To formulate the parenteral delivery of a new cephalosporin derivative, 7-β-[(2)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(2,3-cyclopenteno-4-carbamoyl-1-pyridinium)methyl]-3-cephem-4-carboxylate sulfate(CKD-604), the stability and solubil...
To formulate the parenteral delivery of a new cephalosporin derivative, 7-β-[(2)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(2,3-cyclopenteno-4-carbamoyl-1-pyridinium)methyl]-3-cephem-4-carboxylate sulfate(CKD-604), the stability and solubility of CKD-604 in various aqueous media were investigated. The degradation kinetics of CKD-604 in aqueous solutions (ionic strength 0.1, pH 1-8) were studied at 37℃. The observed degradation rates followed pseudo-first order kinetics. The pH-rate profile exhibited a minimum degradation rate at pH 5. The Arrhenius activation energy was 14.2 ㎉/mol in pH 5 buffer solution. Excellent agreement between the cephalosporins` theoretical pH-rate profile and the experimental data indicated that the degradation pathway of CKD-604 could be predicted according to the general pathway of cephalosporins. The solubility of CKD-604 was 8.16 ㎎/㎖ at 25℃. To enhance the solubility and adjust the suitable pH, CKD-604 was solubilized by using sodium ascorbate, ascorbic acid and urea. The compositions were obtained to satisfy optimum pH and concentration, and the total amount of additives was several times of the active ingredient, CKD-604.