Estimating shelf-life of drugs in solution.

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.