Patent ID: 6111098
Filing Date: 2000-08-29
Classification: A61K,C07D

Abstract:
A lyophilized crystalline preparation comprising a crystal of (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-2-[(3S,5S)-5-sulfamoylaminomethyl-1-pyr rolidin-3-yl]thio-1-methyl-1-carba-2-penem-3-carboxylic acid represented by the following formula: ##STR6## or an inner salt thereof, wherein the crystal is a Type I crystal, which has a powder X-ray diffraction pattern having a primary peak at a diffraction angle (2.theta.)=7.32, 14.72, 16.62, 20.42, 21.1, 22.18, 23.88 and 29.76 (degree); or a Type II crystal, which has a powder X-ray diffraction pattern having a primary peak at a diffraction angle (2.theta.)=6.06, 12.2, 14.56, 17.0, 18.38, 20.68, 24.38, 24.60, 25.88 and 30.12 (degree); or wherein the lyophilized crystalline preparation comprises a mixture of the Type I crystal and the Type II crystal;wherein the lyophilized crystalline preparation exhibits an increased storage stability compared to a lyophilized amorphous preparation of (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-2-[(3S,5S)-5-sulfamoylaminomethyl-1-pyr rolidin-3-yl]thio-1-methyl-1-carba-2-penem-3-carboxylic acid, and wherein the lyophilized amorphous preparation is prepared by cooling an 8 percent aqueous solution of (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-2-[(3S,5S)-5-sulfamoylaminomethyl-1-pyr rolidin-3-yl]thio-1-methyl-1-carba-2-penem-3-carboxylic acid to -30.degree. C. over 1 hour and then vacuum drying the frozen solution, and wherein said storage stability is measured for at least one month either in a hermetic container at 40.degree. C. or in a hermetic container at 50.degree. C., or at zero percent relative humidity at 40.degree. C.; andwherein the lyophilized crystalline preparation may further comprise at least one of the following compounds selected from the group consisting of mannitol, an inorganic salt, and a pH adjusting or controlling agent.