JP5041774B2 - Sustained-release tablets containing mesalazine as an active ingredient - Google Patents
Sustained-release tablets containing mesalazine as an active ingredient Download PDFInfo
- Publication number
- JP5041774B2 JP5041774B2 JP2006257683A JP2006257683A JP5041774B2 JP 5041774 B2 JP5041774 B2 JP 5041774B2 JP 2006257683 A JP2006257683 A JP 2006257683A JP 2006257683 A JP2006257683 A JP 2006257683A JP 5041774 B2 JP5041774 B2 JP 5041774B2
- Authority
- JP
- Japan
- Prior art keywords
- sustained
- tablet
- release
- release tablet
- mesalazine
- 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.)
- Active
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- 229960004963 mesalazine Drugs 0.000 title claims description 21
- 239000004480 active ingredient Substances 0.000 title description 10
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- 238000013268 sustained release Methods 0.000 claims description 23
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Images
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明はメサラジンを有効成分として含有する徐放性錠剤に関する。 The present invention relates to a sustained-release tablet containing mesalazine as an active ingredient.
メサラジン（ｍｅｓａｌａｚｉｎｅ ５−アミノサリチル酸）は、潰瘍性大腸炎、クローン病治療剤として広く使用されている。
その剤型としては、錠剤と注腸剤が知られている。
ところで、従来メサラジンの錠剤は１錠中の主薬含量が２５０ｍｇと多いことから、比較的大きな錠剤で、患者にとって服用しづらくコンプライアンスの向上が望まれていた。（特許文献１）
最近、患者に服用しやすい小型のメサラジン徐放性錠剤が提供されるようになった。（特許文献２）
特許文献２に記載のメサラジン徐放性錠剤では、錠剤硬度と良好な徐放性を得るため二酸化ケイ素等の帯電防止剤を必須成分として含有している。
Mesalazine (mesalazine 5-aminosalicylic acid) is widely used as a therapeutic agent for ulcerative colitis and Crohn's disease.
As its dosage form, tablets and enemas are known.
By the way, the conventional mesalazine tablet has a large active ingredient content of 250 mg in one tablet. Therefore, it is a comparatively large tablet, and it is difficult for patients to take it. (Patent Document 1)
Recently, small mesalazine sustained-release tablets that are easy to take for patients have been provided. (Patent Document 2)
The mesalazine sustained release tablet described in Patent Document 2 contains an antistatic agent such as silicon dioxide as an essential component in order to obtain tablet hardness and good sustained release.
本発明の目的は、帯電防止剤を含有しないにもかかわらず、製造、輸送、保管に耐えられる錠剤硬度を有し、しかも良好な徐放性を併せ持つメサラジンの徐放性錠剤を提供することにある。 An object of the present invention is to provide a sustained release tablet of mesalazine that has a tablet hardness that can withstand manufacture, transportation, and storage, and that has a good sustained release property, even though it does not contain an antistatic agent. is there.
即ち、本発明は、次の（ａ）〜（ｄ）を含有し、１錠中の有効成分の含有量が６０％以上である徐放性錠剤に関する。
（ａ）有効成分及び結合剤を含有する粒子を徐放性基剤でコーティングしてなる顆粒
（ｂ）結晶セルロース
（ｃ）乾燥水酸化アルミニウムゲル又は酸化マグネシウム
（ｄ）滑沢剤
That is, the present invention relates to a sustained release tablet containing the following (a) to (d), wherein the content of the active ingredient in one tablet is 60% or more.
