JP5502358B2 - Oral rapidly disintegrating tablet and method for producing the same - Google Patents
Oral rapidly disintegrating tablet and method for producing the same Download PDFInfo
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- JP5502358B2 JP5502358B2 JP2009088842A JP2009088842A JP5502358B2 JP 5502358 B2 JP5502358 B2 JP 5502358B2 JP 2009088842 A JP2009088842 A JP 2009088842A JP 2009088842 A JP2009088842 A JP 2009088842A JP 5502358 B2 JP5502358 B2 JP 5502358B2
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- disintegration
- pharmaceutical
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- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- DVQHRBFGRZHMSR-UHFFFAOYSA-N sodium methyl 2,2-dimethyl-4,6-dioxo-5-(N-prop-2-enoxy-C-propylcarbonimidoyl)cyclohexane-1-carboxylate Chemical compound [Na+].C=CCON=C(CCC)[C-]1C(=O)CC(C)(C)C(C(=O)OC)C1=O DVQHRBFGRZHMSR-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 239000003232 water-soluble binding agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Description
本発明は、医薬品、食品等の分野において利用される、口腔内の唾液又は少量の水の存在下において速やかにかつ良好に崩壊する口腔内速崩壊性錠剤及びその製造方法に関する。 The present invention relates to a rapidly disintegrating tablet in the oral cavity that is rapidly and satisfactorily disintegrated in the presence of saliva or a small amount of water in the oral cavity, and a method for producing the same.
医薬品、食品等の分野における経口固形製剤の剤形としては、錠剤、カプセル剤、顆粒剤、散剤等が一般的に知られている。しかしながら、これらの剤形で取り扱い性が良く、かつ服用しやすいものは少ない。例えば、錠剤及びカプセル剤に関しては、その形状が大きくなるにつれ飲み込みにくくなるという問題があり、また、顆粒剤及び散剤に関しては、服用時にむせるという問題や歯の間に入り込むという問題がある。更に、これらの剤形はいずれも服用時に水を必要とし、緊急時や、重症患者が寝ながらにして服用することは困難であるという問題もある。 Tablets, capsules, granules, powders and the like are generally known as dosage forms for oral solid preparations in the fields of pharmaceuticals, foods and the like. However, few of these dosage forms are easy to handle and easy to take. For example, tablets and capsules have a problem that it becomes difficult to swallow as the shape increases, and granules and powders have a problem that they are peeled off when taken and a problem that they enter between teeth. Further, all of these dosage forms require water at the time of taking, and there is a problem that it is difficult to take while sleeping in an emergency or a serious patient.
また、水なしで服用できる剤形としては、錠剤を噛み砕いて服用するチュアブル錠が知られているが、現在提供されているものは崩壊性が低く、咀嚼力の弱い老人や小児には適しているとは言い難いものである。すなわち、崩壊性を上げるためには、錠剤の硬度を低下させることが考えられるが、錠剤の製造作業中や輸送中などでの破損を防ぐためには、ある程度の硬度が必要であり、このために崩壊性が高いチュアブル錠の提供が困難であった。 In addition, chewable tablets are known as dosage forms that can be taken without water, but those currently available are low in disintegration and suitable for the elderly and children with weak chewing ability. It's hard to say. That is, in order to increase disintegration, it is conceivable to reduce the hardness of the tablet, but in order to prevent breakage during tablet manufacturing operations or transportation, a certain degree of hardness is required. It was difficult to provide chewable tablets with high disintegration.
従って、上記に示した観点から、患者が水なしでも容易に服用することができ、また手軽に何時、何処でも随時服用することのできる口腔内速崩壊性錠剤の開発が要望されており、この目的を達成する技術もいくつか知られている。 Therefore, in view of the above, there has been a demand for the development of an orally rapidly disintegrating tablet that can be easily taken by patients without water, and can be taken easily at any time and anywhere. Several techniques for achieving the objective are also known.
このような口腔内速崩壊性錠剤を製造する技術としては、活性成分及び糖類を寒天水溶液に懸濁させたものをPTP包装用樹脂フィルムシートの鋳型に充填した後、ゼリー状に固化させ、更に減圧乾燥若しくは通風乾燥して製造する方法(特許文献1参照)や薬剤、水溶性結合剤及び水溶性賦形剤を含む乾燥状態の錠剤材料を必要最低限の低圧力で加圧成形した後、成形された錠剤を加湿し、更に加湿された錠剤を乾燥させて製造する方法(特許文献2)が知られている。しかしながら、これらの方法においては、特殊な製造設備を必要し、更にそれに関わる製造工程が煩雑であるという問題があった。 As a technique for producing such an intraoral rapidly disintegrating tablet, a suspension of an active ingredient and a saccharide in an agar aqueous solution is filled in a mold of a resin film sheet for PTP packaging, and then solidified into a jelly shape. After pressure-drying the tablet material in a dry state containing a method (see Patent Document 1), a drug, a water-soluble binder, and a water-soluble excipient by vacuum drying or ventilation drying, There is known a method (Patent Document 2) in which a molded tablet is humidified and then the humidified tablet is dried. However, these methods have a problem that a special manufacturing facility is required, and the manufacturing process related to it is complicated.
そのため、通常の製造設備により製造可能であり、かつ口腔内で優れた崩壊性を示すと共に実用上問題のない適度な硬度を有する製剤の開発が望まれていた。 Therefore, it has been desired to develop a preparation that can be produced by ordinary production equipment, has excellent disintegration properties in the oral cavity, and has an appropriate hardness with no practical problems.
従って、本発明は複雑な製造工程や特殊な装置を使用しないで製造でき、且つ使用時に口腔内で速やかな崩壊性を有するとともに実用上問題とならない錠剤硬度を有する医薬として優れた口腔内速崩壊性錠剤及びその製造方法の提供をその課題とするものである。 Therefore, the present invention can be manufactured without using a complicated manufacturing process or a special device, and has a rapid disintegration property in the oral cavity at the time of use, and an excellent intraoral rapid disintegration as a pharmaceutical having a tablet hardness that does not cause a practical problem. It is an object of the present invention to provide a functional tablet and a method for producing the same.
本発明者らは、上記課題を解決するために鋭意検討した結果、医薬有効成分と、D−マンニトール及び/又は乳糖水和物と、ポビドンと、メタケイ酸アルミン酸マグネシウム、合成ケイ酸アルミニウム、軽質無水ケイ酸及び結晶セルロースから選ばれる1種または2種以上と、クロスポビドンを含有する医薬担体との造粒品又は混合品を製造し、次いでこれを圧縮成型することにより、複雑な製造工程や特殊な装置を使用することなく、硬度及び崩壊時間の点において、公知の方法によって製造された製剤と同等もしくはそれ以上の性能を有する口腔内速崩壊性錠剤が製造可能であることを見出し、本発明を完成した。 As a result of intensive studies to solve the above problems, the present inventors have found that the active pharmaceutical ingredient, D-mannitol and / or lactose hydrate, povidone, magnesium aluminate metasilicate, synthetic aluminum silicate, light By producing a granulated product or a mixture of one or more selected from silicic acid anhydride and crystalline cellulose and a pharmaceutical carrier containing crospovidone, and then compression molding this, a complicated production process or It was found that an intraorally rapidly disintegrating tablet having the same or better performance than a preparation produced by a known method in terms of hardness and disintegration time can be produced without using a special device. Completed the invention.
すなわち、本発明は、医薬有効成分と、下記の成分(a)〜(d)を含有する医薬担体との造粒品又は混合品を製造し、次いでこれを圧縮成型することを特徴とする口腔内速崩壊性錠剤の製造方法を提供するものである。
(a)D−マンニトール及び/又は乳糖水和物
(b)ポビドン
(c)メタケイ酸アルミン酸マグネシウム、合成ケイ酸アルミニウム、軽質無水ケイ酸
及び結晶セルロースから選ばれる1種または2種以上
(d)クロスポビドン
That is, the present invention provides an oral cavity characterized by producing a granulated product or a mixed product of a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (d), and then compression-molding the product. The present invention provides a method for producing an internally disintegrating tablet.
(A) D-mannitol and / or lactose hydrate (b) povidone (c) one or more selected from magnesium aluminate metasilicate, synthetic aluminum silicate, light anhydrous silicic acid and crystalline cellulose (d) Crospovidone
本発明の口腔内速崩壊性錠剤は、口腔内で優れた崩壊性を示すと共に実用上問題のない適度な硬度を有する製剤であるため、服用性にも優れたものである。 The intraoral rapidly disintegrating tablet of the present invention is a preparation that exhibits excellent disintegration properties in the oral cavity and has an appropriate hardness with no practical problems, and therefore has excellent dosing properties.
