JP4848558B2 - Rapid-release tablets containing metformin hydrochloride - Google Patents
Rapid-release tablets containing metformin hydrochloride Download PDFInfo
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【０００１】
【発明の属する技術分野】
本発明は、糖尿病用薬である塩酸メトホルミンの速放性錠剤及びその製造方法に関する。
【０００２】
【従来の技術】
塩酸メトホルミンはビグアナイド系の血糖降下剤であり、２型糖尿病に対する経口糖尿病用薬として臨床の場で使用されている。さらに、近年米国において肥満２型糖尿病のインスリン抵抗性を有する患者に対し第一選択薬として汎用されたことから、国内においても塩酸メトホルミン製剤の需要が高まっている。
【０００３】
ところで、国内においては、塩酸メトホルミン２５０ｍｇを含有する普通錠が２品目販売されており、これらは１錠あたりの重量が３５０ｍｇ又は３８０ｍｇと大きく、服用に際して好ましいものとはいえなかった。
【０００４】
また、特表平１０−５０５６０４号には、有効成分として塩酸メトホルミンと、遅延剤としてヒドロキシプロピルセルロースなどのハイドロコロイド形成剤を含有してなる医薬調製物が開示されている。ここで、遅延剤は、錠剤からの塩酸メトホルミンの放出を４時間（０．５〜１０時間）にわたり、コントロールしつつ遅延させることを目的に添加されている。さらに、打錠前の組成物の残留水分が０．５％未満であるときには、キャッピングが起き、打錠ができなかったことも記載されている。
【０００５】
一方、米国では、塩酸メトホルミンを５００ｍｇ、８５０ｍｇ又は１０００ｍｇを含有するフィルムコーティング錠剤が販売されている。このうち、グルコファージ錠（商品名、ブリストルマイヤーズ スクイブ社）は、塩酸メトホルミン、ポリビニルピロリドン及びステアリン酸マグネシウムからなる錠剤にヒドロキシプロピルメチルセルロースなどをコーティングしたものであり（Physicians' Desk Reference 55Editions 2001）、もともとの塩酸メトホルミンの含有量は多いが、賦形剤の添加を少なくすることにより、錠剤を小型化したものといえる。しかし、日本薬局方第１３改正の溶出試験（パドル法、回転数５０ｒｐｍ、試験液 水）を行うとき、試験開始後１５分時点における塩酸メトホルミンの溶出率は６０％以下であり、その放出性は速やかとはいえない。
【０００６】
塩酸メトホルミンを経口投与した場合、その吸収部位は、小腸上部の狭い部分に限局しており、例えば徐放性製剤とした場合に、塩酸メトホルミンの生体利用率が低下することが知られている。このため、塩酸メトホルミンの普通錠を設計する場合には、速放性を有する錠剤とすることが生体利用率の面で好ましいと考えられる。
【０００７】
【発明が解決しようとする課題】
従って、本発明の目的は、塩酸メトホルミンを速やかに溶出でき、錠剤を小型化するとともに、製造性及び保存による安定性に優れた錠剤を提供することにある。
【０００８】
【課題を解決するための手段】
本発明者らは、塩酸メトホルミンを有効成分とする錠剤について鋭意検討を重ねた結果、結合剤として、特定の粘度を有するヒドロキシプロピルセルロースを使用することにより、崩壊剤などの他の添加剤を特に加えることなく、塩酸メトホルミンを速やかに溶出できる錠剤が得られることを見出し、本発明を完成するに至った。
【０００９】
すなわち、本発明は次の成分（Ａ）及び（Ｂ）：
（Ａ）塩酸メトホルミン、
（Ｂ）２０℃における２質量％水溶液の粘度が２．０〜１０．０mPasであるヒドロキシプロピルセルロース
を含有することを特徴とする速放性錠剤を提供するものである。
また、本発明は、（Ａ）塩酸メトホルミン及び（Ｂ）２０℃における２質量％水溶液の粘度が２．０〜１０．０mPasであるヒドロキシプロピルセルロースを含む製剤原料混合粉末を、エタノールを用いて造粒、乾燥した後、（Ｃ）滑沢剤を加えて打錠することを特徴とする速放性錠剤の製造方法を提供するものである。