(A) Granules formed by coating particles containing an active ingredient and a binder with a sustained-release base (b) crystalline cellulose (c) dry aluminum hydroxide gel or magnesium oxide (d) lubricant
次に本発明を更に詳細に説明する。
本発明の徐放性錠剤において、有効成分としてはアルジオキサ、アルプリノール、塩酸エピナスチン、塩酸ジルチアゼム、塩酸タムスロシン、塩酸トルペリゾン、塩酸ピレンゼピン、オキサトミド、ザルトプロフェン、ジクロフェナクナトリウム、シンバスタチン、ドンペリドン、ニフェジピン、ファモチジン、フェンプロバメート、プラバスタチンナトリウム、インドメタシン、スピロノラクトン、イブプロフェン、フロセミド、スルファダイアジン、スルファアメラジン、プロゲステロン、レセルビン、ビルビニウムエンボナート、モフェブタゾン、ヒドロクロロチアジット、テトラサイクリン、トルブタミド、アセトアミノフェン、テストステロン、エストラジオール、アセタゾールアミド、エリスロマイシン、鉄塩、ヒドララジン、キニジン、ジゴキシン、メチルドーパ、モルヒネ、ナブロキセン、アミロライド、アセチルサリチル酸、塩酸ペラパミル、ニカルジピン、テオフィリン、トリメトキオール、カルシトニン、５−アミノサリチル酸、ベクロメタソンジプロピオネート、プレドニゾロン、フルチカソン、ウルソジオール、エストラジオール、メチロシン、ジプロピオン酸ベクロメタゾン、ベタメタゾン、ヒドロコルチゾン、デキサメタゾン、吉草酸ベタメタゾン等が挙げられ、好ましくはメサラジンが挙げられる。
Next, the present invention will be described in more detail.
In the sustained-release tablet of the present invention, the active ingredients are aldioxa, alpurinol, epinastine hydrochloride, diltiazem hydrochloride, tamsulosin hydrochloride, tolperisone hydrochloride, pirenzepine hydrochloride, oxatomide, zaltoprofen, diclofenac sodium, simvastatin, domperidone, nifedipine, famotidine, fen Provamate, pravastatin sodium, indomethacin, spironolactone, ibuprofen, furosemide, sulfadiazine, sulfaamelazine, progesterone, reservin, birubinium embonate, mofebutazone, hydrochlorothiagit, tetracycline, tolbutamide, acetaminophen, testosterone, estradiol , Acetazolamide, erythromycin, iron salt, hydralazine, Nidin, digoxin, methyldopa, morphine, nabroxen, amiloride, acetylsalicylic acid, perapamil hydrochloride, nicardipine, theophylline, trimethyol, calcitonin, 5-aminosalicylic acid, beclomethasone dipropionate, prednisolone, fluticasone, ursodiol, estradiol, Metyrosine, beclomethasone dipropionate, betamethasone, hydrocortisone, dexamethasone, betamethasone valerate and the like are preferable, and mesalazine is preferable.
本発明の徐放性錠剤において、上記（ａ）中の結合剤としては、アルギン酸ナトリウム、アルファー化デンプン、エチルセルロース、ゼラチン、寒天、デキストリン、ヒドロキシエチルセルロース、ヒドロキシエチルメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポビドン、ポリビニルアルコール、メチルセルロース等が挙げられ、好ましくはポビドンが挙げられる。
本発明の徐放性錠剤において、上記（ａ）中の徐放性基剤としては、エチルセルロース、アミノアクリルメタクリレート、メタクリル酸コポリマー、ヒドロキシプロピルメチルセルロースアセテートサクシネート、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、セルロースアセテートフタレート等が挙げられ、好ましくはエチルセルロースが挙げられる。
In the sustained-release tablet of the present invention, the binder in the above (a) includes sodium alginate, pregelatinized starch, ethylcellulose, gelatin, agar, dextrin, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, Povidone, polyvinyl alcohol, methylcellulose and the like can be mentioned, and povidone is preferred.
In the sustained-release tablet of the present invention, the sustained-release base in the above (a) includes ethyl cellulose, aminoacryl methacrylate, methacrylic acid copolymer, hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, hydroxyethylcellulose, hydroxypropyl Examples thereof include cellulose and cellulose acetate phthalate, and preferably ethyl cellulose is used.
