Shin-etsu Chemical Co., Ltd.

Yuichi Nishiyama

Naosuke Maruyama

Hiroaki Muto

Ikuo Fukui

Hiroyasu Kokubo

Mitsuo Narita

Hiroshi Umezawa

Takuya Yokosawa

Fumie Kusaki

Takafumi Hoshino

Kiyoshi Araume

Toru Chiba

Akira Kitamura

Kazuhisa Hayakawa

Yuichi Ito

Noboru Hoshi

Yoshiro Onda

Soji Tanioka

Tohru Chiba

Shingo Kikuchi

Fumie Tanno

Miyuki Fukasawa

Shuichiro Yuasa

Mutsunori Tanji

Tadashi Matsui

Tatsuo Endo

Provided are a drug-containing particle capable of suppressing dissolution of a drug in the oral cavity to suppress an unpleasant taste thereof and having excellent dissolution of the drug in the digestive tract after passing through the oral cavity; a method for preparing the drug-containing particle; a coating composition used for preparing the drug-containing particle; and a solid preparation having the drug-containing particle. More specifically, provided are a coating composition having 100 parts by weight of a cellulose-based enteric base and 50 parts by weight or less of a water-soluble cellulose ether; a drug-containing particle having a drug-containing core and a coat portion obtained by coating the core with the coating composition; a solid preparation having the drug-containing particle; and a method for preparing a drug-containing particle having a step of coating the drug-containing core with the coating composition.

Coating composition, drug-containing particle, solid preparation and method for preparing drug-containing particle

Provided are a method for producing a water-soluble cellulose ether having a low degree of polymerization and enhanced whiteness, and the like. The method includes the steps of: bringing a pulp powder having a multiplication product of less than 0.004 mmwhich is obtained by multiplying a number-average fiber length by a number-average fiber width, each measured with a Kajaani fiber length analyzer, into contact with an alkali metal hydroxide to obtain an alkali cellulose; reacting the alkali cellulose with an etherifying agent to obtain a crude water-soluble cellulose ether having a high degree of polymerization; purifying the crude water-soluble cellulose ether; drying the purified water-soluble cellulose ether; grinding the dried water-soluble cellulose ether into a water-soluble cellulose ether powder; and depolymerizing the water-soluble cellulose ether powder to obtain the water-soluble cellulose ether having a low degree of polymerization.

Method for producing water-soluble cellulose ether having low degree of polymerization and method for producing film coating composition comprising same

Provided is a method for preparing a cellulose ether having a low degree of polymerization and undergoing less yellowing and a cellulose ether prepared thereby. Specifically, provided is a method for preparing a cellulose ether having a low degree of polymerization, the method including a step of bringing pulp and an alkali metal hydroxide solution into contact with each other or mixing them to obtain a corresponding alkali cellulose, a first depolymerization step of reacting the alkali cellulose with oxygen to adjust a viscosity reduction percentage of the alkali cellulose to from 10 to 95%, a step of reacting the depolymerized alkali cellulose with an etherifying agent, a step of washing and drying the reaction product to obtain a cellulose ether, and a second depolymerization step of bringing the cellulose ether into contact with hydrochloric acid to adjust a viscosity reduction percentage of the cellulose ether from 40 to 99.9%.

Method for preparing cellulose ether having low degree of polymerization and cellulose ether prepared thereby

The present invention is an enteric coated granule having controlled dissolution in water even at a small coating amount; and a preparation method thereof. More specifically, provided are an enteric coated granule comprising a raw granule or a granule comprising a raw granule and at least one layer covering the raw granule, a first enteric layer covering the raw granule or the granule, and a second enteric layer formed over the first enteric layer, wherein the first and the second enteric layers comprise a first and a second hydroxypropylmethyl cellulose acetate succinates (HPMCASs) different in solubility pH, respectively, and the solubility pH value of the second HPMCAS of the second enteric layer is lower than that of the first enteric layer; and a preparation method comprising steps of covering a raw granule or a granule comprising a raw granule and at least one layer covering the raw granule with an enteric coating agent comprising a first HPMCAS to form a first enteric layer; and forming, over the first enteric layer, a second coating layer by using a second enteric coating agent comprising a second HPMCAS having a lower solubility pH value than that of the first HPMCAS.

