Ph

Figure 4.9 Log rate-pH profile for the degradation of codeine sulfate in buffer-free solutions at 60°C.

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

A plot of kobs against [OH-] has a gradient of kOH- and an intercept of k0.

From a graph of the above data,

[H2PO-/BT], will have an intercept at [H2PO-/BT] = 0 equal to kHPO2-. Furthermore, the k' value at [H2PO-/BT] = 1 is the other catalytic coefficient, kH PO-.

The degradation of codeine is particularly susceptible to the effects of buffers. Its hydrolysis rate in 0.05 mol dm-3 phosphate buffer at pH 7 is almost 20 times faster than in unbuffered solution at this pH, so this is a good drug to use as an example of the determination of the influence of buffer components on the breakdown rate.

In phosphate buffers of neutral pH, the major buffer species are H2PO- and HPO4-, either of which may act as a catalyst for codeine degradation. To find out which of these is the stronger catalyst, we can treat the experimental data in the following way. In neutral pH solutions we can write the following expression for the observed rate constant, kobs = k0 + kH2pc;[H2PO-] + kHPO4-[HPO4-]

[H2PO4]

0 0

Post a comment