JP2021134217A - Orally disintegrating tablet having coating layer - Google Patents
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本発明は、被覆層を有する口腔内崩壊錠に関するものである。 The present invention relates to an orally disintegrating tablet having a coating layer.
近年、高齢者や小児など嚥下力の弱い患者や水分摂取を制限されている患者、更には多忙で水を持ち合わせていない患者のために、口腔内の唾液のみで錠剤を崩壊させ飲み易くすることを特徴とした口腔内崩壊錠の重要性が増してきている。しかし、口腔内崩壊錠は、少量の唾液で崩壊するように設計されているため、錠剤硬度が低く、１回服用分ずつ分包する（一包化）際に分包機中で割れやすい。更に、光に対して不安定な薬物を含有する口腔内崩壊錠では、保存環境の影響を受けやすい。 In recent years, for patients with weak swallowing ability such as elderly people and children, patients with restricted water intake, and patients who are busy and do not have water, disintegrate tablets with only saliva in the oral cavity to make them easier to swallow. The importance of orally disintegrating tablets characterized by is increasing. However, since the orally disintegrating tablet is designed to disintegrate with a small amount of saliva, the tablet hardness is low and it is easily broken in the packaging machine when it is packaged (packaged) for each dose. Furthermore, orally disintegrating tablets containing a drug that is unstable to light are susceptible to the storage environment.
光に対して不安定な薬物を錠剤化する場合、一般的に、薬物を含む錠剤に着色剤（遮光剤）を配合した被覆層を施す方法や、薬物と着色剤を混合する方法等により遮光することで安定化を図る方法が知られている。 When a drug that is unstable to light is tableted, it is generally shaded by a method of applying a coating layer containing a colorant (light-shielding agent) to the tablet containing the drug, a method of mixing the drug and the colorant, or the like. There is a known method of stabilizing by doing so.
しかし、光に対して不安定な薬物を口腔内崩壊錠にする場合、光安定化を図るために、素錠に着色剤を配合した被覆層を施すと、被覆層による崩壊遅延が懸念される。被覆層を有する口腔内崩壊錠は、口腔内において被覆層がすみやかに溶解し、錠剤本体も速やかに崩壊しなければならない。また、被覆層の溶解に際し、口腔内崩壊錠としてのその味や触感等のマウスフィールも考慮されなければならない。 However, when a drug that is unstable to light is used as an orally disintegrating tablet, if a coating layer containing a colorant is applied to the uncoated tablet in order to stabilize the light, there is a concern that the coating layer may delay disintegration. .. In an orally disintegrating tablet having a coating layer, the coating layer must dissolve promptly in the oral cavity, and the tablet body must also disintegrate rapidly. In addition, when dissolving the coating layer, the mouth feel such as its taste and texture as an orally disintegrating tablet must be taken into consideration.
特許文献１には、マルトース、マルチトール、ソルビトール、キシリトール、フルクトース、ブドウ糖、ラクチトール、イソマルトース、乳糖、エリスリトール、マンニトール、トレハロースおよびショ糖の少なくとも１ 種である２０℃において１０ｍＬ未満の水に１ｇ以上溶け、かつ分子内にヒドロキシ基を有し単位ヒドロキシ基当たりの分子量が２００以下の水溶性物質と、ポリビニルアルコール系樹脂とを含有し、被覆層中のポリビニルアルコール系樹脂と、水溶性物質の重量比が１：０．１〜１：９である被覆層により被覆された、ナルフラフィン又はその薬理学的に許容される塩を除く薬物を含有する安定な口腔内崩壊性被覆錠剤が、優れた速崩壊性を有しながら、高湿度下においても亀裂を生じないことが記載されている。また、被覆層に遮光剤を配合することで、薬物の分解を改善できることも記載されている。しかしながら、そのマウスフィールについては全く不明である。 Patent Document 1 states that 1 g or more in less than 10 mL of water at 20 ° C., which is at least one of maltose, martitol, sorbitol, xylitol, fructose, glucose, lactitol, isomaltose, lactose, erythritol, mannitol, trehalose and sucrose. The weight of the polyvinyl alcohol-based resin and the water-soluble substance in the coating layer, which contains a water-soluble substance that is soluble and has a hydroxy group in the molecule and has a molecular weight of 200 or less per unit hydroxy group and a polyvinyl alcohol-based resin. A stable orally disintegrating coated tablet containing a drug other than nalflafin or a pharmacologically acceptable salt thereof coated with a coating layer having a ratio of 1: 0.1 to 1: 9 is excellent in speed. It is described that it has disintegration property but does not crack even under high humidity. It is also described that the decomposition of the drug can be improved by adding a light-shielding agent to the coating layer. However, its mouthfeel is completely unknown.
本発明者らは、光に対して不安定な薬物、着色剤およびその他の添加剤の混合物を打錠した口腔内崩壊錠を試作したが、光による薬物の分解を十分に抑制する効果は得られなかった。一方、光に対して不安定な薬物を含有する口腔内崩壊錠を、着色剤とポリビニルアルコール系樹脂を含有する被覆層で被覆した口腔内崩壊錠を試作したところ、光による薬物の分解は抑制できた。しかし、被覆層を施したことにより若干の崩壊遅延が起き、口に含んだ時に「口腔内崩壊錠ではない」という違和感が生じてマウスフィールが悪くなるという口腔内崩壊錠に特有の課題を初めて見出した。 The present inventors have prototyped an orally disintegrating tablet in which a mixture of a drug, a colorant and other additives that is unstable to light is beaten, but the effect of sufficiently suppressing the decomposition of the drug by light has been obtained. I couldn't. On the other hand, when a prototype of an orally disintegrating tablet containing a drug that is unstable to light was coated with a coating layer containing a colorant and a polyvinyl alcohol-based resin, the decomposition of the drug by light was suppressed. did it. However, the application of the coating layer causes a slight delay in disintegration, and when it is put in the mouth, it causes a discomfort that it is not an orally disintegrating tablet, and the mouth feel deteriorates. I found it.
本発明は、口腔内での速崩壊性と硬度という口腔内崩壊錠に必要とされる特性を満たしつつ、光に対して不安定な薬物の光による分解が抑制され、マウスフィールに優れた、被覆層を有する口腔内崩壊錠を提供することを目的とする。 INDUSTRIAL APPLICABILITY The present invention satisfies the characteristics required for an orally disintegrating tablet, such as rapid disintegration and hardness in the oral cavity, and suppresses the decomposition of a drug that is unstable to light by light, and has an excellent mouth feel. It is an object of the present invention to provide an orally disintegrating tablet having a coating layer.
