Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Tetsuro Tabata

Tadashi Makino

Shin-Ichiro Hirai

Toshihiro Shimizu

Shuji Morimoto

Hiroshi Fukada

Junichi Kikuta

Jun-ichi Kikuta

Hikaru Fukuyama

Toshihide Saito

Hiroki Itoh

Shigehiro Higuchi

Norio Kameoka

Etsuji Nakamura

An orally disintegrable tablet, of the present invention, which comprises (i) fine granules having an average particle diameter of 400 &#x3bc;m or less, which fine granules comprise a composition coated by an enteric coating layer, said composition having 10 weight % or more of an acid-labile physiologically active substance and (ii) an additive, has superior disintegrability or dissolution in the oral cavity so that it can be used for treatment or prevention of various diseases, as an orally disintegrable tablet capable of being administered to the aged or children and easily administered without water. Also, because the tablet of the present invention contains fine granules having the average particle diameter such that it will not impart roughness in mouth, it can be administered easily without discomfort at the administration.

Orally disintegrable tablets

It is intended to provide a method of producing a solid preparation disintegrating in the oral cavity characterized by comprising mixing fine subtilaes containing a medicinal ingredient with an additive containing &#x3b4;-mannitol and tableting the mixture; and a solid preparation disintegrating in the oral cavity produced thereby. This solid preparation disintegrating in the oral cavity has such a strength (hardness) as suffering from no defect even under stresses in transporting, packaging with the use of an automated packaging machine, taking out from a PTP and soon.

Method of producing solid preparation disintegrating in the oral cavity

An orally disintegrable tablet of the present invention, which comprises (i) fine granules having an average particle diameter of 400 &#x3bc;m or less, which fine granules comprise a composition coated by an enteric coating layer, said composition having 10 weight % or more of an acid-labile physiologically active substance and (ii) an additive, has superior disintegrability or dissolution in the oral cavity so that it can be used for treatment or prevention of various diseases, as an orally disintegrable tablet capable of being administered to the aged or children and easily administered without water. Also, because the tablet of the present invention contains fine granules having the average particle diameter such that it will not impart roughness in mouth, it can be administered easily without discomfort at the administration.

The punch coated with Cr-Dop&eacute;-N is advantageous as a punch for preparing tablets containing an acidic substance or an adhesive substance and is excellent in corrosion resistance and releasing property.

Compressing mallet with coating treatment

Stabilized pharmaceutical composition

Stabilized pharmaceutical composition and its production

An orally disintegrable tablet, of the present invention, which comprises (i) fine granules having an average particle diameter of 400 &mgr;m or less, which fine granules comprise a composition coated by an enteric coating layer, said composition having 10 weight % or more of an acid-labile physiologically active substance and (ii) an additive, has superior disintegrability or dissolution in the oral cavity so that it can be used for treatment or prevention of various diseases, as an orally disintegrable tablet capable of being administered to the aged or children and easily administered without water. Also, because the tablet of the present invention contains fine granules having the average particle diameter such that it will not impart roughness in mouth, it can be administered easily without discomfort at the administration.

The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula

Method for producing a granule

The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula ##STR1## wherein R.sup.1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R.sup.2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R.sup.3 and R.sup.5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R.sup.4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.

Process for producing stabilized pharmaceutical composition

The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula ##STR1## wherein R.sup.1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R.sup.2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonyl methyl, alkoxycarbonylmethyl or alkylsulfonyl, R.sup.3 and R.sup.5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R.sup.4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.

An effervescent composition comprising a core-shell powder consisting of a fine granular core spray-coated with a liquid mixture containing a water-soluble polymer such as hydroxypropylcellulose or hydroxypropylmethylcellulose, and at least one physiologically active substance, especially an acid-sensitive drugs, and enteric coating film, an effervescing component and an auxiliary effervescing agent which provides for controlled release of the physiologically active substance and in useful for preparing uniform solution or suspension having a refreshing sensation on ingestion.

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Osaka, Japan

Tetsuro Tabata