Nissan Chemical Industries Limited

Other

Zeria Pharmaceutical Co., Ltd.

Toshihisa Oda

Misao Miyamoto

Tetsuyuki Nishiyama

Toyohiko Bunrin

Takao Tsunematsu

Yukiya Yamaguchi

Toshio Okabe

Masaharu Miyajima

Method for converting sparingly water-soluble medical substance to amorphous state

An amorphous solid dispersion of efonidipine hydrochloride having a high intestinal absorbability can be formed by subjecting a mixture containing efonidipine hydrochloride of the formula (I), hydroxypropylmethylcellulose acetate succinate and optionally a thermostabilizer to a step A of heat treatment at from 85 to 140&deg; C. or mechanochemical treatment at from 0 to 140&deg; C., and then to a step B of dipping treatment into a water-containing solution, impregnation treatment with a water-containing solution or contacting treatment with a water vapor-containing gas; or treating the above-mentioned mixture with a hot steam at from 100 to 140&deg; C. and a high pressure. Further, in the above-mentioned step A, the mixture is subjected to high frequency heating, making it possible to give a solid dispersion of efonidipine hydrochloride having a high intestinal absorbability without using the step B. This process is quite advantageous in the production in that the use of an organic solvent is not required. Formula (I):

Process for producing efonidipine hydrochloride preparations

A pharmaceutical composition comprising: a 1:1 solvate of 5-(5,5-dimethyl-1,3,2-dioxaphosphorinane-2-yl)-1,4-dihydro-2,6-dimethyl-4- (3- itrophenyl)-3-pyridine carboxylic acid 2-(phenylmethyl)amino) ethyl ester P-oxide hydrochloride-thanol (NZ-105) and hydroxypropylmethylcellulose acetate succinate is disclosed. the composition can easily be prepared into tablets, capsules, granules, and powders, which exhibit an enhanced bioavailability, e.g. provides a high blood concentration of the active component NZ-105 and ensures a high total drug absorption.

Pharmaceutical composition of dihydropyridine compound

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Funabashi, Japan

Toshihisa Oda