JP2005029557A - Quickly disintegrating tablet in oral cavity and method for producing the same - Google Patents
Quickly disintegrating tablet in oral cavity and method for producing the same Download PDFInfo
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- JP2005029557A JP2005029557A JP2004061769A JP2004061769A JP2005029557A JP 2005029557 A JP2005029557 A JP 2005029557A JP 2004061769 A JP2004061769 A JP 2004061769A JP 2004061769 A JP2004061769 A JP 2004061769A JP 2005029557 A JP2005029557 A JP 2005029557A
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- Prior art keywords
- tablet
- trehalose
- disintegrating tablet
- examples
- mixture
- Prior art date
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- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
本発明は、口腔内速崩壊性錠剤に関し、更に詳細には、医薬品、食品等の分野において利用される、水なしでも口腔内で良好な崩壊性を有する口腔内速崩壊性錠剤およびその製造方法に関する。 The present invention relates to an orally rapidly disintegrating tablet, and more specifically, an intraorally rapidly disintegrating tablet that is used in the fields of pharmaceuticals, foods, and the like and has good disintegrability in the oral cavity without water, and a method for producing the same About.
医薬品、食品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、カプセル剤はその形状が大きくなるにつれ飲み込みにくくなるため、特に老人や小児においては大きな問題となる。また、顆粒剤、散剤は服用時にむせたり、歯の間に入り込むといった問題がある。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。 As dosage forms of oral solid preparations in the fields of pharmaceuticals and foods, tablets, capsules, granules, powders and the like are generally known. However, few of these dosage forms are easy to handle and easy to take. For example, tablets and capsules become difficult to swallow as the size of the tablets and capsules increases. In addition, granules and powders have problems such as being peeled off when taken or entering 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.
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、小児には適しているとは言い難いものである。 As dosage forms that can be taken without water, chewable tablets are known that are used by chewing tablets, but what is currently offered is low in disintegration and suitable for elderly people and children with low chewing ability. Is hard to say.
このような観点から、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。 From this point of view, there is a demand for the development of a rapidly disintegrating tablet in the oral cavity that can be easily taken by patients without water and can be taken easily at any time and anywhere. Some techniques are also known.
このような口腔内速崩壊性錠剤を作る技術としては、従来医薬成分を水性溶媒に溶解または懸濁させた後、ブリスターパックの予め成型したポケットに充填し、この溶液を凍結乾燥により、あるいは真空乾燥により水分を除去して製造する方法（特許文献１〜３等参照）や、湿らせた顆粒を低圧で打錠した後、乾燥して製造する方法（特許文献４および特許文献５参照）が知られている。しかし、これらの製造方法は特別な製造設備を使用し、また製造に長時間を必要とすることから、工業生産性に劣るという欠点があった。 As a technique for producing such an orally rapidly disintegrating tablet, a conventional pharmaceutical ingredient is dissolved or suspended in an aqueous solvent and then filled into a pre-molded pocket of a blister pack, and this solution is freeze-dried or vacuumed. There are a method for producing by removing moisture by drying (see Patent Documents 1 to 3, etc.) and a method for producing the granules after compressing the moistened granules at low pressure (see Patent Documents 4 and 5). Are known. However, these production methods use special production equipment and require a long time for production, and thus have a disadvantage of inferior industrial productivity.
また、従来より、無機化合物と糖類とを含む速崩壊性錠剤(特許文献６参照)や、糖類および崩壊剤を含む速崩壊錠（特許文献７参照）は知られていたが、いずれの方法も噴霧乾燥工程や、磨砕型粉砕器による共粉砕物の配合などの特別な工程または製造機器を要するものであり、通常最も広く利用されている造粒法である湿式造粒、乾式造粒や流動層造粒によって製造可能な処方の開発が期待されていた。 Conventionally, a fast disintegrating tablet containing an inorganic compound and a saccharide (see Patent Document 6) and a fast disintegrating tablet containing a saccharide and a disintegrating agent (see Patent Document 7) have been known. It requires a special process or manufacturing equipment such as spray drying process, blending of co-pulverized product by grinding type pulverizer, and is usually the most widely used granulation method, wet granulation, dry granulation, The development of a formulation that can be produced by fluidized bed granulation was expected.
このような観点から、通常の乾式打錠法により製造可能であり、かつ口腔内で優れた崩壊性と溶解性とを示すと共に製剤工程、更には流通過程において損傷することのない適度な強度を有する製剤の開発が望まれている。 From this point of view, it can be produced by a normal dry tableting method, and exhibits excellent disintegration and solubility in the oral cavity and has an appropriate strength that is not damaged in the preparation process and further in the distribution process. Development of the formulation which has is desired.
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医薬として優れた口腔内速崩壊性錠剤およ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 provides an intraorally rapidly disintegrating tablet that can be manufactured without using a complicated manufacturing process or a special device, and is excellent as a pharmaceutical having rapid disintegration in the oral cavity at the time of use, and a manufacturing method thereof. It is to be an issue.
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、トレハロースおよび／またはソルビトール、合成ケイ酸アルミニウムおよび崩壊剤を含有する医薬担体とを適当な比率で混合したもの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、硬度およ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 inventors have obtained a mixture of an active pharmaceutical ingredient and a pharmaceutical carrier containing trehalose and / or sorbitol, synthetic aluminum silicate and a disintegrant at an appropriate ratio. By compression molding, without using a complicated manufacturing process or special equipment, in terms of hardness and disintegration time, the oral disintegration has the same or better performance than the preparation manufactured by a known method. It was found that tablets can be produced, and the present invention was completed.