本発明の徐放性錠剤において、上記（ｄ）の滑沢剤としては、グリセリン脂肪酸エステル、硬化油、ショ糖脂肪酸エステル、ステアリルアルコール、ステアリン酸、ステアリン酸マグネシウム、ステアリン酸カルシウム、タルク、沈降炭酸カルシウム、フマル酸、フマル酸ステアリルナトリウム、マクロゴール、モノステアリン酸グリセリン等が挙げられ、好ましくはタルク、ステアリン酸マグネシウムが挙げられる。
本発明の徐放性錠剤においては、上記（ａ）〜（ｄ）の他、崩壊剤を含有しても良く、かかる崩壊剤としては、アルファー化デンプン、カルボキシメチルスターチナトリウム、カルメロース、カルメロースカルシウム、カルメロースナトリウム、クロスカルメロースナトリウム、クロスポビドン、結晶セルロース、低置換度ヒドロキシプロピルセルロース、トウモロコシデンプン、ヒドロキシプロピルスターチ、部分アルファー化デンプン、リン酸カルシウム等が挙げられ、好ましくはカルメロース、カルメロースカルシウムが挙げられる。
In the sustained-release tablet of the present invention, the lubricant of (d) includes glycerin fatty acid ester, hydrogenated oil, sucrose fatty acid ester, stearyl alcohol, stearic acid, magnesium stearate, calcium stearate, talc, precipitated calcium carbonate. , Fumaric acid, sodium stearyl fumarate, macrogol, glyceryl monostearate and the like, preferably talc and magnesium stearate.
The sustained-release tablet of the present invention may contain a disintegrating agent in addition to the above (a) to (d), such as pregelatinized starch, carboxymethyl starch sodium, carmellose, carmellose calcium. , Carmellose sodium, croscarmellose sodium, crospovidone, crystalline cellulose, low-substituted hydroxypropyl cellulose, corn starch, hydroxypropyl starch, partially pregelatinized starch, calcium phosphate and the like, preferably carmellose and carmellose calcium It is done.
さらには、本発明の徐放性錠剤において、上記（ａ）〜（ｄ）並びに、前記の崩壊剤の他、賦形剤を（ａ）の顆粒内、又は顆粒外に含有していても良く、かかる賦形剤としては、低置換度ヒドロキシプロピルセルロース、トウモロコシデンプン、バレイショデンプン、コムギデンプン、乳糖、白糖、部分アルファー化デンプン、D-マンニトール、リン酸カルシウム、乳酸カレウシウム、グルコース等が挙げられる。
また、本発明の徐放性錠剤において、上記（ａ）の顆粒のコーティングの際、コーティング剤として、メチルセルロース、ポビドン、ポリビニルアルコール、セラック硬化油、酸化チタン、水酸化アルミニウムゲル、ステアリン酸、ステアリン酸マグネシウム、タルク等を有していても良く、可塑剤として、クエン酸トリエチル、グリセリン、ヒマシ油、ポロキシエチレン硬化ヒマシ油、ポリソルベート８０、マクロゴール、ラウロマクロゴール、トリアセチン等を有していても良い。
また、本発明の徐放性錠剤において、結合剤は、上記（ａ）中の他、顆粒外においても含有していても良く、一方、崩壊剤は、上記（ａ）中に含有していても良い。
Furthermore, in the sustained-release tablet of the present invention, in addition to the above-mentioned (a) to (d) and the disintegrant, an excipient may be contained in the granule of (a) or outside the granule. Such excipients include low-substituted hydroxypropylcellulose, corn starch, potato starch, wheat starch, lactose, sucrose, partially pregelatinized starch, D-mannitol, calcium phosphate, calebium lactate, glucose and the like.
Further, in the sustained release tablet of the present invention, when coating the granules of (a) above, as a coating agent, methylcellulose, povidone, polyvinyl alcohol, shellac hydrogenated oil, titanium oxide, aluminum hydroxide gel, stearic acid, stearic acid Magnesium, talc, etc. may be included, and plasticizers may include triethyl citrate, glycerin, castor oil, polyoxyethylene hydrogenated castor oil,
In the sustained-release tablet of the present invention, the binder may be contained outside the granule in addition to (a) above, while the disintegrant is contained in (a) above. Also good.
次に本発明の徐放性錠剤の好ましい例を挙げる。
（１）上記（ａ）の有効成分が、メサラジンである上記（ａ）〜（ｄ）を含有する徐放性錠剤。
（２）（ａ）の結合剤がポビドンである上記（ａ）〜（ｄ）を含有する徐放性錠剤、又は上記（１）記載の徐放性錠剤。
（３）（ａ）の徐放性基剤がエチルセルロースである上記（ａ）〜（ｄ）を含有する徐放性錠剤、又は上記（１）若しくは（２）記載の徐放性錠剤。
（４）（ｄ）の滑沢剤がタルク、ステアリン酸マグネシウムである上記（ａ）〜（ｄ）を含有する徐放性錠剤、又は上記（１）〜（３）記載の徐放性錠剤。
（５）上記（ａ）〜（ｄ）の他、崩壊剤を含有する上記（ａ）〜（ｄ）を含有する徐放性錠剤、又は上記（１）〜（４）記載の徐放性錠剤。
（６）崩壊剤がカルメロース又はカルメロースカルシウムから選ばれる上記（５）記載の徐放性錠剤。
（７）錠剤硬度が５０Ｎ以上である上記（ａ）〜（ｄ）を含有する徐放性錠剤、又は上記（１）〜（６）記載の徐放性錠剤。
Next, the preferable example of the sustained release tablet of this invention is given.
(1) The sustained release tablet containing the above (a) to (d), wherein the active ingredient (a) is mesalazine.
(2) The sustained release tablet containing the above (a) to (d), wherein the binder of (a) is povidone, or the sustained release tablet according to (1) above.
(3) The sustained release tablet containing the above (a) to (d), wherein the sustained release base of (a) is ethyl cellulose, or the sustained release tablet according to (1) or (2) above.
(4) The sustained-release tablet containing the above (a) to (d), wherein the lubricant of (d) is talc or magnesium stearate, or the sustained-release tablet of (1) to (3) above.
(5) In addition to the above (a) to (d), a sustained release tablet containing the above (a) to (d) containing a disintegrant, or a sustained release tablet according to the above (1) to (4) .
(6) The sustained release tablet according to the above (5), wherein the disintegrant is selected from carmellose or carmellose calcium.
(7) The sustained release tablet containing the above (a) to (d) having a tablet hardness of 50 N or more, or the sustained release tablet according to the above (1) to (6).
本発明の徐放性錠剤は例えば以下に示す方法で製造することができる。
（１）徐放性顆粒（ａ）の製造
有効成分（たとえばメサラジン）に、結合剤（たとえばポビドン）水溶液を加え湿式練合し、押し出し造粒してできた顆粒を整粒後、乾燥、篩過して素顆粒を得る。
ここで、得られた素顆粒に、エタノールと精製水の混液により、徐放性基剤（たとえばエチルセルロース）溶液を調整し、流動層造粒機によりフィルムコーティングおよび乾燥をおこない、徐放性顆粒を得る。
（２）徐放性錠剤の製造
上記（１）で得られた徐放性顆粒に結晶セルロース、乾燥水酸化アルミニウムゲル又は酸化マグネシウム及び滑沢剤、所望により崩壊剤を加え、均一に混合し錠剤を得る。
The sustained-release tablet of the present invention can be produced, for example, by the method shown below.
(1) Production of sustained-release granules (a) After sizing granules formed by extruding and granulating the active ingredient (e.g. mesalazine) by adding a binder (e.g. povidone) aqueous solution and wet kneading. Dry and sieve to obtain elementary granules.
Here, to the obtained elementary granule, a sustained release base (for example, ethyl cellulose) solution is prepared with a mixture of ethanol and purified water, and film coating and drying are performed with a fluidized bed granulator to obtain a sustained release granule. obtain.
(2) Manufacture of sustained-release tablets To the sustained-release granules obtained in (1) above, crystalline cellulose, dry aluminum hydroxide gel or magnesium oxide and a lubricant, and optionally a disintegrant are added, and uniform To obtain a tablet.