Enteric coated granule and method for preparing the same

Provided is a method for preparing a cellulose derivative having solubility improved and therefore having less undissolved floating portions when the derivative is added into water. More specifically, provided is a method for preparing a cellulose derivative, comprising a step of depolymerizing a cellulose derivative to produce a depolymerized cellulose derivative having a viscosity at 20&#xb0; C. in a 2% by weight aqueous solution of the depolymerized cellulose derivative reduced by at least 10% compared with that of the cellulose derivative before the depolymerization so that the number of undissolved floating portions in the aqueous solution of the depolymerized cellulose derivative is decreased compared with that of the cellulose derivative before the depolymerization. Depolymerization is effected preferably by an acid, alkali or enzyme.

Method for preparing cellulose derivatives having solubility improved

Provided are a solid dosage form comprising a solid dispersion that allows a drug in the preparation to be rapidly dissolved without compromising the solubility of the solid dispersion, and a method for producing the same. More specifically, provided is a solid dosage form comprising a solid dispersion, the dispersion comprising: a poorly soluble drug, a water-soluble polymer and a disintegrant, wherein the disintegrant is low-substituted hydroxypropylcellulose having an average particle size of 10 to 100 &#x3bc;m and a specific surface area measured by BET method of at least 1.0 m/g. Moreover, provided is a method for producing a solid dosage form comprising a solid dispersion, the method comprising steps of: spraying a water-soluble polymer solution in which a poorly soluble drug has been dispersed or dissolved, on a powder of low-substituted hydroxypropylcellulose having an average particle size of 10 to 100 &#x3bc;m and a specific surface area measured by BET method of at least 1.0 m/g and serving as a disintegrant and granulating the resultant; and drying.

Solid dosage form comprising solid dispersion

Provided are a solid dosage form comprising an enteric solid dispersion that allows a drug in the preparation to be rapidly dissolved without compromising the solubility of the solid dispersion, and a method for producing the same. More specifically, provided is a solid dosage form comprising an enteric solid dispersion comprising a poorly soluble drug, an enteric polymer and a disintegrant, wherein the disintegrant is low-substituted hydroxypropylcellulose having an average particle size of 10 to 100 &#x3bc;m and a specific surface area measured by BET method of at least 1.0 m/g. Moreover, provided is a method for producing a solid dosage form comprising an enteric solid dispersion, the method comprising steps of: spraying an enteric polymer solution in which a poorly soluble drug has been dispersed or dissolved, on a powder of low-substituted hydroxypropylcellulose having an average particle size of 10 to 100 &#x3bc;m and a specific surface area measured by BET method of at least 1.0 m/g and serving as a disintegrant; and granulating the resultant; and drying.

Among the conventional processes for producing solid dispersion, the solid dispersion obtained by a solvent method is excellent in terms of solubility and bioavailability of a poorly soluble drug. However, due to frequent uses of organic solvents in the solvent method, problems have arisen such as organic solvent residue in products, environmental pollution and operational safety as well as corporate problems such as capital investment and the like required to avoid such events. The present invention provides a process for preparing pharmaceutical solid preparations without use of organic solvents frequently used in conventional solvent methods. Specifically, the present invention provides a process for producing a pharmaceutical solid preparation, which is formulated by spraying a solution wherein a poorly soluble drug is dissolved in a plasticizer, and an aqueous solution and/or water dispersion of a water-soluble polymer from nozzle outlets simultaneously and separately in the process for producing the pharmaceutical solid preparation.