すなわち本発明は、医薬有効成分と、下記の成分（ａ）〜（ｃ）を含有する医薬担体とを混合して混合品とし、次いでこれを圧縮成型することにより得られる口腔内速崩壊性錠剤を提供するものである。
（ａ）トレハロースおよび／またはソルビトール
（ｂ）合成ケイ酸アルミニウム
（ｃ）崩壊剤
That is, the present invention relates to an orally rapidly disintegrating tablet obtained by mixing a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (c) into a mixed product and then compressing the mixture. Is to provide.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant
また、本発明は、医薬有効成分と、下記の成分（ａ）〜（ｃ）を含有する医薬担体とを混合して混合品とし、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）トレハロースおよび／またはソルビトール
（ｂ）合成ケイ酸アルミニウム
（ｃ）崩壊剤
In addition, the present invention is an intraoral rapid disintegration characterized by mixing an active pharmaceutical ingredient and a pharmaceutical carrier containing the following components (a) to (c) to form a mixture, and then compression-molding the mixture. The manufacturing method of a sexable tablet is provided.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant
本発明の口腔内速崩壊性錠剤は、口腔内で優れた崩壊性と溶解性とを示すと共に製剤工程や流通過程において損傷することのない適度な硬度を有する製剤であった。また、医薬有効成分である薬物が苦みを有するものであっても、医薬担体中に含まれる糖類の強いもしくは清涼感のある甘味により軽減されるので、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 and solubility in the oral cavity and has an appropriate hardness that is not damaged in the preparation process and distribution process. In addition, even if the drug which is an active pharmaceutical ingredient has bitterness, it is reduced by the strong or refreshing sweetness of the saccharide contained in the pharmaceutical carrier, so that it is excellent in ingestibility.
また、本発明は、複雑な製造工程や特殊な装置を使用しないで上記錠剤を製造できるため工業的な大規模生産に有用なものである。 Moreover, since the said tablet can be manufactured without using a complicated manufacturing process and a special apparatus, this invention is useful for industrial large-scale production.
従って、本発明によれば優れた成型性と崩壊性を兼ね備えた口腔内速崩壊性錠剤およびその製造方法を提供することができる。 Therefore, according to the present invention, an intraoral quick disintegrating tablet having excellent moldability and disintegrating property and a method for producing the same can be provided.
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。このような薬物としては鎮吐剤、催吐剤、鎮けい剤、鎮咳去たん剤、気管支拡張剤、不整脈用剤、強心剤、制酸剤、健胃消化剤、消化性潰瘍剤、整腸剤、止しゃ剤、利胆剤、滋養強壮薬、血管収縮剤、血管拡張剤、血圧降下剤、利尿剤、高脂血症用剤、解熱鎮痛消炎剤、鎮暈剤、催眠鎮静剤、抗うつ薬、抗不安薬剤、向精神薬、抗てんかん剤、抗ヒスタミン剤、糖尿病用剤、痛風治療剤、骨粗鬆症用剤、抗生物質、腫瘍用薬、化学療法剤、抗パーキンソン剤等から選ばれる薬物の１種または２種以上が挙げられる。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が
、本錠剤中に５０質量％以下配合することができる。
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. Such drugs include antiemetics, emetics, antispasmodics, antitussives, bronchodilators, arrhythmic agents, cardiotonic agents, antacids, gastric digestives, peptic ulcers, intestinal adjusters, antistagnation agents, Antibacterial, antihypertensive, antihypertensive, antihypertensive, antihypertensive, antipyretic analgesic, antihypertensive agent, antihypertensive agent Examples include one or more drugs selected from psychotropic drugs, antiepileptic drugs, antihistamines, diabetes drugs, gout treatment drugs, osteoporosis drugs, antibiotics, tumor drugs, chemotherapeutic drugs, anti-parkinsonian drugs, etc. It is done. These drugs can be blended in a range that does not hinder the effects of the present invention, and the range in which these drugs can be blended varies depending on the properties of the drug, but can be blended in an amount of 50% by mass or less in the tablet.