本発明者らは、鋭意研究を重ねた結果、光に対して不安定な薬物を含有する口腔内崩壊錠を、高甘味度甘味剤、ポリビニルアルコール系樹脂および着色剤を含む被覆層で被覆することにより、速崩壊性と硬度を両立しつつ、光による薬物の分解を抑制でき、マウスフィールに優れた、被覆層を有する口腔内崩壊錠を提供できることを見出し、本発明を完成した。 As a result of intensive studies, the present inventors coat an orally disintegrating tablet containing a drug that is unstable to light with a coating layer containing a high-sweetness sweetener, a polyvinyl alcohol-based resin, and a colorant. As a result, they have found that it is possible to provide an orally disintegrating tablet having a coating layer, which can suppress the decomposition of a drug by light while achieving both rapid disintegration property and hardness, and has an excellent mouth feel, and completed the present invention.
本発明によれば、口腔内での速崩壊性と硬度という口腔内崩壊錠に必要とされる特性を満たしつつ、光安定性およびマウスフィールに優れた、被覆層を有する口腔内崩壊錠を提供することができる。より詳細には、光に対して不安定な薬物を含有する口腔内崩壊錠を、水への溶解度が高い高甘味度甘味剤、ポリビニルアルコール系樹脂および遮光効果を有する着色剤を含有する被覆層で被覆することにより、光による薬物の分解を抑制することができる。また、被覆層の溶解時間が短く、かつ、医薬品としての取扱いに十分な錠剤強度を両立するとともに、マウスフィールの優れた、被覆層を有する口腔内崩壊錠を提供できる。 According to the present invention, there is provided an orally disintegrating tablet having a coating layer, which has excellent photostability and mouth feel while satisfying the characteristics required for an orally disintegrating tablet such as rapid disintegration and hardness in the oral cavity. can do. More specifically, an orally disintegrating tablet containing a drug that is unstable to light, a coating layer containing a high-sweetness sweetener having a high solubility in water, a polyvinyl alcohol-based resin, and a coloring agent having a light-shielding effect. By coating with, the decomposition of the drug by light can be suppressed. Further, it is possible to provide an orally disintegrating tablet having a coating layer, which has a short dissolution time of the coating layer, has a sufficient tablet strength for handling as a pharmaceutical product, and has an excellent mouth feel.
本発明について、以下に詳述する。
本明細書において、特に断らない限り、％は質量％である。
本明細書において、「〜」を用いて示された数値範囲は、「〜」の前後に記載される数値をそれぞれ最小値および最大値として含む範囲を意味する。
The present invention will be described in detail below.
In the present specification,% is mass% unless otherwise specified.
In the present specification, the numerical range indicated by using "~" means a range including the numerical values before and after "~" as the minimum value and the maximum value, respectively.
本発明に係る「口腔内崩壊錠」は、被覆層を有しない素錠である。
本発明に係る「被覆層を有する口腔内崩壊錠」は、口腔内崩壊錠の表面を被覆用組成物で被覆を施した口腔内崩壊錠である。
The "orally disintegrating tablet" according to the present invention is an uncoated tablet having no coating layer.
The "orally disintegrating tablet having a coating layer" according to the present invention is an orally disintegrating tablet in which the surface of the orally disintegrating tablet is coated with a coating composition.
本発明に係る「被覆層」は、高甘味度甘味剤、ポリビニルアルコール系樹脂および着色剤を含有する。前記被覆層の量は、錠剤の形状や大きさによって異なるが、口腔内崩壊錠の表面積あたり１０μg／ｍｍ２以上であればよく、１５〜３０μg／ｍｍ２であることが好ましい。 The "coating layer" according to the present invention contains a high-sweetness sweetener, a polyvinyl alcohol-based resin, and a colorant. The amount of the coating layer varies depending on the shape and size of the tablets, as long orally disintegrating tablet surface area per 10 [mu] g / mm 2 or more, preferably a 15~30μg / mm 2.
本明細書において「高甘味度甘味剤」とは、ショ糖の甘味度を１とした場合に１００倍以上の甘味度を有する甘味剤を意味する。「甘味度」とは、甘味の強さを示す尺度であり、ショ糖１質量％（２０℃）の甘味の強さを１とした場合の相対比である。本発明に係る高甘味度甘味剤としては、例えば、サッカリンナトリウム、アセスルファムカリウム、アスパルテーム、スクラロース、ステビア、グリチルリチン酸二カリウム、タウマチンおよびネオテーム等が挙げられ、サッカリンナトリウム、アセスルファムカリウムおよびアスパルテームが好ましく、サッカリンナトリウムがより好ましい。前記高甘味度甘味剤は一種または二種以上を組み合わせて用いることができる。
前記高甘味度甘味剤の量は、被覆層質量に対して、５％以下が好ましく、０．１〜５％がより好ましく、１〜３．５％がさらに好ましい。高甘味度甘味剤は極少量で甘みを感じることができるからである。
As used herein, the term "high-sweetness sweetener" means a sweetening agent having a sweetness of 100 times or more when the sweetness of sucrose is 1. The "sweetness degree" is a measure of the intensity of sweetness, and is a relative ratio when the intensity of sweetness of 1% by mass (20 ° C.) of sucrose is 1. Examples of the high-sweetness sweetener according to the present invention include sodium saccharin, acesulfame potassium, aspartame, sucralose, stevia, dipotassium glycyrrhizinate, taumatin and neotame, with sodium saccharin, acesulfame potassium and aspartame being preferred, and sodium saccharin being more preferred. preferable. The high-sweetness sweetener may be used alone or in combination of two or more.
The amount of the high-sweetness sweetener is preferably 5% or less, more preferably 0.1 to 5%, still more preferably 1 to 3.5%, based on the mass of the coating layer. This is because a high-sweetness sweetener can be sweetened with a very small amount.
