the above components are weighed and mixed, and then added to a stirring and mixing granulator (trade name: Vertical Granulator; manufactured by POWREC), water / ethanol (3: 2) mixed solution Granulated while spraying. The obtained granulated product was dried with a fluidized bed granulation dryer (trade name: FL-MINI; manufactured by Freund Corporation) to obtain 1070.3 g of the granulated product. 227.5 g of this granulated product was mixed with 139.0 g of crystalline cellulose, 12.5 g of hydroxypropyl cellulose, 11.2 g of light anhydrous silicic acid, 37.6 g of croscarmellose sodium, and 2.5 g of magnesium stearate. Tablet granules were obtained. The obtained granules for tableting were tableted with a rotary tableting machine so that the diameter was 9.0 mm and the mass per tablet was 287 mg, to obtain tablets.
実施例１〜５及び比較例１〜５の処方を表１に示す。 Table 1 shows formulations of Examples 1 to 5 and Comparative Examples 1 to 5.
試験例１
（１）方法
実施例１〜５及び比較例１〜５で製造した錠剤２０錠を、２５℃、６０％ＲＨの条件下で５時間吸湿した。それぞれの割れた錠数及び錠剤硬度，錠剤の質量偏差を計測した。結果を表２に示す。
Test example 1
(1) Method The 20 tablets produced in Examples 1 to 5 and Comparative Examples 1 to 5 were moisture-absorbed for 5 hours under the conditions of 25 ° C. and 60% RH. The number of broken tablets, tablet hardness, and tablet mass deviation were measured. The results are shown in Table 2.
（２）結果
表２より、マルトデキストリンを含有しない比較例１〜３及びマルトデキストリンの含有量が少ない比較例４の錠剤では、吸湿時にひび割れが発生した。また、マルトデキストリンの含有量が多い比較例５の錠剤は、ひび割れの発生こそないが、質量偏差が２％を超え、商品性が低いことが確認された。
一方、実施例１〜５の錠剤は、吸湿時のひび割れも確認されず、高湿度化においても安定に錠剤の形状を保つことができた。
(2) Results From Table 2, in the tablets of Comparative Examples 1 to 3 containing no maltodextrin and Comparative Example 4 having a low content of maltodextrin, cracks occurred during moisture absorption. Moreover, although the tablet of the comparative example 5 with much content of maltodextrin did not generate | occur | produce a crack, mass deviation exceeded 2% and it was confirmed that merchantability is low.
On the other hand, in the tablets of Examples 1 to 5, no cracks were observed during moisture absorption, and the tablet shape could be stably maintained even at high humidity.
本発明により、ひび割れを抑制し、コンドロイチン硫酸ナトリウムの含量均一性を確保した、商品性の高いコンドロイチン硫酸ナトリウム含有錠剤の提供が可能となった。 According to the present invention, it has become possible to provide a tablet containing sodium chondroitin sulfate having high commercial properties, in which cracking is suppressed and content uniformity of sodium chondroitin sulfate is ensured.
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| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
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| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |