TW201626989A - Ultra-rapidly-disintegrating tablet - Google Patents

Abstract

To provide an orally disintegrating tablet (ultra-rapidly-disintegrating tablet) that can be manufactured easily without any complicated processes such as freeze-drying, and has both high disintegration properties and high tablet hardness, and a package packaging the ultra-rapidly-disintegrating tablet. Provided is an orally disintegrating tablet characterized by having a disintegration time in water of less than 15 seconds and in that the deformation of the tablet at the time of rupture on the stress-strain curve of the tablet is 1.7 (%) or greater. Also provided is a package such a press through package (PTP) or a packaged body packaging the orally disintegrating tablet.

Description

超高速崩解錠劑 Ultra high speed disintegrating lozenge

本發明係關於一種口腔內崩解錠劑等，該口腔內崩解錠劑能夠以先前技術進行一般之擠壓包裝(PTP，Press Through Package)，具有極短之口腔內崩解時間及實用上充足之錠劑硬度。 The present invention relates to an orally disintegrating tablet or the like which can be subjected to a general extrusion packaging (PTP, Press Through Package) according to the prior art, and has a very short oral disintegration time and practical use. Sufficient tablet hardness.

迄今為止，作為難以吞咽藥劑之患者、高齡者、幼兒等可安全地服用，又不需水便可輕易地服用之方便性高的劑形，開發出口腔內崩解錠劑。關於口腔內崩解錠劑，重要的是與一般錠劑同樣具有在錠劑製造時或運送中或開封時，不會產生錠劑之缺損及粉末化等之充分破壞強度(錠劑硬度)，並且具有於口腔內迅速崩解之優異崩解性(崩解時間)。 In the past, an oral cavity disintegrating tablet has been developed as a highly convenient dosage form which can be safely taken by a patient who is difficult to swallow a drug, an elderly person, or a child, and can be easily taken without water. Regarding the orally disintegrating tablet, it is important that, in the same manner as the general tablet, the sufficient breaking strength (tablet hardness) such as the defect of the tablet and the powdering or the like is not generated at the time of the production of the tablet or during the transportation or opening. Moreover, it has excellent disintegration (disintegration time) which rapidly disintegrates in the oral cavity.

此處，錠劑硬度與崩解性為彼此相反之性質，一般而言，若為了增加硬度而增大成形壓力，則有崩解時間增長之傾向；若為了縮短崩解時間而減小成形壓力，則有硬度減小之傾向。因此，為了達成該兩種性質並存或兩種性質間之最佳平衡，而開發有各種技術。又，為了賦予構成錠劑之粒子或粒子組成物優異的成形性，業界對粒子之成分或造粒方法等進行了研究。 Here, the hardness and disintegration properties of the tablet are opposite to each other. Generally, if the molding pressure is increased in order to increase the hardness, there is a tendency that the disintegration time increases; if the molding pressure is reduced in order to shorten the disintegration time , there is a tendency to reduce the hardness. Therefore, in order to achieve the coexistence of the two properties or the optimal balance between the two properties, various techniques have been developed. Further, in order to impart excellent formability to the particles or particle constituents constituting the tablet, the composition of the particles, the granulation method, and the like have been studied.

已知口腔內崩解錠劑對患者之服藥適應性有所改善，但已知 特別具強烈抗拒服藥傾向之患者，會在20~30秒左右之口腔內崩解時間內吐出錠劑。因此，若顯著提高崩解性，例如數秒左右之崩解時間，則因服藥時錠劑會在患者感到不適前便崩解，亦易於投予此類患者。 Oral disintegrating tablets are known to improve the patient's medication suitability, but are known In particular, patients who are strongly resistant to taking drugs will spit out the tablets within the oral disintegration time of about 20 to 30 seconds. Therefore, if the disintegration property is remarkably improved, for example, the disintegration time of about several seconds, the lozenge disintegrates before the patient feels uncomfortable when taking the medicine, and it is easy to administer such a patient.

作為此種口腔內崩解性顯著為高之錠劑、即「超高速崩解錠劑」之製造技術，已知有Zydis(註冊商標)技術。其係由Cardinal Health公司(現為美國Cataleht公司)開發的口服固體劑形之製造技術，如專利文獻1所記載，為一種使用明膠作為載體材料，使原末(醫藥活性物質)與甘露醇等一併成為懸浮狀態後填充至泡鼓，然後利用冷凍乾燥製作迅速分散性固體口服用劑形的方法。 Zydis (registered trademark) technology is known as a manufacturing technique of such a "high-speed disintegrating tablet" which is a tablet having a high degree of disintegration in the oral cavity. It is a manufacturing technique of an oral solid dosage form developed by Cardinal Health Company (now Cataleht Corporation of the United States), as described in Patent Document 1, which is a use of gelatin as a carrier material to enable the original (medicinal active substance) and mannitol. The method of filling into a bubble drum after being suspended, and then forming a rapidly dispersible solid oral dosage form by freeze-drying.

進而，專利文獻2中記載有關於冷凍乾燥速溶多相劑形之製造方法的發明。該方法係依序投入含有非凝膠化基質形成劑之製劑及含有凝膠化基質之製劑，並冷凍乾燥該等，藉此製備用以傳遞藥學上之活性成分的多相之速溶劑形(FDDF)。作為非凝膠化基質形成劑，使用非凝膠化明膠，且作為凝膠化基質形成劑，則使用凝膠化明膠等。 Further, Patent Document 2 describes an invention relating to a method for producing a freeze-dried instant multiphase dosage form. The method comprises sequentially injecting a preparation containing a non-gelling matrix forming agent and a preparation containing a gelling matrix, and freeze-drying the same, thereby preparing a multi-phase speed solvent form for delivering a pharmaceutically active ingredient ( FDDF). As the non-gelling matrix forming agent, non-gelatinized gelatin is used, and as the gelling matrix forming agent, gelatinized gelatin or the like is used.

又，本發明人等開發有錠劑硬度與崩解性更優異，或實質上未延長崩解時間，而賦予高錠劑高度之崩解性粒子組成物的製造方法(專利文獻3)。 In addition, the inventors of the present invention have developed a method for producing a disintegrable particle composition which is excellent in tablet hardness and disintegration property or which does not substantially prolong the disintegration time and which has a high tablet height (Patent Document 3).

進而，開發有含有如下四種成分之崩解性粒子組成物：由酸型羧甲基纖維素構成之第一崩解劑成分、酸型羧甲基纖維素以外之第二崩解劑成分、由糖或糖醇構成之賦形劑，以及結晶纖維素(專利文獻4)。 Further, a disintegrable particle composition containing four components including a first disintegrant component composed of acid carboxymethylcellulose and a second disintegrator component other than acid carboxymethylcellulose has been developed. An excipient composed of a sugar or a sugar alcohol, and a crystalline cellulose (Patent Document 4).

