Structural Investigations of Crystal Surfaces and Chemical Stability

2 Structural Investigations of Crystal Surfaces and Chemical Stability 

Chemical stability of pharmaceutical materials is a key aspect to ensure product safety. Although the chemical pathway of API degradation is typically studied and understood during the process of drug product development, there are cases where an unexpected increase in degradation rate has been attributed to a change of API particles properties, formulation, or processing alterations. 

Solid-state reactions usually require higher-activation energy compared to solution-state reactions due to the constraints of the crystal lattice. What is very often underestimated is the negative effect of the bulk lattice on the crystal surface. It can be expected that the degradation-sensitive reaction sites in the solid state will be more vulnerable on the crystal surface, where particles are in direct contact with the external environment. Clearly environmental factors such as temperature, humidity, and interactions with excipient particles may have a negative effect on the rate of chemical degradation occurring on a crystal surface. Stractural information on the particle surfaces can potentially provide additional information about the exposure of reaction-sensitive sites. 

This effect has been demonstrated for the surface chemistry of aspirin. Hydrolysis is a well-known degradation chemical reaction occurring for aspirin (Fig. 6.16). 

FIGURE 6.16 Degradation reaction of acetyl salicylic acid due to hydrolysis. 

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