【００１０】
【発明の実施の形態】
本発明においては、成分（Ａ）の塩酸メトホルミンは、１錠中に２５０〜１０００ｍｇを含有することができるが、錠剤の服用感をよくするために、錠剤はできる限り小型であることが望ましい。このとき、錠剤中の塩酸メトホルミンの濃度は高く設定することとなり、８５〜９７．５質量％、特に９０〜９５質量％が好ましい。例えば、１錠中に塩酸メトホルミンを２５０ｍｇ含有する錠剤の場合、錠剤の重量は、８５質量％のときは約２９４ｍｇ、９０質量％のときは約２７８ｍｇとなり、小型化され、服用感が改善された錠剤とすることができる。
【００１１】
本発明に用いられる成分（Ｂ）の２０℃における２質量％水溶液の粘度が２．０〜１０．０mPasであるヒドロキシプロピルセルロースは、結合剤として作用するものである。粘度の測定はＢ型粘度計を用いて行なわれる。
粘度が２．０〜１０．０mPasの範囲であるヒドロキシプロピルセルロースを使用すると、塩酸メトホルミンの溶出はいずれの場合も速やかであるが、粘度の低いヒドロキシプロピルセルロースを用いる方が、より速やかな溶出を得ることができる。このため、なかでも粘度が２．０〜５．９mPasのヒドロキシプロピルセルロースを使用するのが好ましく、さらに、粘度が２．０〜２．９mPasのヒドロキシプロピルセルロースを使用するのがより好ましい。例えば、粘度が２．０〜２．９mPasのヒドロキシプロピルセルロースとして、ＨＰＣ−ＳＳＬ（日本曹達）、粘度が３．０〜５．９mPasのヒドロキシプロピルセルロースとして、ＨＰＣ−ＳＬ（日本曹達）、粘度が６．０〜１０．０mPasのヒドロキシプロピルセルロースとして、ＨＰＣ−Ｌ（日本曹達）を使用することができる。
【００１２】
一方、粘度が１０．０mPasより高いヒドロキシプロピルセルロースとしては、１５０〜４００mPasであるＨＰＣ−Ｍ（日本曹達）、１０００〜４０００mPasであるＨＰＣ−Ｈ（日本曹達）などが挙げられるが、これらの使用は、特表平１０−５０５６０４号に開示されたように、錠剤からの塩酸メトホルミンの溶出を遅延させる結果が得られたほか、打錠する際にキャッピングの打錠障害が認められた。
【００１３】
本発明において、成分（Ｂ）のヒドロキシプロピルセルロースは、塩酸メトホルミンと混合したとき、良好な造粒及び打錠の製造性が得られるものであり、その錠剤中の濃度は、２〜１０質量％、特に４〜９質量％が好ましい。
【００１４】
また、本発明においては、良好な打錠性を確保するために、成分（Ａ）及び成分（Ｂ）を含む造粒物に、タルク、ステアリン酸マグネシウムなどの滑沢剤（Ｃ）を１種又は２種以上を混合した後、打錠操作を行うのが好ましい。錠剤中の滑沢剤の濃度は、０．５〜３質量％、特に１〜２質量％が好ましい。
【００１５】
さらに、本発明では、成分（Ａ）、（Ｂ）及び（Ｃ）の量的な関係を充足する限り、所望により他の添加剤を含んでもよい。他の添加剤としては、乳糖、マンニトール、バレイショデンプン、トウモロコシデンプン、無水リン酸水素カルシウムなどが挙げられる。
【００１６】
本発明の速放性錠剤は、例えば成分（Ａ）及び成分（Ｂ）を含む製剤原料混合粉末を、エタノールで造粒、乾燥した後、滑沢剤を加えて打錠することによって製造することができる。この際の圧縮成形に使用する打錠機としては、通常の回転式打錠機を用いることができる。
【００１７】
なお、本発明によれば、打錠前の組成物の残留水分が０．５％未満（カールフィシャー法）である場合でも、良好に打錠することができる。
【００１８】
また、本発明の速放性錠剤は、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロースなどの水溶性皮膜を施して、フィルムコーティング錠とすることができる。フィルムコーティング方法は、例えば、パンコーティング装置などを用いて、通常この分野で用いられる方法により行うことができる。
【００１９】
