Meiji Seika Kaisha, Ltd.

Tatsuo Watanabe

Yasushi Murai

Katsuharu Iinuma

Masamichi Sukegawa

Masahiro Onodera

Kiyoshi Yasui

Yuichi Yamamoto

Toyomi Sato

Yumiko Okada

Hiroyuki Iwasawa

Processes are provided for the preparation of orally administrable, yellow and powdery compositions essentially consisting of particles composed of a homogeneous mixture of an amorphous Cefditoren pivoxil substance with a water soluble high-molecular additive. These compositions can be produced by dissolving crystalline Cefditoren pivoxil substance and the water-soluble high-molecular additive in an aqueous solution of an acid, then neutralizing the resultant solution, to co-precipitate the product, and drying the thus precipitated product, followed by recovering the product in the form of the above-mentioned particles.

Composition comprising a crystallographically stable, amorphous cephalosporin and processes for the preparation thereof

A crystalline substance of Cefditoren pivoxyl is provided which has a high purity and enhanced thermal stability on storage. This crystalline Cefditoren pivoxyl may be prepared by a process comprising a step of dissolving an amorphous form of Cefditoren pivoxyl in an anhydrous, first organic solvent capable of dissolving said amorphous form well therein, and steps of replacing the first organic solvent component of the resulting solution by an anhydrous alkanol of 1 to 5 carbon atoms as a second organic solvent, in such a manner that the firstly prepared solution of Cefditoren pivoxyl in the first organic solvent is mixed with a volume of the alkanol and then is concentrated below 15&deg; C. under reduced pressure, and so on. Thereby, the process proceeds so as to produce a solution containing 50 mg/ml to 250 mg/ml of Cefditoren pivoxyl dissolved in the alkanol alone. From the latter solution, crystals of Cefditoren pivoxyl are induced to deposit by addition of water at a temperature of 0-10&deg; C. The resulting admixture of the concentrated solution of Cefditoren pivoxyl in alkanol with added water and the deposited Cefditoren pivoxyl is then agitated 10&deg; C. or below, to effect a complete crystallization of Cefditoren pivoxyl.

Crystalline substance of cefditoren pivoxyl and the production of the same

Crystallographically stable amorphous cephalosporin compositions and process for producing the same

As a novel substance is provided such a new, crystalline substance of Cefditoren povoxyl which has a high purity and an enhanced thermal stability on storage. This crystalline Cefditoren pivoxyl may be prepared by a process comprising a step of dissolving amorphous substance of Cefditoren pivoxyl in an anhydrous, first organic solvent capable of dissolving said amorphous substance well therein, and steps of replacing the first organic solvent component of the resulting solution by an anhydrous alkanol of 1 to 5 carbon atoms as a second organic solvent, in such a manner that the firstly prepared solution of Cefditoren pivoxyl in the first organic solvent is mixed with a volume of the alkanol and then is concentrated below 15&deg; C. under reduced pressure, and so on. Thereby, the process proceeds so as to produce a solution containing 50 mg/ml to 250 mg/ml of Cefditoren pivoxyl dissolved in the alkanol alone. From the latter solution, crystals of Cefditoren pivoxyl are induced to deposit by addition of water at a temperature of 0-10&deg; C. The resulting admixture of the concentrated solution of Cefditoren pivoxyl in alkanol with added water and the deposited Cefditoren pivoxyl is then agitated 10&deg; C. or below, to effect a complete crystallization of Cefditoren pivoxyl.

There can be produced, at a high selectivity and in a high yield, the Z-isomer of a 7-N-unsubstituted or substituted-amino-3-&lsqb;2-(4-substituted or unsubstituted-thiazol-5-yl) vinyl&rsqb;-3-cephem-4-carboxylic acid or an ester thereof having the general formula (IV)

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Odawara, Japan

Tatsuo Watanabe