本発明の口腔内速崩壊性錠剤(以下、「本錠剤」という)は、医薬有効成分と医薬担体により構成されるものである。 The intraoral rapidly disintegrating tablet (hereinafter referred to as “the present tablet”) of the present invention is composed of a pharmaceutical active ingredient and a pharmaceutical carrier.
本錠剤の医薬有効成分は、口腔内で嚥下困難でない程度に、苦み、渋み等の不快感を有せず、経口投与可能な薬物であれば特に制限無く使用することができる。また、これらの薬物は本発明の効果に支障のない範囲で配合することができ、その配合できる範囲は薬物の性質等によって異なる。 The pharmaceutical active ingredient of this tablet can be used without particular limitation as long as it is a drug that can be administered orally without causing discomfort such as bitterness and astringency to the extent that it is not difficult to swallow in the oral cavity. In addition, these drugs can be blended within a range that does not hinder the effects of the present invention, and the blendable range varies depending on the properties of the drug.
また、本錠剤の医薬担体のうち、成分(a)であるD−マンニトールは、糖アルコール類として、また、乳糖水和物は、糖類として各々よく知られているものである。これらは、製剤分野で一般的に使用され得るものであれば、いずれも使用することができる。この成分(a)の配合量は、医薬担体全体に対し、10ないし90質量%(以下単に「%」で示す)程度であり、20ないし80%が好ましい。 Among the pharmaceutical carriers of this tablet, D-mannitol which is component (a) is well known as a sugar alcohol, and lactose hydrate is well known as a saccharide. Any of these can be used as long as it can be generally used in the field of pharmaceutical preparations. The amount of component (a) is about 10 to 90% by mass (hereinafter simply referred to as “%”), preferably 20 to 80%, based on the entire pharmaceutical carrier.
また、本錠剤の医薬担体のうち、成分(b)であるポビドンは、ポリビニルピロリドンとも呼ばれる高分子化合物である。このポビドンは、製剤分野で一般的に使用され得るものであれば、いずれも使用することができる。このポビドンとしては、例えばプラスドンK−25(K値:25)、プラスドンK−29/32(K値:29〜32)、プラスドンK−90(K値:90)、プラスドンK−90D(K値:90)、プラスドンK−90M(K値:90)(いずれも商品名、ISPジャパン)、コリドン25(K値:25)、コリドン30(K値:30)、コリドン90F(K値:90)(いずれも商品名、BASFジャパン)等が挙げられる。この成分(b)の配合量は、医薬担体全体に対し、0.1ないし20%程度であり、1ないし10%が好ましい。 Of the pharmaceutical carriers of the tablet, povidone as component (b) is a polymer compound also called polyvinylpyrrolidone. Any povidone can be used as long as it can be generally used in the pharmaceutical field. As this povidone, for example, Plusdon K-25 (K value: 25), Plusdon K-29 / 32 (K value: 29 to 32), Plusdon K-90 (K value: 90), Plusdon K-90D (K value) : 90), Plusdon K-90M (K value: 90) (all trade names, ISP Japan), Kollidon 25 (K value: 25), Kollidon 30 (K value: 30), Kollidon 90F (K value: 90) (Both are trade names, BASF Japan). The amount of component (b) is about 0.1 to 20%, preferably 1 to 10%, based on the entire pharmaceutical carrier.
