Degradation studies drug substance

Oxidation. Oxidative studies are designed to reveal the primary oxidative degradation products due to oxidation. Oxidative degradants in drug substances and drug products normally are the result of reaction with molecular oxygen. As in the case of acid/base hydrolysis, appropriate controls are necessary. 

As described earlier, the contribution of water to the chemical degradation of drug substances is determined by the physical state of water. This is also the case for drug-excipient mixtures. Recent studies have shown that water present in excipients exists in various physical states, being either weakly or strongly adsorbed to the excipient. The physical state of water can affect drug degradation. 

Fig. 4.23. Cyclic DSC studies of the drug substance in Fig. 22 proving that the compound does not degrade at temperatures near or below 150°C.

The culmination of degradation studies is the preparation of a degradation pathway. A degradation pathway will show all the possible degradation products beginning with the drug substance. An example is shown in Figure 9. 

Probably the most important reaction mechanism is the liquid-mediated process (Hi). This is because most drugs, even those not particularly susceptible to hydrolysis, become less stable as the surrounding moisture levels increase. It has been speculated that degradation proceeds via a thin film of moisture on the surface of the drug substance [23], However, studies have indicated that the moisture is concentrated in local regions of molecular disorder, rather than in thin films [24], These regions that are crystal defects or amorphous areas, equate to the reaction nuclei of mechanisms (i) and (ii). 

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