本発明に係る「ポリビニルアルコール系樹脂」は、ポリビニルアルコール（ＰＶＡ）およびその誘導体もしくは共重合体を意味する。ポリビニルアルコール系樹脂は、ポリビニルアルコールを用いることが好ましい。
ポリビニルアルコールは、通常、ポリ酢酸ビニルを完全または部分的にけん化することにより製造される。けん化度が９７ｍｏｌ％以上のものは完全けん化物、けん化度が７８〜９６ｍｏｌ％のものは部分けん化物と呼ばれる。ポリビニルアルコールのけん化度としては、特に制限されないが、部分けん化物を用いることが好ましい。
本発明に係る「ポリビニルアルコール系樹脂」は、市販品を用いることができる。ポリビニルアルコールの市販品としては、例えば、ゴーセノール（登録商標）（三菱ケミカル株式会社）、Ｊ−ポバール（日本酢ビ・ポバール株式会社）、クラレポバール（株式会社クラレ）、ポリビニルアルコール４−８８、５−８８、８−８８、１８−８８、２６−８８、２８−９９、４０−８８（メルク株式会社）等が挙げられる。ポリビニルアルコールの誘導体としては、例えば、ポリビニルアルコールコポリマー等が挙げられ、市販品としては、例えば、ＰＯＶＡＣＯＡＴ（登録商標）Ｔｙｐｅ Ｆ、Ｔｙｐｅ Ｒ、Ｔｙｐｅ Ｌ（大同化成工業株式会社）等が挙げられる。ポリビニルアルコールの共重合体としては、例えば、ポリビニルアルコール・ポリエチレングリコール・グラフトコポリマー等が挙げられ、市販品としては、例えば、コリコートＩＲ（ＢＡＳＦジャパン株式会社）等が挙げられる。
前記ポリビニルアルコール系樹脂は、一種または二種以上を組み合わせて用いることができる。
前記ポリビニルアルコール系樹脂の量は、被覆層質量に対して、３０％以上であることが好ましく、３０〜６９％がより好ましく、３０〜５９％がさらに好ましい。ポリビニルアルコール系樹脂の量が被覆層質量に対して３０％以上である場合、良好な被覆層を形成することができる。
The "polyvinyl alcohol-based resin" according to the present invention means polyvinyl alcohol (PVA) and its derivatives or copolymers. As the polyvinyl alcohol-based resin, it is preferable to use polyvinyl alcohol.
Polyvinyl alcohol is usually produced by saponifying polyvinyl acetate completely or partially. Those with a saponification degree of 97 mol% or more are called completely saponified products, and those with a saponification degree of 78 to 96 mol% are called partially saponified products. The degree of saponification of polyvinyl alcohol is not particularly limited, but it is preferable to use a partially saponified product.
As the "polyvinyl alcohol-based resin" according to the present invention, a commercially available product can be used. Commercially available products of polyvinyl alcohol include, for example, Gosenol (registered trademark) (Mitsubishi Chemical Co., Ltd.), J-Poval (Japan Vam & Poval Co., Ltd.), Kuraray Poval (Kuraray Co., Ltd.), Polyvinyl alcohol 4-88, 5 −88, 8-88, 18-88, 26-88, 28-99, 40-88 (Merck Co., Ltd.) and the like can be mentioned. Examples of the polyvinyl alcohol derivative include polyvinyl alcohol copolymers and the like, and examples of commercially available products include POVACOAT (registered trademark) Type F, Type R, Type L (Daido Kasei Kogyo Co., Ltd.) and the like. Examples of the copolymer of polyvinyl alcohol include polyvinyl alcohol, polyethylene glycol, graft copolymer and the like, and examples of commercially available products include Coricort IR (BASF Japan Ltd.) and the like.
The polyvinyl alcohol-based resin may be used alone or in combination of two or more.
The amount of the polyvinyl alcohol-based resin is preferably 30% or more, more preferably 30 to 69%, still more preferably 30 to 59%, based on the mass of the coating layer. When the amount of the polyvinyl alcohol-based resin is 30% or more with respect to the mass of the coating layer, a good coating layer can be formed.
本発明に係る「着色剤」は、遮光効果を有する着色剤であればよく、例えば、酸化チタン、三二酸化鉄、黄色三二酸化鉄、黒酸化鉄およびタルク等が挙げられる。遮光効果の点で、酸化チタン、三二酸化鉄、黄色三二酸化鉄が好ましく、酸化チタンがより好ましい。前記着色剤は一種または二種以上を組み合わせて用いることができる。
前記着色剤の量は、光に不安定な薬物の量や光感受性によっても異なるが、被覆層質量に対して、３０〜７０％が好ましく、４０〜７０％がより好ましい。
The "colorant" according to the present invention may be any colorant having a light-shielding effect, and examples thereof include titanium oxide, iron sesquioxide, yellow iron sesquioxide, black iron oxide, and talc. Titanium oxide, iron sesquioxide, and yellow iron sesquioxide are preferable, and titanium oxide is more preferable, in terms of the light-shielding effect. The colorant may be used alone or in combination of two or more.
The amount of the colorant varies depending on the amount of the light-unstable drug and the photosensitivity, but is preferably 30 to 70%, more preferably 40 to 70%, based on the mass of the coating layer.
本発明に係る被覆層には、上述の成分のほか、必要に応じて薬学的に許容される添加剤を本発明の効果を損なわない範囲内で加えることができる。当該添加剤としては、例えば、コーティング剤、光沢化剤および着香剤等が挙げられる。コーティング剤としては、例えば、クエン酸トリエチル、グリセリン脂肪酸エステル、ショ糖脂肪酸エステル、タルク、トリアセチン、ヒマシ油；プロピレングリコール、マクロゴール４００、マクロゴール６００、マクロゴール１５００、マクロゴール１５４０、マクロゴール４０００、マクロゴール６０００、マクロゴール２００００およびマクロゴール３５０００等のマクロゴール；コーンスターチ、デンプングリコール酸ナトリウムおよび部分アルファー化デンプン等のデンプン類；微結晶セルロース、軽質無水ケイ酸、、カルメロースカルシウム、低置換度ヒドロキシプロピルセルロース、、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、ヒドロキシプロピルセルロース、アラビアゴム末、ゼラチン、プルラン、カルメロースナトリウム、エチルセルロースおよびアミノアルキルメタルリレートコポリマー等が挙げられる。光沢化剤としては、例えば、タルク、軽質無水ケイ酸、ステアリン酸マグネシウム、ステアリン酸カルシウム、カルナウバロウおよび精製セラック等が挙げられる。着香剤としては、例えば、メントールおよびペパーミント等のハッカ類、レモン、オレンジ、グレープフルーツ、ストロベリー、チョコレート並びにコーヒー等が挙げられる。 In addition to the above-mentioned components, a pharmaceutically acceptable additive, if necessary, can be added to the coating layer according to the present invention within a range that does not impair the effects of the present invention. Examples of the additive include a coating agent, a brightening agent, a flavoring agent and the like. Examples of the coating agent include triethyl citrate, glycerin fatty acid ester, sucrose fatty acid ester, starch, triacetin, castor oil; propylene glycol, macrogol 400, macrogol 600, macrogol 1500, macrogol 1540, macrogol 4000, and the like. Macrogol such as Macrogol 6000, Macrogol 20000 and Macrogol 35000; Starches such as corn starch, sodium starch glycolate and partially pregelatinized starch; microcrystalline cellulose, light anhydrous silicic acid, carmellose calcium, low substitution hydroxy Examples thereof include propyl cellulose, polyvinylpyrrolidone, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, gum arabic powder, gelatin, purulan, sodium carmellose, ethyl cellulose and aminoalkyl metal relate copolymer. Examples of the brightener include talc, light anhydrous silicic acid, magnesium stearate, calcium stearate, carnauba wax, purified shellac and the like. Examples of the flavoring agent include mint such as menthol and peppermint, lemon, orange, grapefruit, strawberry, chocolate and coffee.