本発明の速放性錠剤としては、第１３改正日本薬局方による溶出試験法（パドル法、回転数５０ｒｐｍ、試験液 水）により試験するとき、試験開始後１５分時点で塩酸メトホルミンの溶出率が８５％以上となるのが好ましい。
【実施例】
次に、本発明を実施例によりさらに詳細に説明するが、本発明は、これらの例によって何ら限定されるものではない。
【００２０】
［実施例１］
錠剤の成分分量及び錠剤中の成分の濃度を表１に示す。
【００２１】
【表１】
塩酸メトホルミン２３１．５ｇ及び粘度２．０〜２．９mPasのヒドロキシプロピルセルロース（ＨＰＣ−ＳＳＬ）１６．０ｇをハイスピードミキサー（深江工業）中で混合した後、エタノールで造粒した。造粒物を棚式乾燥機に移し、４５℃で６時間乾燥した。乾燥した造粒物は 目開き５９０ μｍの篩を用いて篩過した。これに、タルク１．２５ｇ及びステアリン酸マグネシウム１．２５ ｇを添加して混合した後、高速回転式打錠機（畑鐡工所）で、１錠重量を２７０ｍｇとして、打錠し、１錠中に塩酸メトホルミンを２５０m含有する錠剤を製造した。造粒性及び打錠性のいずれも良好であった。なお、打錠前の造粒物及び錠剤の残留水分は、いずれも約０．３％であった。
【００２３】
［実施例２］
錠剤の成分分量及び錠剤中の成分の濃度を表２に示す。
【００２４】
【表２】
粘度３．０〜５．９mPasのヒドロキシプロピルセルロース（ＨＰＣ−ＳＬ）を用いた以外は、実施例１と同様に製造した。造粒性及び打錠性のいずれも良好であった。
【００２６】
［実施例３］
錠剤の成分分量及び錠剤中の成分の濃度を表３に示す。
【００２７】
【表３】
粘度６．０〜１０．０mPasのヒドロキシプロピルセルロース（ＨＰＣ−Ｌ）を用いた以外は、実施例１と同様に製造した。造粒性及び打錠性のいずれも良好であった。
【００２９】
［比較例１］
錠剤の成分分量及び錠剤中の成分の濃度を表４に示す。
【００３０】
【表４】
粘度１５０〜４００mPasのヒドロキシプロピルセルロース（ＨＰＣ−M ）を用いた以外は、実施例１と同様に製造したが、キャッピングの打錠障害が見られた。
【００３２】
［試験例１］溶出試験
実施例１〜３の錠剤について、試験液として３７℃に加温した水９００ｍLを用い、第１３改正日本薬局方による溶出試験法第２法（パドル法）により、毎分５０回転で試験を行なった（ｎ＝３）。溶出試験開始後５、１０、及び１５分後に、試験液１０ｍLを採取し、ＨＰＬＣ法（カラム：ＯＤＳ、移動相：１−ヘプタンスルホン酸ナトリウム・リン酸水素二カリウム／水・アセトニトリル混液、検出：紫外吸収２３２ｎｍ）により測定した。図１に示すように、いずれの錠剤も、試験開始後１５分時点における塩酸メトホルミンの溶出率は８５％以上であり、良好な速放性を示した。
【００３３】
［試験例２］保存安定性試験
実施例１及び２の錠剤について、ＰＴＰ包装し４０℃７５％ＲＨに２箇月間保存し、試験例1の溶出試験を行なった（ｎ＝３）。いずれの錠剤についても、錠剤外観にも変化はなかった。さらに、試験開始後１５分時点における塩酸メトホルミンの溶出率は８５％以上であった。このことから、保存安定性は良好であった。
【００３４】
【発明の効果】
本発明によれば、２０℃における２質量％水溶液の粘度が２．０〜１０．０mPasの範囲であるヒドロキシプロピルセルロースを使用することにより、有効成分である塩酸メトホルミンが速やかに溶出できる錠剤が得られる。さらに、塩酸メトホルミンを８５質量％以上含有して小型化した錠剤を得ることができる。また、実生産性及び保存安定性に優れるなどの効果を奏する。
【図面の簡単な説明】
【図１】試験例１に記載した実施例１〜３の錠剤の溶出試験結果を示す。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an immediate-release tablet of metformin hydrochloride, which is a drug for diabetes, and a method for producing the tablet.
