Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Nobuyuki Takechi

Akihiro Nagai

Muneo Nonomura

Seiji Ohtani

Naoru Hamaguchi

Naoki Asakawa

Masao Nagao

Takayuki Doen

Yasaburo Akagi

Shigehiro Higuchi

Toshiharu Beppu

Yuichiro Inoue

Yasuo Doi

An injectable composition comprises a benzimidazole compound having an antiulcer action and a strong alkali (e.g., an alkali metal hydroxide such as sodium hydroxide) in a proportion of about 1 equivalent of the latter relative to 1 mol of the former, and is substantially free from a nonaqueous solvent. The injectable composition may comprise N-methylglucamine, and a saccharide (such as mannitol). The injectable composition may be a freeze-dried preparation. The freeze-dried preparation is dissolvable in or dilutive with a distilled water for injection or an infusion solution without a nonaqueous solvent. The injectable composition is useful as an antiulcer agent.

Injections

Disclosed is a method of producing microspheres which comprises subjecting a w/o/w emulsion or o/w emulsion to an in-water drying method under the following conditions:

Sustained release microspheres and preparation thereof

This invention provides a method for producing a microparticle which comprises pulverizing a solid preparation comprising a compound represented by the formula: ##STR1## wherein ring A is an optionally substituted benzene ring; R is a hydrogen atom or an optionally substituted hydrocarbon group; B is an optionally esterified or amidated carboxyl group; X is --CH(OH)-- or --CO--; k is 0 or 1; and n is 0, 1 or 2 or a pharmaceutically acceptable salt thereof and a biodegradable polymer of .alpha.-hydroxycarboxylic acid in the presence of a pulverizing auxiliary, which can provide microparticles which are less adhesive and involve less aggregation and are thus excellent in drug entrapment ratio and control of drug-release in a desired particle size.

Method for producing a microparticle

Production of microspheres

A novel microparticle preparation comprising microparticles of a polymer which contain a drug and are at least partially or wholly coated with a water-soluble inorganic salt, a water-soluble organic acid or a water-soluble salt of an organic acid, which acts as an agent for preventing aggregation of the microparticle preparation is disclosed. The preparation is produced by spraying a polymer solution containing a drug and a solution or dispersion of a water-soluble inorganic salt, a water-soluble organic acid or a water-soluble salt of an organic acid from different nozzles and contacting them with each other in a spray dryer. In this procedure, if desired, a non-ionic surfactant may be added to the solution of the water-soluble inorganic salt, the water-soluble organic acid or the water-soluble salt of organic acid, or a solution of non-ionic surfactant may be sprayed from the other nozzle simultaneously.

Microparticle preparation and production thereof

This invention comprises a pharmaceutical composition comprising a benzimidazole compound having antiulcer activity and a water-soluble carboxylic acid amide. According to this invention, a water-insoluble benzimidazole compound having antiulcer activity can be solubilized and a stable pharmaceutical composition can be provided. The solid pharmaceutical composition of this invention can be extemporaneously dissolved in sterile distilled water or an infusion (e.g. physiological saline, glucose infusion, etc.) and put to use as an injection with great convenience.

Pharmaceutical composition

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Osaka, Japan

Nobuyuki Takechi