本発明に用いられる被覆層用組成物を調製する方法としては、特に制限されないが、例えば、精製水に前記高甘味度甘味剤、前記ポリビニルアルコール系樹脂、前記着色剤および必要に応じて前記添加剤を溶解または分散させることにより調製することができる。
口腔内崩壊錠に被覆層を形成する方法としては、特に制限されないが、例えば、パン型コーティング装置、流動層コーティング装置または通気式乾燥パン型コーティング装置等を用いて形成することができる。
被覆層を有する口腔内崩壊錠の硬度は、低いと輸送や保管中に錠剤が破損してしまう可能性があるため、１０Ｎ以上であることが好ましく、２５Ｎ以上がより好ましい。
The method for preparing the composition for a coating layer used in the present invention is not particularly limited, and for example, the high-sweetness sweetener, the polyvinyl alcohol-based resin, the colorant, and the addition, if necessary, to purified water. It can be prepared by dissolving or dispersing the agent.
The method for forming the coating layer on the orally disintegrating tablet is not particularly limited, and for example, it can be formed by using a pan-type coating device, a fluidized bed coating device, a breathable dry pan-type coating device, or the like.
If the hardness of the orally disintegrating tablet having a coating layer is low, the tablet may be damaged during transportation or storage, so the hardness is preferably 10 N or more, more preferably 25 N or more.
本願発明において、「マウスフィール」とは、錠剤を口に含んだ際の味や触感、質感等を意味する。口腔内崩壊錠が崩壊し始めるまでの時間（被覆層が溶解する間）に感じる「口腔内崩壊錠ではない」という違和感がない味や舌触りであることを、マウスフィールが優れているという。
被覆層が溶解する間に無味であると被覆層の口腔内溶解時間を実際よりも長く感じ、上記違和感は大きく、マウスフィールは悪い。被覆層の口腔内溶解時間が短いほど上記違和感は小さく、マウスフィールは良好となる。そのため、本発明に係る被覆層の口腔内溶解時間は、１５秒以内が好ましく、１０秒以内がより好ましく、８秒以内がさらに好ましい。
In the present invention, the "mouth feel" means the taste, texture, texture, etc. when a tablet is contained in the mouth. It is said that the mouth feel is excellent because it has a pleasant taste and texture that "it is not an orally disintegrating tablet" that is felt during the time until the orally disintegrating tablet begins to disintegrate (while the coating layer dissolves).
If it is tasteless while the coating layer is dissolved, the oral dissolution time of the coating layer is felt longer than it actually is, the above-mentioned discomfort is large, and the mouth feel is poor. The shorter the oral dissolution time of the coating layer, the smaller the discomfort and the better the mouth feel. Therefore, the oral dissolution time of the coating layer according to the present invention is preferably within 15 seconds, more preferably within 10 seconds, and even more preferably within 8 seconds.
一般的に、口腔内崩壊錠は、口腔内で水なしで６０秒以内に崩壊するように設計される。そのため、本発明に用いられる口腔内崩壊錠は、通常、口腔内に存在する唾液のみによって崩壊および嚥下が可能な錠剤として使用されている範囲内のもの、好ましくは、口腔内での崩壊時間が４５秒以内、より好ましくは４０秒以内、さらに好ましくは３０秒以内であれば、組成および製法に関して特に制限されない。本発明に用いられる口腔内崩壊錠は、例えば、直接打錠法、間接打錠法、鋳型成形法等の製剤分野における慣用の方法により製造することができる。なお、本発明の被覆層を有する口腔内崩壊錠は水なしで服用することを限定した物ではなく、水とともに服用してもよい。 Orally disintegrating tablets are generally designed to disintegrate in the oral cavity within 60 seconds without water. Therefore, the orally disintegrating tablet used in the present invention is usually within the range used as a tablet that can be disintegrated and swallowed only by saliva existing in the oral cavity, preferably the disintegrating time in the oral cavity. The composition and production method are not particularly limited as long as it is within 45 seconds, more preferably within 40 seconds, and even more preferably within 30 seconds. The orally disintegrating tablet used in the present invention can be produced by, for example, a method commonly used in the pharmaceutical field such as a direct tableting method, an indirect tableting method, and a molding method. The orally disintegrating tablet having the coating layer of the present invention is not limited to being taken without water, and may be taken with water.
本発明に用いられる口腔内崩壊錠は、光に対して不安定な薬物および必要に応じて薬学的に許容される添加剤を含有する。
「光に対して不安定な薬物」としては、例えば、ニソルジピン、アゼルニジピン、メコバラミン、シメチジン、メキタジン、オランザピン、ドネペジル、セレギリン、イルソグラジン、ベポタスチン、ラモセトロン、ナフトピジル、ポラプレジンク、リザトリプタン、ミドドリン、リスペリドン、オンダンセトロン、ロラタジン、モンテルカスト、アズレンスルホン酸、エチゾラム、エナラプリル、カプトプリル、グリベンクラミド、クロルマジノン酢酸エステル、ドキサゾシン、トリアゾラム、ドンペリドン、ケトチフェン、ブロムペリドール、プラバスタチン、シンバスタチン、ピタバスタチン、ロスバスタチン、アトルバスタチン、ロペラミド、リシノプリル、リルマザホン、アルファカルシドール、ブロモクリプチン、プラミペキソール、ロサルタン、バルサルタン、カンデサルタンシレキセチル、テルミサルタン、アジルサルタン、ラメルテオンおよびリナグリプチンならびにその薬理学的に許容される塩および溶媒和物等が挙げられる。
当該添加剤としては、例えば、賦形剤、崩壊剤、結合剤、可塑剤、矯味剤、香料、着色剤または滑沢剤等が挙げられる。
The orally disintegrating tablet used in the present invention contains a drug that is unstable to light and, if necessary, a pharmaceutically acceptable additive.
Examples of "light-unstable drugs" include nisoldipine, azernidipine, mecobalamine, cimetidine, mekitadine, olanzapine, donepezil, selegiline, irsogladine, bepotastin, ramosetron, naphthopidine, poraprezinc, lizapritane, middrine, risperidone, ondan. Cetron, loratazine, montelcast, azulene sulfonic acid, etizolam, enarapril, captopril, glibenclamid, chlormaginone acetate, doxazocin, triazolam, donperidone, ketotiphen, bromperidol, pravastatin, simbatatin, pitabastatin, losvastatin , Alphacalcidol, bromperidol, pramipexol, rosaltan, balsartane, candesartan cilexetil, thermisartane, azil sartane, ramerteon and linagliptin, and pharmacologically acceptable salts and solvent products thereof and the like.
Examples of the additive include excipients, disintegrants, binders, plasticizers, flavoring agents, fragrances, coloring agents, lubricants and the like.
本発明の被覆層を有する口腔内崩壊錠の有用性を以下の試験例および実施例で説明するが、本発明はこれらにより、限定されるものではない。 The usefulness of the orally disintegrating tablet having the coating layer of the present invention will be described in the following Test Examples and Examples, but the present invention is not limited thereto.
（参考例１）
アジルサルタン（以下、「化合物Ａ」と略記する。）４０質量部（以下、「部」と略記する。）、乳糖水和物１４部およびトウモロコシデンプン６部を混合し、これにヒドロキシプロピルセルロースおよびマクロゴール６０００各１部を精製水に溶解した液を添加して造粒し、乾燥し、整粒して化合物Ａ含有顆粒を得た。Ｄ−マンニトール７０．８部、クロスポビドン１３部および軽質無水ケイ酸２．７部を混合し、これにヒドロキシプロピルセルロース０．２部を精製水に溶解した液を添加して造粒し、乾燥し、整粒して賦形顆粒を得た。前記化合物Ａ含有顆粒６２部、前記賦形顆粒８６．７部、結晶セルロース２８．６部およびステアリン酸マグネシウム２．７部を混合し、打錠して１錠質量１８０ｍｇ、直径８ｍｍの碁石型錠剤（未被覆の口腔内崩壊錠）を得た。
(Reference example 1)
40 parts by mass of azilsartan (hereinafter abbreviated as "Compound A") (hereinafter abbreviated as "part"), 14 parts of lactose hydrate and 6 parts of corn starch were mixed, and hydroxypropyl cellulose and 6 parts of corn starch were mixed. A solution prepared by dissolving 1 part of each of Macrogol 6000 in purified water was added to granulate, dried, and sized to obtain compound A-containing granules. 70.8 parts of D-mannitol, 13 parts of crospovidone and 2.7 parts of light anhydrous silicic acid are mixed, and a solution prepared by dissolving 0.2 part of hydroxypropyl cellulose in purified water is added to the mixture to granulate and dry. Then, the granules were sized to obtain shaped granules. 62 parts of the compound A-containing granules, 86.7 parts of the shaped granules, 28.6 parts of crystalline cellulose and 2.7 parts of magnesium stearate are mixed and tableted, and one tablet has a mass of 180 mg and a diameter of 8 mm. (Uncoated orally disintegrating tablet) was obtained.
（実施例１）
ポリビニルアルコール１．６部、サッカリンナトリウム０．１部、酸化チタン１．４部および黄色三二酸化鉄０．０７５部を精製水にそれぞれ溶解または分散し、固形分１０％の被覆用液を調製した。スプレー式パン型コーティング機（ＨＣＴ−６０型）を用いて、設定温度７５〜８０℃で、参考例１により製造した未被覆の口腔内崩壊錠に前記被覆用液を噴霧し、１８０ｍｇの錠剤に対して３ｍｇの被覆層を有する口腔内崩壊錠を得た。
(Example 1)
1.6 parts of polyvinyl alcohol, 0.1 part of sodium saccharin, 1.4 parts of titanium oxide and 0.075 parts of yellow iron sesquioxide were dissolved or dispersed in purified water, respectively, to prepare a coating liquid having a solid content of 10%. Using a spray pan-type coating machine (HCT-60 type), the coating solution was sprayed onto the uncoated orally disintegrating tablet produced according to Reference Example 1 at a set temperature of 75 to 80 ° C. to obtain a 180 mg tablet. On the other hand, an orally disintegrating tablet having a coating layer of 3 mg was obtained.
（実施例２）
ポリビニルアルコール１．６部、アセスルファムカリウム０．１部、酸化チタン１．４部および黄色三二酸化鉄０．０７５部をそれぞれ精製水に溶解または分散し、固形分１０％の被覆用液を調製した。実施例１と同じ条件で、参考例１により製造した未被覆の口腔内崩壊錠に前記被覆用液を噴霧し、１８０ｍｇの錠剤に対して３ｍｇの被覆層を有する口腔内崩壊錠を得た。
(Example 2)
1.6 parts of polyvinyl alcohol, 0.1 part of acesulfame potassium, 1.4 parts of titanium oxide and 0.075 parts of yellow iron sesquioxide were dissolved or dispersed in purified water to prepare a coating liquid having a solid content of 10%. .. Under the same conditions as in Example 1, the uncoated orally disintegrating tablet produced in Reference Example 1 was sprayed with the coating liquid to obtain an orally disintegrating tablet having a coating layer of 3 mg with respect to a 180 mg tablet.
（実施例３）
ポリビニルアルコール１．６部、アスパルテーム０．１部、酸化チタン１．４部および黄色三二酸化鉄０．０７５部をそれぞれ精製水に溶解または分散し、固形分７％の被覆用液を調製した。実施例１と同じ条件で、参考例１により製造した未被覆の口腔内崩壊錠に前記被覆用液を噴霧し、１８０ｍｇの錠剤に対して３ｍｇの被覆層を有する口腔内崩壊錠を得た。
(Example 3)
1.6 parts of polyvinyl alcohol, 0.1 part of aspartame, 1.4 parts of titanium oxide and 0.075 parts of yellow iron sesquioxide were dissolved or dispersed in purified water to prepare a coating liquid having a solid content of 7%. Under the same conditions as in Example 1, the uncoated orally disintegrating tablet produced in Reference Example 1 was sprayed with the coating liquid to obtain an orally disintegrating tablet having a coating layer of 3 mg with respect to a 180 mg tablet.
