Effect of initial concentration on stability of panipenem in aqueous solution

被引:10
作者
Ito, N
Suzuki, M
Kusai, A
Takayama, K
机构
[1] Sankyo Co Ltd, Pharmaceut Dev Labs, Kanagawa 2540014, Japan
[2] Hoshi Univ, Dept Pharmaceut, Shinagawa Ku, Tokyo 1428501, Japan
关键词
panipenem; solution; stability; kinetics; degradation;
D O I
10.1248/cpb.53.323
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The effect of initial panipenem (CAS No. 87726-17-8) concentration on its degradation in an aqueous solution was investigated. The degradation of panipenem followed pseudo-first-order kinetics at all the pH values tested. However, in an acidic solution, the degradation rate increased with the initial panipenem concentration. On the other hand, in an alkaline solution, the degradation rate was not affected by its initial concentration. In an acidic solution, the plots of the first-order rate constants versus initial panipenem concentrations showed a linear relationship. Theoretically, the first-order rate constant is independent of the initial concentration, and therefore, the results suggested unusualness. We investigated the results obtained under acidic conditions in detail to find a very complex reaction mechanism: panipenem and its degradation products are factors causing the unusual increase in the degradation rate. Moreover, it was shown that the dissociation of the carboxyl group played an important role in the degradation of panipenem.
引用
收藏
页码:323 / 327
页数:5
相关论文
共 14 条
[1]   Meropenem exists in equilibrium with a carbon dioxide adduct in bicarbonate solution [J].
Almarsson, Ö ;
Kaufman, MJ ;
Stong, JD ;
Wu, YH ;
Mayr, SM ;
Petrich, MA ;
Williams, JM .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1998, 87 (05) :663-666
[2]  
HARNED HS, 1958, PHYSICAL CHEMISTRY E, P643
[3]  
ITO N, 1997, DRUG STABILITY, V1, P196
[4]  
MARTIN A, 1993, PHYS PHARM, P303
[5]  
MARTINMALO A, 1993, P EUR DIAL TRANSPLAN, P147
[6]  
MIYADERA T, 1991, SANKYO KENKYUSYO NEM, V43, P1
[7]  
MOELLERING RC, 1989, J ANTIMICROB CHEMOTH, V24, P1
[8]  
NAKASHIMA M, 1992, DRUG EXP CLIN RES, V18, P371
[9]   INVITRO ACTIVITY AGAINST AEROBIC AND ANAEROBIC GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA AND BETA-LACTAMASE STABILITY OF RS-533, A NOVEL CARBAPENEM [J].
NEU, HC ;
CHIN, NX ;
SAHA, G ;
LABTHAVIKUL, P .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1986, 30 (06) :828-834
[10]  
SHIMADA J, 1994, DRUG EXP CLIN RES, V20, P241