Process for producing a pharmaceutical solid preparation containing a poorly soluble drug

An aqueous coating composition comprising hydroxypropyl methyl cellulose trimellitate typically having a mean particle size of up to 10 &mgr;m and a plasticizer is applied to a solid pharmaceutical preparation to form a coating film having acid resistance and solubility at about pH 4. The coated preparation has an improved bioavailability.

Aqueous coating composition and process for preparing solid pharmaceutical preparation

A method of manufacturing a solid preparation coated with a non-solvent coating which is prepared by feeding a polymeric powder directly as coating agent while continuously spraying a solid medicine with an atomized mixture of a liquid substance, which has a contact angle against the polymer coating agent of 10 degrees or less, and a plasticizer. A method of manufacturing a dry-coated solid preparation in which a solid preparation, coated with a non-solvent coating, is treated by adding or spraying an atomized water or an aqueous solution of a water soluble substance in the amount of 1-10 wt % of the solid preparation to wet said 'coating layer' followed by drying.

Method of manufacturing a solid preparation coated with non-solvent

The present invention provides a powdery starting material for preparing a drug-coating solution, which has high safety as a drug component and is very rapidly dissolved in room temperature water upon preparation of a coating solution. The powdery starting material for preparing a drug-coating solution comprises hydroxypropylmethyl cellulose and/or methyl cellulose particles having an average particle size ranging from 200 to 1000 .mu.m and whose content of particles having a particle size of 75 .mu.m or smaller is not more than 30% by weight. More preferably, the viscosity of a 2% by weight aqueous solution of the powdery starting material as determined at room temperature ranges from 2 to 60 cP and preferably 2 to 20 cP.

Powdery material for preparing drug-coating solution

An apparatus for manufacturing capsules which causes a solution of thermo-gelling material to gelatinize, and then drys the gel, whereby the process of manufacturing capsules is less affected by drying conditions, thus providing capsules of uniform wall thickness without wrinkles. In the apparatus of this invention, circulating capsule pins are dipped in the solution of thermo-gelling material, thus the solution adheres to the pins, and, the pins are rotated upside down, thus thickness of the solution adhering to the pins becomes uniform. Then, the pins are retained in the vessel maintained at a higher temperature than the gelling temperature of the solution, and the solution adhering to the pins is accelerated to gelatinization. The formed gel is dried in a drying device, and the dried gel bodies, i.e. capsules, are removed from the capsule pins.

Apparatus for manufacturing hard capsules for medicament use

A method for manufacturing capsules causes the solution of thermo-gelling material to gelatinize once, and then drys the gel. Therefore the process of manufacturing capsules is less affected by drying conditions, thus providing capsules of uniform wall thickness without wrinkle. In the apparatus, circulating capsule pins are dipped in the solution of thermo-gelling material, thus the solution adheres to the pins. The pins are rotated upside down, thus thickness of the solution adhering to the pins becoming uniform. Then the pins are retained in the vessel maintained at a higher temperature than the gelling temperature of the solution, and the solution adhering to the pins is gelatinized. The thus-formed gel is dried through a drying device, and the dried gel, i.e. capsules, is removed from capsule pins.

Method of manufacturing hard capsules

In place of gelatin conventionally used as a material for shaping hard medicinal capsules, the invention proposes a hard capsule for medicinal use shaped of a polymer blend of a water-soluble cellulose ether, e.g., alkyl cellulose, hydroxyalkyl cellulose and alkyl hydroxyalkyl cellulose, and a polyvinyl alcohol in a weight ratio of 70:30 to 98:2. The inventive hard medicinal capsules have remarkably low permeability to oxygen and moisture with little influences on the medicament contained therein along with sufficiently high mechanical strengths and are much more stable than conventional gelatin-made capsules against the influences of the ambient conditions, such as, the crack formation unavoidable in a gelatin-made hard capsule when it is kept under an extremely low humidity.

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Niigata-ken, Japan

Yuichi Nishiyama