JPH10298061A - Shaped preparation and its production - Google Patents
Shaped preparation and its productionInfo
- Publication number
- JPH10298061A JPH10298061A JP10799197A JP10799197A JPH10298061A JP H10298061 A JPH10298061 A JP H10298061A JP 10799197 A JP10799197 A JP 10799197A JP 10799197 A JP10799197 A JP 10799197A JP H10298061 A JPH10298061 A JP H10298061A
- Authority
- JP
- Japan
- Prior art keywords
- lubricant
- molding
- fluidizing agent
- weight
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、障害を生じること
なく高速で連続的に薬物処方成分を成型する方法および
該方法により得られる成型製剤に関する。[0001] The present invention relates to a method for continuously and rapidly molding a drug prescription component without causing any obstacle, and a molded preparation obtained by the method.
【０００２】[0002]
【従来の技術】医薬品錠剤の製造時、打錠障害の防止の
ため、ステアリン酸マグネシウムなどの滑沢剤を使用す
るのが技術常識であり、多くは滑沢剤を薬物処方成分と
共に混合して打錠している。しかし、滑沢剤を多量に使
用すると錠剤の崩壊時間、溶出速度が著しく遅くなり、
極端な場合、錠剤が数時間にもわたって崩壊しない場合
もある。2. Description of the Related Art In the production of pharmaceutical tablets, it is common technical knowledge to use a lubricant such as magnesium stearate in order to prevent tableting trouble, and in many cases, a lubricant is mixed with a drug prescription component. I'm tableting. However, when a large amount of lubricant is used, the disintegration time of the tablet, the dissolution rate becomes extremely slow,
In extreme cases, tablets may not disintegrate for hours.
【０００３】このため、滑沢剤を圧縮成型機側に付着さ
せて成型する方法が考えられ、例えば、大塚ら（第１１
回製剤と粒子設計シンポジウム講演要旨集（１９９４
年）、１３７頁）は、オートグラフの臼と杵にステアリ
ン酸マグネシウムを予め塗布した後、薬物処方成分を圧
縮成型することにより、薬物処方成分に滑沢剤を添加し
て得られる錠剤に比べ硬度が高く、しかも溶出速度が極
めて速い錠剤を得ている。しかしながら、この方法は、
１錠ごとにオートグラフの臼と杵に滑沢剤を塗る必要が
あるため、工業的な製法とはなりえない。[0003] For this reason, a method of forming a lubricant by adhering it to the compression molding machine side is considered. For example, Otsuka et al.
Abstracts of Annual Symposium on Preparation and Particle Design (1994)
Pp. 137) compared with tablets obtained by pre-coating magnesium stearate on the mortar and punch of the autograph and then compression-molding the drug prescription component to add a lubricant to the drug prescription component. A tablet having a high hardness and an extremely fast dissolution rate is obtained. However, this method
Since it is necessary to apply a lubricant to the mortar and punch of the autograph for each tablet, it cannot be an industrial production method.
【０００４】また、打錠機の上杵・下杵または上杵・下
杵及び臼に滑沢剤の粉を噴射した後、薬物処方成分を臼
内に充填し圧縮成型する方法（特公昭４１−１２７３、
特開昭４８−２０１０３など）も知られている。この方
法は微粒子である滑沢剤をスプレーするため滑沢剤の周
辺への飛散、ノズルのつまり、スプレーした滑沢剤を回
収するには大きな装置が必要であるなどの問題に加え、
滑沢剤が均一に杵や臼に付着せず、下杵付近に不要の滑
沢剤が多く残るため多量の滑沢剤が必要であるなどの問
題点もある。Further, a method of injecting a lubricant powder into an upper punch / lower punch or an upper punch / lower punch and a die of a tableting machine, filling a drug prescription component in the die, and compression-molding the same (Japanese Patent Publication No. Sho 41) -1273,
JP-A-48-20103) is also known. In addition to the problem that this method sprays a lubricant that is fine particles, the lubricant scatters around the lubricant, that is, the nozzle, that is, a large device is required to collect the sprayed lubricant,
There is also a problem that the lubricant does not uniformly adhere to the punches and dies and a large amount of unnecessary lubricant remains near the lower punch, so that a large amount of lubricant is required.
【０００５】更に、潤滑剤を圧縮成型機で圧縮した後、
押型壁に残る潤滑剤を利用して加工物質を圧縮成型する
方法も知られている（特公昭４７−３１８２７号）。し
かしこの方法は、セラミックや酸化ウランなどのペレッ
ト化技術であるため、医薬品の製造に適用するには問題
がある。すなわち、医薬品錠剤において通常使用される
ステアリン酸アルカリ土類金属塩などの滑沢剤は、単独
では流動性が悪く、打錠機への安定した供給は困難であ
り、さらに、たとえ供給できたとしても、これら滑沢剤
を単独で打錠すると滑沢剤が大量に杵に付着し、ひどい
場合には杵上に固着してしまい、続く薬物処方成分の打
錠に障害をきたすおそれがある。Further, after the lubricant is compressed by a compression molding machine,
There is also known a method of compression-molding a processed material by using a lubricant remaining on a stamping wall (Japanese Patent Publication No. 47-31827). However, since this method is a technique for pelletizing ceramic, uranium oxide, or the like, there is a problem in applying it to the production of pharmaceuticals. That is, a lubricant such as an alkaline earth metal stearate commonly used in pharmaceutical tablets is poor in fluidity by itself, and it is difficult to stably supply it to a tableting machine. However, when these lubricants are tableted alone, a large amount of the lubricant adheres to the punch, and in severe cases, the lubricant adheres to the punch, which may hinder the subsequent tableting of drug components.
【０００６】[0006]
【発明が解決しようとする課題】本発明の目的は、滑沢
剤の流動性を改善し、効率よく成型製剤を製造すること
にある。SUMMARY OF THE INVENTION An object of the present invention is to improve the flowability of a lubricant and to efficiently produce a molded preparation.
【０００７】[0007]
【課題を解決するための手段】本発明者らは、滑沢剤単
独では流動性が悪く、連続打錠において滑沢剤のみを打
錠機に供給するのは困難であるが、結晶セルロース等と
滑沢剤と混合した場合には格段に流動性が改善されるこ
と、該混合物を打錠すると、滑沢剤が打錠機の杵、臼の
表面に適度に付着すること、該打錠機で薬物処方成分を
打錠することにより、処方成分中に滑沢剤を添加しなく
ても打錠障害を起こすことなく製錠できることを見出し
た。Means for Solving the Problems The present inventors have found that a lubricant alone has poor fluidity and it is difficult to supply only a lubricant to a tableting machine in continuous tableting. And when mixed with a lubricant, the fluidity is remarkably improved, and when the mixture is compressed, the lubricant is appropriately adhered to the surface of a punch and a die of a tableting machine; It has been found that, by tableting a drug prescription component with a machine, tableting can be performed without causing a tableting trouble without adding a lubricant to the prescription component.
【０００８】更に、本方法により得られた錠剤は、薬物
処方成分中に滑沢剤を添加して打錠して得た錠剤に比
べ、滑沢剤による崩壊、溶出の遅延がなくなることを見
出した。Furthermore, it has been found that the tablets obtained by the present method have less disintegration and delay of dissolution due to the lubricant than tablets obtained by adding a lubricant to the drug formulation and tableting. Was.
【０００９】すなわち、本発明は、滑沢剤と流動化剤と
の混合物を成型機で成型し、成型物を排出したのち、該
成型機で薬物処方成分を成型することを特徴とする成型
製剤の製法及び該製法により得られる成型製剤である。That is, the present invention provides a molded preparation characterized by molding a mixture of a lubricant and a fluidizing agent by a molding machine, discharging the molded product, and then molding the drug prescription component by the molding machine. And a molded preparation obtained by the method.
【００１０】[0010]
【発明の実施の形態】本発明の方法は、滑沢剤と流動化
剤との混合物の成型機による成型（以下、一次成型）
と、一次成型による成型物を排出したのち該成型機で薬
物処方成分を成型（以下、二次成型）することからなる
が、一次成型において使用される滑沢剤としては、ステ
アリン酸、パルミチン酸、ステアリン酸マグネシウム、
ステアリン酸カルシウムなどの高級脂肪酸またはそのア
ルカリ土類金属塩、軟質無水ケイ酸、合成ケイ酸アルミ
ニウム、含水二酸化ケイ素、タルクなどのケイ素化合
物、コムギデンプン、コメデンプン、トウモロコシデン
プンなどのデンプン類、ショ糖脂肪酸エステルなどがあ
げられる。なかでも、ステアリン酸マグネシウム、ステ
アリン酸カルシウムなどのステアリン酸アルカリ土類金
属塩が好ましい。BEST MODE FOR CARRYING OUT THE INVENTION The method of the present invention comprises molding a mixture of a lubricant and a fluidizing agent by a molding machine (hereinafter, primary molding).
After the molded product of the primary molding is discharged, the drug prescription component is molded by the molding machine (hereinafter, secondary molding). Lubricants used in the primary molding include stearic acid and palmitic acid. ,Magnesium stearate,
Higher fatty acids such as calcium stearate or alkaline earth metal salts thereof, soft silicic anhydride, synthetic aluminum silicate, hydrous silicon dioxide, silicon compounds such as talc, starches such as wheat starch, rice starch, corn starch, and sucrose fatty acids Esters and the like. Of these, alkaline earth metal stearate such as magnesium stearate and calcium stearate are preferred.
【００１１】また、滑沢剤と混合する流動化剤として
は、経口投与用製剤に通常用いられる製剤添加物であっ
て流動性に優れた粉体であれば特に制限されない。流動
性に優れた粉体とは、例えば、注入法により測定した安
息角が６０゜以下、好ましくは４０゜以下の粉体を意味
し、このような粉体であれば、製剤添加物そのままであ
っても、粉砕、造粒したものであっても、さらにはこれ
らを混合したものであってもよい。滑沢剤との混合性の
面からは、該流動化剤の粒度は、粒子径が５〜２０００
μｍの範囲内であることが好ましく、さらに好ましくは
５０〜７５０μｍの範囲内である。また、成型手段とし
て圧縮成型法を用いる場合には、圧縮成型性に優れたも
のであることがより好ましい。[0011] The fluidizing agent to be mixed with the lubricant is not particularly limited as long as it is a pharmaceutical additive usually used for oral administration and is a powder having excellent fluidity. The powder having excellent fluidity means, for example, a powder having an angle of repose of 60 ° or less, preferably 40 ° or less as measured by an injection method. It may be one obtained by pulverization or granulation, or a mixture thereof. From the viewpoint of miscibility with the lubricant, the particle size of the fluidizing agent is 5 to 2,000.
It is preferably in the range of μm, more preferably in the range of 50 to 750 μm. Further, when a compression molding method is used as the molding means, it is more preferable that the molding method is excellent.
【００１２】上記条件を満たすものであれば、いかなる
製剤添加物であっても流動化剤として好適に用いること
ができるが、製剤添加物をそのままで用いることができ
れば、粉砕や造粒などの操作が必要なく、とくに好まし
い。このような製剤添加物としては、例えば、結晶セル
ロース、乳糖、白糖、マンニトール、リン酸カルシウ
ム、クエン酸カルシウムなどがあげられ、これらは入手
容易であり、流動性、圧縮成型性、滑沢剤との混合性に
優れており、中でも結晶セルロース、乳糖が最も好まし
い。Any formulation additive can be suitably used as a fluidizing agent as long as it satisfies the above conditions. However, if the formulation additive can be used as it is, operations such as pulverization and granulation can be performed. Is not particularly required. Such pharmaceutical additives include, for example, crystalline cellulose, lactose, sucrose, mannitol, calcium phosphate, calcium citrate, and the like, which are easily available, and have fluidity, compression moldability, and mixing with lubricants. And crystalline cellulose and lactose are most preferred.
【００１３】また、そのままでは流動性、滑沢剤との混
合性、圧縮成型性などに問題がある場合であっても、粉
砕または造粒することによりそれらは改善することが可
能である。[0013] Even if there are problems with fluidity, mixing with a lubricant and compression moldability as they are, they can be improved by pulverization or granulation.
【００１４】粉砕は、ジェットミル、ハンマーミル、ボ
ールミル、振動ボールミル、ピンミルなどを用いて、常
法により実施することができる。The pulverization can be carried out by a conventional method using a jet mill, a hammer mill, a ball mill, a vibrating ball mill, a pin mill or the like.