本発明の徐放性錠剤の質量は２８０ｍｇ〜４００ｍｇ、好ましくは３００ｍｇ〜３８０ｍｇである。
本発明の徐放性錠剤の直径は８〜１０ｍｍ、より好ましくは８．８〜９．５ｍｍである。
本発明の徐放性錠剤の錠厚は４．５〜５．３ｍｍ、より好ましくは４．７〜５．２ｍｍである。
本発明の徐放性錠剤の錠剤硬度は５０〜９０Ｎが好ましい。
また上記の（ａ）〜（ｄ）の１錠中の含有比率（質量比）は以下の範囲が好ましい。
（ａ）：（ｂ）：（ｃ）：（ｄ）＝１：０．３５〜０．５０：０．００２〜０．０１５：０．０１〜０．０６
崩壊剤を更に追加する場合、崩壊剤は（ａ）を１とした場合の質量比は、０．００１５〜０．０１の範囲が好ましい。
なお、（ａ）の徐放性顆粒中の有効成分含量は２００〜２７５ｍｇが好ましい。
（ａ）中の結合剤及び徐放性基剤の含量は、有効成分を１とした場合の質量比は、それぞれ０．１５０〜０．０３５，０．００８〜０．０３０の範囲が好ましい。
The mass of the sustained release tablet of the present invention is 280 mg to 400 mg, preferably 300 mg to 380 mg.
The sustained-release tablet of the present invention has a diameter of 8 to 10 mm, more preferably 8.8 to 9.5 mm.
The tablet thickness of the sustained-release tablet of the present invention is 4.5 to 5.3 mm, more preferably 4.7 to 5.2 mm.
The tablet hardness of the sustained release tablet of the present invention is preferably 50 to 90N.
Moreover, the following ranges are preferable for the content ratio (mass ratio) in one tablet of said (a)-(d).
(A) :( b) :( c) :( d) = 1: 0.35-0.50: 0.002-0.015: 0.01-0.06
When the disintegrant is further added, the disintegrant preferably has a mass ratio of 0.0015 to 0.01 when (a) is 1.
In addition, as for the active ingredient content in the sustained release granule of (a), 200-275 mg is preferable.
As for the content of the binder and the sustained release base in (a), the mass ratio when the active ingredient is 1 is preferably in the range of 0.150 to 0.035 and 0.008 to 0.030, respectively.
本発明の徐放性錠剤であるメサラジン錠を潰瘍性大腸炎の治療に使用する場合は、通常、成人にはメサラジンとして１日１５００ｍｇ（本剤６錠）を３回に分けて食後経口投与する。なお、年齢、症状により適宜増減するが、１日２２５０ｍｇ（本剤９錠）を上限とする。
一方、クローン病の治療に使用する場合は、通常、成人にはメサラジンとして１日１５００〜３０００ｍｇ（本剤６〜１２錠）を３回に分けて食後経口投与する。なお、年齢、症状により適宜増減する。
When the mesalazine tablet, which is a sustained-release tablet of the present invention, is used for the treatment of ulcerative colitis, usually for adults, 1500 mg of mesalazine (6 tablets of this drug) is orally administered in three divided doses after meals. . The dose may be adjusted according to age and symptoms, but the upper limit is 2250 mg (9 tablets of this drug) per day.
On the other hand, when used for the treatment of Crohn's disease, usually, for adults, 1500 to 3000 mg (6 to 12 tablets of this drug) per day as mesalazine is orally administered in three divided doses. The dosage may be adjusted according to age and symptoms.
本発明の徐放性錠剤は、二酸化ケイ素等の帯電防止剤を含有しないにもかかわらず、製造、輸送、保管に耐えられる錠剤硬度を有し（図１参照）、しかも良好な徐放性を有する（図２参照）。
次に、実施例、比較例を挙げ、本発明を更に詳細に説明するが、本発明はこれらに限定されるものではない。
The sustained-release tablet of the present invention has a tablet hardness that can withstand production, transportation, and storage even though it does not contain an antistatic agent such as silicon dioxide (see FIG. 1), and has a good sustained-release property. (See FIG. 2).
