Takeda Chemical Industries, Inc.

Shin-Ichiro Hirai

Tadashi Makino

Tetsuro Tabata

Naoki Nagahara

Yohko Akiyama

Hiroyoshi Koyama

Takatsuka Yashiki

Shunichi Itoh

Hiroaki Okada

Yoshiaki Uda

Toshio Kashihara

Yoshio Mizukami

Toshiaki Ikenaga

Tai Matsuzawa

Stabilized pharmaceutical composition

Stabilized pharmaceutical composition and its production

A solid matrix composition which is solid at ambient temperature, which comprises a viscogenic agent, such as an acrylic acid polymer, capable of developing viscosity on contact with water, as dispersed at least in the neighborhood of the surface layer of a matrix particle containing a polyglycerol fatty acid ester or a lipid and an active ingredient. The matrix may be such that a matrix particle containing a polyglycerol fatty acid ester or a lipid and an active ingredient has been coated with a coating composition containing at least one viscogenic agent. Such composition can adhere to the digestive tract and remain there for a prolonged period of time, thereby increasing the bioavailability of the active ingredient. Solid preparations, such as fine granules and granules, contain the above matrix composition.

Gastrointestinal mucosa-adherent matrixes pharmaceutical preparations and a coating composition

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.

Granules having a core are produced by spraying core granules with a dispersion of a low substituted hydroxypropylcellulose (L-HPC), and, if necessary, simultaneously applying a dusting powder. The granules having a core thus obtained exhibit increased granule strength and improved disintegrating property as compared with those produced by known methods. An active ingredient such as a drug can be contained in the dispersion, dusting powder or core granules.

Granules having core and their production

Gastrointestinal mucosa-adherent granules, pharmaceutical preparations

Method to stabilize a pharmaceutical composition and its production

Gastrointestinal mucosa-adherent matrixes, pharmaceutical preparations

A tablet having first and second surfaces opposite to each other and a side surface lying perpendicular to any one of the first and second surfaces. A peripheral tablet edge delimited between each of the first and second surfaces and the side surface is chamfered to provide a respective inclined peripheral edge face over the entire perimeter of the tablet. This tablet also has at least a first generally V-sectioned score defined in the first surface so as to leave two tablet divisions of uniform size on respective sides of the V-sectioned first score. A pair of generally V-sectioned side scores are defined in the side surface of the tablet at respective locations opposite to each other and are continuous with opposite ends of the V-sectioned first score. The tablet can be divided along the V-sectioned score in the first surface by the application of a minimized finger pressure. The tablet of the invention is particularly suited to the pharmaceutical field.

Divisible tablet

The spherical granules having a core coated with spraying powder containing a drug and low substituted hydroxypropylcellulose, because of their excellent hardness, can be coated further evenly, (e.g. sustained release coating, gastric coating, enteric coating), and at the time the granules are excellent in disintegration.

Growing community of inventors

Kyoto, Japan

Shin-Ichiro Hirai