更に、本錠剤の医薬担体のうち、成分(c)は、メタケイ酸アルミン酸マグネシウム、合成ケイ酸アルミニウム、軽質無水ケイ酸および結晶セルロースから選ばれるものである。このうち、メタケイ酸アルミン酸マグネシウムとしては、ノイシリン、ノイシリンUFL2(いずれも商品名、富士化学工業)等が、合成ケイ酸アルミニウムとしては、重質、軽質、特軽質の合成ケイ酸アルミニウム(協和化学工業)等が、軽質無水ケイ酸としては、アドソリダー101(商品名、フロイント産業)が、結晶セルロースとしては、セオラスUF−702、セオラスUF−711、セオラスKG−802、セオラスKG−1000 、セオラスPH−101、セオラスPH−101D、セオラスPH−102、セオラスPH−301、セオラスPH−301D、セオラスPH−301Z、セオラスPH−302、セオラスPH−F20JP(いずれも商品名、旭化成ケミカルズ)等が挙げられる。これらの成分は、ここに列挙されたものに限らず、製剤分野で一般的に使用され得るものであれば、いずれも使用することができる。この成分(c)の配合量は、医薬担体全体に対し、0.1ないし20%程度であり、1ないし10%が好ましい。 Furthermore, among the pharmaceutical carriers of the present tablet, component (c) is selected from magnesium metasilicate aluminate, synthetic aluminum silicate, light anhydrous silicic acid and crystalline cellulose. Of these, magnesium metasilicate aluminate is Neusilin, Neusilin UFL2 (both trade names, Fuji Chemical Industry), and synthetic aluminum silicate is heavy, light and extraordinary synthetic aluminum silicate (Kyowa Chemical). Industrial), etc., as light anhydrous silicic acid, AdSolider 101 (trade name, Freund Industries), and as crystalline cellulose, Theolas UF-702, Theolas UF-711, Theolas KG-802, Theolas KG-1000, Theolas PH -101, Theolas PH-101D, Theolas PH-102, Theolas PH-301, Theolas PH-301D, Theolas PH-301Z, Theolas PH-302, Theolas PH-F20JP (all are trade names, Asahi Kasei Chemicals) . These components are not limited to those listed here, and any of those that can be generally used in the pharmaceutical field can be used. The amount of component (c) is about 0.1 to 20%, preferably 1 to 10%, based on the entire pharmaceutical carrier.
更にまた、本錠剤の医薬担体の成分(d)であるクロスポビドンは、架橋型のポリビニルピロリドンであり、製剤分野で一般的に使用され得るものであれば、いずれも使用することができる。この成分(d)の配合量は、医薬担体全体に対し、0.1ないし20%程度であり、1ないし10%が好ましい。 Furthermore, crospovidone which is the component (d) of the pharmaceutical carrier of the tablet is a cross-linked polyvinyl pyrrolidone, and any can be used as long as it can be generally used in the pharmaceutical field. The amount of component (d) is about 0.1 to 20%, preferably 1 to 10%, based on the entire pharmaceutical carrier.
上記した各成分を用いて、本錠剤を製造するには、まず、上記医薬有効成分と医薬担体との造粒品又は混合品を製造し、次いでこれを圧縮成型すればよい。 In order to produce the tablet using each of the above-described components, first, a granulated product or a mixed product of the pharmaceutically active ingredient and a pharmaceutical carrier is produced, and then this is compression molded.
上記製造における造粒処理としては湿式造粒処理、乾式造粒処理及び流動層造粒処理が挙げられ、特に湿式造粒処理が好ましい。 Examples of the granulation treatment in the production include wet granulation treatment, dry granulation treatment and fluidized bed granulation treatment, and wet granulation treatment is particularly preferable.
湿式造粒処理は、医薬有効成分と医薬担体とを混合した後、これを溶媒と練合し、次いでこれを造粒する処理である。この処理においては、破砕造粒法、押出し造粒法、攪拌造粒法、転動造粒法等の一般的な製剤の製造に用いられる方法や装置を使用することができる。また、この処理で用いられる溶媒として、一般的な製剤の製造に用いられるエタノール、イソプロパノール等のアルコール類や水を溶媒として使用することができる。 The wet granulation treatment is a treatment in which a pharmaceutically active ingredient and a pharmaceutical carrier are mixed, kneaded with a solvent, and then granulated. In this treatment, methods and apparatuses used for production of general preparations such as crushing granulation method, extrusion granulation method, stirring granulation method, and rolling granulation method can be used. In addition, as a solvent used in this treatment, alcohols such as ethanol and isopropanol used for production of general preparations and water can be used as a solvent.
乾式造粒処理は、医薬有効成分と医薬担体とを混合した後、これを篩過し、次いでこれを造粒する処理である。この処理においては、圧縮造粒法等の一般的な製剤の製造に用いられる方法や装置を使用することができる。 The dry granulation treatment is a treatment in which a pharmaceutically active ingredient and a pharmaceutical carrier are mixed, sieved, and then granulated. In this treatment, a method or apparatus used for production of general preparations such as compression granulation can be used.