【００１５】造粒も既知の方法、例えば撹拌造粒、押し
出し造粒、流動層造粒、転動流動層造粒などの湿式造
粒、ローラーコンパクター及びロールグラニュレーター
などによる乾式圧縮造粒などにより好適に実施すること
ができる。また、造粒に際しては、必要に応じポリビニ
ルピロリドン、ヒドロキシプロピルメチルセルロース、
ヒドロキシプロピルセルロース、デキストリンなどの結
合剤を添加してもよい。Granulation is also performed by a known method, for example, wet granulation such as stirring granulation, extrusion granulation, fluidized bed granulation, and tumbling fluidized bed granulation, and dry compression granulation using a roller compactor or a roll granulator. It can be suitably implemented. When granulating, polyvinylpyrrolidone, hydroxypropyl methylcellulose,
A binder such as hydroxypropylcellulose and dextrin may be added.
【００１６】一次成型において、滑沢剤と流動化剤との
比率は、成型方法、成型に用いる成型機の種類、滑沢
剤、流動化剤の種類、薬物処方成分の性質などによって
変動するが、滑沢剤の流動性を改善し成型機への供給を
良好にすること、成型後の成型物排出が容易であるこ
と、かつ成型物排出後の成型機内部の表面、例えば打錠
機であれば臼、杵などの表面に二次成型物が付着せず、
効率的に成型しうる程度に滑沢剤が付着するような比率
であればよく、特に限定されない。In the primary molding, the ratio between the lubricant and the fluidizing agent varies depending on the molding method, the type of molding machine used for molding, the type of the lubricant and the fluidizing agent, the properties of the drug prescription components, and the like. Improve the flowability of the lubricant to improve the supply to the molding machine, make it easy to discharge the molded product after molding, and use the surface inside the molding machine after the molded product is discharged, such as a tableting machine. If there is no secondary molding on the surface of the mortar, punch, etc.,
The ratio is not particularly limited as long as the ratio allows the lubricant to adhere to such an extent that it can be efficiently molded.
【００１７】かかる比率は当業者であれば、実際に適宜
試みに成型し、一次成型物、二次成型物及び成型機の状
態を確認すればよく、容易に決定することができるが、
一例をあげるとすれば、例えば滑沢剤１重量部に対し流
動化剤が約２〜２０重量部の範囲内が好ましく、さらに
好ましくは約２〜１０重量部の範囲内である。The ratio can be easily determined by those skilled in the art by actually molding as appropriate and confirming the condition of the primary molded product, the secondary molded product and the molding machine.
For example, the amount of the fluidizing agent is preferably in the range of about 2 to 20 parts by weight, more preferably in the range of about 2 to 10 parts by weight with respect to 1 part by weight of the lubricant.
【００１８】上記の成分を使用した一次成型は、固形製
剤の成型に際して通常用いられる手段および条件で行う
ことができる。成型手段としては、例えば打錠、ロール
圧縮などの圧縮成型方法のほか、鋳型成型などの圧縮を
伴わない成型方法であってもよい。本発明の方法は、滑
沢剤を成型機の内部表面に残留させて、二次成型物の付
着を防止しようとするものであるから、この目的にかな
う方法であれば、何ら制限を受けない。The primary molding using the above-mentioned components can be carried out by means and conditions usually used for molding a solid preparation. Examples of the molding means include a compression molding method such as tableting and roll compression, and a molding method that does not involve compression, such as mold molding. The method of the present invention is to leave the lubricant on the inner surface of the molding machine and to prevent the adhesion of the secondary molded product. .
【００１９】また、圧縮成型による場合には、その圧縮
圧力は成型機の内部表面に二次成型物の付着を防止でき
る程度に滑沢剤が残留し、かつ一次成型物の排出に困難
をきたさない範囲の圧力であればよい。該圧力の例を打
錠機を例にとってより具体的に説明するとすれば、例え
ば約０．０１〜５０００ｋｇ／杵、好ましくは約０．１
〜４０００ｋｇ／杵、より好ましくは約１〜３０００ｋ
ｇ／杵、とりわけ好ましくは約５〜２０００ｋｇ／杵で
あり、約１０〜１０００ｋｇ／杵が最も好ましい。In the case of compression molding, the compression pressure is such that the lubricant remains on the inner surface of the molding machine to the extent that the secondary molding can be prevented from adhering, and it is difficult to discharge the primary molding. It is sufficient if the pressure is in a range that does not exist. If the example of the pressure is described more specifically by taking a tableting machine as an example, for example, about 0.01 to 5000 kg / punch, preferably about 0.1
~ 4000kg / punch, more preferably about 1-3000k
g / punch, particularly preferably about 5-2000 kg / punch, with about 10-1000 kg / punch being most preferred.
【００２０】なお、本発明方法においては、一次成型と
いう表現は使用しているが、一次成型物は必ずしも排出
したのち、明確な形状を維持するようなものである必要
はなく、成型機の内部表面に上記したように滑沢剤が二
次成型容易なように残留する限り、排出と同時に崩壊す
るようなものであっても、これを含むものである。Although the term "primary molding" is used in the method of the present invention, the primary molded product does not necessarily have to maintain a clear shape after being discharged. As long as the lubricant remains on the surface as described above so as to be easily formed into a secondary form, the lubricant includes any one that collapses upon discharge.
【００２１】かくして一次成型された成型物は排出さ
れ、二次成型が行われる。二次成型は、通常の成型手
段、条件で容易に実施することができるが、本発明方法
においては、既に述べたとおり、一次成型により滑沢剤
が成型機の内部表面に残留しているので、滑沢剤を使用
する必要がない。また本発明方法によれば、滑沢剤を含
む薬物処方成分でも、より効率的に成型できるので、何
ら支障がない。The molded product thus formed is discharged and subjected to secondary molding. The secondary molding can be easily carried out by ordinary molding means and conditions. However, in the method of the present invention, as described above, since the lubricant remains on the inner surface of the molding machine due to the primary molding. No need to use lubricants. Further, according to the method of the present invention, even a drug prescription component containing a lubricant can be molded more efficiently, so that there is no problem at all.
【００２２】二次成型は、目的とする薬物、各種製剤添
加物（賦形剤、結合剤、崩壊剤など）からなる薬物処方
成分を、成型機に供給して一次成型と同様、固形製剤の
成型に際して用いられる手段および条件で行うことがで
きる。In the secondary molding, a drug formulation comprising a target drug and various pharmaceutical additives (excipients, binders, disintegrants, etc.) is supplied to a molding machine and, as in the primary molding, a solid preparation is prepared. It can be carried out by the means and conditions used in molding.
【００２３】薬物としては、経口投与可能な薬物であれ
ば特に限定されない。例えば化学療法剤、抗生物質、呼
吸促進剤、鎮咳去たん剤、抗悪性腫瘍剤、自律神経用薬
剤、精神神経用薬剤、局所麻酔剤、筋弛緩剤、消化器官
用薬剤、抗ヒスタミン剤、中毒治療剤、催眠鎮静剤、抗
てんかん剤、解熱鎮痛消炎剤、強心剤、不整脈治療剤、
利尿剤、血管拡張剤、抗脂血剤、滋養強壮剤、抗凝血
剤、肝臓用薬剤、血糖降下剤、血圧降下剤等種々の薬物
があげられる。The drug is not particularly limited as long as it can be administered orally. For example, chemotherapeutics, antibiotics, respiratory stimulants, antitussives, anticancer drugs, drugs for autonomic nerves, drugs for psychiatric nerves, local anesthetics, muscle relaxants, drugs for digestive organs, antihistamines, drugs for poisoning , Sedative, hypnotic, antiepileptic, antipyretic analgesic and anti-inflammatory, inotropic, antiarrhythmic,
Examples include various drugs such as diuretics, vasodilators, antilipidemic agents, nutrient tonics, anticoagulants, drugs for the liver, hypoglycemic agents, hypotensive agents and the like.
【００２４】製剤添加物としては、特に制限されず固形
製剤として使用しうるものは全て好適に使用することが
出来る。かかる添加物としては、例えば乳糖、白糖、マ
ンニトール、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、クエン酸カルシウム、リン酸カル
シウム、結晶セルロースなどの賦形剤、トウモロコシデ
ンプン、馬鈴薯デンプン、カルボキシメチルスターチナ
トリウム、部分アルファ化デンプン、カルボキシメチル
セルロースカルシウム、カルボキシメチルセルロース、
低置換度ヒドロキシプロピルセルロース、架橋カルボキ
シメチルセルロースナトリウムなどの崩壊剤、ヒドロキ
シプロピルセルロース、ヒドロキシプロピルメチルセル
ロース、ポリビニルピロリドン、ポリエチレングリコー
ル、デキストリン、アルファー化デンプンなどの結合
剤、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、軽質無水ケイ酸、含水二酸化ケイ素などの
滑沢剤、更にはリン脂質、グリセリン脂肪酸エステル、
ソルビタン脂肪酸エステル、ポリオキシエチレン脂肪酸
エステル、ポリエチレングリコール脂肪酸エステル、ポ
リオキシエチレン硬化ヒマシ油、ポリオキシエチレンア
ルキルエーテル、ショ糖脂肪酸エステルなどの界面活性
剤、或いはオレンジ、ストロベリーなどの香料、三二酸
化鉄、黄色三二酸化鉄、食用黄色５号、食用黄色４号、
アルミニウムキレートなどの着色剤、サッカリン、アス
パルテームなどの甘味剤、クエン酸、クエン酸ナトリウ
ム、コハク酸、酒石酸、フマル酸、グルタミン酸などの
矯味剤、シクロデキストリン、アルギニン、リジン、ト
リスアミノメタンなどの溶解補助剤が上げられる。There are no particular restrictions on the pharmaceutical additives, and all additives that can be used as solid pharmaceuticals can be suitably used. Such additives include, for example, lactose, sucrose, mannitol, xylitol, erythritol, sorbitol, maltitol, calcium citrate, calcium phosphate, excipients such as crystalline cellulose, corn starch, potato starch, sodium carboxymethyl starch, partially pregelatinized. Starch, carboxymethylcellulose calcium, carboxymethylcellulose,
Disintegrants such as low-substituted hydroxypropylcellulose and crosslinked sodium carboxymethylcellulose, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyethylene glycol, dextrin, pregelatinized starch, magnesium stearate, calcium stearate, talc, light Lubricants such as silicic anhydride, hydrous silicon dioxide, and further phospholipids, glycerin fatty acid esters,
Surfactants such as sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, sucrose fatty acid ester, or flavors such as orange and strawberry, iron sesquioxide, Yellow iron sesquioxide, Food Yellow No. 5, Food Yellow No. 4,
Coloring agents such as aluminum chelates, sweeteners such as saccharin and aspartame, flavoring agents such as citric acid, sodium citrate, succinic acid, tartaric acid, fumaric acid, and glutamic acid, dissolution aids such as cyclodextrin, arginine, lysine, and trisaminomethane The agent is raised.
【００２５】なお、滑沢剤は、製剤の目的に応じて全く
配合しない状態から適当量を配合した状態まで、種々の
状態を選択することが出来る。The lubricant can be selected from various states depending on the purpose of the preparation, from a state in which the lubricant is not blended at all to a state in which an appropriate amount is blended.
【００２６】供給される薬物処方成分中には造粒顆粒が
含まれていてもよく、造粒は既知の方法、例えば撹拌造
粒、押し出し造粒、流動層造粒、転動流動層造粒などの
湿式造粒の他、白糖、結晶セルロースなどの不活性な担
体上に薬物を被覆していくレイヤリング造粒、加熱によ
り溶融するワックス類を用いる加熱溶融造粒、乾式圧縮
造粒などにより好適に実施することができる。Granulation granules may be contained in the drug formulation component to be supplied, and the granulation may be performed by a known method, for example, stirring granulation, extrusion granulation, fluidized bed granulation, tumbling fluidized bed granulation. In addition to wet granulation, such as layering granulation to coat the drug on an inert carrier such as sucrose, crystalline cellulose, heat-melt granulation using wax that melts by heating, dry compression granulation, etc. It can be suitably implemented.
【００２７】更に、成型時の薬物処方成分は、水分や各
種溶媒を含まない状態であっても、また含む状態であっ
てもよい。Further, the drug prescription component at the time of molding may be in a state not containing water or various solvents, or may be in a state containing it.
【００２８】成型手段としては、一次成型と同一の手段
で行えばよい。The molding means may be the same as the primary molding.
【００２９】成型手段が圧縮成型による場合、その圧縮
圧力を打錠機を例にとってより具体的に説明するとすれ
ば、例えば約０．０１〜５０００ｋｇ／杵、好ましくは
約０．１〜４０００ｋｇ／杵、より好ましくは約１〜３
０００ｋｇ／杵、とりわけ好ましくは約５〜２０００ｋ
ｇ／杵であり、約１０〜１０００ｋｇ／杵が最も好まし
い。When the molding means is compression molding, the compression pressure will be described more specifically by taking a tableting machine as an example. For example, about 0.01 to 5000 kg / punch, preferably about 0.1 to 4000 kg / punch , More preferably about 1-3
000 kg / punch, particularly preferably about 5 to 2000 k
g / punch, with about 10-1000 kg / punch being most preferred.