具体的な薬物としては以下のものを挙げることができる。鎮吐剤としては、例えば塩酸オンダンセトロン、塩酸トロピセトロンなどが挙げられる。催吐剤としては、例えばメトクロプラミドなどが挙げられる。鎮けい剤としては、例えば塩酸パパベリン、バクロフェンなどが挙げられる。鎮咳去たん剤としては、例えば臭化水素酸デキストロメトルファン、グアヤコールスルホン酸カリウム、リン酸コデインなどが挙げられる。気管支拡張剤としては、例えばテオフィリン、硫酸サルブタモール、塩酸ツロブテロールなどが挙げられる。不整脈用剤としては、例えば塩酸プロカインアミド、塩酸プロプラノロールなどが挙げられる。強心剤としては、例えばジゴキシン、アミノフィリン、ユビデカレノンなどが挙げられる。制酸剤としては、例えば炭酸水素ナトリウム、炭酸マグネシウム、メタケイ酸アルミン酸マグネシウム、合成ヒドロタルサイトなどが挙げられる。健胃消化剤としては、例えばジアスターゼ、パンクレアチン、ケイヒ油などが挙げられる。消化性潰瘍剤としては、例えばファモチジン、ラニチジン、シメチジン、オメプラゾールなどが挙げられる。整腸剤としては、例えば塩化ベルベリン、有胞子性乳酸菌、ビフィズス菌などが挙げられる。止しゃ剤としては、例えば塩酸ロペラミドなどが挙げられる。利胆剤としては、例えばウルソデオキシコール酸などが挙げられる。滋養強壮薬としては、例えばビタミンＡ、ビタミンＢ類、ビタミンＣ、ビタミンＥなどのビタミン、アミノ酸、オリゴ糖、生薬などが含まれる。血管収縮剤としては、例えば塩酸フェニレフリン、塩酸エフェドリンなどが挙げられる。血管拡張剤としては、例えば硝酸イソソルビドなどが挙げられる。血圧降下剤としては、例えばカプトプリルなどのアンジオテンシン変換酵素阻害薬、塩酸ラベタロールなどのα、β遮断薬、ニフェジピン、塩酸ジルチアゼムなどのカルシウム拮抗薬などが挙げられる。利尿剤としてはイソソルビド、フロセミドなどが挙げられ有。高脂血症用剤としては、例えばプラバスタチンナトリウム、シンバスタチンなどが挙げられる。解熱鎮痛消炎剤としては、例えばアスピリン、アセトアミノフェン、イブプロフェン、ジクロフェナクナトリウム、インドメタシン、ケトプロフェンなどが挙げられる。鎮暈剤としては、例えば塩酸メクリジン、ジメンヒドリナートなどが挙げられる。催眠鎮静剤としては、例えばエスタゾラム、ニトラゼパムなどが挙げられる。抗うつ薬としては、例えばイミプラミンなどが挙げられる。抗不安薬としては、例えばジアゼパムなどが挙げられる。向精神薬としては、例えばクロルプロマジン、レセルピンなどが挙げられる。抗てんかん剤としては、例えばカルバマゼピン、フェニトインなどが挙げられる。抗ヒスタミン剤としては、例えば塩酸ジフェンヒドラミン、マレイン酸クロルフェニラミン、メキタジンなどが挙げられる。糖尿病用剤としては、例えばトルブタミド、トログリダゾン、アカルボースなどが挙げられる。痛風治療剤としては、例えば、コルヒチン、アロプリノールなどが挙げられる。骨粗鬆症用剤としては、例えばイプリフラボンなどが挙げられる。抗生物質としては、例えばセファクロル、アンピシリン、ジョサマイシン、ナリジスク酸などが挙げられる。腫瘍用薬としては、例えば、シクロホスファミド、フルオロウラシルなどが挙げられる。化学療法剤としては、例えばスルファメトキサゾールなどが挙げられる。抗パーキンソン剤としては、塩酸アマンタジン、レボドパなどが挙げられる。 Specific examples of the drug include the following. Examples of the antiemetic include ondansetron hydrochloride and tropisetron hydrochloride. Examples of the emetic include metoclopramide. Examples of the antispasmodic agent include papaverine hydrochloride and baclofen. Examples of antitussive removal agents include dextromethorphan hydrobromide, potassium guaiacol sulfonate, and codeine phosphate. Examples of bronchodilators include theophylline, salbutamol sulfate, and tulobuterol hydrochloride. Examples of the arrhythmic agent include procainamide hydrochloride and propranolol hydrochloride. Examples of the cardiotonic agent include digoxin, aminophylline, ubidecarenone and the like. Examples of the antacid include sodium hydrogen carbonate, magnesium carbonate, magnesium aluminate metasilicate, and synthetic hydrotalcite. Examples of the healthy stomach digestive agent include diastase, pancreatin, cinnamon oil and the like. Examples of the peptic ulcer agent include famotidine, ranitidine, cimetidine, omeprazole and the like. Examples of the intestinal regulating agent include berberine chloride, spore-forming lactic acid bacteria, and bifidobacteria. Examples of the anti-blocking agent include loperamide hydrochloride. Examples of the bile agent include ursodeoxycholic acid. Examples of nourishing tonics include vitamins such as vitamin A, vitamin B, vitamin C and vitamin E, amino acids, oligosaccharides, herbal medicines and the like. Examples of the vasoconstrictor include phenylephrine hydrochloride and ephedrine hydrochloride. Examples of the vasodilator include isosorbide nitrate. Examples of the antihypertensive agent include angiotensin converting enzyme inhibitors such as captopril, α and β blockers such as labetalol hydrochloride, and calcium antagonists such as nifedipine and diltiazem hydrochloride. Diuretics include isosorbide and furosemide. Examples of the hyperlipidemia agent include pravastatin sodium and simvastatin. Examples of antipyretic analgesic / anti-inflammatory agents include aspirin, acetaminophen, ibuprofen, diclofenac sodium, indomethacin, ketoprofen and the like. Examples of the antipruritic agent include meclizine hydrochloride and dimenhydrinate. Examples of the hypnotic sedative include estazolam, nitrazepam and the like. Examples of the antidepressant include imipramine. Examples of the antianxiety drug include diazepam. Examples of psychotropic drugs include chlorpromazine, reserpine and the like. Examples of antiepileptic agents include carbamazepine and phenytoin. Examples of the antihistamine include diphenhydramine hydrochloride, chlorpheniramine maleate, mequitazine, and the like. Examples of the agent for diabetes include tolbutamide, troglidazone, acarbose and the like. Examples of the gout treatment agent include colchicine and allopurinol. Examples of the osteoporosis agent include ipriflavone. Antibiotics include, for example, cefaclor, ampicillin, josamycin, nalidixic acid and the like. Examples of the tumor drug include cyclophosphamide and fluorouracil. Examples of the chemotherapeutic agent include sulfamethoxazole. Examples of the antiparkinson agent include amantadine hydrochloride and levodopa.