[0002]
[Prior art]
Metformin hydrochloride is a biguanide hypoglycemic agent and is used in the clinical setting as an oral diabetes drug for type 2 diabetes. Furthermore, since it has been widely used as a first-line drug for patients with obesity type 2 diabetes and insulin resistance in the United States in recent years, there is an increasing demand for a metformin hydrochloride preparation in Japan.
[0003]
Meanwhile, in Japan, two types of ordinary tablets containing metformin hydrochloride 250 mg are sold, and the weight per tablet is as large as 350 mg or 380 mg, which is not preferable for taking.
[0004]
JP-T-10-505604 discloses a pharmaceutical preparation containing metformin hydrochloride as an active ingredient and a hydrocolloid-forming agent such as hydroxypropylcellulose as a retarder. Here, the retarder is added for the purpose of delaying the release of metformin hydrochloride from the tablet over a period of 4 hours (0.5 to 10 hours). Furthermore, it is also described that capping occurred and tableting was not possible when the residual moisture of the composition before tableting was less than 0.5%.
[0005]
On the other hand, in the United States, film-coated tablets containing 500 mg, 850 mg, or 1000 mg of metformin hydrochloride are on the market. Of these, Glucophage Tablets (trade name, Bristol-Myers Squibb) is a tablet comprising metformin hydrochloride, polyvinylpyrrolidone and magnesium stearate coated with hydroxypropyl methylcellulose (Physicians' Desk Reference 55 Editions 2001). Although the content of metformin hydrochloride is large, it can be said that the tablet is miniaturized by reducing the addition of excipients. However, when the dissolution test (paddle method, rotation speed 50 rpm, test solution water) of the 13th revision of the Japanese Pharmacopoeia is conducted, the dissolution rate of metformin hydrochloride at 15 minutes after the start of the test is 60% or less, and its release property is Not promptly.
[0006]
When metformin hydrochloride is orally administered, the absorption site is limited to a narrow portion in the upper small intestine, and it is known that the bioavailability of metformin hydrochloride decreases when, for example, a sustained-release preparation is used. For this reason, when designing an ordinary tablet of metformin hydrochloride, it is considered that it is preferable in terms of bioavailability to have a tablet having a quick release property.
[0007]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to provide a tablet that can rapidly dissolve metformin hydrochloride, miniaturizes the tablet, and is excellent in manufacturability and stability by storage.
[0008]
[Means for Solving the Problems]
As a result of intensive investigations on tablets containing metformin hydrochloride as an active ingredient, the present inventors have made use of hydroxypropyl cellulose having a specific viscosity as a binder, so that other additives such as disintegrants can be used. The inventors have found that a tablet capable of quickly dissolving metformin hydrochloride can be obtained without adding, and the present invention has been completed.
[0009]
That is, the present invention includes the following components (A) and (B):
(A) metformin hydrochloride,
(B) An immediate-release tablet characterized by containing hydroxypropylcellulose having a viscosity of 2.0 to 10.0 mPas in a 2% by mass aqueous solution at 20 ° C.
In addition, the present invention provides a preparation raw material mixed powder containing (A) metformin hydrochloride and (B) hydroxypropyl cellulose having a viscosity of 2.0 to 10.0 mPas in a 2% by mass aqueous solution at 20 ° C. using ethanol. After the granules are dried, (C) a lubricant is added and tableting is provided.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, metformin hydrochloride as the component (A) can contain 250 to 1000 mg in one tablet, but it is desirable that the tablet be as small as possible in order to improve the tablet feeling. At this time, the concentration of metformin hydrochloride in the tablet is set high, and is preferably 85 to 97.5% by mass, particularly preferably 90 to 95% by mass. For example, in the case of a tablet containing 250 mg of metformin hydrochloride in one tablet, the weight of the tablet is about 294 mg when it is 85% by mass, and about 278 mg when it is 90% by mass. It can be a tablet.
