[D [D0 expkf

where [D]0 is the initial concentration of the drug. From these equations, the degradation rate is seen to be proportional to drug concentration. Most drug degradation kinetics in solutions conform to apparent or pseudo-first-order kinetics, and the data are summarized by recording the apparent first-order rate constants, k.

The rate equations for pseudo-zero-order kinetics are

In this case, the drug degradation rate is independent of drug concentration. A specific example of pseudo-zero-order kinetics can be seen with drug degradation in suspensions. If a drug degrades in the solution phase of a suspension according to pseudo-first-order kinetics but is stable in the solid phase of the suspension, the degradation rate is proportional to the drug concentration in solution. Because the drug concentration in solution is given by the saturated solubility [S] and is maintained constant while drug in excess of its solubility is present, the amount of total drug remaining, M, decreases according to a pseudo-zero-order equation:

Degradation of aspirin in suspension has been reported to follow zero-order kinetics (Fig. 7).249 Simple Pseudo-Second-Order Reaction k k D + A ->P or 2D P

The rate and concentration changes when drug D reacts with a reactant A are given by

Figure 7. Time course of degradation of aspirin in suspension (pH 3.0), showing apparent zero-order behavior and a dependency on temperature but no dependency on particle size. Particle size: 60 mesh; O, 100 mesh. (Reproduced from Ref. 249 with permission of the American Pharmaceutical Association.)

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