一方、本錠剤の医薬担体のうち、成分（ａ）であるトレハロースおよび／またはソルビトールとしては、特に制約はなく、公知の方法により製造されたものを使用することができる。このトレハロースおよびソルビトールは、それぞれを単独で配合、使用しても、また、これらを組み合わせて配合、使用しても良い。組み合わせて使用する場合の好ましい配合割合は、それらの重量比で、トレハロース１に対し、ソルビトール０.５〜１.５である。このトレハロースおよび／またはソルビトールは、本錠剤中に１０〜９０質量％、好ましくは２０〜８０質量％配合することができる。 On the other hand, among the pharmaceutical carriers of this tablet, the component (a) trehalose and / or sorbitol is not particularly limited, and those manufactured by known methods can be used. These trehalose and sorbitol may be blended and used alone, or may be blended and used in combination. A preferable blending ratio when used in combination is 0.5 to 1.5 sorbitol with respect to trehalose 1 in the weight ratio thereof. The trehalose and / or sorbitol can be blended in the tablet in an amount of 10 to 90% by mass, preferably 20 to 80% by mass.
また、本錠剤の医薬担体のうち、成分（ｂ）である合成ケイ酸アルミニウムも特に制約なく使用することができ、市販の、重質、軽質、特軽質の各種グレードのいずれをも使用することができる。これは本錠剤中に１〜３０質量％、好ましくは５〜２５質量％配合することができる。 In addition, among the pharmaceutical carriers of this tablet, the synthetic aluminum silicate as the component (b) can be used without any particular limitation, and any of commercially available heavy, light, and extra light grades should be used. Can do. This can be incorporated in the tablet in an amount of 1 to 30% by mass, preferably 5 to 25% by mass.
更に、本錠剤の医薬担体のうち、成分（ｃ）である崩壊剤は、製剤分野で一般的に使用され得る崩壊剤であればいずれをも使用することができる。これらの崩壊剤としては、クロスポビドン、クロスカルメロースナトリウム、カルメロースカルシウムおよび低置換度ヒドロキシプロピルセルロースが挙げられる。これらの崩壊剤の中でもクロスポビドン、クロスカルメロースナトリウムおよび低置換度ヒドロキシプロピルセルロースが好ましく、クロスポビドンおよびクロスカルメロースナトリウムがより好ましく、クロスポピドンが特に好ましい。これらの崩壊剤は、本錠剤中に１〜３０質量％、好ましくは５〜２０質量％配合することができる。 Furthermore, the disintegrant which is a component (c) among the pharmaceutical carriers of this tablet can be used as long as it can be generally used in the pharmaceutical field. These disintegrants include crospovidone, croscarmellose sodium, carmellose calcium and low substituted hydroxypropylcellulose. Among these disintegrants, crospovidone, croscarmellose sodium and low-substituted hydroxypropylcellulose are preferred, crospovidone and croscarmellose sodium are more preferred, and crospovidone is particularly preferred. These disintegrants can be blended in the tablet in an amount of 1 to 30% by mass, preferably 5 to 20% by mass.
上記した各成分を用いて本錠剤を製造するには、上記医薬有効成分と医薬担体とを混合して混合品とし、次いで、これを圧縮成型するか、上記医薬有効成分と医薬担体とを混合した後、更に、混合品を造粒処理して造粒品を製造し、この造粒品を圧縮成型すればよい。 In order to produce the tablet using each of the above-mentioned components, the above-mentioned pharmaceutically active ingredient and a pharmaceutical carrier are mixed to make a mixed product, and then compressed or molded, or the above-mentioned pharmaceutically active ingredient and the pharmaceutical carrier are mixed. Then, the mixed product may be further granulated to produce a granulated product, and the granulated product may be compression molded.
上記製造において混合品は、医薬有効成分と医薬坦体とを、対流混合、拡散混合または剪断混合等の混合法によって混合することにより得られる。これらの混合法においては、容器回転型混合機や容器固定型混合機等の混合装置が使用される。 In the above production, a mixed product is obtained by mixing the active pharmaceutical ingredient and the pharmaceutical carrier by a mixing method such as convection mixing, diffusion mixing or shear mixing. In these mixing methods, a mixing device such as a container rotation type mixer or a container fixed type mixer is used.
斯くして得られる混合品の圧縮成型には、例えばロータリー式打錠機、油圧プレス機あるいは単発打錠機等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。なお、この圧縮成型に先立ち混合品の粒度をスクリーンミル、ローミル、ハンマーミルを用いた整粒、振動ふるいを用いた篩過等の一般の製剤の製造に必要な操作に付すことにより整えてから実施すると比較的低い圧縮圧で成型することができる。具体的な圧縮圧としては５００ｋｇ／ｃｍ２〜１０００ｋｇ／ｃｍ２が挙げられる。 For compression molding of the mixed product thus obtained, for example, a method or an apparatus generally used for tablet molding such as a rotary tableting machine, a hydraulic press machine, or a single tableting machine can be used. Prior to this compression molding, the particle size of the mixed product is adjusted by subjecting it to operations necessary for production of general preparations such as sizing using a screen mill, low mill, hammer mill, and sieving using a vibrating sieve. When implemented, it can be molded at a relatively low compression pressure. Specific compression pressure include 500kg / cm 2 ~1000kg / cm 2 .
