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In this equation, Ea is the activation energy, that is the energy barrier which has to be overcome if reaction is going to occur when two

Figure 4.12 Log rate-pH profiles for the degradation of codeine sulfate in buffer-free solutions at several temperatures. The dashed line is the log rate-pH profile calculated from the Arrhenius equation.

Reproduced from M. F. Powell, J. Pharm. Sci., 75, 901 (1986).

reactant molecules collide. A is the frequency factor and this is assumed to be independent of temperature for a given reaction. R is the gas constant (8.314 J mol 1 K-1) and T is the temperature in kelvins. We can see from equation (4.51) that a plot of the log of the rate constant k against the reciprocal of the temperature should be linear with a gradient of -Ea/2.303R. Therefore, assuming that there is not a change in the order of the reaction as the temperature is changed, we can extrapolate plots of log k against 1/T to any required temperature and so determine the rate of breakdown at that temperature. We can also, of course, calculate the activation energy from the gradient of this plot. Figure 4.13 shows Arrhenius plots for the breakdown of the drug ciclosidomine at several pH values.

When it is clear from stability determinations that a drug is particularly unstable at room temperature, then of course it will need to be labelled with instructions to store in a cool place. This is the case, for example, with

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