流動層造粒処理は、医薬有効成分と医薬担体とを混合した後、これと溶媒もしくは溶媒と結合剤との混合液等を噴霧しながら造粒する処理である。この処理においては、流動層造粒法等の一般的な製剤の製造に用いられる方法や装置を使用することができる。 The fluidized bed granulation process is a process in which a pharmaceutically active ingredient and a pharmaceutical carrier are mixed and then granulated while spraying a mixed solution of the solvent and a solvent and a binder or the like. In this treatment, a method or apparatus used for production of a general preparation such as a fluidized bed granulation method can be used.
上記の造粒処理により得られた造粒品の圧縮成型には、例えばロータリー式打錠機や単発打錠機の一般に錠剤の成型に使用される方法や装置を使用することができる。また、この圧縮成型における圧縮圧としては、100kgf/cm2〜2000kgf/cm2が好ましい。 For compression molding of the granulated product obtained by the above granulation treatment, for example, a method or an apparatus generally used for molding a tablet of a rotary tableting machine or a single tableting machine can be used. As the compression pressure in the compression molding, 100kgf / cm 2 ~2000kgf / cm 2 is preferred.
なお、上記圧縮成型に先立ち、造粒品を、例えば、流動層乾燥機や棚式乾燥装置を用いた乾燥、スクリーンミル、ジェットミル、ハンマーミル、ピンミルを用いた整粒、振動ふるいを用いた篩過等の製剤の製造に必要な操作に付しても良い。 Prior to the compression molding, the granulated product was dried using, for example, a fluidized bed dryer or a shelf dryer, a screen mill, a jet mill, a hammer mill, a pin mill using a pin mill, or a vibrating screen. You may attach to operation required for manufacture of preparations, such as sieving.
更に、本錠剤には発明の効果に支障のない限り、製剤分野で一般的に使用され得る添加剤を配合しても良い。これらの添加剤は、主に医薬担体中に配合されるが、その例としては、賦形剤、結合剤、嬌味剤、流動化剤、滑沢剤、着色剤、香料、甘み剤等が挙げられる。このうち、賦形剤としては、例えば果糖、ショ糖、ブドウ糖、トレハロース等の糖類、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、コメデンプン等のデンプン類、キシリトール、エリスリトール、ソルビトール、マルチトール等の糖アルコール類、粉末セルロース等のセルロース類、結合剤としては、例えばカルメロースナトリウム、エチルセルロース、アラビアゴム、アルギン酸ナトリウム、デキストリン、ゼラチン、プルラン、ヒプロメロース、ポリビニルアルコール、メチルセルロース、カルボキシビニルポリマー等が、矯味剤としては、例えばクエン酸、酒石酸、リンゴ酸、アスコルビン酸、塩化ナトリウム等が挙げられる。また、滑沢剤としては、例えば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、ショ糖脂肪酸エステル等が、着色剤としては、例えば食用色素、食用レーキ色素、三二酸化鉄、黄色三二酸化鉄等が挙げられる。更に、香料としては、例えばウイキョウ油、オレンジ油、カミツレ油、スペアミント油、ケイヒ油、チョウジ油、ハッカ油、ベルガモット油、ユーカリ油、ラベンダー油、レモン油、ローズ油、ローマカミツレ油、メントール等が、甘味剤としては、例えばアスパルテーム、アセスルファムカリウム、サッカリン、サッカリンナトリウム、グリチルリチン酸二カリウム、ステビア、ソーマチン、スクラロース等が挙げられる。これらの添加剤は単独あるいは併用して使用することができる。 Furthermore, as long as there is no hindrance to the effect of the invention, the tablet may be blended with additives that can be generally used in the pharmaceutical field. These additives are mainly blended in a pharmaceutical carrier. Examples thereof include excipients, binders, flavoring agents, fluidizing agents, lubricants, coloring agents, flavoring agents, sweetening agents, and the like. Can be mentioned. Among these, excipients include, for example, sugars such as fructose, sucrose, glucose and trehalose, starches such as corn starch, potato starch, wheat starch and rice starch, and sugar alcohols such as xylitol, erythritol, sorbitol and maltitol As cellulose, powdered cellulose and other binders, for example, carmellose sodium, ethyl cellulose, gum arabic, sodium alginate, dextrin, gelatin, pullulan, hypromellose, polyvinyl alcohol, methylcellulose, carboxyvinyl polymer, etc. Examples thereof include citric acid, tartaric acid, malic acid, ascorbic acid, sodium chloride and the like. Examples of the lubricant include magnesium stearate, calcium stearate, talc, and sucrose fatty acid ester. Examples of the colorant include edible dyes, edible lake dyes, iron sesquioxide, and yellow iron sesquioxide. . Furthermore, examples of the fragrances include fennel oil, orange oil, chamomile oil, spearmint oil, cinnamon oil, clove oil, mint oil, bergamot oil, eucalyptus oil, lavender oil, lemon oil, rose oil, roman chamomile oil, menthol and the like. Examples of the sweetening agent include aspartame, acesulfame potassium, saccharin, saccharin sodium, dipotassium glycyrrhizinate, stevia, thaumatin, sucralose and the like. These additives can be used alone or in combination.