然而，專利文獻3及4未具體地揭示具有10(秒)以下之極短水中崩解時間的口腔內崩解錠劑。並且，未揭示含有輕質無水矽酸(light anhydrous silicic acid)之口腔內崩解錠劑。 However, Patent Documents 3 and 4 do not specifically disclose an orally disintegrating tablet having an extremely short water disintegration time of 10 (seconds) or less. Also, it is not disclosed that it contains light anhydrous citric acid (light An oral silicic acid tablet.

[專利文獻1]日本專利第4943581號說明書 [Patent Document 1] Japanese Patent No. 4,493,581

[專利文獻2]日本特表2013-522308號公報 [Patent Document 2] Japanese Patent Publication No. 2013-522308

[專利文獻3]國際公開手冊WO2013/146917 [Patent Document 3] International Publication Manual WO2013/146917

[專利文獻4]國際公開手冊WO2014/046035 [Patent Document 4] International Publication Manual WO2014/046035

上述之先前技術中，需要用以實施冷凍乾燥之特殊設備，而無法使用製造一般錠劑時各種生產效率良好之壓錠機。又，先前技術所製作之超高速崩解錠劑的錠劑硬度極低，故展現可進行一般PTP包裝之等級的錠劑硬度之超高速崩解錠正受到業界所期待。 In the above prior art, special equipment for performing freeze-drying is required, and various presses having high production efficiency when manufacturing a general tablet are not available. Further, since the ultra-high-speed disintegrating tablet produced by the prior art has extremely low tablet hardness, an ultra-high-speed disintegrating ingot exhibiting the hardness of a tablet which can be graded in a general PTP package is expected by the industry.

因此，本發明所欲解決之課題係解決此種被發現於先前超高速崩解錠劑之技術課題，提供一種具有可確認患者確實服藥之極高崩解性(短崩解時間)，且兼備可期許錠劑的破裂缺損降低至實用等級程度之高錠劑硬度的口腔內崩解錠劑(超高速崩解錠劑)，並且提供一種可不經冷凍乾燥等繁雜操作而製造此種超高速崩解錠劑的簡便方法，以及將該口腔內崩解錠劑包裝而成之包裝體等。 Therefore, the problem to be solved by the present invention is to solve such a technical problem that has been found in a conventional ultra-high-speed disintegrating tablet, and to provide an extremely high disintegratability (short disintegration time) which can confirm that a patient actually takes a drug, and has both It is expected that the rupture defect of the tablet can be reduced to an orally disintegrating tablet (ultra-high-speed disintegrating tablet) having a high degree of tablet hardness, and a high-speed collapse can be produced without complicated operations such as freeze drying. A simple method of dissolving the tablet, a package obtained by packaging the orally disintegrating tablet, and the like.

本發明人發現如下情形，從而完成本發明：使口腔內崩解錠劑含有酸型羧甲基纖維素等作為崩解劑成分的一種，藉此可使用先前之造粒步驟製造具有如下特徵之口腔內崩解錠劑：崩解兼具極高崩解性及實用上充足之錠劑硬度，於應力-應變曲線中未顯示一般性之破裂點；以及進而該超高速崩解錠劑可作為包裝體而提供，該包裝體係經由作為先前公知 之一般且簡便的技術之擠壓包裝(PTP：Press Through Package)等而獲得。 The present inventors have found out a case in which the orally disintegrating tablet contains an acid type carboxymethylcellulose or the like as one of disintegrant components, whereby the prior granulation step can be used to produce the following characteristics. Oral disintegrating lozenge: disintegration has extremely high disintegration and practically sufficient tablet hardness, and does not show a general fracture point in the stress-strain curve; and further, the ultra-high-speed disintegrating tablet can be used as Provided by a package that is known as previously It is obtained by a general and simple technique of PTP (Press Through Package).

更具體而言，本發明提供以下態樣。 More specifically, the present invention provides the following aspects.

[態樣1] [Scenario 1]

一種口腔內崩解錠劑，其特徵為水中崩解時間未達15秒，錠劑之應力-應變曲線中，破裂時之錠劑的應變為1.7(%)以上。 An orally disintegrating tablet which is characterized in that the disintegration time in water is less than 15 seconds, and in the stress-strain curve of the tablet, the strain of the tablet at the time of rupture is 1.7 (%) or more.

[態樣2] [Surface 2]

如態樣1之口腔內崩解錠劑，其水中崩解時間未達9秒。 The oral disintegration tablet of the aspect 1 has a disintegration time of less than 9 seconds in water.

[態樣3] [Surface 3]

如態樣1或2之口腔內崩解錠劑，其口腔內崩解時間為6秒以下。 The orally disintegrating tablet of the aspect 1 or 2 has an intraoral disintegration time of 6 seconds or less.

[態樣4] [Surface 4]

如態樣3之口腔內崩解錠劑，其口腔內崩解時間為5秒以下。 The oral disintegration tablet of the aspect 3 has an intraoral disintegration time of 5 seconds or less.

[態樣5] [Surface 5]

如態樣1至4中任一者之口腔內崩解錠劑，進而錠劑硬度為10N~30N。 The orally disintegrating lozenge according to any one of the aspects 1 to 4, wherein the tablet hardness is 10N to 30N.

[態樣6] [Figure 6]

如態樣1至5中任一者之口腔內崩解錠劑，其係以包括如下步驟之方法製造：將含有酸型羧甲基纖維素、結晶纖維素及糖或糖醇之崩解性粒子組成物與醫藥活性物質進行混合，將所獲得之混合物打錠。 An orally disintegrating tablet according to any one of the aspects 1 to 5, which is produced by a method comprising the steps of: disintegrating the acid-containing carboxymethylcellulose, crystalline cellulose, and sugar or sugar alcohol; The particle composition is mixed with a pharmaceutically active substance, and the obtained mixture is tableted.

[態樣7] [Stage 7]

如態樣6之口腔內崩解錠劑，其中，於崩解性粒子組成物進一步含有輕質無水矽酸。 An orally disintegrating tablet according to aspect 6, wherein the disintegrable particle composition further contains light anhydrous citric acid.

[態樣8] [Surface 8]

如態樣6或7之口腔內崩解錠劑，其中，施加打錠壓縮力2至8kN而 進行打錠。 Oral disintegrating lozenge according to aspect 6 or 7, wherein the compression force of the tablet is applied to 2 to 8 kN Make ingots.

[態樣9] [Surface 9]

一種包裝體，其係將態樣1至8中任一者之口腔內崩解錠劑包裝而成。 A package obtained by packaging an orally disintegrating tablet of any of the aspects 1 to 8.