【００３０】本発明の方法は、一次および二次成型を交
互に連続して行うことが最も効果的であることから、打
錠機を用いる場合には、通常の打錠機よりも多層錠剤機
（畑鐵工所の積層打錠機、菊水製作所の三層回転式錠剤
機）及び複式錠剤機（畑鐵工所の複式打錠機、菊水製作
所の複式超強圧回転式粉末成型機）などを用いた方が効
率的である。In the method of the present invention, it is most effective to alternately perform primary and secondary molding alternately. Therefore, when a tableting machine is used, a multi-layer tableting machine is used rather than an ordinary tableting machine. (Laminated tableting machine of Hata Iron Works, three-layer rotary tablet machine of Kikusui Seisakusho) and double tablet machine (double tableting machine of Hata Iron Works, double super high pressure rotary powder molding machine of Kikusui Seisakusho), etc. It is more efficient to use.
【００３１】複式錠剤機を用いる場合には、一方の圧縮
部位（以下、圧縮部位Ａと称す）に滑沢剤と流動化剤と
の混合物を供給し、もう一方の圧縮部位（以下、圧縮部
位Ｂと称す）に薬物処方成分を供給して操作すればよ
い。圧縮部位Ａに供給された滑沢剤と流動化剤との混合
物は、圧縮成型され（一次成型）、この際臼と杵の表面
に滑沢剤が付着する。一次成型物は直ちに排出され回収
される。続いて滑沢剤が付着した臼中に薬物処方成分が
供給され、圧縮部位Ｂにおいて圧縮成型される（二次成
型）。二次成型物、すなわち目的錠剤は直ちに排出され
回収される。そして、再び圧縮部位Ａに滑沢剤と流動化
剤との混合物が供給され、上記のサイクルが繰り返され
る。When a double tablet machine is used, a mixture of a lubricant and a fluidizing agent is supplied to one compression section (hereinafter, referred to as compression section A), and the other compression section (hereinafter, compression section A). B) is supplied with the drug prescription component. The mixture of the lubricant and the fluidizing agent supplied to the compression site A is compression-molded (primary molding), and at this time, the lubricant adheres to the surfaces of the mill and the punch. The primary molded product is immediately discharged and collected. Subsequently, the drug prescription component is supplied into the die to which the lubricant has adhered, and compression-molded at the compression site B (secondary molding). The secondary molded product, that is, the target tablet is immediately discharged and collected. Then, the mixture of the lubricant and the fluidizing agent is supplied to the compression portion A again, and the above cycle is repeated.
【００３２】多層錠剤機として三層錠剤機を用いる場合
には、予備圧縮部位２カ所、主圧縮部位１カ所の３カ所
ある圧縮部位のうち、２カ所の予備圧縮部位のいづれか
１カ所に滑沢剤と流動化剤との混合物を供給し、主圧縮
部位に薬物処方成分を供給して操作すればよい。例え
ば、第一の予備圧縮部位に滑沢剤と流動化剤との混合物
を供給し、第二の予備圧縮部位には何も供給せず、主圧
縮部位に薬物処方成分を供給した場合について以下に説
明する。第１の予備圧縮部位に供給された滑沢剤と流動
化剤との混合物は、圧縮成型され（一次成型）、この際
臼と杵の表面に滑沢剤が付着する。一次成型物は直ちに
排出され回収される。続く第二の予備圧縮部位では何も
供給されず、主圧縮部位で薬物処方成分が供給され、圧
縮成型される（二次成型）。二次成型物、すなわち目的
錠剤は直ちに排出され回収される。そして、再び第一の
予備圧縮部位に滑沢剤と流動化剤との混合物が供給さ
れ、上記のサイクルが繰り返される。When a three-layer tablet machine is used as a multilayer tablet machine, lubricating is performed in one of two pre-compression sites out of two compression sites, ie, two pre-compression sites and one main compression site. The operation may be performed by supplying a mixture of the agent and the fluidizing agent, and supplying the drug prescription component to the main compression site. For example, a case where a mixture of a lubricant and a fluidizing agent is supplied to the first pre-compression section, nothing is supplied to the second pre-compression section, and the drug prescription component is supplied to the main compression section is as follows. Will be described. The mixture of the lubricant and the fluidizing agent supplied to the first preliminary compression section is compression molded (primary molding), and at this time, the lubricant adheres to the surfaces of the mortar and the punch. The primary molded product is immediately discharged and collected. Nothing is supplied in the subsequent second pre-compression section, and the drug prescription component is supplied in the main compression section and compression-molded (secondary molding). The secondary molded product, that is, the target tablet is immediately discharged and collected. Then, the mixture of the lubricant and the fluidizing agent is supplied to the first pre-compression portion again, and the above cycle is repeated.
【００３３】上記装置を用いれば、同じ杵と臼で常に滑
沢剤と流動化剤との混合物と薬物処方成分が交互に打錠
されるので、常に滑沢剤の付着した杵と臼で薬物処方成
分が打錠され、処方成分中に滑沢剤を添加しなくても打
錠障害を起こすことなく連続打錠が可能である。With the above apparatus, a mixture of a lubricant and a fluidizing agent and a drug prescription component are alternately tableted with the same punch and die. The prescription component is tableted, and continuous tableting is possible without causing a tableting trouble without adding a lubricant to the prescription component.
【００３４】また、回収した一次成型物、すなわち滑沢
剤と流動化剤との混合物の圧縮成型物は、そのまま廃棄
してもよいが、粉砕して再利用した方が経済的にも好ま
しい。The recovered primary molded product, that is, the compression molded product of the mixture of the lubricant and the fluidizing agent may be discarded as it is, but it is more economically preferable to grind and reuse it.
【００３５】本発明により得られた薬物含有錠は、その
まま素錠として経口投与可能であるが、必要に応じ、糖
衣、フィルムコーティング、圧縮コーティングなどを施
してもよく、これらはいずれも常法により実施すること
ができる。The drug-containing tablet obtained according to the present invention can be orally administered as it is as an uncoated tablet, but it may be coated with sugar coating, film coating, compression coating or the like, if necessary. Can be implemented.
【００３６】さらに本発明の方法は、成型工程を含むも
のであれば、いかなる製剤の製造にも適用することが可
能であるが、とりわけ、最近注目されている口腔内速崩
壊性製剤の製造に際して非常に有効である。すなわち、
このような口腔内速崩壊性製剤は、口中で非常に短時間
で溶解する必要があるため、滑沢剤を処方成分中には配
合しがたいが、本発明の方法によれば、成型した固形製
剤の表面にのみ薄く滑沢剤の層が形成されているため、
連続成型に支障がなく、かつ溶解速度にも全く影響しな
い。Further, the method of the present invention can be applied to the production of any pharmaceutical preparation as long as it includes a molding step. Very effective. That is,
Such a rapidly disintegrating preparation in the oral cavity needs to be dissolved in the mouth in a very short time, so that it is difficult to mix a lubricant into the prescription component, but according to the method of the present invention, the lubricant is molded. Because a thin lubricant layer is formed only on the surface of the solid preparation,
It does not hinder continuous molding and has no effect on the dissolution rate.
【００３７】かかる口腔内速崩壊性製剤としては、
（ａ）薬物処方成分を成型したのち加湿し乾燥する方法
により得られる製剤であっても、（ｂ）適度に湿潤させ
た薬物処方成分を成型後乾燥する方法により得られる製
剤であっても、いずれも好適に本発明と組み合わせるこ
とができる。[0037] Such a rapidly disintegrating preparation in the oral cavity includes:
(A) a preparation obtained by a method of molding and then humidifying and drying a drug prescription component, or (b) a preparation obtained by a method of molding and drying a moderately moistened drug prescription component, Any of them can be suitably combined with the present invention.
【００３８】（ａ）法について具体的に説明すると、滑
沢剤と流動化剤との混合物を成型機に供給して一次成型
し、成型物を排出する。続いて薬物処方成分を成型機に
供給し、低密度に二次成型したのち、成型物を加湿下に
維持し、乾燥することにより口腔内速崩壊性製剤が得ら
れる。The method (a) will be specifically described. A mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and the molded product is discharged. Subsequently, the drug prescription component is supplied to a molding machine, which is secondarily molded to a low density, and then the molded article is maintained under humidification and dried to obtain a rapidly disintegrating oral preparation.
【００３９】薬物処方成分としては、薬物および加湿に
より成型可能に湿潤し、かつ加湿後の乾燥により形状を
維持する物質（以下、単に湿潤物質という）からなる混
合物を用いるのが好ましい。かかる混合物は、必要に応
じ常法により造粒されていてもよい。As the drug prescription component, it is preferable to use a mixture of a drug and a substance which is moisturized by humidification so as to be moldable and which maintains its shape by drying after humidification (hereinafter, simply referred to as a wet substance). Such a mixture may be granulated by an ordinary method, if necessary.
【００４０】湿潤物質としては、かかる性状を有する糖
類、糖アルコールまたは水溶性高分子物質があげられ、
糖類としては、ブドウ糖、果糖、乳糖、白糖などの単糖
類または少糖類があげられ、糖アルコールとしては、マ
ンニトール、ソルビトール、マルチトール、エリスリト
ール、キシリトールなどがあげられ、水溶性高分子物質
としては、ヒドロキシプロピルセルロース、ヒドロキシ
プロピルメチルセルロース、ポリビニルピロリドン、デ
キストリン、ヒドロキシエチルセルロース、ポリエチレ
ングリコールなどがあげられる。このうち、特に、ブド
ウ糖、白糖、マンニトール、キシリトール、デキストリ
ン、ポリビニルピロリドン、ポリエチレングリコールが
好ましい。Examples of the wetting substance include saccharides, sugar alcohols and water-soluble high-molecular substances having such properties.
Examples of sugars include monosaccharides and oligosaccharides such as glucose, fructose, lactose, and sucrose.Examples of sugar alcohols include mannitol, sorbitol, maltitol, erythritol, xylitol, and the like. Examples include hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, dextrin, hydroxyethylcellulose, polyethylene glycol and the like. Of these, glucose, sucrose, mannitol, xylitol, dextrin, polyvinylpyrrolidone and polyethylene glycol are particularly preferred.
【００４１】これらの物質は、通常、製剤の分野で使用
される程度のグレードのものであればよく、特に限定さ
れない。またこれらの湿潤物質は単独または任意の割合
で混合して用いることもできる。These substances are not particularly limited, as long as they are of a grade generally used in the field of pharmaceuticals. These wetting substances can be used alone or as a mixture at an arbitrary ratio.
【００４２】これらの湿潤物質には、当然のことなが
ら、それぞれ吸湿性に強弱があり、例えば、ブドウ糖、
果糖、白糖、キシリトール、ソルビトール、マルチトー
ル、デキストリン、ポリビニルピロリドン、ヒドロキシ
エチルセルロース、ポリエチレングリコールなどは強
く、マンニトール、エリスリトールなどは比較的弱いの
で、これらを適宜組み合わせることによって、好適な製
剤とすることができる。Of course, these moist substances have different levels of hygroscopicity, for example, glucose,
Fructose, sucrose, xylitol, sorbitol, maltitol, dextrin, polyvinylpyrrolidone, hydroxyethylcellulose, polyethylene glycol and the like are strong, and mannitol, erythritol and the like are relatively weak, so that a suitable formulation can be obtained by appropriately combining these. .
【００４３】例えば、吸湿性の強い物質を多くすれば成
型性に優れ、かつ強固な製剤を得ることができ、また吸
湿性の弱い物質を多くすれば、速く崩壊する製剤とする
ことができる。For example, by increasing the amount of a substance having a high hygroscopicity, it is possible to obtain a preparation having excellent moldability and strong, and by increasing the substance having a low hygroscopicity, it is possible to obtain a preparation which rapidly disintegrates.
【００４４】湿潤性物質を複数組み合わせて使用する場
合の比較的好ましい組合わせとしては、例えばブドウ
糖、果糖、白糖などの単糖類または少糖類とマンニトー
ル、ソルビトール、エリスリトールなどの糖アルコール
の組合わせ、単糖類または少糖類とポリビニルピロリド
ン、ヒドロキシエチルセルロース、ポリエチレングリコ
ールなどの水溶性高分子物質の組合わせ、糖アルコール
と水溶性高分子物質の組合わせなどがあげられる。When a plurality of wettable substances are used in combination, a relatively preferable combination is, for example, a combination of a monosaccharide or oligosaccharide such as glucose, fructose or sucrose with a sugar alcohol such as mannitol, sorbitol or erythritol. Examples include a combination of a saccharide or oligosaccharide with a water-soluble polymer such as polyvinylpyrrolidone, hydroxyethyl cellulose, and polyethylene glycol, and a combination of a sugar alcohol and a water-soluble polymer.