このようにして得られる本錠剤は、実用上問題ない適度な硬度、好ましくは5kgf以上の硬度を有し、更に口腔内での優れた崩壊性、好ましくは日本薬局方の崩壊試験による崩壊時間が30秒以内の崩壊性を有しているものである。 The tablet thus obtained has an appropriate hardness with no practical problem, preferably a hardness of 5 kgf or more, and has excellent disintegration properties in the oral cavity, preferably the disintegration time according to the disintegration test of the Japanese Pharmacopoeia. It has a disintegration property within 30 seconds.
以下、実施例および比較例を挙げて本発明をさらに詳しく説明するが、これらは本発明を何ら限定するものではない。 EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated in more detail, these do not limit this invention at all.
実 施 例 1
下記表1に示す処方および下記製法により、本発明品1ないし5の本錠剤および比較品1ないし5の比較錠剤を製造した。得られた本発明品および比較品について、下記試験方法により、その硬度および崩壊時間を測定した。この結果も表1中に示す。
Example 1
According to the formulation shown in the following Table 1 and the following production method, the present tablets 1 to 5 and the comparative tablets 1 to 5 were produced. The obtained product of the present invention and comparative product were measured for hardness and disintegration time by the following test methods. The results are also shown in Table 1.
なお、使用した商品名またはグレード、並びにメーカーまたは取扱業者は次のとおりである。D−マンニトール(マンニット−S、三菱商事フードテック)、乳糖水和物(200M、DMV)、トレハロース(トレハロースP、旭化成ケミカルズ)、エリスリトール(微粉、三菱化学フーズ)キシリトール(キシリットP、東和化成工業)、ソルビトール(ソルビットDP−50M、物産フードサイエンス)、グリシン(微粉、有機合成薬品工業)、メタケイ酸アルミン酸マグネシウム(ノイシリンUFL2、富士化学工業)、軽質無水ケイ酸(アドソリダー101、フロイント産業)合成ケイ酸アルミニウム(軽質、協和化学工業)、結晶セルロース(セオラスPH―101、旭化成ケミカルズ)、ポビドン(プラスドンK−29/30、ISPジャパン)、ヒドロキシプロピルセルロース(HPC−L、日本曹達)、クロスポビドン(コリドンCL−F、BASFジャパン)、クロスカルメロースナトリウム(キッコレートND−200、ニチリン化学工業)、カルメロース(NS−300、ニチリン化学工業)、低置換度ヒドロキシプロピルセルロース(LH−11、信越化学工業)、カルメロースカルシウム(ECG−505、ニチリン化学工業)、クエン酸水和物(100M、小松屋化学) The product names or grades used, and the manufacturers or dealers are as follows. D-mannitol (Mannit-S, Mitsubishi Corporation Foodtech), lactose hydrate (200M, DMV), trehalose (Trehalose P, Asahi Kasei Chemicals), erythritol (fine powder, Mitsubishi Chemical Foods) xylitol (Xylit P, Towa Kasei Kogyo) ), Sorbitol (Sorbit DP-50M, product food science), glycine (fine powder, organic synthetic chemical industry), magnesium metasilicate aluminate (Neusilin UFL2, Fuji Chemical Industry), light anhydrous silicic acid (Adsolider 101, Freund Industries) Aluminum silicate (light, Kyowa Chemical Industry), crystalline cellulose (Theolas PH-101, Asahi Kasei Chemicals), povidone (Prasdon K-29 / 30, ISP Japan), hydroxypropyl cellulose (HPC-L, Nippon Soda), crospovid (Kollidon CL-F, BASF Japan), croscarmellose sodium (Kickolate ND-200, Nichirin Chemical Industry), carmellose (NS-300, Nichirin Chemical Industry), low-substituted hydroxypropylcellulose (LH-11, Shin-Etsu Chemical Industry) ), Carmellose calcium (ECG-505, Nichirin Chemical Industries), citric acid hydrate (100M, Komatsuya Chemical)
< 製 法 >
表中の有効成分及び(a)成分を撹拌造粒機で混合した後、造粒溶媒であるエタノール250gを徐々に加えて練合した。次に、この練合品を棚式乾燥機で乾燥した後、この乾燥品を整粒した。更に、この整粒品に上記以外の成分を加えて、混合した後、打錠機を用い、1000kgf/cm2の打錠圧で、1錠の直径が8.5mmで、その質量が240mgの錠剤を得た。
<Production method>
After mixing the active ingredient and the component (a) in the table with a stirring granulator, 250 g of ethanol as a granulating solvent was gradually added and kneaded. Next, after drying this kneaded product with a shelf dryer, the dried product was sized. Furthermore, after adding ingredients other than the above to this sized product and mixing, using a tableting machine, the tablet diameter is 8.5 mm and the mass is 240 mg at a tableting pressure of 1000 kgf / cm 2 . Tablets were obtained.