[態樣10] [Surface 10]

如態樣9之包裝體，該包裝體為擠壓包裝(PTP)體或一包化體。 In the package of the aspect 9, the package is a squeeze package (PTP) body or a package body.

本發明之口腔內崩解錠劑(超高速崩解錠劑)兼具極短之口腔內崩解時間以及實用上充足之錠劑硬度。 The orally disintegrating tablet (ultra-high-speed disintegrating tablet) of the present invention has a very short oral disintegration time and a practically sufficient tablet hardness.

並且，相較於以往之錠劑，本發明之口腔內崩解錠劑於錠劑之應力-應變曲線中破裂時之錠劑的應變顯示出顯著地高之值。因此，顯示如下優異特性：表現如橡膠般之行為(屈曲點)，即便於受到屈曲點附近的高衝擊之情形時，在錠劑外觀亦不會產生「破裂」、「缺損」及「裂縫」等。又，由於表現在即將破裂前，相對於應力緩慢地變形之如橡膠般之行為(屈曲點)，故顯示如下優異特性：即便於受到屈曲點附近的衝擊之情形時，在錠劑外觀亦不會產生「破裂」、「缺損」及「裂縫」等。 Further, the strain of the tablet of the present invention when the orally disintegrating tablet of the present invention is broken in the stress-strain curve of the tablet exhibits a significantly higher value than the conventional tablet. Therefore, it exhibits the following excellent characteristics: it exhibits rubber-like behavior (buckling point), and even in the case of high impact near the buckling point, there is no "breakage", "defect" and "crack" in the appearance of the tablet. Wait. Further, since it exhibits a rubber-like behavior (buckling point) which is slowly deformed with respect to stress immediately before the rupture, it exhibits the following excellent characteristics: even in the case of an impact near the buckling point, the appearance of the tablet is not There will be "rupture", "defect" and "crack".

進而，該超高速崩解錠劑可使用與一般錠劑相同之裝置而簡便地製造，且可作為包裝體而提供，該包裝體係經由以往公知之一般且簡便的技術之擠壓包裝(PTP：Press Through Package)等而獲得。 Further, the ultra-high-speed disintegrating tablet can be easily produced by using the same apparatus as a general tablet, and can be provided as a package which is extruded by a conventionally known general and simple technique (PTP: Press Through Package) and so on.

【圖1】表示與發明之口腔內崩解錠劑以及由比較例而得之錠劑相關而獲得的應力-應變曲線。 Fig. 1 is a graph showing stress-strain curves obtained in association with the orally disintegrating tablet of the invention and the tablet obtained in the comparative example.

【圖2】將與由製造例3~4而得之錠劑相關而獲得的應力-應變曲線 示於圖2。 Fig. 2 is a stress-strain curve obtained by correlating the tablets obtained in Production Examples 3 to 4. Shown in Figure 2.

為了防止已投予錠劑之患者感到不適而吐出錠劑，期望至崩解進行之時間儘可能縮短至無法吐出之程度。又，亦期望至崩解結束為止之時間儘可能縮短，以迅速完成服藥而不對下次及後續之投藥產生排斥。 In order to prevent the patient who has administered the tablet from feeling uncomfortable and spit out the tablet, it is desirable that the time until the disintegration proceeds is as short as possible to the extent that it cannot be discharged. Also, it is expected that the time until the end of the disintegration is as short as possible, so that the medication can be completed quickly without rejection of the next and subsequent administration.

本發明之口腔內崩解錠劑其水中崩解時間未達約15秒，較佳未達約9秒，更佳為約7秒以下。並且，較佳口腔內崩解時間為約6秒以下，更佳為約5秒以下，最佳為約4秒以下。 The orally disintegrating tablet of the present invention has a disintegration time in water of less than about 15 seconds, preferably less than about 9 seconds, more preferably about 7 seconds or less. Further, the intraoral disintegration time is preferably about 6 seconds or less, more preferably about 5 seconds or less, and most preferably about 4 seconds or less.

並且，本發明之口腔內崩解錠劑之特徵在於：錠劑之應力-應變曲線中，破裂時之錠劑的應變為1.7(%)以上，較佳為1.9(%)以上。 Further, the orally disintegrating tablet of the present invention is characterized in that the strain of the tablet in the stress-strain curve of the tablet is 1.7 (%) or more, preferably 1.9 (%) or more.

此處，所謂「應力-應變曲線」，係表示於物體產生變形之情形時的應力變化之曲線圖，可使用公知之試驗機器而容易地進行測量。應力-應變曲線中破裂時之「破裂點」(表示最大應力值之點)或「屈曲點」之應變的值越大，彈性區域越廣，越具有柔軟的物性，因此對於落下等物理性衝擊，不易產生破裂、缺損以及裂縫等之損壞等。 Here, the "stress-strain curve" is a graph showing the change in stress when the object is deformed, and can be easily measured using a known test machine. The larger the value of the "fracture point" (the point indicating the maximum stress value) or the "buckling point" in the stress-strain curve, the wider the elastic region, the softer the physical property, and therefore the physical impact on the fall. It is not easy to cause damage such as cracks, defects, cracks, and the like.

又，自製造使用時之實用上的觀點而言，錠劑硬度必須高達一定程度，本發明之口腔內崩解錠劑的錠劑硬度較佳為約10N~30N，更加為約20N。 Further, from the viewpoint of practical use at the time of manufacture, the hardness of the tablet must be as high as a certain degree, and the tablet hardness of the orally disintegrating tablet of the present invention is preferably from about 10 N to 30 N, more preferably about 20 N.

本發明進而關於一種將該口腔內崩解錠劑包裝而成之包裝體。包裝體若為將錠劑進行包裝之公知的方法，則何種方法皆可。例如，作為包裝體較佳為一包化體。一包化係藥局等為了防止忘記服用藥物，而 將一日內服用之藥物集中於一個袋子者。又，藥物之瓶裝等一般之錠劑，亦適於容易產生破裂、缺損者。進而尤佳為擠壓包裝(PTP)體。再者，PTP(包裝)係於將作為「泡鼓包裝」而為人所知之包裝形態特別應用於藥劑之情形的稱呼，。泡鼓包裝一般而言係如下者：單面使用相對較堅固之材質的厚紙等作為底紙，將商品名等印刷於其上，另一方面，以真空成形等將板狀之塑膠成形，接著於底紙，將商品包裝於此底紙及接著於該底紙之成形塑膠之間而成。 The present invention further relates to a package in which the orally disintegrating tablet is packaged. If the package is a well-known method of packaging a tablet, any method is acceptable. For example, the package is preferably a package. a package of pharmacies, etc., in order to prevent forgetting to take drugs, Concentrate on the drugs taken in one day to one bag. In addition, a general tablet such as a bottle of a drug is also suitable for those who are prone to breakage or defect. Further preferred is a extruded package (PTP) body. In addition, PTP (packaging) is a designation in which a packaging form known as "bubble drum packaging" is particularly applied to a medicine. In general, the drum packaging is as follows: a thick paper having a relatively strong material is used as a base paper on one side, and a product name or the like is printed thereon, and a plate-shaped plastic is formed by vacuum forming or the like. On the backing paper, the product is packaged between the backing paper and the formed plastic of the backing paper.