一方、上記製造において造粒品は上記混合品を造粒処理することにより得られる。この造粒処理としては湿式造粒処理、乾式造流処理および流動層造粒処理が挙げられる。これらの造粒処理の中でも湿式造流処理が好ましい。 On the other hand, in the production, the granulated product is obtained by granulating the mixed product. Examples of the granulation treatment include wet granulation treatment, dry flow granulation treatment, and fluidized bed granulation treatment. Among these granulation treatments, wet flow treatment is preferred.
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も、一般的な製剤の製造に用いられるエタノール、メタノール、イソプロパノール等のアルコール、水等の溶媒を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, an alcohol such as ethanol, methanol and isopropanol used for production of general preparations, and a solvent such as water can be used.
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.
斯くして得られる造粒品の圧縮成型には、例えばロータリー式打錠機、油圧プレス機あるいは単発打錠機等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。なお、この圧縮成型においても、混合品を圧縮成型する場合と同様に、圧縮成型に先立ち造粒品の粒度を整えてから実施すると比較的低い圧縮圧で成型することができる。具体的な圧縮圧としては５００ｋｇ／ｃｍ２〜１０００ｋｇ／ｃｍ２が挙げられる。 For compression molding of the granulated product thus obtained, for example, a method or apparatus generally used for tablet formation such as a rotary tableting machine, a hydraulic press machine or a single tableting machine can be used. In this compression molding as well, as in the case of compression molding of the mixed product, it is possible to mold at a relatively low compression pressure if the granulated product is prepared after adjusting the particle size prior to compression molding. Specific compression pressure include 500kg / cm 2 ~1000kg / cm 2 .
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、湿式造粒後の造粒品に加えても良い。この添加剤の例としては、結合剤、嬌味剤、流動化剤、滑沢剤、着色剤、香料等が挙げられる。このうち、結合剤としては、例えばアラビアゴム末、ゼラチン、プルラン、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、ポリビニルアルコール、メチルセルロース等が、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、クエン酸ナトリウム、塩化ナトリウム、ｌ−メントール等が挙げられる。また、流動化剤としては、例えば含水二酸化ケイ素、軽質無水ケイ酸等が、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、例えば食用赤色３号、食用黄色５号、食用青色１号等の食用色素等がそれぞれ挙げられる。更に、香料としては、例えばオレンジ、ストロベリー、ヨーグルト、バニラ、メントール等が、甘味剤としてはアスパルテーム、サッカリン、グリチルリチン酸二カリウム、ステビア等がそれぞれ挙げられる。これらの添加剤は単独あるいは混合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, but may be added to the granulated product after wet granulation. Examples of the additive include a binder, a flavoring agent, a fluidizing agent, a lubricant, a coloring agent, and a fragrance. Among these, examples of the binder include gum arabic powder, gelatin, pullulan, hydroxypropylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, polyvinyl alcohol, methylcellulose, and the like, and examples of the corrigent include citric acid, tartaric acid, malic acid, ascorbine. Acid, sodium citrate, sodium chloride, l-menthol and the like can be mentioned. Examples of the fluidizing agent include hydrous silicon dioxide and light anhydrous silicic acid. Examples of the lubricant include magnesium stearate, calcium stearate, talc, and sucrose fatty acid ester. Examples of the colorant include edible. Examples include food colors such as Red No. 3, Edible Yellow No. 5, Edible Blue No. 1, and the like. Furthermore, examples of the flavor include orange, strawberry, yogurt, vanilla and menthol, and examples of the sweetener include aspartame, saccharin, dipotassium glycyrrhizinate and stevia. These additives can be used alone or in combination.
斯くして得られる本錠剤は製剤工程、更には流通過程において損傷することのない適度な硬度、好ましくは３ｋｇ以上の硬度を有し、口腔内で優れた崩壊性を示するものである。また、本錠剤は日本薬局方による崩壊試験において崩壊時間が６０秒以内のものである。 The thus obtained tablet has an appropriate hardness that is not damaged in the preparation process and further in the distribution process, preferably a hardness of 3 kg or more, and exhibits excellent disintegration properties in the oral cavity. Further, this tablet has a disintegration time of 60 seconds or less in a disintegration test by the Japanese Pharmacopoeia.
以下、実施例と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.
なお、実施例および比較例で得られた錠剤は下記試験法によって、その物性を評価した。
（１）硬度試験：
試験は錠剤硬度計（ＫＨＴ−２０：藤原製作所製）を用いて実施した。試験数は１０錠とし、その硬度の平均値で評価した。
（２）崩壊試験：
日本薬局方による崩壊試験を参考に、試験は崩壊試験器（ＮＴ−１ＨＭ：富山産業製）を用いて実施した。試験数は６錠とし、崩壊までに要した時間の平均値で評価した。
The physical properties of the tablets obtained in Examples and Comparative Examples were evaluated by the following test methods.
