A SIMPLIFIED METHOD FOR PREDICTING THE STABILITY OF PHARMACEUTICALS——THE INITIAL AVERAGE RATE METHOD

The initial average rate method for predicting the shelflife of pharmaceuticals is established by using the logarithm of the average rate of the initial stage of reaction (lg V0) instead of the logarithm of the rate constant (lg k) in the Arrhenius equation. It was found that the regression curve of lg V0 by plotting against the reciprocal of Kelvin temperature (1/T)is a contended well straight line. The linear equation so obtained is in accordance with Arrhenius' exponential equation and can be used to calculate the activation energy and shelflife at room temperature. Since k is not needed here, the calculation can be made without knowledge of the order of reaction. Thus this method is simple and convenient. Under each testing temperature only one analysis of initial stage sample is needed, so laboratory work and data treatment are greatly reduced.We applied this initial average rate method and also classical isothermal kinetic method to determine the stability of ascorbic acid solution, the activation energies of oxidation of ascorbic acid obtained were 18.60 and 18.50 kcal mol^-1 respectively; the shelflives at 20℃ were 125 and 111 days. The results agreed satisfactorily.This method was also used to determine the stabilities of solutions of arabinosylcytosine and streptomycin sulfate. The activation energies obtained were comparable to published values.