因此，將本發明之口腔內崩解錠劑包裝而成之包裝體，係該行業者依據公知之方法而可容易地製造者。擠壓包裝(PTP)體亦可依該行業者公知之方法(例如日本實開昭51-139176、日本實開昭50-32371等所記載)而可容易地製造。 Therefore, the package in which the orally disintegrating tablet of the present invention is packaged can be easily manufactured by those skilled in the art according to a known method. The extrusion-packaged (PTP) body can be easily produced by a method known to those skilled in the art (for example, as described in Japanese Laid-Open Patent Publication No. Sho-51-139176, No. Sho.

本發明之口腔內崩解錠劑可藉包括如下步驟之方法製造：將含有酸型羧甲基纖維素、結晶纖維素及糖或糖醇之崩解性粒子組成物與醫藥活性物質進行混合，將所獲得之混合物打錠。 The orally disintegrating tablet of the present invention can be produced by a method comprising the steps of mixing a disintegrable particle composition containing an acid type carboxymethyl cellulose, a crystalline cellulose, and a sugar or a sugar alcohol with a pharmaceutically active substance. The obtained mixture was tableted.

並且，為了更加提高崩解性，可使崩解性粒子組成物進一步含有輕質無水矽酸。 Further, in order to further improve the disintegration property, the disintegrable particle composition may further contain light anhydrous citric acid.

再者，本發明之口腔內崩解錠劑中，不需含有明膠，該明膠係先前技術之超高速崩解錠劑中作為載體而實質上所需要者。 Further, in the orally disintegrating tablet of the present invention, gelatin is not required, and the gelatin is substantially required as a carrier in the ultrahigh-speed disintegrating tablet of the prior art.

本發明之口腔內崩解錠劑除了藥效成份(醫藥活性物質)外，可視需要含有賦形劑、界面活性劑、潤滑劑、酸化劑、甜味料、矯味劑、香料、著色劑、穩定劑等醫藥上容許之其他任意成分。作為該等任意成分，例如可使用醫藥品添加物辭典(藥事日報社)、日本藥典中記載之相 符成分。又，只要發揮出本發明所欲之效果，則各成分之摻合比例並無特別限制，該行業者可適當決定。此種口腔內崩解錠劑可藉由打錠等該行業者所公知之任意方法而製劑化。 The oral disintegrating tablet of the present invention may contain an excipient, a surfactant, a lubricant, an acidifying agent, a sweetener, a flavoring agent, a flavoring agent, a coloring agent, and the like, in addition to the medicinal ingredient (medicinal active substance). Other optional ingredients that are pharmaceutically acceptable. As such an optional component, for example, a pharmaceutical additive dictionary (Pharmacy Daily) and a phase described in the Japanese Pharmacopoeia can be used. Symbol component. Moreover, as long as the effect of the present invention is exerted, the blending ratio of each component is not particularly limited, and those skilled in the art can appropriately determine it. Such an orally disintegrating tablet can be formulated by any method known to those skilled in the art, such as tableting.

作為其較佳製造方法之例，可舉如下製作方法，該方法包括將崩解性粒子組成物與醫藥活性物質(或含有該物質之醫藥組成物)混合，使用該行業者所公知之適當打錠機，將獲得之混合物以例如打錠壓縮力為2至8kN，較佳為2至5kN進行打錠。因此，本發明亦關於用於此種製造方法之崩解性粒子組成物。 As an example of a preferred production method, there is prepared a method comprising mixing a disintegrable particle composition with a pharmaceutically active substance (or a pharmaceutical composition containing the substance), and using a suitable one known to those skilled in the art. Ingot machine, the obtained mixture is subjected to tableting with, for example, a tableting compression force of 2 to 8 kN, preferably 2 to 5 kN. Accordingly, the present invention also relates to a disintegrable particle composition used in such a production method.

醫藥活性物質等之形態(狀態)並無特別限制，例如可為粉末狀態。又，醫藥活性物質等與崩解性添加劑摻合物之混合(固體碾磨)及打錠，可藉由該行業者所公知之任意手段、方法而實施。此時，可根據投予對象及投予目的等，以成為適當之投藥用量之方式，容易地調整該口腔內崩解錠所含有之有效成分量。 The form (state) of the pharmaceutically active substance or the like is not particularly limited, and may be, for example, a powder state. Further, the mixing (solid milling) and tableting of the pharmaceutically active substance and the disintegrating additive blend can be carried out by any means or method known to those skilled in the art. In this case, the amount of the active ingredient contained in the orally disintegrating ingot can be easily adjusted so as to be an appropriate dosage amount depending on the intended subject, the purpose of administration, and the like.

作為錠劑等之崩解機制，主張有如下4種：「毛細作用(Wicking)」、「膨潤作用(Swelling)」、「變形作用(Deformation)」及「排斥作用(Repulsion)」。其中，所謂毛細作用，係指水分經由錠劑中含有之崩解劑等成分而滲透，結果使錠劑含有之各粒子間結合力減弱而進行的崩解機制。作為促進此種毛細作用之效果高的崩解劑之代表例，已知有酸型羧甲基纖維素。又，所謂膨潤作用，係指水滲透於崩解劑，結果使崩解劑本身膨潤而進行的崩解機制。 As a disintegration mechanism of a tablet or the like, there are four types of "Wicking", "Swelling", "Deformation", and "Repulsion". Here, the term "capillary action" refers to a mechanism of disintegration in which water permeates through a component such as a disintegrant contained in a tablet, and the binding force between the particles contained in the tablet is weakened. An acid carboxymethylcellulose is known as a representative example of a disintegrant having a high effect of promoting such capillary action. In addition, the swelling action refers to a disintegration mechanism in which water permeates the disintegrant and the disintegrating agent itself swells.