(1) Hardness test:
The test was carried out using a tablet hardness meter (KHT-20: manufactured by Fujiwara Seisakusho). The number of tests was 10 tablets, and the average value of the hardness was evaluated.
(2) Disintegration test:
With reference to the disintegration test by the Japanese Pharmacopoeia, the test was conducted using a disintegration tester (NT-1HM: manufactured by Toyama Sangyo). The number of tests was 6 tablets, and the average value of the time required until disintegration was evaluated.
実 施 例 １
錠剤の製造（１）：
塩酸メクリジン６２.５ｇ、トレハロース７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびクロスポビドン５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Example 1
Manufacture of tablets (1):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. I got a thing. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
実 施 例 ２
錠剤の製造（２）：
塩酸メクリジン６２.５ｇ、ソルビトール７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびクロスポビドン５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Example 2
Tablet production (2):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of sorbitol, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. I got a thing. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
比 較 例 １
比較錠剤の製造（１）：
塩酸メクリジン６２.５ｇ、エリスリトール７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびクロスポビドン５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合した混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Comparative Example 1
Production of comparative tablets (1):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of erythritol, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. I got a thing. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating the granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
比 較 例 ２
比較錠剤の製造（２）：
塩酸メクリジン６２.５ｇ、粉末還元麦芽糖水飴７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびクロスポビドン５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Comparative Example 2
Production of comparative tablets (2):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of powdered reduced maltose starch syrup, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. , Got a kneaded product. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
試 験 例 １
性能試験（１）：
実施例１〜２の錠剤および比較例１〜２の錠剤の成分組成並びにこれらの錠剤の硬度試験および崩壊性試験結果を併せて表１に示した。
Test example 1
Performance test (1):
The component compositions of the tablets of Examples 1 and 2 and Comparative Examples 1 and 2 and the hardness test and disintegration test results of these tablets are shown in Table 1.
この結果より、トレハロースまたはソルビトールを使用した錠剤（実施例１および２）は、３ｋｇ以上の硬度と６０秒以内の崩壊時間という、口腔内速崩壊型錠剤として優れた特性を示すことが分かった。しかしながら、エリスリトールまたは粉末還元麦芽糖水飴を使用した錠剤（比較例１および２）は、硬度の上昇と崩壊時間の遅延が生じ、口腔内速崩壊型錠剤としての特性を満たすことができないことが分かった。 From this result, it was found that the tablets using Examples (1 and 2) using trehalose or sorbitol showed excellent characteristics as an intraoral fast disintegrating tablet having a hardness of 3 kg or more and a disintegration time within 60 seconds. However, it was found that the tablets using erythritol or powdered reduced maltose starch syrup (Comparative Examples 1 and 2) have increased hardness and delayed disintegration time, and cannot satisfy the characteristics as an orally rapidly disintegrating tablet. .
比 較 例 ３
比較錠剤（３）：
塩酸メクリジン６２.５ｇ、トレハロース７２２.５ｇ、結晶セルロース１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびクロスポビドン５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Comparative Example 3
Comparative tablet (3):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of crystalline cellulose, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. Obtained. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
比 較 例 ４
比較錠剤（４）：
塩酸メクリジン６２.５ｇ、トレハロース７２２.５ｇ、部分アルファー化デンプン１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびクロスポビドン５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Comparative Example 4
Comparative tablet (4):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of partially pregelatinized starch, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. I got a thing. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
比 較 例 ５
比較錠剤（５）：
塩酸メクリジン６２.５ｇ、トレハロース７２２.５ｇ、ヒドロキシプロピルスターチ１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびクロスポビドン５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Comparative Example 5
Comparative tablet (5):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of hydroxypropyl starch, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. Got. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
試 験 例 ２
性能試験（２）：
比較例３〜５の成分組成およびこれらの錠剤と実施例１の錠剤の硬度試験および崩壊性試験を行った結果とを併せて表２に示した。
Test example 2
Performance test (2):
The component compositions of Comparative Examples 3 to 5 and the results of the hardness test and disintegration test of these tablets and the tablet of Example 1 are shown in Table 2.
この結果より、実施例１の錠剤の合成ケイ酸アルミニウムに代えて、結晶セルロース、部分アルファー化デンプンおよびヒドロキシプロピルスターチを使用した場合（比較例３〜５）、硬度上昇と崩壊時間の遅延が認められ、口腔内速崩壊型錠剤としての特性を満たすことができなくなることが分かった。 From these results, when crystalline cellulose, partially pregelatinized starch and hydroxypropyl starch were used in place of the synthetic aluminum silicate in the tablet of Example 1 (Comparative Examples 3 to 5), an increase in hardness and a delay in disintegration time were recognized. As a result, it was found that the characteristics as an intraoral rapidly disintegrating tablet cannot be satisfied.