【００４５】更に、より好ましい組合わせをあげるとす
れば、例えば、マンニトール／白糖、エリスリトール／
ブドウ糖、マンニトール／マルチトール、キシリトール
／ポリビニルピロリドン、マンニトール／ポリビニルピ
ロリドン、エリスリトール／白糖、キシリトール／ポリ
ビニルピロリドンなどをあげることができる。これら
は、２成分に限られることなく、何成分であっても配合
して使用することが出来る。例えば、３成分の組合わせ
をあげるとすれば、好ましいものとして、マンニトール
・エリスリトール・白糖、マンニトール・エリスリトー
ル・ポリビニルピロリドンなどあげることが出来る。と
りわけ、単糖類、少糖類または糖アルコールは水に対す
る挙動が類似するものが多く、同じカテゴリーに属する
ものであれば、容易に配合の変更や追加を行うことが出
来る。Further, a more preferable combination is, for example, mannitol / sucrose, erythritol /
Examples include glucose, mannitol / maltitol, xylitol / polyvinylpyrrolidone, mannitol / polyvinylpyrrolidone, erythritol / sucrose, xylitol / polyvinylpyrrolidone, and the like. These are not limited to two components, and any components can be blended and used. For example, if a combination of three components is used, preferred examples include mannitol, erythritol and sucrose, mannitol, erythritol and polyvinylpyrrolidone. In particular, many monosaccharides, oligosaccharides, and sugar alcohols have similar behaviors to water, and if they belong to the same category, the composition can be easily changed or added.
【００４６】また、上記の成分、すなわち薬物と湿潤物
質以外に、製剤技術の分野で汎用される添加物を添加す
ることが出来る。In addition to the above-mentioned components, ie, a drug and a wetting substance, additives commonly used in the field of formulation technology can be added.
【００４７】かかる添加物としては、前記の賦形剤、結
合剤、崩壊剤、滑沢剤、界面活性剤、香料、着色剤、甘
味剤、矯味剤、溶解補助剤を上げられる。Examples of such additives include the above-mentioned excipients, binders, disintegrants, lubricants, surfactants, flavors, coloring agents, sweeteners, corrigents, and solubilizers.
【００４８】これらの成分は、口腔内速崩壊性製剤の崩
壊性と成型性を損なわない範囲であれば、適宜、任意の
量を単独あるいは混合して使用することができ、例えば
乳糖／白糖／ステアリン酸マグネシウム，マンニトール
／トウモロコシデンプン／ポリビニルピロリドン／オレ
ンジ香料などあげることが出来る。Any of these components can be used alone or in an appropriate mixture as appropriate as long as the disintegration and moldability of the orally rapidly disintegrating preparation are not impaired. For example, lactose / sucrose / Examples include magnesium stearate, mannitol / corn starch / polyvinylpyrrolidone / orange flavor.
【００４９】薬物と湿潤物質の配合比率は、特に限定さ
れないが、薬物の水に対する溶解度のバラエティを考慮
すれば、湿潤物質１重量部に対して薬物が約０．０００
０１〜約３重量部含まれていればよく、とりわけ約０．
０００１〜約１重量部含まれているのが好ましい。The mixing ratio of the drug and the wetting substance is not particularly limited, but considering the solubility of the drug in water, the amount of the drug is about 0.000 per part by weight of the wetting substance.
It is sufficient if it is contained in an amount of from about 0.1 to about 3 parts by weight, and especially about 0.
Preferably, it is present in an amount of from 0001 to about 1 part by weight.
【００５０】成型は、成型物が低密度を維持しつつ所望
の形状となるよう本発明の成型法により実施することが
できる。具体的には、滑沢剤と流動化剤との混合物を成
型機に供給して一次成型し、成型物を排出したのち、薬
物、湿潤物質及びその他の製剤添加物を混合した混合物
を成型機に供給し、二次成型すればよい。成型手段とし
て圧縮成型法を用いる場合には、例えば、約１０００ｋ
ｇ／杵以下、好ましくは約０．０１ｋｇ〜５００ｋｇ／
杵程度の範囲の圧力で適宜選択することができ、圧力
は、密度を所望の範囲に維持しつつ、配合される薬物と
湿潤物質の成型維持力と崩壊性を加味して決定すること
ができる。The molding can be carried out by the molding method of the present invention so that the molded article has a desired shape while maintaining a low density. Specifically, a mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and after the molded product is discharged, a mixture obtained by mixing a drug, a wet substance, and other formulation additives is molded. , And then subjected to secondary molding. When the compression molding method is used as the molding means, for example, about 1000 k
g / punch or less, preferably about 0.01 kg to 500 kg /
The pressure can be appropriately selected in the range of a punch or the like, and the pressure can be determined in consideration of the molding maintaining power and disintegration of the compounded drug and the wet substance while maintaining the density in a desired range. .
【００５１】本製法により得られる口腔内速崩壊性製剤
は、低密度に成型後、加湿し乾燥することによって、空
隙が大きく口中で高い崩壊性を得ることができるので、
この点が重要となる。かかる密度を具体的に示すとすれ
ば、約０．４〜約１．３ｇ／ｃｍ3 であり、この範囲で
あれば、不都合はない。The rapidly disintegrating preparation in the oral cavity obtained by this production method can be formed into a low density, then humidified and dried to obtain a large pore and high disintegration in the mouth.
This is important. The specific density is about 0.4 to about 1.3 g / cm 3 , and there is no inconvenience in this range.
【００５２】加湿条件は、通常の湿度以上となる条件で
あれば、特に限定されないが、薬物と湿潤物質の混合物
の成型物が全体的にしっとりと湿り気を帯びるような条
件、あるいは成型物内の湿潤物質の一部ないし全部が吸
湿して湿り気を帯びるような条件であればよい。更には
湿潤物質の一部または特定成分が潮解するような条件で
あってもよい。要するに、加湿・乾燥後の成型物の硬度
が、加湿前よりも高くなるような条件を設定すればよ
く、作業性の面からは、湿度が高いほど所要時間が短縮
できるので、この意味からエルダーの仮説〔一番ケ瀬監
修、新しい製剤学（広川書店）平成５年９月１０日発
刊、９６頁〕により算出される混合物の臨界相対湿度以
上で、適宜、最適湿度を選択すればよい。The humidification condition is not particularly limited as long as it is a condition that is equal to or higher than the normal humidity. The humidification condition is such that the molded product of the mixture of the drug and the moist substance is moist and moist as a whole, or Any condition may be used as long as some or all of the wet substance absorbs moisture and becomes moist. Further, the condition may be such that a part or a specific component of the wet substance deliquesces. In short, it is only necessary to set conditions so that the hardness of the molded product after humidification and drying is higher than that before humidification.From the viewpoint of workability, the higher the humidity, the shorter the required time. The optimum relative humidity may be appropriately selected at a value equal to or higher than the critical relative humidity of the mixture calculated by the hypothesis [edited by Ichigase, New Pharmaceutical Science (Hirokawa Shoten), published on September 10, 1993, page 96].
【００５３】加湿は、加温下でもよく常温でもよく特に
限定されないが、配合される薬物と湿潤物質の温度に対
する影響を考慮して温度を設定すればよい。更に加湿手
段は特に限定されず、既知の手段、例えば噴霧式加湿
機、加温式加湿機（具体例をあげるとすれば、恒温恒湿
機、タバイエスペックコーポレーション製）などの加湿
機を使用すればよい。The humidification may be performed at elevated temperature or at ordinary temperature, and is not particularly limited. The temperature may be set in consideration of the effects of the compounded drug and the wet substance on the temperature. Further, the humidifying means is not particularly limited, and a known means, for example, a humidifier such as a spray-type humidifier, a warming-type humidifier (for example, a constant temperature / humidifier, manufactured by Tabai Espec Corporation) may be used. I just need.
【００５４】最適な加湿条件は、混合物の見かけの臨界
相対湿度によって異なるが、加湿条件を例示するとすれ
ば、マンニトール／白糖の場合、例えば湿度が約７０〜
１００ＲＨ％、より好ましくは約８０〜１００ＲＨ％、
とりわけ好ましくは約９０〜１００ＲＨ％程度であり、
温度が約１０〜約７０℃、より好ましくは約１５〜約５
０℃、とりわけ好ましくは約２０〜約３０℃であるよう
な条件があげられる。The optimum humidification conditions vary depending on the apparent critical relative humidity of the mixture. To illustrate the humidification conditions, in the case of mannitol / sucrose, for example, a humidity of about 70 to
100 RH%, more preferably about 80 to 100 RH%,
Particularly preferably, it is about 90 to 100 RH%,
The temperature is from about 10 to about 70C, more preferably from about 15 to about 5
Conditions such as 0 ° C., particularly preferably from about 20 to about 30 ° C. are mentioned.
【００５５】乾燥は、加湿後の製剤の硬度上昇および水
分除去のために実施するものであり、常温〜加温下、常
圧〜減圧下に、適宜条件を組み合わせて実施することが
できる。The drying is carried out to increase the hardness of the preparation after humidification and to remove moisture, and can be carried out at normal temperature to warming and normal pressure to reduced pressure under appropriate conditions.
【００５６】本製法において、薬物および添加物の粒子
径は特に限定されないが、粒子径が小さい方が服用感に
優れているので好ましい。In the present production method, the particle size of the drug and the additive is not particularly limited, but the smaller the particle size, the better the feeling of taking.
【００５７】また、薬物が苦み、臭いなどの不快感が強
い場合は、これらを隠蔽することもできるコーティング
剤や矯味剤、矯臭剤で加工して使用することができる。
これらのコーティング剤や矯味剤、矯臭剤ならびに加工
方法は通常の技術分野で使用されているものであれば、
何ら制限なく使用することができる。When the discomfort such as bitterness and smell of the drug is strong, the drug can be used after being processed with a coating agent, a flavoring agent, or a flavoring agent capable of concealing them.
If these coating agents and flavoring agents, flavoring agents and processing methods are used in the ordinary technical field,
It can be used without any restrictions.
【００５８】本製剤の形状に際しては、どのような形状
をも採用することができ、例えばタブレット型、楕円
形、球形、角型など種々の形状に成型することができ
る。更に一定の形状に成型し、加湿、乾燥の後に粉砕し
て、顆粒、細粒、散剤とすることもできる。The present preparation can be formed into any shape, for example, into various shapes such as a tablet, an ellipse, a sphere and a square. Furthermore, it can be molded into a certain shape, humidified, dried and then pulverized to obtain granules, fine granules and powder.
【００５９】本製剤の空隙率は、例えば約１０〜７０
％，より好ましくは約１５〜約６５％，とりわけ好まし
くは約２０〜約５０％である。The porosity of the preparation is, for example, about 10 to 70.
%, More preferably from about 15 to about 65%, particularly preferably from about 20 to about 50%.
【００６０】また、上記（ａ）法の変法であるが、薬物
処方成分を成型したのちアルコールで湿潤させ、該アル
コールを除去することによっても同様の口腔内速崩壊性
製剤を得ることができる。具体的には、滑沢剤と流動化
剤との混合物を成型機に供給して一次成型し、成型物を
排出する。続いて薬物処方成分を成型機に供給し、低密
度に二次成型したのち、成型物をアルコールで湿潤さ
せ、該アルコールを除去すればよい。As a modification of the above method (a), a similar rapidly disintegrating preparation in the oral cavity can be obtained by molding a drug prescription component, moistening it with alcohol, and removing the alcohol. . Specifically, a mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and the molded product is discharged. Subsequently, the drug prescription component is supplied to a molding machine, and after low-density secondary molding, the molded product is wetted with alcohol to remove the alcohol.
【００６１】本方法において、アルコールとしては、メ
タノール、エタノール、イソプロパノールなどの低級ア
ルコールがあげられ、なかでもエタノールが好ましい。In the present method, examples of the alcohol include lower alcohols such as methanol, ethanol and isopropanol, and among them, ethanol is preferred.
【００６２】薬物処方成分としては、薬物および上記ア
ルコールに可溶な結合剤（アルコール可溶性結合剤）か
らなる混合物を用いるのが好ましく、かかる混合物は、
必要に応じ常法により造粒されていてもよい。It is preferable to use a mixture of the drug and the above-mentioned alcohol-soluble binder (alcohol-soluble binder) as the drug formulation component.
If necessary, granulation may be performed by a conventional method.
【００６３】アルコール可溶性結合剤としては、ポリビ
ニルピロリドン、ヒドロキシプロピルセルロース、エチ
ルセルロースなどがあげられ、なかでもポリビニルピロ
リドンが好ましい。Examples of the alcohol-soluble binder include polyvinylpyrrolidone, hydroxypropylcellulose, ethylcellulose and the like, with polyvinylpyrrolidone being preferred.