作為本發明之崩解性粒子組成物所含有之第一崩解劑成分的酸型羧甲基纖維素，係被稱為羧甲基纖維素(carmellose)之物質，且作 為醫藥品添加劑而被使用。與酸型羧甲基纖維素相同，例如羧甲基纖維素之鈣鹽及羧甲基纖維素鈉之交聯物均不溶於水，作為崩解劑被使用於錠劑等。另一方面，羧甲基纖維素之鈉鹽為水溶性且以結合劑等目的被使用。再者，亦有將羧甲基纖維素之鹽記載為羧甲基纖維素之情況。 The acid type carboxymethyl cellulose which is the first disintegrator component contained in the disintegrable particle composition of the present invention is a substance called carmellose, and It is used for pharmaceutical additives. Like the acid type carboxymethylcellulose, for example, the calcium salt of carboxymethylcellulose and the crosslinked product of sodium carboxymethylcellulose are insoluble in water, and are used as a disintegrating agent in a tablet or the like. On the other hand, the sodium salt of carboxymethylcellulose is water-soluble and is used for the purpose of a binder or the like. Further, there is a case where the salt of carboxymethylcellulose is described as carboxymethylcellulose.

於崩解性粒子組成物，較佳含有該行業者所公知之結晶纖維素。作為其代表例，可列舉：Avicel(FMC公司)、Ceolus(旭化成化學公司)、Vivapur(RETTEN MAIER)等市售品。 The disintegrable particle composition preferably contains crystalline cellulose known to those skilled in the art. Typical examples thereof include commercially available products such as Avicel (FMC), Ceolus (Asahi Kasei Chemical Co., Ltd.), and Vivapur (RETTEN MAIER).

又，作為本發明之崩解性粒子組成物之第二崩解劑成分，可使用除酸型羧甲基纖維素以外之該行業者所公知的任意崩解劑。然而，為了獲得如上述所示般不同崩解機制之複合效果，較佳使用促進毛細作用以外之機制例如促進膨潤作用之效果優異之崩解劑作為第二崩解劑成分。作為此種崩解劑之較佳例，可列舉：交聯聚維酮、交聯羧甲基纖維素鈉、羧甲基澱粉鈉、低取代度羥丙基纖維素、羧甲基纖維素鈣、羥丙基澱粉、及澱粉等。再者，交聯聚維酮係1-乙烯基-2-吡咯啶酮之交聯聚合物的通稱，交聯羧甲基纖維素鈉係羧甲基纖維素鈉之交聯物的通稱。 Further, as the second disintegrant component of the disintegrable particle composition of the present invention, any disintegrator known to those skilled in the art other than the acid type carboxymethylcellulose can be used. However, in order to obtain a composite effect of different disintegration mechanisms as described above, it is preferable to use a disintegrant which is excellent in the effect of promoting the swelling action other than the capillary action as the second disintegrator component. Preferred examples of such a disintegrator include crospovidone, croscarmellose sodium, sodium carboxymethyl starch, low-substituted hydroxypropylcellulose, and carboxymethylcellulose calcium. , hydroxypropyl starch, and starch. Further, a general term for a crosslinked polymer of crospovidone-based 1-vinyl-2-pyrrolidone, a general term for a crosslinked product of croscarmellose sodium-based sodium carboxymethylcellulose.

其中，較佳為選自交聯聚維酮、交聯羧甲基纖維素鈉、羧甲基澱粉鈉、低取代度羥丙基纖維素、或羧甲基纖維素鈣中之一種或兩種以上之任意組合。 Among them, one or two selected from the group consisting of crospovidone, croscarmellose sodium, sodium carboxymethyl starch, low-substituted hydroxypropylcellulose, or carboxymethylcellulose calcium are preferred. Any combination of the above.

進而，含有作為賦形劑而被該行業者所公知之任意化合物。作為其代表例，可列舉：甘露醇、赤藻糖醇、山梨糖醇、D-葡萄糖醇(麥芽糖醇)、木糖醇、海藻糖、乳糖及麥芽糖等糖或糖醇。進而，作為較佳例，可列舉：甘露醇、赤藻糖醇、海藻糖、山梨糖醇、及D-葡萄糖醇(麥芽 糖醇)。作為賦形劑，亦可使用自該等中適當選擇之兩種以上的化合物。 Further, it contains any compound known to those skilled in the art as an excipient. Typical examples thereof include sugars or sugar alcohols such as mannitol, erythritol, sorbitol, D-glucitol (maltitol), xylitol, trehalose, lactose, and maltose. Further, preferred examples thereof include mannitol, erythritol, trehalose, sorbitol, and D-glucitol (malt Sugar alcohol). As the excipient, two or more kinds of compounds appropriately selected from these may be used.

進而，為了調整崩解力、結合力及錠劑之服用感等各種特性，亦可於本發明之崩解性粒子組成物適當添加混合該行業者所公知之各種任意成分。作為此種成分之例，可列舉：流化劑、甜味劑、香料及著色料等。 Furthermore, in order to adjust various characteristics, such as a disintegration force, a binding force, and the feeling of the feeling of a tablet, the arbitrary disintegrating particle composition of this invention can also mix and mix the arbitrary arbitrary components of the well-known. Examples of such a component include a fluidizing agent, a sweetener, a flavor, and a coloring material.

關於本發明之崩解性粒子組成物中各成分之摻合量，該行業者可根據各成分之種類、崩解性粒子組成物之使用對象即藥效成分之種類及用途、作為最終製品之口腔內崩解錠劑之用途等而適當決定。通常相對於崩解性粒子組成物總重量，第一崩解劑成分為10~50重量%，第二崩解劑成分為1~20重量%，賦形劑為30~88重量%之範圍，及結晶纖維素為1~40重量%之範圍。 The blending amount of each component in the disintegrable particle composition of the present invention can be used as a final product depending on the type of each component, the type and use of the medicinal component which is the object of use of the disintegrable particle composition. The use of the orally disintegrating tablet is determined as appropriate. Usually, the first disintegrant component is 10 to 50% by weight, the second disintegrant component is 1 to 20% by weight, and the excipient is 30 to 88% by weight based on the total weight of the disintegrable particle composition. And the crystalline cellulose is in the range of 1 to 40% by weight.

本發明之崩解性粒子組成物可藉由該行業者所公知之任意方法而製造。例如可以由使用任意一種成分或二種成分之第一濕式造粒步驟，及至少使用第一濕式造粒步驟中獲得之造粒物與剩餘成分之第二濕式造粒步驟構成的二段造粒步驟，或者包括進而於第二濕式造粒步驟獲得之造粒物中混合成分之第三步驟的三段造粒步驟等而製造。 The disintegrable particle composition of the present invention can be produced by any method known to those skilled in the art. For example, it may be composed of a first wet granulation step using any one or two components, and a second wet granulation step using at least the granules obtained from the first wet granulation step and the remaining components. The stage granulation step, or a three-stage granulation step including the third step of mixing the components in the granules obtained in the second wet granulation step, or the like.

除上述製造方法以外，例如亦可藉由一起使用全部成分之一階段造粒步驟而製造本發明之崩解性粒子組成物。 In addition to the above production method, for example, the disintegrable particle composition of the present invention can be produced by using one stage granulation step of all the components together.