< 試験方法 >
硬度試験:
試験は、錠剤硬度計(富山産業製)を用いて実施し、試験数は10錠とし、その硬度の平均値で評価した。
<Test method>
Hardness test:
The test was carried out using a tablet hardness tester (manufactured by Toyama Sangyo Co., Ltd.), the number of tests was 10 tablets, and the average value of the hardness was evaluated.
崩壊試験:
試験は、日本薬局方による崩壊試験法を参考に、崩壊試験器(富山産業製)を用いて実施し、試験数は6錠とし、その崩壊時間の平均値で評価した。
Disintegration test:
The test was conducted using a disintegration tester (manufactured by Toyama Sangyo Co., Ltd.) with reference to the disintegration test method by the Japanese Pharmacopoeia, and the number of tests was 6 tablets, and the average value of disintegration time was evaluated.
表1の結果から明らかなように、本発明品1ないし5は、いずれも5ないし6kgf程度の実用上問題ない硬度と、日本薬局方の崩壊試験による崩壊時間が11ないし16秒程度と優れた崩壊性を示すものであった。これに対し、比較品では、錠剤硬度が高いものは、崩壊性が悪く(比較品1、3、4)、逆に崩壊性が良いものは、錠剤硬度が極めて低く(比較品2、5)、実用性のあるものではなかった。 As is clear from the results in Table 1, the products 1 to 5 of the present invention are excellent in hardness that is practically no problem of about 5 to 6 kgf and a disintegration time of about 11 to 16 seconds according to the disintegration test of the Japanese Pharmacopoeia. It was disintegrating. On the other hand, in comparative products, those with high tablet hardness have poor disintegration properties (Comparative products 1, 3, 4), and conversely those with good disintegration properties have extremely low tablet hardness (Comparative products 2, 5). It was not practical.
この結果から、本発明の口腔内速崩壊型錠剤には、(a)D−マンニトール及び/又は乳糖水和物が極めて重要であることが示された。 From this result, it was shown that (a) D-mannitol and / or lactose hydrate are extremely important for the intraoral rapidly disintegrating tablet of the present invention.
比 較 例 1
本発明の各担体成分の作用を確認するため、表2の処方、実施例1の製法により、比較品6ないし11の比較錠剤を製造した。得られた各比較錠剤について、実施例1と同様にその硬度および崩壊時間を測定した。この結果も表2中に示す。
Comparative Example 1
In order to confirm the action of each carrier component of the present invention, comparative tablets 6 to 11 were produced according to the formulation shown in Table 2 and the production method of Example 1. About each obtained comparative tablet, the hardness and disintegration time were measured similarly to Example 1. The results are also shown in Table 2.
表2の結果から明らかなように、比較品6ないし11では、ある程度の崩壊性は得られるものの、錠剤の硬度が5kgf以下と低く、本発明品1のように、崩壊性と錠剤の硬度を両立させることはできなかった。 As is apparent from the results in Table 2, the comparative products 6 to 11 have a certain level of disintegration, but the hardness of the tablet is as low as 5 kgf or less. It was not possible to achieve both.