実 施 例 ３
錠剤の製造（３）：
塩酸メクリジン６２.５ｇ、トレハロース７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびクロスカルメロースナトリウム５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Example 3
Production of tablets (3):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of croscarmellose sodium, 350 g of ethanol was gradually added and kneaded. A kneaded product was obtained. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
実 施 例 ４
錠剤の製造（４）：
塩酸メクリジン６２.５ｇ、トレハロース７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよびカルメロースカルシウム５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Example 4
Tablet manufacture (4):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of carmellose calcium, 350 g of ethanol was gradually added and kneaded. A compound was obtained. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
実 施 例 ５
錠剤の製造（５）：
塩酸メクリジン６２.５ｇ、トレハロース７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇおよび低置換度ヒドロキシプロピルセルロース５０ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Example 5
Tablet manufacture (5):
62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of low-substituted hydroxypropylcellulose were mixed with a stirring granulator, and 350 g of ethanol was gradually added and kneaded. And kneaded material was obtained. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm 2 using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
比 較 例 ６
比較錠剤（６）：
塩酸メクリジン６２.５ｇ、トレハロース７７２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇおよびアセスルファムカリウム５ｇを撹拌造粒装置で混合した後、エタノール３５０ｇを徐々に加えて練合し、練合物を得た。この練合物を押出し造粒装置で造粒した後、棚式乾燥装置で乾燥して造粒品を得た。この造粒品を整粒した後、ステアリン酸マグネシウム５ｇを加えて混合して混合物を得た。この混合物をロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Comparative Example 6
Comparative tablet (6):
62.5 g of meclizine hydrochloride, 772.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame and 5 g of acesulfame potassium were mixed with a stirring granulator, and then 350 g of ethanol was gradually added and kneaded to obtain a kneaded product. . This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted using a rotary tableting machine at a compression pressure of 700 kg / cm 2 to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
試 験 例 ３
性能試験（３）：
実施例３〜５および比較例６の成分組成並びにこれらの錠剤と実施例１の錠剤の硬度試験および崩壊性試験を行った結果を併せて表３に示した。
Test example 3
Performance test (3):
The component compositions of Examples 3 to 5 and Comparative Example 6, and the results of the hardness test and disintegration test of these tablets and the tablet of Example 1 are shown together in Table 3.
この結果より、実施例１の錠剤の崩壊剤であるクロスポビドンに代えて、クロスカルメロースナトリウム、カルメロースカルシウムおよび低置換度ヒドロキシプロピルセルロースの何れの崩壊剤を使用した場合（実施例３〜５）でも、３ｋｇ以上の硬度と６０秒以内の崩壊時間という、口腔内速崩壊型錠剤として優れた特性を示すことが分かった。しかしながら、崩壊剤を配合しない場合（比較例６）では、崩壊時間が６０秒以上となり、口腔内速崩壊型錠剤としての特性を満たすことができないことが分かった。 From these results, when disintegrating agents of croscarmellose sodium, carmellose calcium and low-substituted hydroxypropylcellulose were used instead of crospovidone which is the disintegrant of the tablet of Example 1 (Examples 3 to 5) However, it has been found that the tablet exhibits excellent characteristics as an intraoral fast disintegrating tablet, having a hardness of 3 kg or more and a disintegration time within 60 seconds. However, in the case where no disintegrant was blended (Comparative Example 6), it was found that the disintegration time was 60 seconds or longer, and the characteristics as an intraoral fast disintegrating tablet could not be satisfied.
以上の試験結果から、本発明の口腔内速崩壊型錠剤には、トレハロースおよび／またはソルビトール、合成ケイ酸アルミニウム、崩壊剤の配合が必須であることが判明した。 From the above test results, it was found that the intraoral fast disintegrating tablet of the present invention must contain trehalose and / or sorbitol, synthetic aluminum silicate, and a disintegrant.
実 施 例 ６
錠剤の製造（６）：
塩酸メクリジン６２.５ｇ、トレハロース７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇ、クロスポビドン５０ｇおよびステアリン酸マグネシウム５ｇを撹拌装置で混合して混合物を得た。この混合物を整粒した後、ロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Example 6
Tablet production (6):
62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium, 50 g of crospovidone and 5 g of magnesium stearate were mixed with a stirrer to obtain a mixture. After the mixture was sized, it was tableted using a rotary tableting machine at a compression pressure of 700 kg / cm 2 to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
実 施 例 ７
錠剤の製造（７）：
塩酸メクリジン６２.５ｇ、ソルビトール７２２.５ｇ、合成ケイ酸アルミニウム１５０ｇ、アスパルテーム５ｇ、アセスルファムカリウム５ｇ、クロスポビドン５０ｇおよびステアリン酸マグネシウム５ｇを撹拌装置で混合して混合物を得た。この混合物を整粒した後、ロータリー式の打錠装置を用いて、圧縮圧７００ｋｇ／ｃｍ２で打錠して、１錠あたり塩酸メクリジンを２５ｍｇ含む４００ｍｇの錠剤を得た。
Example 7
Tablet production (7):
62.5 g of meclizine hydrochloride, 722.5 g of sorbitol, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium, 50 g of crospovidone and 5 g of magnesium stearate were mixed with a stirrer to obtain a mixture. After the mixture was sized, it was tableted using a rotary tableting machine at a compression pressure of 700 kg / cm 2 to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.
試 験 例 ４
性能試験（４）：
実施例１、２、６、および７の成分組成並びにこれらの錠剤と実施例１の錠剤の硬度試験および崩壊性試験を行った結果を併せて表４に示した。
Test example 4
Performance test (4):
The component compositions of Examples 1, 2, 6, and 7 and the results of the hardness test and disintegration test of these tablets and the tablet of Example 1 are shown together in Table 4.