上述製造方法中，各造粒步驟係藉由在水的存在下使各成分分散並乾燥而形成複合體的方法，即濕式造粒法而進行。作為濕式造粒法之具體例，可列舉：噴霧乾燥、滾動造粒、攪拌造粒、及流動層造粒等噴霧法、冷凍乾燥法、以及混練造粒等，可藉由該等該行業者所公知之任意 方法而製造。 In the above production method, each granulation step is carried out by a method of forming a composite by dispersing and drying each component in the presence of water, that is, a wet granulation method. Specific examples of the wet granulation method include spray drying, rolling granulation, stirring granulation, and spray layer granulation, a freeze-drying method, and kneading granulation, and the like. Anyone known to the industry Manufactured by the method.

由於酸型羧甲基纖維素等崩解劑為親水性，故而藉由濕式造粒而於水的存在下進行攪拌等施加物理性外力之操作，藉此會使粒子自乾燥粉末時之凝集狀態成為進一步分散之狀態。進行利用水噴霧之分散化及乾燥的流動層造粒、噴霧乾燥、滾動造粒及攪拌造粒等，能夠最容易地進行分散，乾燥速度迅速，因此以該等方法為佳。 Since the disintegrant such as acid carboxymethyl cellulose is hydrophilic, a physical external force is applied by stirring in the presence of water by wet granulation, whereby the particles are agglomerated from the dry powder. The state becomes a state of further dispersion. The flow layer granulation by water spray dispersing and drying, spray drying, rolling granulation, stirring granulation, and the like can be carried out most easily, and the drying speed is rapid. Therefore, these methods are preferred.

其中，流動層造粒法係一面利用暖風吹起粉體，一面霧狀噴出含有水或結合劑之水溶液等而實施之造粒法，就容易調整噴霧條件等等而言為最佳之方法。 Among them, the fluidized bed granulation method is a method in which the powder is sprayed by a warm air and the aqueous solution containing water or a binder is sprayed in a mist form, and it is easy to adjust the spray conditions and the like.

進而，於各造粒步驟中，關於噴霧(spray)速度或空氣供給溫度、排氣溫度、空氣供給量等各條件，該行業者可根據各成分之種類、量等而適當決定。 Further, in each granulation step, each of the conditions such as the spray speed, the air supply temperature, the exhaust gas temperature, and the air supply amount can be appropriately determined depending on the type, amount, and the like of each component.

於各造粒步驟之任一步驟中，作為噴霧液之媒液，例如可列舉：水、乙醇、甲醇、及丙酮等醫藥品或食品所容許之溶劑。或者作為噴霧液，可舉溶有未達10%之該崩解性粒子組成物成分的水溶液等，以水或該水溶液尤佳。 In any of the granulation steps, examples of the vehicle for the spray liquid include a solvent which is acceptable for a pharmaceutical product such as water, ethanol, methanol or acetone or a food. Alternatively, the spray liquid may be an aqueous solution or the like in which less than 10% of the disintegrable particle composition component is dissolved, and water or the aqueous solution is particularly preferable.

再者，上述崩解性添加劑摻合物以具有如下物性為佳。 Further, the above disintegrating additive blend is preferably one having the following physical properties.

(1)平均粒徑：50~200微米，(2)水分：0.5~6重量%。 (1) Average particle diameter: 50 to 200 μm, (2) Moisture: 0.5 to 6% by weight.

再者，該等物性值係藉由以下之條件、方法測量。 Furthermore, the physical property values are measured by the following conditions and methods.

平均粒徑：使用φ75mm自動震動篩選器(M-2型，筒井理化學器械股份有限公司)對崩解性添加劑摻合物2g進行測量。 Average particle diameter: 2 g of the disintegrating additive blend was measured using a φ75 mm automatic vibration filter (M-2 type, Tsutsui Chemical Instruments Co., Ltd.).

水分：使用鹵素水分測量器(HB43型，Mettler Toledo股份有限公司) 對崩解性添加劑摻合物5g進行測量。 Moisture: Halogen moisture meter (HB43, Mettler Toledo Co., Ltd.) 5 g of the disintegrating additive blend was measured.

再者，本說明書中所引用之全部先前技術文獻之記載內容係以參照之形式併入本說明書。 Furthermore, the contents of all prior art documents cited in the specification are incorporated herein by reference.

以下，藉由實施例更具體地說明本發明，但本發明並不限制於該等實施例。 Hereinafter, the present invention will be specifically described by way of examples, but the invention is not limited to the examples.

[實施例] [Examples]

[崩解性粒子組成物之製造] [Manufacture of disintegrating particle composition]

作為第一濕式造粒步驟，將甘露醇(D-甘露醇，Merck股份有限公司)280g、羧甲基纖維素(NS-300，五德藥品股份有限公司)75g、結晶纖維素(Ceolus PH-101，旭化成化學股份有限公司)100g投入至流動層造粒機(LAB-1，Powrex股份有限公司)，以24g/min之速度霧狀噴出精製水240g，藉此進行造粒，進而作為第二濕式造粒步驟，添加交聯聚維酮(Polyplasdone INF-10，ISP-Japan股份有限公司)40g，以10g/min霧狀噴出精製水300g，藉此獲得造粒物(本發明之崩解性粒子組成物)。再者，造粒物具有以下之物性值。(1)平均粒徑：93微米，(2)水分：2.3重量%。 As the first wet granulation step, mannitol (D-mannitol, Merck Co., Ltd.) 280 g, carboxymethylcellulose (NS-300, Wude Pharmaceutical Co., Ltd.) 75 g, crystalline cellulose (Ceolus PH) -101, Asahi Kasei Chemicals Co., Ltd.) 100 g was charged to a fluidized bed granulator (LAB-1, Powrex Co., Ltd.), and 240 g of purified water was sprayed at a rate of 24 g/min to granulate it. In the second wet granulation step, 40 g of crospovidone (Polyplasdone INF-10, ISP-Japan Co., Ltd.) was added, and 300 g of purified water was sprayed in a mist of 10 g/min, thereby obtaining granules (the rupture of the present invention) Decomposable particle composition). Further, the granulated product has the following physical property values. (1) Average particle diameter: 93 μm, (2) Moisture: 2.3% by weight.

[口腔內崩解錠劑之製造例1] [Production Example 1 of Oral Disintegrating Lozenge]

於實施例1[崩解性粒子組成物之製造]所獲得之崩解性粒子組成物99.8重量份中混合硬脂酸鎂0.2重量份，使用旋轉式打錠機(HT-EX12SS-U，Hata Iron Works股份有限公司)，以轉盤旋轉數20rpm，打錠壓縮力3kN進行打錠，從而獲得直徑6.0mm、隅角平錠(flat-faced bevel-edged tablet)、重量60mg之錠劑。 To 99.8 parts by weight of the disintegrable particle composition obtained in Example 1 [Production of disintegrable particle composition], 0.2 parts by weight of magnesium stearate was mixed, and a rotary tableting machine (HT-EX12SS-U, Hata) was used. Iron Works Co., Ltd., ingots were rotated at a number of 20 rpm and an ingot compression force of 3 kN to obtain a tablet having a diameter of 6.0 mm, a flat-faced bevel-edged tablet, and a weight of 60 mg.