（比較例１）
ポリビニルアルコール１．６部、酸化チタン１．４部および黄色三二酸化鉄０．０７５部をそれぞれ精製水に溶解または分散し、被覆用液を調製した。実施例１と同じ条件で、参考例１により製造した未被覆の口腔内崩壊錠に前記被覆用液を噴霧し、１８０ｍｇの錠剤に対して３ｍｇの被覆層を有する口腔内崩壊錠を得た。
(Comparative Example 1)
1.6 parts of polyvinyl alcohol, 1.4 parts of titanium oxide and 0.075 parts of yellow iron sesquioxide were dissolved or dispersed in purified water to prepare a coating liquid. Under the same conditions as in Example 1, the uncoated orally disintegrating tablet produced in Reference Example 1 was sprayed with the coating liquid to obtain an orally disintegrating tablet having a coating layer of 3 mg with respect to a 180 mg tablet.
（比較例２）
ポリビニルアルコール１．６部、マルチトール０．１部、酸化チタン１．４部および黄色三二酸化鉄０．０７５部をそれぞれ精製水に溶解または分散し、被覆用液を調製した。実施例１と同じ条件で、参考例１により製造した未被覆の口腔内崩壊錠に前記被覆用液を噴霧し、１８０ｍｇの錠剤に対して３ｍｇの被覆層を有する口腔内崩壊錠を得た。
(Comparative Example 2)
1.6 parts of polyvinyl alcohol, 0.1 part of maltitol, 1.4 parts of titanium oxide and 0.075 parts of yellow iron sesquioxide were dissolved or dispersed in purified water to prepare a coating liquid. Under the same conditions as in Example 1, the uncoated orally disintegrating tablet produced in Reference Example 1 was sprayed with the coating liquid to obtain an orally disintegrating tablet having a coating layer of 3 mg with respect to a 180 mg tablet.
（試験例１）錠剤硬度の測定
参考例１の未被覆の口腔内崩壊錠ならびに実施例１〜３および比較例１〜２の被覆層を有する口腔内崩壊錠について、デジタル硬度計を用いて錠剤の硬度を測定し、各３錠の平均硬度を算出した。結果を表１に示す。
(Test Example 1) Measurement of Tablet Hardness Tablets using an uncoated orally disintegrating tablet of Reference Example 1 and an orally disintegrating tablet having a coating layer of Examples 1 to 3 and Comparative Examples 1 and 2 using a digital hardness tester. The hardness of each of the three tablets was measured, and the average hardness of each of the three tablets was calculated. The results are shown in Table 1.
（試験例２）被覆層の溶解時間の測定およびマウスフィールの評価
参考例１の未被覆の口腔内崩壊錠ならびに実施例１〜３および比較例１〜２の被覆層を有する口腔内崩壊錠について、健康な成人４名により口腔内崩壊時間を測定した。被覆層を有する口腔内崩壊錠の口腔内崩壊時間から、未被覆の口腔内崩壊錠の口腔内崩壊時間を差し引いた時間を被覆層の溶解時間として算出した。また、被覆層の溶解過程におけるマウスフィールについて、口腔内崩壊錠として違和感を感じない場合は「良好」、違和感を感じる場合は「不快」と評価した。結果を表１に示す。
(Test Example 2) Measurement of dissolution time of coating layer and evaluation of mouthfeel About uncoated orally disintegrating tablets of Reference Example 1 and orally disintegrating tablets having coating layers of Examples 1 to 3 and Comparative Examples 1 and 2. The oral disintegration time was measured by 4 healthy adults. The time obtained by subtracting the orally disintegrating time of the uncoated orally disintegrating tablet from the orally disintegrating time of the orally disintegrating tablet having the coating layer was calculated as the dissolution time of the coating layer. In addition, the mouth feel in the dissolution process of the coating layer was evaluated as "good" when it did not feel uncomfortable as an orally disintegrating tablet, and as "unpleasant" when it felt uncomfortable. The results are shown in Table 1.
（試験例３）光安定性試験
参考例１の未被覆の口腔内崩壊錠ならびに実施例１〜３および比較例１〜２の被覆層を有する口腔内崩壊錠をシャーレ上に均一に広げ、白色蛍光灯１０００ＬＸの光照射下で１週間保管した。保管後、下記条件のＨＰＬＣ法により化合物Ａおよびその類縁物質を測定した。化合物Ａおよびその類縁物質に由来する総ピーク面積に対する光分解物（相対保持時間０．４９）の面積百分率（％）を算出し、光安定性を評価した。結果を表１に示す。
カラム：液体クロマトグラフィー用オクタデシルシリル化シリカゲル
移動相：水／酢酸（１００）混液（１０００：１）とアセトニトリルの混合比を変えて濃度勾配制御
流量：約０．７ｍＬ／ｍｉｎ
測定波長：２５０ｎｍ
(Test Example 3) Photostability test An uncoated orally disintegrating tablet of Reference Example 1 and an orally disintegrating tablet having a coating layer of Examples 1 to 3 and Comparative Examples 1 and 2 are uniformly spread on a chalet and white. It was stored for 1 week under the light irradiation of a fluorescent lamp 1000LX. After storage, compound A and its related substances were measured by the HPLC method under the following conditions. The area percentage (%) of the photodegraded product (relative retention time 0.49) with respect to the total peak area derived from compound A and its related substances was calculated, and the photostability was evaluated. The results are shown in Table 1.
Column: Octadecylsilylated silica gel mobile phase for liquid chromatography: Concentration gradient control flow rate by changing the mixing ratio of water / acetic acid (100) mixed solution (1000: 1) and acetonitrile: Approximately 0.7 mL / min
Measurement wavelength: 250 nm
実施例１〜３および比較例１〜２において、医薬品として取扱いに十分な錠剤強度と、被覆層の速やかな溶解性を示した。なお、参考例の未被覆の口腔内崩壊錠の口腔内崩壊時間は２５秒だった。
実施例１〜３においては、被覆層が溶解する間に甘味を感じるため、口腔内崩壊錠として違和感なく、マウスフィールが良好であった。一方、被覆層に甘味剤を含有しない比較例１および被覆層にマルチトール（ショ糖の甘味度を１とした場合に０．８〜０．９倍の甘味度を有する）を含有する比較例２においては、被覆層が溶解する間は無味であり、口腔内崩壊錠として違和感があり、不快であった。
着色剤を含有する被覆層を設けた実施例１〜３および比較例１〜２では、光に不安定な薬物の光安定化効果を示した。
In Examples 1 to 3 and Comparative Examples 1 and 2, the tablet strength sufficient for handling as a pharmaceutical product and the rapid solubility of the coating layer were shown. The orally disintegrating time of the uncoated orally disintegrating tablet of the reference example was 25 seconds.