[0011]
Hydroxypropyl cellulose having a viscosity of 2.0 to 10.0 mPas of a 2 mass% aqueous solution at 20 ° C of the component (B) used in the present invention acts as a binder. The viscosity is measured using a B-type viscometer.
When hydroxypropylcellulose having a viscosity in the range of 2.0 to 10.0 mPas is used, elution of metformin hydrochloride is quicker in all cases, but using hydroxypropylcellulose having a lower viscosity results in faster elution. Obtainable. For this reason, it is preferable to use hydroxypropyl cellulose having a viscosity of 2.0 to 5.9 mPas, and it is more preferable to use hydroxypropyl cellulose having a viscosity of 2.0 to 2.9 mPas. For example, as the hydroxypropyl cellulose having a viscosity of 2.0 to 2.9 mPas, HPC-SSL (Nippon Soda), as the hydroxypropyl cellulose having a viscosity of 3.0 to 5.9 mPas, HPC-SL (Nippon Soda), the viscosity is HPC-L (Nippon Soda) can be used as 6.0-10.0 mPas hydroxypropylcellulose.
[0012]
On the other hand, examples of the hydroxypropyl cellulose having a viscosity higher than 10.0 mPas include HPC-M (Nippon Soda) having a viscosity of 150 to 400 mPas, HPC-H (Nippon Soda) having a viscosity of 1000 to 4000 mPas, and the like. As disclosed in JP-T-10-505604, results of delaying dissolution of metformin hydrochloride from the tablets were obtained, and capping tableting troubles were observed when tableting.
[0013]
In the present invention, the hydroxypropyl cellulose of component (B) is one which can obtain good granulation and tableting manufacturability when mixed with metformin hydrochloride, and the concentration in the tablet is 2 to 10% by mass. In particular, 4 to 9% by mass is preferable.
[0014]
Moreover, in this invention, in order to ensure favorable tableting property, 1 type of lubricants (C), such as a talc and a magnesium stearate, are added to the granulated material containing a component (A) and a component (B). Or after mixing 2 or more types, it is preferable to perform tableting operation. The concentration of the lubricant in the tablet is preferably 0.5 to 3% by mass, particularly preferably 1 to 2% by mass.
[0015]
Furthermore, in this invention, as long as the quantitative relationship of component (A), (B) and (C) is satisfied, you may contain another additive depending on necessity. Other additives include lactose, mannitol, potato starch, corn starch, anhydrous calcium hydrogen phosphate, and the like.
[0016]
The immediate-release tablet of the present invention is produced, for example, by granulating and drying a preparation raw material powder containing the component (A) and the component (B) with ethanol, and then adding a lubricant and tableting. Can do. A normal rotary tableting machine can be used as a tableting machine used for compression molding at this time.
[0017]
In addition, according to this invention, even when the residual water | moisture content of the composition before tableting is less than 0.5% (Karl Fischer method), it can tablet favorably.
[0018]
Moreover, the immediate release tablet of the present invention can be formed into a film-coated tablet by applying a water-soluble film such as hydroxypropylcellulose, hydroxypropylmethylcellulose and the like. The film coating method can be performed by a method usually used in this field, for example, using a pan coating apparatus or the like.
[0019]
The immediate release tablet of the present invention has a metformin hydrochloride dissolution rate at 15 minutes after the start of the test when tested by the dissolution test method (paddle method, rotation speed 50 rpm, test solution water) according to the 13th revised Japanese Pharmacopoeia. It is preferably 85% or more.
【Example】
EXAMPLES Next, although an Example demonstrates this invention still in detail, this invention is not limited at all by these examples.
[0020]
[Example 1]
Table 1 shows the component amount of the tablet and the concentration of the component in the tablet.
[0021]
[Table 1]
231.5 g of metformin hydrochloride and 16.0 g of hydroxypropylcellulose (HPC-SSL) having a viscosity of 2.0 to 2.9 mPas were mixed in a high speed mixer (Fukae Industrial Co., Ltd.) and granulated with ethanol. The granulated product was transferred to a shelf dryer and dried at 45 ° C. for 6 hours. The dried granulated product was sieved using a sieve having an opening of 590 μm. To this was added 1.25 g of talc and 1.25 g of magnesium stearate, mixed, and then tableted with a high-speed rotary tableting machine (Hatabe Kogyo Co., Ltd.) with a tablet weight of 270 mg. A tablet containing 250 m of metformin hydrochloride was produced. Both granulation and tableting properties were good. In addition, the residual moisture of the granulated product before tableting and the tablet were both about 0.3%.