この結果から、本発明の口腔内速崩壊型錠剤には、(b)ポビドンと、(c)メタケイ酸アルミン酸マグネシウム、合成ケイ酸アルミニウム、軽質無水ケイ酸及び結晶セルロースから選ばれる1種または2種以上と、(d)クロスポビドンの配合が必須であることが判明した。 From this result, in the intraoral quick disintegrating tablet of the present invention, one or two selected from (b) povidone, (c) magnesium aluminate metasilicate, synthetic aluminum silicate, light anhydrous silicic acid and crystalline cellulose. It was found that blending of more than seeds and (d) crospovidone was essential.
実 施 例 2
有効成分および成分(a)の配合量を表3に示すように変更し、実施例1に示す製法で本発明品6〜8の本錠剤を調製した。得られた錠剤について、実施例1と同様にしてその硬度および崩壊時間を測定した。この結果も表3中に示す。
Example 2
The active ingredient and the amount of component (a) were changed as shown in Table 3, and the tablets of the present invention products 6 to 8 were prepared by the production method shown in Example 1. About the obtained tablet, it carried out similarly to Example 1, and measured the hardness and disintegration time. The results are also shown in Table 3.
この結果から明らかなように医薬有効成分を代えても、(a)D−マンニトール及び/又は乳糖水和物と、(b)ポビドンと、(c)メタケイ酸アルミン酸マグネシウム、合成ケイ酸アルミニウム、軽質無水ケイ酸及び結晶セルロースから選ばれる1種または2種以上と、(d)クロスポビドンを配合することで、崩壊性と錠剤硬度を両立させた口腔内速崩壊型錠剤が得られることが示された。 As is clear from this result, even if the active pharmaceutical ingredient is replaced, (a) D-mannitol and / or lactose hydrate, (b) povidone, (c) magnesium aluminate metasilicate, synthetic aluminum silicate, It is shown that by incorporating one or more selected from light silicic anhydride and crystalline cellulose and (d) crospovidone, an intraoral rapidly disintegrating tablet having both disintegration property and tablet hardness can be obtained. It was done.
本発明の口腔内速崩壊型錠剤は、複雑な製造工程や特殊な装置を使用しないで製造できるものであり、かつ、優れた成型性と崩壊性を兼ね備えたものである。 The intraoral quick disintegrating tablet of the present invention can be manufactured without using a complicated manufacturing process or a special apparatus, and has both excellent moldability and disintegrating property.
従って、このものは、工業的な大規模生産に適すると同時に、口腔内で優れた崩壊性を示すと共に実用上問題のない適度な硬度を有する製剤として、種々の医薬有効成分を配合することのできる口腔内崩壊剤として、広く利用可能なものである。 Therefore, this product is suitable for industrial large-scale production, and at the same time exhibits excellent disintegration properties in the oral cavity and has a suitable hardness with no practical problems. It can be widely used as an orally disintegrating agent.
Claims (2)
(a)D−マンニトール及び/又は乳糖水和物
(b)ポビドン
(c)メタケイ酸アルミン酸マグネシウム、合成ケイ酸アルミニウム及び軽質無水ケイ酸から選ばれる1種または2種以上
(d)クロスポビドン It is obtained by producing a granulated product or mixed product of an active pharmaceutical ingredient and a pharmaceutical carrier containing the following components (a) to (d), and then compressing only this, and the hardness is 5 kgf or more. In addition, rapidly disintegrating tablets in the oral cavity whose disintegration time is 30 seconds or less in the disintegration test by the Japanese Pharmacopoeia (except for those containing crystalline cellulose).
(A) D-mannitol and / or lactose hydrate (b) povidone (c) one or more selected from magnesium metasilicate aluminate, synthetic aluminum silicate and light anhydrous silicic acid (d) crospovidone
(a)D−マンニトール及び/又は乳糖水和物
(b)ポビドン
(c)メタケイ酸アルミン酸マグネシウム、合成ケイ酸アルミニウム及び軽質無水ケイ酸から選ばれる1種または2種以上
(d)クロスポビドン
A hardness characterized by producing a granulated product or a mixture of a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (d), and then only compression molding this: A method for producing an orally rapidly disintegrating tablet (excluding those containing crystalline cellulose) whose disintegration time in a disintegration test by the Japanese Pharmacopoeia is within 30 seconds.
(A) D-mannitol and / or lactose hydrate (b) povidone (c) one or more selected from magnesium metasilicate aluminate, synthetic aluminum silicate and light anhydrous silicic acid (d) crospovidone
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