Newton D W, Miller K W
Am J Hosp Pharm. 1987 Jul;44(7):1633-40.
The use of pseudo-first-order chemical reaction kinetics and Arrhenius thermodynamic principles in estimating the effect of temperature on shelf-life of drug solutions is described. The degradation of many drugs in aqueous solutions occurs by hydrolysis. Equations using activation energy of the hydrolysis reaction (Ea) derived from Arrhenius principles, rate constants, and temperature are used to illustrate the exponential decrease in drug shelf-life proportional to an arithmetic increase in temperature. Use of the Q value, a factor based on Ea, rate constants, and temperature change, is described. The range of Ea for pharmaceutically important degradation reactions is relatively limited; thus, near room temperature, Q values of 2-5 can be used to estimate the effect of temperature change on shelf-lives of drugs in solution. To conservatively estimate effect on shelf-life when Ea is not known, a Q value of 2 is used to predict the increase in shelf-life obtained by decreasing storage temperature, and a Q of 5 is used to predict decrease in shelf-life from increasing the temperature. Sample calculations are used to show the application of equations based on these principles to practical temperature-dependent problems regarding shelf-life. Given information about shelf-life at a certain temperature, pharmacists can estimate safe shelf-life under other temperature conditions by using these equations.
描述了使用伪一级化学反应动力学和阿伦尼乌斯热力学原理来估计温度对药物溶液保质期的影响。许多药物在水溶液中的降解是通过水解发生的。利用从阿伦尼乌斯原理推导出来的水解反应活化能（Ea）、速率常数和温度的方程，来说明药物保质期与温度算术增加成比例的指数下降。描述了基于Ea、速率常数和温度变化的Q值的使用。药学上重要的降解反应的Ea范围相对有限；因此，在接近室温时，Q值为2 - 5可用于估计温度变化对溶液中药物保质期的影响。当Ea未知时，为保守估计对保质期的影响，Q值为2用于预测通过降低储存温度获得的保质期增加，Q值为5用于预测因温度升高导致的保质期缩短。示例计算用于展示基于这些原理的方程在关于保质期的实际温度相关问题中的应用。给定某一温度下的保质期信息，药剂师可以通过使用这些方程来估计其他温度条件下的安全保质期。