In Examples 1 to 3, since the sweetness was felt while the coating layer was dissolved, there was no discomfort as an orally disintegrating tablet, and the mouthfeel was good. On the other hand, Comparative Example 1 in which the coating layer does not contain a sweetener and Comparative Example in which the coating layer contains maltitol (having a sweetness of 0.8 to 0.9 times when the sweetness of sucrose is 1). In No. 2, it was tasteless while the coating layer was dissolved, and it was unpleasant and unpleasant as an orally disintegrating tablet.
In Examples 1 to 3 and Comparative Examples 1 and 2 in which the coating layer containing the colorant was provided, the light-stabilizing effect of the light-unstable drug was shown.
（参考例２）
化合物Ａ４０部、乳糖水和物１４部およびトウモロコシデンプン６部を混合し、これにヒドロキシプロピルセルロースおよびマクロゴール６０００各１部を精製水に溶解した液を添加して造粒し、乾燥し、整粒して化合物Ａ含有顆粒を得た。Ｄ−マンニトール７０．１８部、クロスポビドン１４．３部および軽質無水ケイ酸３．３部を混合し、これにヒドロキシプロピルセルロース０．２２部を精製水に溶解した液を添加して造粒し、乾燥し、整粒して賦形顆粒を得た。前記化合物Ａ含有顆粒６２部、前記賦形顆粒８８部、結晶セルロース２７．３部およびステアリン酸マグネシウム２．７部を混合し、打錠して１錠質量１８０ｍｇ、直径８ｍｍの碁石型錠剤（未被覆の口腔内崩壊錠）を得た。
参考例２の未被覆の口腔内崩壊錠について上記試験例１〜３と同様に試験を行ったところ、硬度は４２．７Ｎ、口腔内崩壊時間は２５秒、マウスフィールは良好、光分解物は０．２０６％であった。
(Reference example 2)
40 parts of compound A, 14 parts of lactose hydrate and 6 parts of corn starch are mixed, and a solution prepared by dissolving 1 part each of hydroxypropyl cellulose and macrogol 6000 in purified water is added to the mixture, granulated, dried and adjusted. Granulation was obtained to obtain compound A-containing granules. 70.18 parts of D-mannitol, 14.3 parts of crospovidone and 3.3 parts of light silicic acid anhydride were mixed, and 0.22 parts of hydroxypropyl cellulose was dissolved in purified water to granulate the mixture. , Dried and sized to give shaped granules. 62 parts of the compound A-containing granules, 88 parts of the shaped granules, 27.3 parts of crystalline cellulose and 2.7 parts of magnesium stearate are mixed and tableted, and one tablet has a mass of 180 mg and a diameter of 8 mm. A coated orally disintegrating tablet) was obtained.
When the uncoated orally disintegrating tablet of Reference Example 2 was tested in the same manner as in Test Examples 1 to 3, the hardness was 42.7N, the orally disintegrating time was 25 seconds, the mouth feel was good, and the photodegraded product was. It was 0.206%.
（実施例４）
ポリビニルアルコール１．３部、サッカリンナトリウム０．０５部、マクロゴール６０００ ０．０８部、酸化チタン２．７部および黄色三二酸化鉄０．１部を精製水にそれぞれ溶解または分散し、固形分１０％の被覆用液を調製した。スプレー式パン型コーティング機（ＨＣＴ−６０型）を用いて、設定温度７５〜８０℃で、参考例２により製造した未被覆の口腔内崩壊錠に前記被覆用液を噴霧し、１８０ｍｇの錠剤に対して４．２３ｍｇの被覆層を有する口腔内崩壊錠を得た。
実施例４の被覆層を有する口腔内崩壊錠について上記試験例１〜３と同様に試験を行ったところ、硬度は３９．２Ｎ、被覆層溶解時間は８秒、マウスフィールは良好、光分解物は０．０００％であった。
(Example 4)
1.3 parts of polyvinyl alcohol, 0.05 parts of sodium saccharin, 0.08 parts of macrogol 6000, 2.7 parts of titanium oxide and 0.1 parts of yellow iron sesquioxide were dissolved or dispersed in purified water, respectively, and the solid content was 10%. A coating solution was prepared. Using a spray pan-type coating machine (HCT-60 type), the coating solution was sprayed onto the uncoated orally disintegrating tablet produced according to Reference Example 2 at a set temperature of 75 to 80 ° C. to obtain a 180 mg tablet. In contrast, an orally disintegrating tablet having a coating layer of 4.23 mg was obtained.
When the orally disintegrating tablet having the coating layer of Example 4 was tested in the same manner as in Test Examples 1 to 3, the hardness was 39.2N, the coating layer dissolution time was 8 seconds, the mouth feel was good, and the photodegraded product. Was 0.000%.