EXAMPLES Next, although an Example and a comparative example are given and this invention is demonstrated further in detail, this invention is not limited to these.
（錠剤の評価）
錠剤の評価には以下に示す測定機器及び評価方法を使用した。
（１）錠剤硬度の測定
測定機器：
木屋式デジタル硬度計（ＫＨＴ−２０Ｎ型）（株式会社藤原製作所）
測定方法：
任意に選択した錠剤１０錠の直径方向における錠剤硬度を測定し、測定された値から平均値を算出した。
（２）溶出試験
測定機器：
溶出試験機（ＮＴＲ−６１００Ａ）（富山産業株式会社）
測定方法：
第１４改正日本薬局方中の溶出試験法第２法（パドル法）に従って試験を行った。
試験液はｐＨ７．５のリン酸緩衝液を用い、回転数は５０ｒｐｍとした。
測定波長は３００ｎｍとし、経時的にサンプリングを行い、吸光度を測定した。
(Tablet evaluation)
For the evaluation of tablets, the following measuring instruments and evaluation methods were used.
(1) Measurement device for tablet hardness:
Kiyama digital hardness tester (KHT-20N type) (Fujiwara Seisakusho Co., Ltd.)
Measuring method:
The tablet hardness in the diameter direction of 10 arbitrarily selected tablets was measured, and an average value was calculated from the measured values.
(2) Dissolution test measuring instrument:
Dissolution tester (NTR-6100A) (Toyama Sangyo Co., Ltd.)
Measuring method:
The test was conducted in accordance with the dissolution test method No. 2 (paddle method) in the 14th revised Japanese Pharmacopoeia.
The test solution was a phosphate buffer solution with pH 7.5, and the rotation speed was 50 rpm.
The measurement wavelength was 300 nm, sampling was performed over time, and the absorbance was measured.
（調製例１）
（徐放性顆粒の製造）
メサラジン１５０００ｇに、６％ポビドン水溶液を加え湿式練合し、押し出し造粒してできた顆粒を整粒後、乾燥、篩過（１０〜３０号）して素顆粒を得た。
得られた素顆粒４５００ｇに、エタノール：精製水＝８：２の混液により、３％エチルセルロース溶液１４７１ｇを調整し、流動層造粒機によりフィルムコーティングおよび乾燥をおこない、徐放性顆粒を得た。
得られた徐放性顆粒の組成は以下の通りである。
メサラジン ：９７．１重量％
ポピドン ： １．９重量％
エチルセルロース ： １．０重量％
(Preparation Example 1)
(Manufacture of sustained release granules)
A 6% povidone aqueous solution was added to 15000 g of mesalazine, wet-kneaded, and the granules formed by extrusion granulation were sized, dried and sieved (No. 10-30) to obtain elementary granules.
To 4500 g of the obtained elementary granules, 1471 g of a 3% ethylcellulose solution was prepared with a mixed solution of ethanol: purified water = 8: 2, and film coating and drying were performed with a fluid bed granulator to obtain sustained-release granules.
The composition of the obtained sustained release granules is as follows.
Mesalazine: 97.1% by weight
Popidone: 1.9% by weight
Ethyl cellulose: 1.0% by weight
（比較例１）
調製例１で得られた徐放性顆粒２１５．９ｇに結晶セルロース８１．９ｇ及びステアリン酸マグネシウム２．１ｇを均一に混合し、１錠重量３２０ｍｇ、直径９．０ｍｍφ、６００ｋｇの圧力で錠厚４．７ｍｍに圧縮成形した錠剤を得た。
（実施例１）
(Comparative Example 1)
215.9 g of sustained-release granules obtained in Preparation Example 1 were mixed uniformly with 81.9 g of crystalline cellulose and 2.1 g of magnesium stearate, and the tablet thickness was 4 with a tablet weight of 320 mg, a diameter of 9.0 mmφ, and a pressure of 600 kg. A tablet compressed to 7 mm was obtained.
