Takeda Pharmaceutical Company Limited

Takeda Chemical Industries, Inc.

Muneo Nonomura

Hiroki Ito

Hideo Hashimoto

Tadashi Urai

Naoki Nagahara

Tomomichi Futo

Naoki Asakawa

Nobuyuki Takechi

Hisayoshi Shimizu

Masayuki Yamada

Kohei Nishikawa

Yasuyuki Suzuki

Nobuo Tanaka

Yukihiro Nomura

Masahiko Kato

Makoto Kakiuti

Yasuhiro Hiraishi

Yasaburo Akagi

Shigehiro Higuchi

Kei Mukai

Toshiharu Beppu

It is intended to provide a process for producing unstable amorphous benzimidazole compounds having a proton pump inhibitor function, and stable solid preparations for medicinal use containing these compounds which are produced by blending such an amorphous benzimidazole compound with a nontoxic base such as a basic inorganic salt, forming an intermediate coating layer on the layer containing the active ingredient and further forming an enteric coating layer or a release-controlling coating layer.

Stable solid preparations

The present invention provides a pharmaceutical composition or a solid preparation containing a stabilized pharmaceutically active ingredient and a stabilizing method thereof. According to the present invention, a pharmaceutical composition can be stabilized by containing a nonpeptidic pharmaceutically active ingredient having a primary or secondary amino group, an excipient and an acidic compound. In addition, a solid preparation containing a pharmaceutically active ingredient, titanium oxide, a plasticizer and a chain organic acid can enhance the stability of the pharmaceutically active ingredient during light irradiation.

Pharmaceutical composition

In a production process of granules containing a biologically active substance, variation in the elution profile of the biologically active substance is reduced by heating the temperature of granules to about 50&#xb0; C. or higher and maintaining the temperature for about 1 minute or longer. By setting the spray speed to about 90 mg/min or more per 1 g of cores when a spray agent for a primary agent containing the biologically active substance is sprayed while spraying a binding liquid to the cores and setting the total feeding weight per unit area for a centrifugal fluidized bed coating granulation machine to about 1.5 g/cmor more, the variation in the elution profile of the biologically active substance from the granules is reduced.

Method for producing granules

This invention provides a production method for a solid sustained-release preparation, characterized in that a sustained-release preparation (a sustained-release preparation suspension) is freeze-dried in a freeze-drying container whose inner face is partially or totally coated with an ice layer or water-repelling base material.

Producing a sustained-release preparation

A drug comprising either a peptide having the LH-RH action or an LH-RH antagonist is carried on an intrauterine contraceptive device (IUD) so as to be able to provide controlled release. Once the IUD is put in the uterus, the carried drug is gradually released over such a prolonged period of treatment time as, for example, several months to be continuously absorbed through the uterus mucosa or the vagina mucosa. This construction makes it possible to reduce the patient's pain and such a troublesomeness as frequent drug administration and continuously administer a necessary drug over a prolonged period of time while taking a contraceptive measures.

Pharmaceutical product for application to uterus mucosa

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

A two-compartment type prefilled syringe includes a first rubber stopper fitted into a front sleeve, a second rubber stopper fitted into a rear end portion of a cartridge, a third rubber stopper for hermetically dividing the interior of the cartridge into front and rear compartments and a bypass formed by radially outwardly bulging a portion of a peripheral wall of the cartridge. In an axial direction of the cartridge, a length of the third rubber stopper is slightly smaller than an inner length of the bypass. When the third rubber stopper has been displaced into the bypass, the sealing property of the rear compartment with the front compartment is cancelled such that the dissolving agent, suspension or the like in the rear compartment is carried, via the bypass, into the front compartment containing dry medicament or the like. A ratio of a maximum width of one end of the bypass adjacent to the front sleeve to a maximum width of the other end of the bypass adjacent to the rear end portion of the cartridge is set to range from 1.2 to 5.0.

Two-compartment type prefilled syringe

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

When a transdermal therapeutic composition which contains a pharmaceutically effective ingredient, a water-soluble absorption enhancer, a fat-soluble absorption enhancer and a super water-absorbent resin is applied to the skin of mammals, release of the pharmaceutically effective ingredient and the absorption enhancers is controlled and the pharmacological action lasts for a long period of time.

Transdermal therapeutic composition

The present invention concerns a sustained-release microcapsule preparation comprising an ion exchange resin with 6 to 16% crosslinking, containing a drug adsorbed in an amount not less than 80% of its theoretical ion adsorption amount and coated with a water-permeable polymer.

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Osaka, Japan

Muneo Nonomura