[口腔內崩解錠劑之製造例2] [Production Example 2 of Oral Disintegrating Lozenge]

於實施例1[崩解性粒子組成物之製造]所獲得之崩解性粒子組成物98.8重量份中混合輕質無水矽酸(Adsolider)1.0重量份、硬脂酸鎂0.2重量份，使用旋轉式打錠機(HT-EX12SS-U，Hata Iron Works股份有限公司)，以轉盤旋轉數20rpm，打錠壓縮力3kN進行打錠，從而獲得直徑6.0mm、隅角平錠、重量60mg之錠劑。 In an amount of 98.8 parts by weight of the disintegrable particle composition obtained in Example 1 [Production of the disintegrable particle composition], 1.0 part by weight of light anhydrous decanoic acid (Adsolider) and 0.2 parts by weight of magnesium stearate were mixed, and rotation was used. Ingot tableting machine (HT-EX12SS-U, Hata Iron Works Co., Ltd.), ingots with a turntable rotation number of 20 rpm and an ingot compression force of 3 kN, thereby obtaining a tablet having a diameter of 6.0 mm, a flat-angled ingot, and a weight of 60 mg. .

[比較例] [Comparative example]

將乳糖(FlowLac90，Meggre股份有限公司)350g、玉米澱粉(White Cornstarch，Nihon Cornstarch股份有限公司)150g進行混合，獲得混合物。 350 g of lactose (FlowLac90, Meggre Co., Ltd.) and 150 g of corn starch (White Cornstarch, Nihon Cornstarch Co., Ltd.) were mixed to obtain a mixture.

將硬脂酸鎂0.2重量份混合於所獲得之混合物99.8重量份，與實施例1同樣地進行打錠，獲得直徑6.0mm、隅角平錠、重量60mg之錠劑。 0.2 parts by weight of the obtained magnesium stearate was mixed with 99.8 parts by weight of the obtained mixture, and tableting was carried out in the same manner as in Example 1 to obtain a tablet having a diameter of 6.0 mm, a rectangular tablet and a weight of 60 mg.

[硬度及崩解性之評價] [Evaluation of hardness and disintegration]

對由實施例及比較例所獲得之各錠劑，藉以下方法測量硬度及水中崩解時間。將硬度及水中崩解時間之測量結果示於表1。 For each of the tablets obtained in the examples and the comparative examples, the hardness and the disintegration time in water were measured by the following methods. The measurement results of the hardness and the disintegration time in water are shown in Table 1.

再者，該等物性值係藉由以下之條件、方法進行測量。 Further, the physical property values are measured by the following conditions and methods.

硬度：使用數位木屋式硬度計(藤原製作所股份有限公司)，測量硬度(N)。 Hardness: Hardness (N) was measured using a digital wooden house hardness tester (Fujiri Manufacturing Co., Ltd.).

水中崩解時間：根據日本藥典記載(其中，無輔助盤)之方法，使用崩解試驗器(NT-400，富山產業股份有限公司)測量水中崩解時間。 Disintegration time in water: The disintegration time in water was measured using a disintegration tester (NT-400, Toyama Industries Co., Ltd.) according to the method described in the Japanese Pharmacopoeia (with no auxiliary tray).

口腔內崩解時間：使用口腔內崩解試驗器(TRICORPTESTER，；岡田精工股份有限公司)測量口腔內崩解時間。 Oral disintegration time: The intraoral disintegration time was measured using an intraoral disintegration tester (TRICORPTESTER,; Okada Seiko Co., Ltd.).

對硬度及各崩解時間分別進行10次測量，將該等之平均值設為測量結果。 The hardness and each disintegration time were measured 10 times, and the average value of these was set as the measurement result.

[應力-應變曲線之評價] [Evaluation of stress-strain curve]

進而，對由實施例及比較例所獲得之各錠劑，藉以下方法取得錠劑之應力-應變曲線。使用Tensilon萬能試驗機，以壓縮模式、壓縮速度1mm/min之速度壓縮錠劑，將相對於錠劑之應變(%)的應力(N/mm²)之變化進行作圖，獲得曲線。對各錠劑評價破裂之時間點(破裂點)的應變及衝擊吸收能量(impact energy absorption)。 Further, the stress-strain curves of the tablets were obtained by the following methods for each of the tablets obtained in the examples and the comparative examples. The tablet was compressed at a speed of 1 mm/min in a compression mode and a compression speed using a Tensilon universal testing machine, and a change in stress (N/mm ² ) with respect to the strain (%) of the tablet was plotted to obtain a curve. The strain and the impact energy absorption at the time point (breaking point) at which the rupture was evaluated were evaluated for each tablet.

[落下試驗及評價] [fall test and evaluation]

於不銹鋼板上，使合計50錠之錠劑一錠一錠地自1m高落下，評價落下前後之錠劑硬度的變化、錠劑外觀之變化。 On a stainless steel plate, a total of 50 tablets of the tablet was dropped from 1 m in one loft, and the change in the hardness of the tablet before and after the drop and the change in the appearance of the tablet were evaluated.

[錠劑之各種物性值] [Various physical properties of lozenges]

將如此製造之本發明之錠劑(製造例1及製造例2)以及比較例中獲得之錠劑的各種物性值示於以下之表1。又，將所獲得之應力-應變曲線示於圖1。 The various physical properties of the tablet of the present invention (Production Example 1 and Production Example 2) and the tablet obtained in the comparative example thus produced are shown in Table 1 below. Further, the obtained stress-strain curve is shown in Fig. 1.

對製造例1及2，以及比較例所示之各種錠劑實施落下試驗之結果，製造例1未確認到落下試驗所造成之錠劑的破裂或缺損，製造例2僅於落下試驗後之2錠確認到微小的缺損，表示可適用於PTP包裝或一包化等廣泛之捆包體。另一方面，比較例於落下試驗後之錠劑中，確認到2 錠之明顯的破裂、缺損，因此表示錠劑被***，不適合此種包裝。 As a result of performing the drop test on the various tablets shown in Production Examples 1 and 2 and the comparative examples, the crack or defect of the tablet caused by the drop test was not confirmed in Production Example 1, and Production Example 2 was only 2 spindles after the drop test. A small defect is confirmed, indicating that it can be applied to a wide range of packages such as PTP packaging or one pack. On the other hand, the comparative example was confirmed in the lozenge after the drop test. The obvious breakage and defect of the ingot, thus indicating that the tablet is split, is not suitable for such packaging.

