Temperature stable crystalline salts OF PHYSICAL MIXTURES OF SALTS AND METHOD FOR THE MANUFACTURE OF SVOVLSYREADDITIONSSALTET

摘要

Cephalosporin Salts and Injectable Compositions Crystalline sulfuric, di-nitric, mono-hydrochloric, dihydrochloric, and di- and sesqui-orthosphosphoric acid addition salts of 7-¢.alpha.-(2-aminothiazol-4-yl)-.alpha.-(Z)-methoxyimino-acetamido!-3-¢(1-methyl-1-pyrrolidinio)-methyl!-3-cephem-4-carboxylate are stable even at elevated temperatures. The crystalline sulfuric acid addition salt is made by forming an admixture of (a) at least one molar equivalent of sulfuric acid with (b) zwitterion in an amount so as to be present in the admixture at a concentration of greater than 25 milligrams/ml, causing crystallization, separating the crystals, washing and drying. The crystalline monohydrochloride, dihydrochloride, and orthophosphate salts are prepared by dissolving the zwitterion in the appropriate amount of acid, causing crystallization by adding acetone and isolating the crystal. Physical admixtures of the salts with certain bases in proportions to give a pH ranging from about 3 5 to about 7 on dilution with water provide injectable compositions on dilution. Brief Description of the Drawing Figure 1 is a graphical representation of the infra red absorption spectrum of crystalline 7-¢.alpha.-(2-aminothiazol-4-yl)-.alpha.- (Z)-methoxyiminoacetamido!-3-¢(1-methyl-1-pyrrolidinio)methyl!-3-cephem-4-carboxylate sulfate salt measured on a KBr dilution thereof. BMY-28142.H2SO4 - IR Spectrum.