[0023]
[Example 2]
Table 2 shows the component amount of the tablet and the concentration of the component in the tablet.
[0024]
[Table 2]
It was produced in the same manner as in Example 1 except that hydroxypropyl cellulose (HPC-SL) having a viscosity of 3.0 to 5.9 mPas was used. Both granulation and tableting properties were good.
[0026]
[Example 3]
Table 3 shows the component amount of the tablet and the concentration of the component in the tablet.
[0027]
[Table 3]
It was produced in the same manner as in Example 1 except that hydroxypropylcellulose (HPC-L) having a viscosity of 6.0 to 10.0 mPas was used. Both granulation and tableting properties were good.
[0029]
[Comparative Example 1]
Table 4 shows the component amount of the tablet and the concentration of the component in the tablet.
[0030]
[Table 4]
This was produced in the same manner as in Example 1 except that hydroxypropylcellulose (HPC-M) having a viscosity of 150 to 400 mPas was used, but capping tableting troubles were observed.
[0032]
[Test Example 1] Dissolution Test For tablets of Examples 1 to 3, 900 mL of water heated to 37 ° C was used as a test solution, and the dissolution test method 2nd (paddle method) by the 13th revised Japanese Pharmacopoeia was used. The test was performed at 50 revolutions per minute (n = 3). At 5, 10 and 15 minutes after the start of the dissolution test, 10 mL of the test solution was collected and HPLC method (column: ODS, mobile phase: 1-heptanesulfonic acid sodium / dipotassium hydrogen phosphate / water / acetonitrile mixed solution, detection: UV absorption (232 nm). As shown in FIG. 1, the dissolution rate of metformin hydrochloride at 15 minutes after the start of the test was 85% or more, and all tablets showed good immediate release properties.
[0033]
[Test Example 2] Storage stability test The tablets of Examples 1 and 2 were PTP packed and stored at 40 ° C and 75% RH for 2 months, and the dissolution test of Test Example 1 was performed (n = 3). There was no change in the tablet appearance for any of the tablets. Furthermore, the dissolution rate of metformin hydrochloride at 15 minutes after the start of the test was 85% or more. From this, the storage stability was good.
[0034]
【The invention's effect】
According to the present invention, a tablet in which metformin hydrochloride as an active ingredient can be rapidly dissolved is obtained by using hydroxypropylcellulose whose viscosity of a 2 mass% aqueous solution at 20 ° C. is in the range of 2.0 to 10.0 mPas. It is done. Furthermore, a miniaturized tablet containing 85% by mass or more of metformin hydrochloride can be obtained. In addition, there are effects such as excellent actual productivity and storage stability.
[Brief description of the drawings]
1 shows the dissolution test results of the tablets of Examples 1 to 3 described in Test Example 1. FIG.
Claims (6)
（Ａ）塩酸メトホルミン、
（Ｂ）２０℃における２質量％水溶液の粘度が２．０〜１０．０mPasであるヒドロキシプロピルセルロース
を含有し、成分（Ａ）の含有量が、８５〜９７．５質量％であることを特徴とする速放性錠剤。The following components (A) and (B):
(A) metformin hydrochloride,
(B) Hydroxypropyl cellulose having a viscosity of 2.0 to 10.0 mPas in a 2% by mass aqueous solution at 20 ° C. is contained , and the content of component (A) is 85 to 97.5% by mass. And an immediate release tablet.