この結果より、実施例１または実施例２と処方がそれぞれ同一で、造粒工程を経ていない実施例６または実施例７は、いずれも、３ｋｇ以上の硬度と６０秒以内の崩壊時間という、口腔内速崩壊型錠剤として優れた特性を示すことが分かった。 From this result, the formulation of Example 1 or Example 2 is the same as that of Example 1 and Example 6 or Example 7 that has not undergone the granulation step has a hardness of 3 kg or more and a disintegration time of 60 seconds or less. It was found that it exhibits excellent properties as an internal fast disintegrating tablet.
以上の試験結果から、本発明の口腔内速崩壊型錠剤は造粒工程を行わなくとも、造粒工程を経て得られる錠剤と同等の性能を有することが分かった。 From the above test results, it was found that the intraoral rapidly disintegrating tablet of the present invention has the same performance as the tablet obtained through the granulation step without performing the granulation step.
本発明の口腔内速崩壊性錠剤は、口腔内で優れた崩壊性と溶解性とを示すと共に製剤工程や流通過程において損傷することのない適度な硬度を有する製剤となる。また、前記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することができる。 The intraoral rapidly disintegrating tablet of the present invention is a preparation that exhibits excellent disintegration and solubility in the oral cavity and has an appropriate hardness that is not damaged in the preparation process and distribution process. Moreover, the said tablet can be manufactured without using a complicated manufacturing process and a special apparatus.
従って、本発明は口腔内速崩壊性錠剤の工業的な大規模生産に極めて有用なものである。
以 上
Therefore, the present invention is extremely useful for industrial large-scale production of intraoral rapidly disintegrating tablets.
more than
Claims (8)
（ａ）トレハロースおよび／またはソルビトール
（ｂ）合成ケイ酸アルミニウム
（ｃ）崩壊剤 An intraoral rapidly disintegrating tablet obtained by mixing a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (c) to obtain a mixed product, and then compression molding the mixture.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant
（ａ）トレハロースおよび／またはソルビトール
（ｂ）合成ケイ酸アルミニウム
（ｃ）崩壊剤 An intraoral rapidly disintegrating tablet obtained by granulating a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (c) to produce a granulated product, and then compressing the granulated product .
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant
（ａ）トレハロースおよび／またはソルビトール
（ｂ）合成ケイ酸アルミニウム
（ｃ）崩壊剤 A method for producing an orally rapidly disintegrating tablet, comprising mixing an active pharmaceutical ingredient and a pharmaceutical carrier containing the following components (a) to (c) to form a mixture, and then compressing the mixture.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant
（ａ）トレハロースおよび／またはソルビトール
（ｂ）合成ケイ酸アルミニウム
（ｃ）崩壊剤
An intraoral quick disintegration characterized by producing a granulated product by granulating a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (c), and then compression-molding the granulated product: Tablet manufacturing method.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004061769A JP2005029557A (en) | 2003-06-19 | 2004-03-05 | Quickly disintegrating tablet in oral cavity and method for producing the same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003174966 | 2003-06-19 | ||
| JP2004061769A JP2005029557A (en) | 2003-06-19 | 2004-03-05 | Quickly disintegrating tablet in oral cavity and method for producing the same |
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| JP2005029557A true JP2005029557A (en) | 2005-02-03 |
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| Application Number | Title | Priority Date | Filing Date |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010084637A1 (en) * | 2009-01-20 | 2010-07-29 | ライオン株式会社 | Tablet for oral administration having excellent disintegrability and dissolvability |
| JP2019216714A (en) * | 2018-06-14 | 2019-12-26 | 株式会社東洋新薬 | tablet |
| CN114129525A (en) * | 2021-10-13 | 2022-03-04 | 山东齐都药业有限公司 | Meclozine orally disintegrating tablet and preparation method thereof |
| JP2022093470A (en) * | 2016-07-13 | 2022-06-23 | 日本ケミファ株式会社 | Intraoral disintegrable tablet of 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid |
| CN114652690A (en) * | 2022-03-31 | 2022-06-24 | 山东新时代药业有限公司 | New metoclopramide preparation for intestinal obstruction and process thereof |
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2004
- 2004-03-05 JP JP2004061769A patent/JP2005029557A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010084637A1 (en) * | 2009-01-20 | 2010-07-29 | ライオン株式会社 | Tablet for oral administration having excellent disintegrability and dissolvability |
| JP2022093470A (en) * | 2016-07-13 | 2022-06-23 | 日本ケミファ株式会社 | Intraoral disintegrable tablet of 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid |
| JP7361833B2 (en) | 2016-07-13 | 2023-10-16 | 日本ケミファ株式会社 | Orally disintegrating tablet of 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid |
| JP2019216714A (en) * | 2018-06-14 | 2019-12-26 | 株式会社東洋新薬 | tablet |
| JP7426685B2 (en) | 2018-06-14 | 2024-02-02 | 株式会社東洋新薬 | tablet |
| CN114129525A (en) * | 2021-10-13 | 2022-03-04 | 山东齐都药业有限公司 | Meclozine orally disintegrating tablet and preparation method thereof |
| CN114129525B (en) * | 2021-10-13 | 2022-11-25 | 山东齐都药业有限公司 | Meclozine orally disintegrating tablet and preparation method thereof |
| CN114652690A (en) * | 2022-03-31 | 2022-06-24 | 山东新时代药业有限公司 | New metoclopramide preparation for intestinal obstruction and process thereof |
| CN114652690B (en) * | 2022-03-31 | 2023-03-21 | 山东新时代药业有限公司 | New metoclopramide preparation for intestinal obstruction and process thereof |
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