【００６４】また、上記の成分、すなわち薬物とアルコ
ール可溶性結合剤以外に、製剤技術の分野で汎用される
添加物を添加することができる。かかる添加物として
は、前記の賦形剤、結合剤、崩壊剤、滑沢剤、界面活性
剤、香料、着色剤、甘味剤、矯味剤、溶解補助剤があげ
られ、とりわけ、上記（ａ）法における糖、糖アルコー
ルが特に好ましい。これらの成分は、口腔内速崩壊性製
剤における崩壊性と成型性を損なわない範囲であれば、
適宜、任意の量を単独あるいは混合して使用することが
できる。In addition to the above-mentioned components, that is, the drug and the alcohol-soluble binder, additives commonly used in the field of formulation technology can be added. Examples of such additives include the above-mentioned excipients, binders, disintegrants, lubricants, surfactants, fragrances, coloring agents, sweeteners, corrigents, and solubilizers. Sugars and sugar alcohols in the method are particularly preferred. These components are in a range that does not impair the disintegration and moldability of the rapidly disintegrating oral preparation,
Any appropriate amount can be used alone or as a mixture.
【００６５】アルコール可溶性結合剤の配合量は、特に
限定されず、製剤の所望の崩壊性と硬度に応じて適宜決
定できるが、あえて例示するとすれば、製剤中に約０．
１〜３０重量％、好ましくは約１〜１０重量％である。The blending amount of the alcohol-soluble binder is not particularly limited and can be appropriately determined according to the desired disintegration and hardness of the preparation.
It is 1 to 30% by weight, preferably about 1 to 10% by weight.
【００６６】本方法により得られる製剤は、（ａ）法同
様、成型後の密度が重要であり、かかる密度を具体的に
例示すれば、約０．４〜約１．３ｇ／ｃｍ3 が適当であ
る。In the preparation obtained by this method, the density after molding is important as in the method (a), and when this density is specifically exemplified, about 0.4 to about 1.3 g / cm 3 is appropriate. It is.
【００６７】成型は（ａ）法と同様、低密度を維持しつ
つ所望の形状となるよう本発明の成型法により実施すれ
ばよい。As in the case of the method (a), the molding may be carried out by the molding method of the present invention so as to obtain a desired shape while maintaining a low density.
【００６８】アルコールによる湿潤方法としては、特に
限定されないが、成型物中のアルコール可溶性水溶性結
合剤の一部ないし全てが湿り気を帯び、アルコール除去
後の製剤硬度がアルコール湿潤前に比べ高くなるような
条件であればよい。例えば、成型物をアルコール蒸気の
存在下に維持する、成型物にアルコールを噴霧する、成
型物にアルコールを注加する、などの方法があげられ
る。The method of wetting with alcohol is not particularly limited, but some or all of the alcohol-soluble water-soluble binder in the molded product is moist, and the hardness of the preparation after alcohol removal is higher than that before alcohol wetting. Conditions are acceptable. For example, there are methods such as maintaining the molded product in the presence of alcohol vapor, spraying the molded product with alcohol, and pouring alcohol into the molded product.
【００６９】成型物をアルコール蒸気の存在下に維持す
る場合には、アルコール蒸気で満たしたデシケータなど
の中に成型物を一定時間保存すればよい。保存時間は、
製剤の崩壊性、硬度に応じて適宜決定でき、一般に保存
時間が長いほど硬度の高い製剤が得られる。When the molded product is maintained in the presence of alcohol vapor, the molded product may be stored in a desiccator or the like filled with alcohol vapor for a certain period of time. The storage time is
It can be appropriately determined according to the disintegration and hardness of the preparation, and in general, the longer the storage time, the higher the preparation having a higher hardness.
【００７０】成型物にアルコールを噴霧する場合には、
スプレーガンなど製剤機械において一般的に使用される
噴霧装置を用いて行えばよい。その噴霧量は、成型物が
崩壊してしまわない程度の範囲内で、目的とする製剤の
崩壊性、硬度に応じて決定することができる。When spraying alcohol on a molded product,
What is necessary is just to perform using the spraying apparatus generally used in the formulation machine such as a spray gun. The spray amount can be determined according to the disintegration and hardness of the target preparation within a range that does not cause the molded product to collapse.
【００７１】成型物にアルコールを注加する場合には、
一般的に使用される定量供給装置を用いて行えばよい。
その注加量は、成型物が崩壊してしまわない程度の範囲
内で、目的とする製剤の崩壊性、硬度に応じて決定する
ことができる。When pouring alcohol into a molded product,
What is necessary is just to perform using the fixed-quantity supply apparatus generally used.
The amount to be added can be determined according to the disintegration property and hardness of the target preparation within a range that does not cause the molded product to collapse.
【００７２】アルコールの除去は、アルコールを蒸発さ
せて成型物から除去してやればよく、（ａ）法における
乾燥と同様、常温〜加温下、常圧〜減圧下に、適宜条件
を組み合わせて実施することができる。The alcohol may be removed from the molded product by evaporating the alcohol. Similar to the drying in the method (a), the alcohol is removed under normal temperature to heating and normal pressure to reduced pressure under appropriate conditions. be able to.
【００７３】次に（ｂ）法について具体的に説明する
と、滑沢剤と流動化剤との混合物を成型機に供給して一
次成型し、成型物を排出したのち、湿潤した状態の薬物
処方成分を成型機に供給し二次成型後、成型物を乾燥さ
せることによって製造出来る。Next, the method (b) will be specifically described. A mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and after the molded product is discharged, a wet drug formulation is prepared. It can be manufactured by supplying the components to a molding machine, performing secondary molding, and then drying the molded product.
【００７４】湿潤した状態の薬物処方成分としては、薬
物と糖類と前記糖類の粒子表面が湿る程度の水分を含む
混合物であることが好ましい。It is preferable that the drug prescription component in a wet state is a mixture containing a drug, a saccharide, and water enough to wet the particle surface of the saccharide.
【００７５】糖類としては、水溶性で薬物に対して悪影
響（例えば、薬物の分解など）を及ぼさないものであれ
ば如何なるものでもよく、例えば、白糖、ブドウ糖、麦
芽糖、果糖、乳糖などの単糖類もしくは少糖類、ソルビ
トール、マンニトール、マルチトール、キシリトール、
エリスリトールなどの糖アルコールなどが用いられる。
これらの糖類は、単独、または二種以上を併用して用い
てもよい。As the saccharide, any saccharide can be used as long as it is water-soluble and does not adversely affect the drug (for example, decomposition of the drug). For example, monosaccharides such as sucrose, glucose, maltose, fructose, and lactose can be used. Or oligosaccharides, sorbitol, mannitol, maltitol, xylitol,
A sugar alcohol such as erythritol is used.
These saccharides may be used alone or in combination of two or more.
【００７６】糖類の好ましものとしては、例えば白糖、
ブドウ糖、マルチトール、キシリトール、エリスリトー
ルなどがある。Preferred sugars include, for example, sucrose,
Glucose, maltitol, xylitol, erythritol and the like.
【００７７】前記糖類の平均粒子径は、通常１〜１００
μｍ好ましくは１０〜８０μｍ、さらに好ましくは４０
〜６０μｍ程度である。The average particle size of the saccharide is usually from 1 to 100.
μm, preferably 10 to 80 μm, more preferably 40 μm.
〜60 μm.
【００７８】薬物処方成分中の糖類の含有量は、薬物の
種類によって異なるが、通常５〜９５重量％、好ましく
は１０〜９０重量％、さらに好ましくは２０〜８０重量
％程度である。The content of the saccharide in the drug prescription component varies depending on the kind of the drug, but is usually about 5 to 95% by weight, preferably about 10 to 90% by weight, and more preferably about 20 to 80% by weight.
【００７９】例えば、投与量の少ない薬物を用い、薬物
処方成分中の薬物の含有量を０．１〜１０重量％とする
場合には、糖類の含有量は、通常２０〜９０重量％、好
ましくは３０〜９０重量％、さらに好ましくは５０〜９
０重量％程度である。For example, when a small dose of a drug is used and the drug content in the drug formulation is 0.1 to 10% by weight, the saccharide content is usually 20 to 90% by weight, preferably Is 30 to 90% by weight, more preferably 50 to 9% by weight.
It is about 0% by weight.
【００８０】また、投与量の中程度の薬物を用い、薬物
処方成分中の薬物の含有量を１０〜３０重量％とする場
合には、糖類の含有量は、通常２０〜９０重量％、好ま
しくは３０〜８０重量％、さらに好ましくは５０〜８０
重量％程度である。When a moderate amount of drug is used and the drug content in the drug formulation is 10 to 30% by weight, the saccharide content is usually 20 to 90% by weight, preferably Is 30 to 80% by weight, more preferably 50 to 80% by weight.
% By weight.
【００８１】さらに、投与量の多い薬物を用い、薬物処
方成分中の薬物の含有量を３０〜７０重量％とする場合
には、糖類の含有量は、通常１０〜７０重量％、好まし
くは２０〜６０重量％、さらに好ましくは３０〜５０重
量％程度である。Further, when a drug with a large dose is used and the content of the drug in the drug formulation is 30 to 70% by weight, the saccharide content is usually 10 to 70% by weight, preferably 20 to 70% by weight. About 60% by weight, more preferably about 30 to 50% by weight.
【００８２】薬物処方成分中には、本方法の効果に支障
のない限り、製剤の製造に一般に用いられる種々の製剤
添加物を含んでいてもよい。[0082] The drug formulation components may contain various pharmaceutical additives generally used for the production of pharmaceuticals, as long as the effects of the present method are not hindered.
【００８３】かかる添加物としては、前記の賦形剤、結
合剤、崩壊剤、滑沢剤、界面活性剤、香料、着色剤、甘
味剤、矯味剤、溶解補助剤をあげられる。Examples of such additives include the above-mentioned excipients, binders, disintegrants, lubricants, surfactants, flavors, coloring agents, sweeteners, corrigents, and solubilizers.
【００８４】これらの添加物は、１種または２種以上、
例えば、薬物と糖類との混合時、水分添加時、練合時あ
るいはそれらの前後の工程で、適宜適量添加することが
できる。These additives may be used alone or in combination of two or more.
For example, an appropriate amount can be appropriately added at the time of mixing of the drug and the saccharide, at the time of adding water, at the time of kneading, or before and after these steps.
【００８５】薬物処方成分中の水分量は、薬物処方成分
中に含まれる糖類の粒子表面が湿る程度の量であればよ
い。本方法では、糖類粒子の表面が湿る程度の水分が添
加されるため、成型し乾燥すると、糖類粒子同士が融着
し、口腔内速崩壊性製剤として適度な空隙率および硬度
を有する多孔性成型製剤が得られる。The amount of water in the drug prescription component may be such that the surface of the saccharide particles contained in the drug prescription component gets wet. In the present method, since water is added to the extent that the surface of the saccharide particles is moistened, when molded and dried, the saccharide particles are fused together, and a porous material having an appropriate porosity and hardness as a rapidly disintegrating preparation in the oral cavity. A molded preparation is obtained.
【００８６】水分の添加量は、薬物、糖類および添加物
の種類や量によっても異なるが、通常、薬物処方成分中
に０．１〜１０重量％、好ましくは０．３〜１０重量
％、より好ましくは０．５〜８重量％、さらに好ましく
は０．５〜５重量％、最も好ましくは１〜５重量％程度
添加されていればよい。水分の添加量が少ないと、製剤
強度が小さくなり、逆に多い場合は、成型時に薬効成分
等が成型機（例えば、杵、臼、など）に付着し易く製造
が困難となる。The amount of water to be added varies depending on the types and amounts of drugs, sugars and additives, but is usually 0.1 to 10% by weight, preferably 0.3 to 10% by weight, in the drug formulation components. Preferably 0.5 to 8% by weight, more preferably 0.5 to 5% by weight, most preferably about 1 to 5% by weight is added. When the amount of water added is small, the strength of the preparation decreases, and when it is large, the medicinal component and the like easily adhere to a molding machine (for example, a punch, a die, etc.) at the time of molding, and production becomes difficult.
【００８７】より具体的には、例えば、薬物処方成分中
に糖類としてキシリトールおよび／またはマルチトール
を２０〜４０重量％含む場合は、通常、水分が１〜５重
量％、好ましくは２〜３重量％添加されていればよい。
また、糖類として白糖および／またはブドウ糖を６０〜
８０重量％含む場合は、通常、水分が２〜４重量％添加
されていればよい。さらに、糖類としてエリスリトール
を５５〜７５重量％含む場合は、通常、水分が１〜３重
量％添加されていればよい。More specifically, for example, when 20 to 40% by weight of xylitol and / or maltitol is contained as a saccharide in a drug component, the water content is usually 1 to 5% by weight, preferably 2 to 3% by weight. % May be added.
In addition, sucrose and / or glucose are used as sugars for 60 to
In the case of containing 80% by weight, it is usually sufficient that 2 to 4% by weight of water is added. Further, when erythritol is contained as a saccharide in an amount of 55 to 75% by weight, it is usually sufficient that water is added in an amount of 1 to 3% by weight.