Example 1
調製例１で得られた徐放性顆粒２１５．９ｇに結晶セルロース８１．２ｇ、乾燥水酸化アルミニウムゲル０．７ｇ及びステアリン酸マグネシウム２．１ｇを均一に混合し、１錠重量３２０ｍｇ、直径９．０ｍｍφ、６００ｋｇの圧力で錠厚４．７ｍｍに圧縮成形した錠剤を得た。
（実施例２）
215.9 g of sustained-release granules obtained in Preparation Example 1 were uniformly mixed with 81.2 g of crystalline cellulose, 0.7 g of dry aluminum hydroxide gel and 2.1 g of magnesium stearate, and each tablet weight was 320 mg and the diameter was 9. Tablets that were compression-molded to a tablet thickness of 4.7 mm at a pressure of 0 mmφ and 600 kg were obtained.
(Example 2)
調製例１で得られた徐放性顆粒２１５．９ｇに結晶セルロース８１．２ｇ、酸化マグネシウム０．７ｇ及びステアリン酸マグネシウム２．１ｇを均一に混合し、１錠重量３２０ｍｇ、直径９．０ｍｍφ、６００ｋｇの圧力で錠厚４．７ｍｍに圧縮成形した錠剤を得た。 215.9 g of sustained-release granules obtained in Preparation Example 1 were uniformly mixed with 81.2 g of crystalline cellulose, 0.7 g of magnesium oxide and 2.1 g of magnesium stearate, and each tablet weight 320 mg, diameter 9.0 mmφ, 600 kg A tablet compressed to a tablet thickness of 4.7 mm with a pressure of was obtained.
（比較実験１）
（試験方法）
比較例１並びに実施例１及び２で得られた錠剤について、各々ランダムにサンプリングした錠剤１０錠について、直径方向における錠剤硬度を測定し、その平均値を算出し、その結果を表１に示す。
（試験結果）
(Comparative Experiment 1)
(Test method)
For the tablets obtained in Comparative Example 1 and Examples 1 and 2, the tablet hardness in the diameter direction was measured for 10 tablets sampled at random, the average value was calculated, and the results are shown in Table 1.
(Test results)
表１から乾燥水酸化アルミニウムゲルまたは酸化マグネシウムを含有する実施例１及び２の錠剤は、含有しない比較例１の錠剤と比較して、圧縮成形条件が同等であるにもかかわらず、優れた錠剤硬度を有することが明らかになった。
（比較例２及び実施例３〜５）
From Table 1, the tablets of Examples 1 and 2 containing dry aluminum hydroxide gel or magnesium oxide are excellent tablets, although the compression molding conditions are equivalent as compared to the tablets of Comparative Example 1 not containing It was found to have hardness.
(Comparative Example 2 and Examples 3-5)
調製例１で得られた徐放性顆粒、結晶セルロース及び乾燥水酸化アルミニウムゲル、ステアリン酸マグネシウムを表２に示す量で均一に混合した。
次にロータリー打錠機により、４００ｋｇ、６００ｋｇ、８００ｋｇ、１０００ｋｇ、１２００ｋｇ、１４００ｋｇの圧力で圧縮成形し、１錠重量３２０ｍｇ、直径９．０ｍｍφの錠剤を得た。
The sustained release granules, crystalline cellulose, dried aluminum hydroxide gel and magnesium stearate obtained in Preparation Example 1 were uniformly mixed in the amounts shown in Table 2.
Next, the mixture was compression-molded with a rotary tableting machine under the pressures of 400 kg, 600 kg, 800 kg, 1000 kg, 1200 kg, and 1400 kg to obtain tablets having a tablet weight of 320 mg and a diameter of 9.0 mmφ.