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| JP2001136873A JP4848558B2 (en) | 2001-05-08 | 2001-05-08 | Rapid-release tablets containing metformin hydrochloride |
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| JP2001136873A JP4848558B2 (en) | 2001-05-08 | 2001-05-08 | Rapid-release tablets containing metformin hydrochloride |
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| US9060941B2 (en) * | 2002-09-20 | 2015-06-23 | Actavis, Inc. | Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative |
| FR2858556B1 (en) * | 2003-08-06 | 2006-03-10 | Galenix Innovations | DISPERSIBLE AND / OR ORODISPERSIBLE SOLID PHARMACEUTICAL COMPOSITION, NOT PELLETIZED, CONTAINING AT LEAST THE METFORMIN ACTIVE INGREDIENT, AND PROCESS FOR PREPARING THE SAME |
| EP1510208A1 (en) | 2003-08-22 | 2005-03-02 | Fournier Laboratories Ireland Limited | Pharmaceutical composition comprising a combination of metformin and statin |
| JP2005068116A (en) * | 2003-08-28 | 2005-03-17 | Toa Eiyo Ltd | Quickly releasable film-coated tablet including metformin hydrochloride |
| JP4361461B2 (en) * | 2003-10-31 | 2009-11-11 | 武田薬品工業株式会社 | Solid preparation |
| EP1900368B1 (en) * | 2005-06-22 | 2011-05-11 | Takeda Pharmaceutical Company Limited | Tablet containing hardly soluble active ingredient |
| JOP20180109A1 (en) * | 2005-09-29 | 2019-01-30 | Novartis Ag | New Formulation |
| BRPI0808889A2 (en) | 2007-03-13 | 2014-11-11 | Dainippon Sumitomo Pharma Co | ORAL DISINTERRANTING PILL |
| TW201021832A (en) * | 2008-09-30 | 2010-06-16 | Astellas Pharma Inc | Pharmaceutical composition for oral administration |
| ES2693686T3 (en) | 2009-11-13 | 2018-12-13 | Astrazeneca Ab | Immediate-release tablet formulations |
| US8581001B2 (en) | 2010-04-16 | 2013-11-12 | Codman & Shurtleff | Metformin-cysteine prodrug |
| KR101518143B1 (en) * | 2010-08-13 | 2015-05-06 | 유로-셀티큐 에스.에이. | Use of binders for manufacturing storage stable formulations |
| EP3763419A1 (en) | 2011-01-07 | 2021-01-13 | Anji Pharma (US) LLC | Chemosensory receptor ligand-based therapies |
| US11974971B2 (en) | 2011-01-07 | 2024-05-07 | Anji Pharmaceuticals Inc. | Compositions and methods for treating metabolic disorders |
| US9572784B2 (en) | 2011-01-07 | 2017-02-21 | Elcelyx Therapeutics, Inc. | Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk |
| US9211263B2 (en) | 2012-01-06 | 2015-12-15 | Elcelyx Therapeutics, Inc. | Compositions and methods of treating metabolic disorders |
| US11759441B2 (en) | 2011-01-07 | 2023-09-19 | Anji Pharmaceuticals Inc. | Biguanide compositions and methods of treating metabolic disorders |
| US9480663B2 (en) | 2011-01-07 | 2016-11-01 | Elcelyx Therapeutics, Inc. | Biguanide compositions and methods of treating metabolic disorders |
| US8796338B2 (en) | 2011-01-07 | 2014-08-05 | Elcelyx Therapeutics, Inc | Biguanide compositions and methods of treating metabolic disorders |
| NZ626578A (en) | 2012-01-06 | 2016-11-25 | Elcelyx Therapeutics Inc | Compositions and methods for treating metabolic disorders |
| JP2015503582A (en) * | 2012-01-06 | 2015-02-02 | エルセリクス セラピューティクス インコーポレイテッド | Biguanide compositions and methods of treating metabolic disorders |
| JP6866113B2 (en) * | 2016-11-01 | 2021-04-28 | 日本化薬株式会社 | Pharmaceutical preparation containing capecitabine as an active ingredient |
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| JPS62123117A (en) * | 1985-11-22 | 1987-06-04 | Nippon Chemiphar Co Ltd | Nicardipine hydrochloride composition for oral administration |
| JP4292588B2 (en) * | 1997-01-31 | 2009-07-08 | 日産化学工業株式会社 | Oral formulation of pyridazinone compounds |
| AU2256702A (en) * | 2000-12-01 | 2002-06-11 | Kyowa Hakko Kogyo Kk | Composition improved in solubility or oral absorbability |
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