【００８８】水分の添加法は特に限定されず、一度に添
加してもよく、また、滴下或いは噴霧して添加してもよ
い。The method of adding water is not particularly limited, and may be added all at once, or may be added dropwise or sprayed.
【００８９】また、薬物と糖類などとの混合は、製剤の
製造において一般に用いられる混合方法、例えば、混
合、練合、篩過などにより行われる。具体的には、二重
円錐混合機、流動層造粒機、高速撹拌造粒機、振動篩な
どを用いて混合することができる。The mixing of the drug with the saccharide and the like is carried out by a mixing method generally used in the production of pharmaceuticals, for example, mixing, kneading, sieving and the like. Specifically, mixing can be performed using a double cone mixer, a fluidized bed granulator, a high-speed stirring granulator, a vibration sieve, or the like.
【００９０】薬物、糖類および水を含む混合物は、成型
する前に練合される。水分を含む混合物の練合には、製
剤の製造手段として一般に用いられる方法を用いること
ができる。例えば、薬効成分と糖類等とを混合する際に
用いられる上述の装置などを用いて練合できる。The mixture containing the drug, saccharide and water is kneaded before molding. For kneading the mixture containing water, a method generally used as a means for producing a preparation can be used. For example, kneading can be carried out using the above-described device used when mixing a medicinal ingredient and a saccharide or the like.
【００９１】成型は、本発明の成型法より実施すること
ができ、具体的には、滑沢剤と流動化剤との混合物を成
型機に供給して一次成型し、成型物を排出したのち、湿
った状態の薬物処方成分を成型機に供給し、二次成型す
ればよい。成型手段として圧縮成型法を用いる場合に
は、２〜１３０ｋｇ／杵、好ましくは４〜１００ｋｇ／
杵、より好ましくは６〜４０ｋｇ／杵程度で圧縮すれば
よい。成型時の温度は、糖類粒子が溶解又は溶融しない
程度であり、通常室温（例えば２０〜３０℃程度）、好
ましくは約２５℃である。The molding can be performed by the molding method of the present invention. Specifically, a mixture of a lubricant and a fluidizing agent is supplied to a molding machine to perform primary molding, and after the molded product is discharged, The wet prescription component may be supplied to a molding machine to perform secondary molding. When the compression molding method is used as the molding means, 2 to 130 kg / punch, preferably 4 to 100 kg / punch
It may be compressed with a punch, more preferably about 6 to 40 kg / punch. The temperature at the time of molding is such that the saccharide particles do not dissolve or melt, and is usually room temperature (for example, about 20 to 30 ° C), and preferably about 25 ° C.
【００９２】また、上述のように得られた成型物を、さ
らに乾燥するのが好ましい。乾燥は、例えば真空乾燥、
凍結乾燥、自然乾燥など一般に製剤の製造において用い
られるいずれの方法によっても行うことができる。It is preferable to further dry the molded product obtained as described above. Drying is, for example, vacuum drying,
It can be carried out by any method generally used in the production of preparations, such as freeze-drying and natural drying.
【００９３】これらの成型製剤は、さらに、それが有す
る強度、溶解性に悪影響を与えない程度に、一般に被覆
製剤の製造において用いられるコーティング法によって
被覆されていてもよい。These molded preparations may be further coated by a coating method generally used in the production of coated preparations to such an extent that the strength and solubility of the preparations are not adversely affected.
【００９４】かくして得られる口腔内速崩壊性製剤は、
多孔性構造を有している。ここで言う多孔性構造とは、
通常空隙率が１０〜７０％、好ましくは１５〜６０％の
ものを意味する。そのため、本発明の錠剤は、口腔内で
の崩壊性および溶解性に優れ、さらに落下強度も強い。The orally rapidly disintegrating preparation thus obtained is
It has a porous structure. The porous structure here means
It usually means that the porosity is 10 to 70%, preferably 15 to 60%. Therefore, the tablet of the present invention is excellent in disintegration and solubility in the oral cavity, and also has high drop strength.
【００９５】以下、実験例および実施例によって、更に
本発明を詳細に説明する。Hereinafter, the present invention will be described in more detail with reference to Experimental Examples and Examples.
【００９６】[0096]
実験例１ マンニトール１９３重量部、塩酸イミダプリル５重量部
を混合し、流動層造粒機中で流動下にポリビニルピロリ
ドン２重量部を５％（ｗ／ｗ）水溶液で噴霧して造粒
し、得られた造粒顆粒を薬物処方成分とした。また、滑
沢剤としてステアリン酸マグネシウム、流動化剤として
結晶セルロース（アビセルＰＨ１０２：旭化成製）を用
い、滑沢剤１重量部に対して流動化剤を２．３、４、
９、１９重量部の割合で混合し、混合比の異なる４種類
の混合物を調製した。三層錠剤機（菊水製作所製、杵サ
イズ：直径１０ｍｍ）を用い、第１の予備圧縮部位に滑
沢剤と流動化剤との混合物を供給し（一次成型）、第２
の予備圧縮部位には何も供給せず、主圧縮部位に薬物処
方成分を供給（二次成型）し、連続打錠した。一次成型
物は２００ｍｇ／錠、硬度が１ｋｇになるよう打錠し、
二次成型物は３００ｍｇ／錠、硬度が９ｋｇになるよう
打錠した。Experimental Example 1 193 parts by weight of mannitol and 5 parts by weight of imidapril hydrochloride were mixed and granulated by spraying 2 parts by weight of polyvinylpyrrolidone with a 5% (w / w) aqueous solution in a fluidized bed granulator under flow. The obtained granules were used as drug formulation components. Further, magnesium stearate was used as a lubricant, and crystalline cellulose (Avicel PH102: manufactured by Asahi Kasei) was used as a fluidizing agent.
The mixture was mixed at a ratio of 9, 19 parts by weight to prepare four types of mixtures having different mixing ratios. Using a three-layer tablet machine (manufactured by Kikusui Seisakusho, punch size: diameter 10 mm), a mixture of a lubricant and a fluidizing agent was supplied to the first pre-compression portion (primary molding), and the second
Nothing was supplied to the pre-compressed part, and the drug prescription component was supplied (secondary molding) to the main compressed part and continuous tableting was performed. The primary molded product is tableted to 200 mg / tablet and the hardness is 1 kg.
The secondary molded product was tableted so as to have a hardness of 300 mg / tablet and a hardness of 9 kg.
【００９７】一次成型に滑沢剤と流動化剤との混合比が
異なるいづれの混合物を用いて連続打錠した場合にも、
二次成型物を１００錠製錠して何ら打錠障害は発生しな
かった。In the case of continuous tableting using any mixture having a different mixing ratio between the lubricant and the fluidizing agent in the primary molding,
100 tablets were produced from the secondary molded product, and no tableting trouble occurred.
【００９８】実験例２ マレイン酸トリメブチン７３重量部、ヒドロキシプロピ
ルメチルセルロース（ＴＣ−５：信越化学製）２重量
部、結晶セルロース２５重量部を混合し、これを薬物処
方成分とした。また、滑沢剤としてステアリン酸マグネ
シウム、流動化剤として結晶セルロース（アビセルＰＨ
１０２：旭化成製）を用い、滑沢剤１重量部に対して流
動化剤を４、９重量部の割合で混合し、混合比の異なる
２種類の混合物を調製した。実験例１と同様に、滑沢剤
と流動化剤との混合物、薬物処方成分を三層錠剤機を用
いて連続打錠した。一次成型物は２００ｍｇ／錠、硬度
が１ｋｇになるよう打錠し、二次成型物は２５０ｍｇ／
錠、硬度が１１ｋｇになるよう打錠した。Experimental Example 2 73 parts by weight of trimebutine maleate, 2 parts by weight of hydroxypropylmethylcellulose (TC-5, manufactured by Shin-Etsu Chemical Co., Ltd.) and 25 parts by weight of crystalline cellulose were mixed and used as a drug formulation component. In addition, magnesium stearate is used as a lubricant, and crystalline cellulose (Avicel PH) is used as a fluidizing agent.
102: manufactured by Asahi Kasei Co., Ltd.), and a fluidizing agent was mixed at a ratio of 4.9 parts by weight with respect to 1 part by weight of a lubricant to prepare two kinds of mixtures having different mixing ratios. As in Experimental Example 1, a mixture of a lubricant and a fluidizing agent and a drug formulation component were continuously tableted using a three-layer tablet machine. 200 mg / tablet for the primary molded product, tableting with hardness of 1 kg, 250 mg / tablet for the secondary molded product
Tablets and tablets were pressed to a hardness of 11 kg.
【００９９】一次成型に滑沢剤と流動化剤との混合比が
異なるいづれの混合物を用いて連続打錠した場合にも、
二次成型物を１００錠製錠して何ら打錠障害は発生しな
かった。In the case of continuous tableting using any mixture having a different mixing ratio between the lubricant and the fluidizing agent in the primary molding,
100 tablets were produced from the secondary molded product, and no tableting trouble occurred.
【０１００】実験例３ 滑沢剤としてステアリン酸マグネシウムを用い、流動化
剤として結晶セルロース（アビセルＰＨ１０２：旭化成
製）、β−無水乳糖もしくは造粒乳糖（乳糖Ｇ：フロイ
ント産業製）を用い、滑沢剤１重量部に対し流動化剤９
重量部を混合し、それぞれ流動化剤の種類の異なる３種
類の混合物を調製した。薬物処方成分としては、実験例
２で調製したものを用い、実験例１と同様に、滑沢剤と
流動化剤との混合物、薬物処方成分を三層錠剤機を用い
て連続打錠した。一次成型物は２００ｍｇ／錠、硬度が
１ｋｇになるよう打錠し、二次成型物は２５０ｍｇ／
錠、硬度が１１ｋｇになるよう打錠した。Experimental Example 3 Magnesium stearate was used as a lubricant, and crystalline cellulose (Avicel PH102: manufactured by Asahi Kasei), β-anhydrolactose or granulated lactose (lactose G: manufactured by Freund Corporation) was used as a fluidizing agent. Fluidizing agent 9 per 1 part by weight of powder
Parts by weight were mixed to prepare three types of mixtures each having a different type of fluidizing agent. As a drug prescription component, the one prepared in Experimental Example 2 was used, and a mixture of a lubricant and a fluidizing agent and a drug prescription component were continuously tableted using a three-layer tableting machine in the same manner as in Experimental Example 1. 200 mg / tablet for the primary molded product, tableting with hardness of 1 kg, 250 mg / tablet for the secondary molded product
Tablets and tablets were pressed to a hardness of 11 kg.
【０１０１】流動化剤の種類の異なるいづれの混合物を
用いても、連続打錠中において何ら打錠障害なく製錠で
きた。Even when any mixture of different types of fluidizing agents was used, tableting could be performed without any tableting trouble during continuous tableting.
【０１０２】実施例１ 塩酸イミダプリル５重量部、乳糖７５重量部、ポリエチ
レングリコール（分子量６０００）２０重量部を混合
後、ハイスピードミキサー（深江工業製）中で外浴温度
８０℃で加熱造粒し、薬物処方成分を調製した。また、
滑沢剤としてステアリン酸マグネシウム１５重量部と流
動化剤として造粒乳糖（乳糖Ｇ：フロイント産業製）８
５重量部を混合し、滑沢剤と流動化剤との混合物を調製
した。三層錠剤機（菊水製作所製、杵サイズ：直径７ｍ
ｍ）を用い、第１の予備圧縮部位に滑沢剤と流動化剤と
の混合物を供給し（一次成型）、第２の予備圧縮部位に
は何も供給せず、主圧縮部位に薬物処方成分を供給（二
次成型）し、連続打錠した。一次成型物は１００ｍｇ／
錠、硬度が１ｋｇになるよう打錠し、二次成型物は１０
０ｍｇ／錠、硬度が４ｋｇになるよう打錠した。連続打
錠中においても何ら打錠障害なく製錠できた。Example 1 After mixing 5 parts by weight of imidapril hydrochloride, 75 parts by weight of lactose and 20 parts by weight of polyethylene glycol (molecular weight: 6000), the mixture was granulated by heating at 80 ° C. in an external bath at a high speed mixer (Fukae Kogyo). A drug formulation was prepared. Also,
15 parts by weight of magnesium stearate as a lubricant and granulated lactose (lactose G: manufactured by Freund Corporation) as a fluidizing agent 8
5 parts by weight were mixed to prepare a mixture of a lubricant and a fluidizing agent. Three-layer tablet machine (Kikusui Seisakusho, punch size: 7m in diameter)
m), the mixture of the lubricant and the fluidizing agent is supplied to the first precompression section (primary molding), nothing is supplied to the second precompression section, and the drug prescription is supplied to the main compression section. The components were supplied (secondary molding) and continuously tableted. 100 mg /
Tablets, tableted to a hardness of 1 kg, secondary molding 10
Tablets were pressed so that the hardness was 0 mg / tablet and the hardness was 4 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.