（参考例３）
ラメルテオン（以下、「化合物Ｂ」と略記する。）８部、部分アルファー化デンプン３０部および軽質無水ケイ酸０．５部を混合し、これにヒドロキシプロピルセルロース０．５部を水／エタノールに溶解した液を添加して造粒し、乾燥し、整粒して核顆粒を得た。得られた核顆粒に、ヒプロメロース１部およびタルク０．１部を精製水にそれぞれ溶解または分散した液を噴霧し、乾燥し、さらにアミノアルキルメタクリレートコポリマーＥ３．５部、エチルセルロース３．５部およびタルク３．５部を水／エタノールにそれぞれ溶解または分散した液を噴霧し、乾燥して化合物Ｂ含有顆粒を得た。乳糖水和物５０部、軽質無水ケイ酸２．５部、クロスポビドン１０．７部および黄色三二酸化鉄０．０８部を混合し、これにヒドロキシプロピルセルロース０．８部を精製水に溶解した液を添加して造粒し、乾燥し、整粒して賦形顆粒を得た。前記化合物Ｂ含有顆粒５０．６部、前記賦形顆粒６４．０８部、結晶セルロース３４．５部、乳糖水和物１０部、香料０．２２部、スクラロース０．１６部およびステアリン酸マグネシウム１部を混合し、打錠して１錠質量１６０．５６ｍｇ、直径７．５ｍｍの碁石型錠剤（未被覆の口腔内崩壊錠）を得た。
参考例３の未被覆の口腔内崩壊錠について上記試験例１および２と同様に試験を行ったところ、硬度は５３．６Ｎ、口腔内崩壊時間は３０秒以下であった。
(Reference example 3)
8 parts of ramelteon (hereinafter abbreviated as "Compound B"), 30 parts of partially pregelatinized starch and 0.5 part of light anhydrous silicic acid are mixed, and 0.5 part of hydroxypropyl cellulose is dissolved in water / ethanol. The solution was added, granulated, dried, and sized to obtain nuclear granules. The obtained nuclear granules were sprayed with a solution in which 1 part of hypromerose and 0.1 part of talc were dissolved or dispersed in purified water, respectively, and dried. Further, 3.5 parts of aminoalkyl methacrylate copolymer E, 3.5 parts of ethyl cellulose and talc were obtained. A solution prepared by dissolving or dispersing 3.5 parts in water / ethanol was sprayed and dried to obtain compound B-containing granules. 50 parts of lactose hydrate, 2.5 parts of light anhydrous silicic acid, 10.7 parts of crospovidone and 0.08 part of yellow sesquioxide were mixed, and 0.8 part of hydroxypropyl cellulose was dissolved in purified water. The liquid was added, granulated, dried, and sized to obtain shaped granules. 50.6 parts of the compound B-containing granules, 64.08 parts of the shaped granules, 34.5 parts of crystalline cellulose, 10 parts of lactose hydrate, 0.22 parts of fragrance, 0.16 parts of sclarose and 1 part of magnesium stearate. Was mixed and tableted to obtain a gostone-shaped tablet (uncoated orally disintegrating tablet) having a mass of 160.56 mg and a diameter of 7.5 mm.
When the uncoated orally disintegrating tablet of Reference Example 3 was tested in the same manner as in Test Examples 1 and 2, the hardness was 53.6N and the orally disintegrating time was 30 seconds or less.
（実施例５）
ポリビニルアルコール１．３部、タウマチン０．０５部、ヒプロメロース０．１部、酸化チタン１．７部および黄色三二酸化鉄０．０１部を精製水にそれぞれ溶解または分散し、固形分１０％の被覆用液を調製した。スプレー式パン型コーティング機（ＨＣＴ−６０型）を用いて、設定温度７５〜８０℃で、参考例３により製造した未被覆の口腔内崩壊錠に前記被覆用液を噴霧し、１６０．５６ｍｇの錠剤に対して３．１６ｍｇの被覆層を有する口腔内崩壊錠を得た。
実施例５の被覆層を有する口腔内崩壊錠について上記試験例１〜３と同様に試験を行ったところ、硬度は５７．１Ｎ、被覆層溶解時間は１０秒未満、マウスフィールは良好であった。
(Example 5)
1.3 parts of polyvinyl alcohol, 0.05 parts of taumatin, 0.1 parts of hypromellose, 1.7 parts of titanium oxide and 0.01 parts of yellow iron sesquioxide are dissolved or dispersed in purified water, respectively, and coated with a solid content of 10%. A solution was prepared. Using a spray-type pan-type coating machine (HCT-60 type), the coating liquid was sprayed onto the uncoated orally disintegrating tablet produced according to Reference Example 3 at a set temperature of 75 to 80 ° C., and 160.56 mg was sprayed. Orally disintegrating tablets with a coating layer of 3.16 mg relative to the tablets were obtained.
When the orally disintegrating tablet having the coating layer of Example 5 was tested in the same manner as in Test Examples 1 to 3, the hardness was 57.1N, the coating layer dissolution time was less than 10 seconds, and the mouthfeel was good. ..
（試験例４）光安定性試験
参考例３の未被覆の口腔内崩壊錠ならびに実施例５の被覆層を有する口腔内崩壊錠をシャーレ上に均一に広げ、白色蛍光灯１０００ＬＸの光照射下で１週間保管した。保管後、下記条件のＨＰＬＣ法により化合物Ｂおよびその類縁物質を測定した。化合物Ｂおよびその類縁物質に由来する総ピーク面積に対する光分解物（相対保持時間０．４３）の面積百分率（％）を算出し、光安定性を評価した。
カラム：液体クロマトグラフィー用フェニルヘキシルシリル化シリカゲル
移動相：過塩素酸溶液（１→１０００）とメタノール／アセトニトリル混液（１７：３）の混合比を変えて濃度勾配制御
流量：約１．２ｍＬ／ｍｉｎ
測定波長：２８８ｎｍ
(Test Example 4) Photostability test The uncoated orally disintegrating tablet of Reference Example 3 and the orally disintegrating tablet having the coating layer of Example 5 were spread uniformly on a chalet and under the light irradiation of a white fluorescent lamp 1000LX. Stored for 1 week. After storage, compound B and related substances thereof were measured by the HPLC method under the following conditions. The area percentage (%) of the photodegraded product (relative retention time 0.43) with respect to the total peak area derived from compound B and its related substances was calculated, and the photostability was evaluated.
Column: Phenylhexyl silylated silica gel for liquid chromatography Mobile phase: Concentration gradient control flow rate by changing the mixing ratio of perchloric acid solution (1 → 1000) and methanol / acetonitrile mixed solution (17: 3): Approximately 1.2 mL / min
Measurement wavelength: 288 nm
参考例３の未被覆の口腔内崩壊錠の光分解物は０．０８８％（総照度１２０万ｌｘ・ｈｒ）であったのに対し、実施例５の被覆層を有する口腔内崩壊錠の光分解物は０．０２８％（総照度１２０万ｌｘ・ｈｒ）であった。着色剤を含有する被覆層を設けた実施例５では、光に不安定な薬物の光安定化効果を示した。
The photodegradable product of the uncoated orally disintegrating tablet of Reference Example 3 was 0.088% (total illuminance of 1.2 million lux · hr), whereas the light of the orally disintegrating tablet having the coating layer of Example 5 was obtained. The decomposition product was 0.028% (total illuminance 1.2 million lux · hr). In Example 5 in which the coating layer containing the colorant was provided, the light-stabilizing effect of the light-unstable drug was shown.
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