【實施例3】 [Example 3]

[口腔內崩解錠劑之製造例3] [Production Example 3 of Oral Disintegrating Lozenge]

於實施例1[崩解性粒子組成物之製造]所獲得之崩解性粒子組成物88.8重量份中添加混合抗壞血酸10.0重量份、輕質無水矽酸(Adsolider)1.0重量份、硬脂酸鎂0.2重量份，使用旋轉式打錠機(HT-EX12SS-U，Hata Iron Works股份有限公司)，以轉盤旋轉數20rpm，打錠壓縮力4kN進行打錠，從而獲得直徑6.0mm、隅角平錠、重量60mg之錠劑。 To 88.8 parts by weight of the disintegrable particle composition obtained in Example 1 [Production of the disintegrable particle composition], 10.0 parts by weight of ascorbic acid and 1.0 part by weight of light anhydrous decanoic acid (Adsolider) and magnesium stearate were added. 0.2 parts by weight, using a rotary tableting machine (HT-EX12SS-U, Hata Iron Works Co., Ltd.), the spindle was rotated at a number of 20 rpm, and the ingot compression force was 4 kN for ingot casting, thereby obtaining a diameter of 6.0 mm and a flat-angled ingot. A tablet weighing 60 mg.

【實施例4】 [Embodiment 4]

[口腔內崩解錠劑之製造例4] [Production Example 4 of Oral Disintegrating Lozenge]

於實施例1[崩解性粒子組成物之製造]所獲得之崩解性粒子組成物99.8重量份中混合硬脂酸鎂0.2重量份，使用手壓打錠機(HANDTAB-100，市橋精機股份有限公司)，於打錠壓縮力8kN進行打錠，從而獲得直徑14mm、隅角平錠、重量250mg之錠劑。 0.2 parts by weight of magnesium stearate was mixed with 99.8 parts by weight of the disintegrable particle composition obtained in Example 1 [Production of disintegrating particle composition], and a hand press machine (HANDTAB-100, Shiqiao Seiki Co., Ltd.) was used. Co., Ltd., ingots were injected at a compression force of 8 kN to obtain a tablet having a diameter of 14 mm, a flat-angled ingot, and a weight of 250 mg.

[錠劑之各種物性值] [Various physical properties of lozenges]

將如此製造之本發明之錠劑(製造例3~製造例4)中獲得之錠劑的各種物性值示於以下之表2。又，將所獲得之應力-應變曲線示於圖2。 The various physical properties of the tablet obtained in the tablet of the present invention (Production Example 3 to Production Example 4) thus produced are shown in Table 2 below. Further, the obtained stress-strain curve is shown in Fig. 2.

又，針對製造例4之口腔內崩解時間，係將錠劑1錠含於口腔內，以不施加力道之方式保持以舌與上顎夾持之狀態，測量錠劑完全崩解之時間。經由成年男性2名每人各3錠之實施，測量其等之平均值，結果為4.7秒。 Further, in the oral disintegration time of Production Example 4, one tablet of the tablet was contained in the oral cavity, and the state in which the tablet was completely disintegrated was measured while holding the tongue and the upper jaw without applying a force. The average value of the three males per adult was measured, and the average value was 4.7 seconds.

[產業上之可利用性] [Industrial availability]

根據本發明，可將口腔內崩解錠劑(超高速崩解錠劑)作為由擠壓包裝(PTP：Press Through Package)而得之包裝體而提供，該口腔內崩解錠劑具有高崩解性(短崩解時間)，並且兼備可期待降低錠劑之破裂缺損至實用等級程度之高錠劑硬度。 According to the present invention, an orally disintegrating tablet (ultra-high-speed disintegrating tablet) can be provided as a package obtained by a PTP (Press Through Package) having a high collapse Solubility (short disintegration time), and also has a high tablet hardness which can be expected to reduce the rupture defect of the tablet to a practical level.

Claims (10)

一種口腔內崩解錠劑，其水中崩解時間未達15秒，錠劑之應力-應變曲線中，破裂時之錠劑的應變為1.7(%)以上。 An orally disintegrating tablet in which the disintegration time in water is less than 15 seconds, and in the stress-strain curve of the tablet, the strain of the tablet at the time of rupture is 1.7 (%) or more. 如申請專利範圍第1項之口腔內崩解錠劑，其水中崩解時間未達9秒。 For example, in the oral disintegrating tablet of claim 1, the disintegration time in water is less than 9 seconds. 如申請專利範圍第1或2項之口腔內崩解錠劑，其口腔內崩解時間為6秒以下。 The orally disintegrating tablet of the oral cavity of claim 1 or 2 has an intraoral disintegration time of 6 seconds or less. 如申請專利範圍第3項之口腔內崩解錠劑，其口腔內崩解時間為5秒以下。 The oral disintegration tablet of the third aspect of the patent application has an intraoral disintegration time of 5 seconds or less. 如申請專利範圍第1或2項之口腔內崩解錠劑，其硬度為10N~30N。 For example, the oral disintegrating tablet of claim 1 or 2 has a hardness of 10N to 30N. 如申請專利範圍第1項之口腔內崩解錠劑，其係以包括如下步驟之方法製造：將含有酸型羧甲基纖維素、結晶纖維素及糖或糖醇之崩解性粒子組成物與醫藥活性物質進行混合，將所獲得之混合物打錠。 An orally disintegrating tablet according to claim 1, which is produced by a method comprising the steps of: disintegrating particle composition containing acid type carboxymethyl cellulose, crystalline cellulose, and sugar or sugar alcohol; The mixture is mixed with a pharmaceutically active substance, and the obtained mixture is tableted. 如申請專利範圍第6項之口腔內崩解錠劑，其中，於崩解性粒子組成物進一步含有輕質無水矽酸(light anhydrous silicic acid)。 The orally disintegrating tablet of claim 6, wherein the disintegrable particle composition further contains light anhydrous silicic acid. 如申請專利範圍第6或7項之口腔內崩解錠劑，其係施加打錠壓縮力2至8kN進行打錠。 Oral disintegrating tablet according to claim 6 or 7, which is subjected to tableting by applying a compression force of 2 to 8 kN. 一種包裝體，其係將申請專利範圍第1至8項中任一項之口腔內崩解錠劑包裝而成。 A package obtained by packaging the orally disintegrating tablet of any one of claims 1 to 8. 如申請專利範圍第9項之包裝體，其為擠壓包裝(PTP，Press Through Package)體或一包化體。 The package body of claim 9 is a PTP (Press Through Package) body or a package body.