【０１０３】実施例２ 実施例１で調製した薬物処方成分、滑沢剤と流動化剤と
の混合物を複式錠剤機（畑鉄工所製、杵サイズ：直径７
ｍｍ）を用いて打錠した。一方の圧縮部位に滑沢剤と流
動化剤との混合物を供給し、もう一方の圧縮部位に薬物
処方成分を供給し、連続打錠した。一次成型物は１００
ｍｇ／錠、硬度が１ｋｇになるよう打錠し、二次成型物
は１００ｍｇ／錠、硬度が４ｋｇになるよう打錠した。
連続打錠中においても何ら打錠障害なく製錠できた。Example 2 A mixture of a drug formulation component, a lubricant and a fluidizing agent prepared in Example 1 was mixed with a compound tablet machine (manufactured by Hata Iron Works, punch size: diameter 7
mm). A mixture of a lubricant and a fluidizing agent was supplied to one compression site, and a drug prescription component was supplied to the other compression site, and continuous tableting was performed. The primary molded product is 100
mg / tablet and hardness were 1 kg, and the secondary molded product was 100 mg / tablet and hardness was 4 kg.
Even during continuous tableting, tableting could be performed without any tableting trouble.
【０１０４】実施例３ マンニトール１７５重量部、塩酸イミダプリル５重量部
を混合し、流動層造粒機中で流動下に白糖２０重量部を
３０％（ｗ／ｗ）水溶液で噴霧して造粒し、得られた造
粒顆粒を薬物処方成分とした。また、滑沢剤としてステ
アリン酸カルシウム２０重量部と流動化剤としてマンニ
トール８０重量部を混合し、滑沢剤と流動化剤との混合
物を調製した。なお、マンニトールは、ローラーコンパ
クター及びロールグラニュレーターで乾式圧縮造粒した
ものを流動化剤として用いた。実施例１と同様に上記滑
沢剤と流動化剤との混合物、薬物処方成分を三層錠剤機
を用いて連続打錠した。一次成型物は２００ｍｇ／錠、
硬度が２ｋｇになるよう打錠し、二次成型物は２００ｍ
ｇ／錠、硬度が５ｋｇになるよう打錠した。連続打錠中
においても何ら打錠障害なく製錠できた。Example 3 175 parts by weight of mannitol and 5 parts by weight of imidapril hydrochloride were mixed, and granulated by spraying 20 parts by weight of sucrose with a 30% (w / w) aqueous solution under fluidization in a fluidized bed granulator. The obtained granules were used as drug formulation components. Further, 20 parts by weight of calcium stearate as a lubricant and 80 parts by weight of mannitol as a fluidizing agent were mixed to prepare a mixture of the lubricant and the fluidizing agent. In addition, what carried out dry compression granulation with the roller compactor and the roll granulator was used for mannitol as a fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. 200mg / tablet for primary molding,
The tablet is pressed to a hardness of 2 kg, and the secondary molded product is 200 m
g / tablet, and tableted to a hardness of 5 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.
【０１０５】実施例４ ナプロキセン１００重量部、トウモロコシデンプン１
２．５重量部を混合し、ポリビニルピロリドン６重量部
を８％（ｗ／ｗ）溶液（５０％エタノール溶液）で加
え、品川式混合機を用いて撹拌造粒し、得られた造粒顆
粒にカルボキシメチルセルロースカルシウム６．５重量
部を加え、薬物処方成分とした。また、滑沢剤としてス
テアリン酸マグネシウム２０重量部、含水二酸化ケイ素
５重量部と流動化剤として白糖７５重量部を混合し、滑
沢剤と流動化剤との混合物を調製した。実施例１と同様
に上記滑沢剤と流動化剤との混合物、薬物処方成分を三
層錠剤機を用いて連続打錠した。一次成型物は１５０ｍ
ｇ／錠、硬度が３ｋｇになるよう打錠し、二次成型物は
１２５ｍｇ／錠、硬度が５ｋｇになるよう打錠した。連
続打錠中においても何ら打錠障害なく製錠できた。Example 4 Naproxen 100 parts by weight, corn starch 1
2.5 parts by weight were mixed, 6 parts by weight of polyvinylpyrrolidone was added as an 8% (w / w) solution (50% ethanol solution), and the mixture was stirred and granulated using a Shinagawa mixer to obtain granulated granules. Was added with 6.5 parts by weight of carboxymethylcellulose calcium to give a drug formulation component. Also, 20 parts by weight of magnesium stearate as a lubricant, 5 parts by weight of hydrous silicon dioxide and 75 parts by weight of sucrose as a fluidizing agent were mixed to prepare a mixture of the lubricant and the fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. 150m for primary molding
g / tablet and hardness were 3 kg, and the secondary molded product was 125 mg / tablet and hardness was 5 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.
【０１０６】実施例５ フマル酸ビソプロロール５重量部、マンニトール８７重
量部を混合し、ポリエチレングリコール８重量部を１０
％（ｗ／ｗ）溶液（５０％エタノール溶液）で加え、品
川式混合機を用いて撹拌造粒し、得られた造粒顆粒を薬
物処方成分とした。また、滑沢剤としてステアリン酸マ
グネシウム１０重量部、ステアリン酸５重量部と流動化
剤としてリン酸カルシウム８５重量部を混合し、滑沢剤
と流動化剤との混合物を調製した。実施例１と同様に上
記滑沢剤と流動化剤との混合物、薬物処方成分を三層錠
剤機を用いて連続打錠した。一次成型物は１５０ｍｇ／
錠、硬度が４ｋｇになるよう打錠し、二次成型物は１０
０ｍｇ／錠、硬度が４ｋｇになるよう打錠した。連続打
錠中においても何ら打錠障害なく製錠できた。Example 5 5 parts by weight of bisoprolol fumarate and 87 parts by weight of mannitol were mixed, and 8 parts by weight of polyethylene glycol was added to 10 parts by weight.
% (W / w) solution (50% ethanol solution), and the mixture was stirred and granulated using a Shinagawa mixer, and the obtained granulated granules were used as drug formulation components. Also, 10 parts by weight of magnesium stearate as a lubricant, 5 parts by weight of stearic acid, and 85 parts by weight of calcium phosphate as a fluidizing agent were mixed to prepare a mixture of a lubricant and a fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. 150mg /
Tablets, tableted to a hardness of 4 kg, secondary molded product 10
Tablets were pressed so that the hardness was 0 mg / tablet and the hardness was 4 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.
【０１０７】実施例６ 塩酸イミダプリル５重量部、乳糖６８重量部を混合し、
流動層造粒機中で流動下にポリエチレングリコール（分
子量６０００）７重量部を２０％（ｗ／ｗ）溶液（５０
％エタノール溶液）で噴霧して造粒し、得られた造粒顆
粒を薬物処方成分とした。また、滑沢剤としてステアリ
ン酸カルシウム５重量部、合成ケイ酸アルミウム５重量
部と流動化剤としてクエン酸カルシウム９０重量部を混
合し、滑沢剤と流動化剤との混合物を調製した。実施例
１と同様に上記滑沢剤と流動化剤との混合物、薬物処方
成分を三層錠剤機を用いて連続打錠した。一次成型物は
１５０ｍｇ／錠、硬度が２ｋｇになるよう打錠し、二次
成型物は８０ｍｇ／錠、硬度が３．５ｋｇになるよう打
錠した。連続打錠中においても何ら打錠障害なく製錠で
きた。Example 6 5 parts by weight of imidapril hydrochloride and 68 parts by weight of lactose were mixed.
In a fluidized bed granulator, 7 parts by weight of polyethylene glycol (molecular weight: 6000) was fluidized in a 20% (w / w) solution (50%).
% Ethanol solution) and granulated, and the obtained granules were used as drug formulation components. Also, 5 parts by weight of calcium stearate, 5 parts by weight of synthetic aluminum silicate and 90 parts by weight of calcium citrate as a fluidizing agent were mixed to prepare a mixture of a lubricant and a fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. The primary molded product was tableted at 150 mg / tablet and hardness of 2 kg, and the secondary molded product was tableted at 80 mg / tablet and hardness of 3.5 kg. Even during continuous tableting, tableting could be performed without any tableting trouble.
【０１０８】実施例７ マンニトール１８９重量部、塩酸イミダプリル５重量部
を混合し、流動層造粒機中で流動下にポリビニルピロリ
ドン６重量部を１０％（ｗ／ｗ）水溶液で噴霧して造粒
し、得られた造粒顆粒を薬物処方成分とした。また、滑
沢剤としてステアリン酸カルシウム１０重量部と流動化
剤としてβ−無水乳糖９０重量部を混合し、滑沢剤と流
動化剤との混合物を調製した。実施例１と同様に上記滑
沢剤と流動化剤との混合物、薬物処方成分を三層錠剤機
を用いて連続打錠した。一次成型物は２００ｍｇ／錠、
硬度が１ｋｇになるよう打錠し、二次成型物は２００ｍ
ｇ／錠、硬度が０．５ｋｇになるよう打錠した。連続打
錠中においても何ら打錠障害なく製錠できた。得られた
二次成型物を、２５℃、エタノール蒸気で満たしたデシ
ケータ中に５時間放置後、箱型乾燥器中（４０℃）に３
時間保持してエタノールを除去し、口腔内速崩壊性錠を
得た。Example 7 189 parts by weight of mannitol and 5 parts by weight of imidapril hydrochloride were mixed, and granulated by spraying 6 parts by weight of polyvinylpyrrolidone with a 10% (w / w) aqueous solution in a fluidized bed granulator under flow. Then, the obtained granules were used as drug formulation components. Also, 10 parts by weight of calcium stearate as a lubricant and 90 parts by weight of β-anhydrolactose as a fluidizing agent were mixed to prepare a mixture of the lubricant and the fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. 200mg / tablet for primary molding,
The tablet is pressed to a hardness of 1 kg, and the secondary molded product is 200 m
g / tablet, and tableting was performed so that the hardness became 0.5 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was left in a desiccator filled with ethanol vapor at 25 ° C. for 5 hours, and then placed in a box dryer (40 ° C.) for 3 hours.
The ethanol was removed by holding for a period of time to obtain an orally rapidly disintegrating tablet.
【０１０９】実施例８ 滑沢剤としてステアリン酸マグネシウム２５重量部と流
動化剤として造粒乳糖（乳糖Ｇ：フロイント産業製）７
５重量部を混合し、滑沢剤と流動化剤との混合物を調製
した。上記滑沢剤と流動化剤との混合物、実施例７で調
製した薬物処方成分を、実施例１と同様に３層錠剤機を
用いて連続打錠した。一次成型物は１８０ｍｇ／錠、硬
度が１ｋｇになるよう打錠し、二次成型物は２００ｍｇ
／錠、硬度１ｋｇになるよう打錠した。連続打錠中にお
いても何ら打錠障害なく製錠できた。得られた二次成型
物は、２５℃、９０％ＲＨの湿度下に５時間放置後、箱
型乾燥器中（４５℃）に５時間保持して乾燥し、口腔内
速崩壊性錠を得た。Example 8 25 parts by weight of magnesium stearate as a lubricant and granulated lactose (lactose G: manufactured by Freund Corporation) 7 as a fluidizing agent
5 parts by weight were mixed to prepare a mixture of a lubricant and a fluidizing agent. The mixture of the lubricant and the fluidizing agent, and the drug prescription component prepared in Example 7 were continuously tableted using a three-layer tablet machine in the same manner as in Example 1. 180 mg / tablet for primary molded product, tableting with hardness of 1 kg, 200 mg for secondary molded product
/ Tablet, tableted to a hardness of 1 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was allowed to stand at 25 ° C. and 90% RH for 5 hours, and then dried in a box dryer (45 ° C.) for 5 hours to obtain a rapidly disintegrating tablet in the oral cavity. Was.
【０１１０】実施例９ マンニトール１８９重量部、フマル酸ビソプロロール５
重量部を混合し、流動層造粒機中で流動下にポリビニル
ピロリドン６重量部を１０％（ｗ／ｗ）水溶液で噴霧し
て造粒し、得られた造粒顆粒を薬物処方成分とした。ま
た、滑沢剤としてステアリン酸カルシウム１０重量部と
流動化剤としてβ−無水乳糖９０重量部を混合し、滑沢
剤と流動化剤との混合物を調製した。実施例１と同様に
上記滑沢剤と流動化剤との混合物、薬物処方成分を３層
打錠機を用いて連続打錠した。一次成型物は２００ｍｇ
／錠、硬度が１．５ｋｇになるよう打錠し、二次成型物
は２００ｍｇ／錠、硬度が１ｋｇになるよう打錠した。
連続打錠中においても何ら打錠障害なく製錠できた。得
られた二次成型物を、２５℃、エタノール蒸気で満たし
たデシケータ中に５時間放置後、箱型乾燥器中（４０
℃）で３時間保持してエタノールを除去し、口腔内速崩
壊性錠を得た。Example 9 189 parts by weight of mannitol, bisoprolol fumarate 5
Parts by weight, and 6 parts by weight of polyvinylpyrrolidone was sprayed with a 10% (w / w) aqueous solution under a fluidized bed in a fluidized bed granulator to granulate, and the obtained granules were used as drug formulation components. . Also, 10 parts by weight of calcium stearate as a lubricant and 90 parts by weight of β-anhydrolactose as a fluidizing agent were mixed to prepare a mixture of the lubricant and the fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug formulation components were continuously tableted using a three-layer tableting machine. 200mg for primary molding
/ Tablet, tablet hardness was 1.5 kg, and the secondary molded product was 200 mg / tablet, tablet hardness was 1 kg.
Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was left in a desiccator filled with ethanol vapor at 25 ° C. for 5 hours, and then placed in a box-shaped drier (40
° C) for 3 hours to remove ethanol to obtain a rapidly disintegrating tablet in the oral cavity.
【０１１１】実施例１０ 滑沢剤としてステアリン酸マグネシウム２５重量部と流
動化剤として造粒乳糖（乳糖Ｇ：フロイント産業製）７
５重量部を混合し、滑沢剤と流動化剤との混合物を調製
した。上記滑沢剤と流動化剤との混合物、実施例９で調
製した薬物処方成分を、実施例１と同様に三層錠剤機を
用いて連続打錠した。一次成型物は１８０ｍｇ／錠、硬
度が２ｋｇになるよう打錠し、二次成型物は２００ｍｇ
／錠、硬度が１ｋｇになるよう打錠した。連続打錠中に
おいても何ら打錠障害なく製錠できた。得られた二次成
型物は、２５℃、９０％ＲＨの湿度下に５時間放置後、
箱型乾燥器中（４５℃）に５時間保持して乾燥し、口腔
内速崩壊性錠を得た。Example 10 25 parts by weight of magnesium stearate as a lubricant and granulated lactose (lactose G: manufactured by Freund Corporation) 7 as a fluidizing agent
5 parts by weight were mixed to prepare a mixture of a lubricant and a fluidizing agent. The mixture of the lubricant and the fluidizing agent, and the drug prescription component prepared in Example 9 were continuously tableted using a three-layer tableting machine in the same manner as in Example 1. 180 mg / tablet for primary molded product, tableting with hardness of 2 kg, 200 mg for secondary molded product
/ Tablets were pressed so that the hardness became 1 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was left at 25 ° C. and 90% RH for 5 hours,
It was kept in a box dryer (45 ° C.) for 5 hours and dried to obtain a rapidly disintegrating tablet in the oral cavity.
【０１１２】実施例１１ マンニトール１６０重量部、（１−メチル−Ｌ−４，５
−ジヒドロオロチル）−Ｌ−ヒスチジル−Ｌ−プロリン
アミド５重量部を混合し、流動層造粒機中で流動下に白
糖４０重量部を３０％（ｗ／ｗ）水溶液で噴霧して造粒
し、得られた造粒顆粒を薬物処方成分とした。滑沢剤と
してステアリン酸マグネシウム１０重量部、ステアリン
酸カルシウム１０重量部と流動化剤として結晶セルロー
ス（アビセルＰＨ１０２：旭化成製）８０重量部を混合
し、滑沢剤と流動化剤との混合物を調製した。実施例１
と同様に上記滑沢剤と流動化剤との混合物、薬物処方成
分を三層錠剤機を用いて連続打錠した。一次成型物は１
８０ｍｇ／錠、硬度が１．５ｋｇになるよう打錠し、二
次成型物は２０５ｍｇ／錠、硬度が０．４ｋｇになるよ
う打錠した。連続打錠中においても何ら打錠障害なく製
錠できた。得られた二次成型物は、２５℃、８２％ＲＨ
の湿度下に一晩放置後、箱型乾燥器中（４５℃）に５時
間保持して乾燥し、口腔内速崩壊性錠を得た。Example 11 160 parts by weight of mannitol, (1-methyl-L-4,5
-Dihydroorotyl) -L-histidyl-L-prolinamide 5 parts by weight, and granulation by spraying 40 parts by weight of sucrose with a 30% (w / w) aqueous solution under flow in a fluidized bed granulator. Then, the obtained granules were used as drug formulation components. 10 parts by weight of magnesium stearate and 10 parts by weight of calcium stearate as a lubricant were mixed with 80 parts by weight of crystalline cellulose (Avicel PH102: manufactured by Asahi Kasei) as a fluidizing agent to prepare a mixture of the lubricant and the fluidizing agent. . Example 1
In the same manner as in the above, the mixture of the lubricant and the fluidizing agent and the drug formulation components were continuously tableted using a three-layer tablet machine. Primary molding is 1
The tablet was pressed so as to have a hardness of 80 mg / tablet and a hardness of 1.5 kg. The secondary molded product was tableted so as to have a hardness of 205 mg / tablet and a hardness of 0.4 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was obtained at 25 ° C. and 82% RH.
, And dried in a box drier (45 ° C) for 5 hours to obtain an orally rapidly disintegrating tablet.
【０１１３】実施例１２ マンニトール１６０重量部、ニセルゴリン５重量部を混
合し、流動層造粒機中で流動下に白糖４０重量部を２５
％（ｗ／ｗ）水溶液で噴霧して造粒し、得られた造粒顆
粒を薬物処方成分とした。滑沢剤としてステアリン酸マ
グネシウム１０重量部、ステアリン酸カルシウム５重量
部と流動化剤として結晶セルロース（アビセルＰＨ１０
２：旭化成製）８５重量部を混合し、滑沢剤と流動化剤
との混合物を調製した。実施例１と同様に上記滑沢剤と
流動化剤との混合物、薬物処方成分を三層錠剤機を用い
て連続打錠した。一次成型物は１８０ｍｇ／錠、硬度が
３ｋｇになるよう打錠し、二次成型物は２０５ｍｇ／
錠、硬度が０．８ｋｇになるよう打錠した。連続打錠中
においても何ら打錠障害なく製錠できた。得られた二次
成型物は、２５℃、８２％ＲＨの湿度下に一晩放置後、
箱型乾燥器中（４５℃）に５時間保持して乾燥し、口腔
内速崩壊性錠を得た。Example 12 160 parts by weight of mannitol and 5 parts by weight of nicergoline were mixed, and 40 parts by weight of sucrose was added to 25 parts by flow in a fluidized bed granulator.
% (W / w) aqueous solution and granulated, and the obtained granulated granules were used as drug formulation components. 10 parts by weight of magnesium stearate and 5 parts by weight of calcium stearate as a lubricant and microcrystalline cellulose (Avicel PH10) as a fluidizing agent
2: Asahi Kasei) (85 parts by weight) were mixed to prepare a mixture of a lubricant and a fluidizing agent. In the same manner as in Example 1, the mixture of the lubricant and the fluidizing agent and the drug components were continuously tableted using a three-layer tablet machine. The primary molded product was pressed at 180 mg / tablet and the hardness was 3 kg, and the secondary molded product was 205 mg / tablet.
Tablets were tableted to a hardness of 0.8 kg. Even during continuous tableting, tableting could be performed without any tableting trouble. The obtained secondary molded product was left overnight at 25 ° C. and 82% RH,
It was kept in a box dryer (45 ° C.) for 5 hours and dried to obtain a rapidly disintegrating tablet in the oral cavity.
【０１１４】[0114]
【発明の効果】本発明の方法によれば、滑沢剤と流動化
剤とを混合して用いることにより、滑沢剤を安定して成
型機へ供給することが可能になり、まずこの滑沢剤と流
動化剤との混合物を成型機に供給して成型（一次成型）
すると、一次成型物の排出後も滑沢剤が成型機内に付着
残留しているため、一次成型後、続けて薬物処方成分を
該成型機で成型（二次成型）すれば、成型物の成型機へ
の付着などが生じることなく成型が可能となる。したが
って、一次成型と二次成型を交互に行うことにより、薬
物処方成分中に滑沢剤を添加しておかなくても効率よく
連続的な成型が可能である。According to the method of the present invention, it is possible to stably supply a lubricant to a molding machine by mixing and using a lubricant and a fluidizing agent. Supplying a mixture of a lubricant and a fluidizing agent to a molding machine and molding (primary molding)
Then, since the lubricant remains in the molding machine even after discharging the primary molded product, if the drug prescription component is continuously molded (secondarily molded) by the molding machine after the primary molding, the molded product is molded. Molding can be performed without adhesion to the machine. Therefore, by alternately performing the primary molding and the secondary molding, efficient and continuous molding is possible without adding a lubricant to the drug formulation component.
【０１１５】また、本方法によれば、薬物処方成分中に
全く滑沢剤を含んでいなくても連続的な成型が可能であ
り、したがって、滑沢剤による成型物の崩壊・溶出の遅
延が皆無であることから、口腔内速崩壊性製剤の製造に
本方法を適用すれば、極めて効果的である。Further, according to the present method, continuous molding is possible even if no lubricant is contained in the drug prescription component. Therefore, the disintegration and dissolution of the molded product by the lubricant is delayed. Since this method is completely absent, applying this method to the production of a rapidly disintegrating preparation in the oral cavity is extremely effective.
Claims (8)
成型し、成型物を排出したのち、該成型機で薬物処方成
分を成型することを特徴とする成型製剤の製法。1. A method for producing a molded preparation, which comprises molding a mixture of a lubricant and a fluidizing agent with a molding machine, discharging the molded product, and then molding the drug prescription component with the molding machine.
糖、マンニトール、リン酸カルシウムおよびクエン酸カ
ルシウムから選ばれる１種又は２種以上である請求項１
記載の成型製剤の製法。2. The fluidizing agent is one or more selected from crystalline cellulose, lactose, sucrose, mannitol, calcium phosphate and calcium citrate.
A method for producing the molded preparation according to the above.
塩である請求項１又は２記載の成型製剤の製法。3. The method according to claim 1, wherein the lubricant is an alkaline earth metal stearate.
剤１重量部に対し、流動化剤が２〜２０重量部である請
求項１、２又は３記載の成型製剤の製法。4. The molded preparation according to claim 1, wherein the mixing ratio of the lubricant to the fluidizing agent is 2 to 20 parts by weight based on 1 part by weight of the lubricant. Manufacturing method.
ある請求項１、２、３又は４記載の成型製剤の製法。5. The method according to claim 1, wherein the molding machine is a multi-layer tablet machine or a multiple tablet machine.
により得られる成型製剤。6. A molded preparation obtained by the method according to claim 1, 2, 3, 4 or 5.
成型し、成型物を排出したのち、該成型機に薬物および
加湿により成型可能に湿潤しかつ加湿後の乾燥により形
状を維持する物質からなる薬物処方成分を供給して成型
し、得られた成型物を加湿後乾燥することを特徴とする
口腔内速崩壊性製剤の製法。7. A mixture of a lubricant and a fluidizing agent is molded by a molding machine, and after the molded product is discharged, the mixture is moistened by a drug and humidification in the molding machine, and the shape is formed by drying after humidification. A method for producing a rapidly disintegrating oral preparation, characterized in that a drug formulation comprising a substance to be maintained is supplied and molded, and the resulting molded article is dried after humidification.
成型し、成型物を排出したのち、該成型機に薬物および
アルコール可溶性結合剤からなる薬物処方成分を供給し
て成型し、得られた成型物をアルコールで湿潤させた
後、該アルコールを除去することを特徴とする口腔内速
崩壊性製剤の製法。8. A mixture of a lubricant and a fluidizing agent is molded by a molding machine, and after discharging the molded product, a drug prescription component comprising a drug and an alcohol-soluble binder is supplied to the molding machine to mold the mixture. A method for producing a rapidly disintegrating preparation in the oral cavity, comprising: moistening an obtained molded product with alcohol and removing the alcohol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10799197A JP3296412B2 (en) | 1997-04-25 | 1997-04-25 | Molded preparation and its manufacturing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10799197A JP3296412B2 (en) | 1997-04-25 | 1997-04-25 | Molded preparation and its manufacturing method |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001345320A Division JP3815301B2 (en) | 2001-11-09 | 2001-11-09 | Molded preparation and its production method |
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| Publication Number | Publication Date |
|---|---|
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| JP3296412B2 JP3296412B2 (en) | 2002-07-02 |
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ID=14473219
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Cited By (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1043009A1 (en) | 1997-12-03 | 2000-10-11 | Kyowa Hakko Kogyo Co., Ltd. | Process for the production of tablets and tablets |
| JP2001058944A (en) * | 1999-06-18 | 2001-03-06 | Takeda Chem Ind Ltd | Rapidly disintegrating solid formulation |
| WO2001026632A1 (en) * | 1999-10-13 | 2001-04-19 | Kyowa Hakko Kogyo Co., Ltd. | Compression molded product and production method therefor |
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