（比較実験２）
（試験方法）
比較例２及び実施例３〜５で得られた錠剤の錠剤硬度を測定し、プレス圧力と乾燥水酸化アルミニウムゲルの使用量との関係を図１に示す。
（試験結果）
図１から明らかなように実施例３〜５は、乾燥水酸化アルミニウムゲルを含有しない比較例２と比較して、良好な硬度を有することが明らかになった。なお、本発明の徐放性錠剤においては、乾燥水酸化アルミニウムゲルの含有量とプレス圧力が高くなるにつれて、硬度も高くなる傾向があった。
（実施例６）
(Comparative experiment 2)
(Test method)
The tablet hardness of the tablets obtained in Comparative Example 2 and Examples 3 to 5 was measured, and the relationship between the press pressure and the amount of dry aluminum hydroxide gel used is shown in FIG.
(Test results)
As is clear from FIG. 1, Examples 3 to 5 were found to have good hardness as compared with Comparative Example 2 that did not contain dry aluminum hydroxide gel. In the sustained release tablet of the present invention, the hardness tends to increase as the content of the dry aluminum hydroxide gel and the press pressure increase.
(Example 6)
調製例１で得られた徐放性顆粒、結晶セルロース、乾燥水酸化アルミニウムゲル、カルボキシメチルセルロース、タルク、ステアリン酸マグネシウムを表３に示す仕込み得量で混合し、次にロータリー打錠機により、８００ｋｇの圧力で圧縮成形し、１錠重量３７５ｍｇ、直径９．０ｍｍφ、錠厚５．１５ｍｍの錠剤を得た。
The sustained-release granules, crystalline cellulose, dry aluminum hydroxide gel, carboxymethylcellulose, talc, and magnesium stearate obtained in Preparation Example 1 were mixed in the amounts shown in Table 3, and then 800 kg using a rotary tableting machine. Was compressed at a pressure of 1 tablet to obtain a tablet having a tablet weight of 375 mg, a diameter of 9.0 mmφ and a tablet thickness of 5.15 mm.
（比較実験３）
（試験方法）
実施例６で得られた錠剤のメサラジンの溶出率を測定し、図２にその結果を示す。
（試験結果）
図２から明らかなように実施例６で得られた錠剤は良好な徐放性を示した。
(Comparative Experiment 3)
(Test method)
The dissolution rate of mesalazine in the tablets obtained in Example 6 was measured, and the results are shown in FIG.
(Test results)
As is apparent from FIG. 2, the tablet obtained in Example 6 showed good sustained release properties.
Claims (7)
剤。
（ａ）メサラジン及び結合剤を含有する粒子を徐放性基剤でコーティングしてなる顆粒
（ｂ）結晶セルロース
（ｃ）乾燥水酸化アルミニウムゲル又は酸化マグネシウム
（ｄ）滑沢剤 A sustained release tablet comprising the following (a) to (d), wherein the content of mesalazine in one tablet is 60% or more.
(A) Granules formed by coating particles containing mesalazine and a binder with a sustained-release base (b) crystalline cellulose (c) dry aluminum hydroxide gel or magnesium oxide (d) lubricant
性錠剤。 The sustained-release tablet according to claim 1 or 2, wherein the sustained-release base of (a) is ethyl cellulose.
に記載の徐放性錠剤。 The sustained-release tablet according to any one of claims 1 to 3, wherein the lubricant of (d) is talc or magnesium stearate.
剤。 6. The sustained release tablet according to claim 5, wherein the disintegrant is selected from carmellose or carmellose calcium.
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| JP2006257683A JP5041774B2 (en) | 2006-09-22 | 2006-09-22 | Sustained-release tablets containing mesalazine as an active ingredient |
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| EP2425826A1 (en) * | 2010-09-01 | 2012-03-07 | Disphar International B.V. | Mesalazine tablet having improved dissolution |
| EP2468264A1 (en) * | 2010-12-27 | 2012-06-27 | Laboratorios Liconsa, S.A. | Oral pharmaceutical tablet for controled release of mesalazine and process for obtaining it |
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| JP4443834B2 (en) * | 2003-01-24 | 2010-03-31 | 杏林製薬株式会社 | Sustained release tablet and method for producing the same |
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