Yeh M K
Department of Clinical Pharmacy, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Drug Dev Ind Pharm. 2000 Nov;26(11):1221-6. doi: 10.1081/ddc-100100996.
The degradation kinetics of neostigmine were studied in aqueous solutions with varied pH from 1.5 to 9.9 under accelerated storage conditions. The stability of neostigmine in solutions containing propylene glycol or polyethylene glycol 400 was also investigated. The reaction order of neostigmine in these aqueous and solvent systems followed pseudo-first-order degradation kinetics. The degradation rates of neostigmine under various buffer concentrations within the investigated pH range were obtained. They indicated that the degradation was independent of the species of buffering agent. Maximum stability of neostigmine was determined at pH 5.0 buffer species conditions. The activation energy could be estimated from the Arrhenius plot as 15.72 kcal/mole. The half-life of 883.7 days was estimated at room temperature in 0.1 M, pH 4.9 acetate buffer solution (mu = 0.5). Ultraviolet (UV) irradiation at 254 nm of the neostigmine solutions in pH 4.9 acetate buffer showed an accelerated degradation in comparison with light-protected samples. Incorporation of propylene glycol into the neostigmine solution at pH 4.9 enhanced the stability; however, an adverse effect on the stability of neostigmine was noted when a polyethylene glycol 400 solvent system was used.
在加速储存条件下，研究了新斯的明在pH值为1.5至9.9的水溶液中的降解动力学。还研究了新斯的明在含有丙二醇或聚乙二醇400的溶液中的稳定性。新斯的明在这些水性和溶剂体系中的反应级数遵循准一级降解动力学。获得了在所研究的pH范围内不同缓冲浓度下新斯的明的降解速率。结果表明，降解与缓冲剂种类无关。在pH 5.0缓冲剂种类条件下测定了新斯的明的最大稳定性。根据阿仑尼乌斯图估计活化能为15.72千卡/摩尔。在室温下，在0.1 M、pH 4.9的醋酸盐缓冲溶液（μ = 0.5）中，新斯的明的半衰期估计为883.7天。与避光样品相比，pH 4.9醋酸盐缓冲溶液中的新斯的明溶液在254 nm处的紫外线（UV）照射显示降解加速。在pH 4.9的新斯的明溶液中加入丙二醇可提高稳定性；然而，当使用聚乙二醇400溶剂体系时，发现对新斯的明的稳定性有不利影响。
