State and Polymorphism in Solid Drugs

Many drug substances exhibit polymorphism. Each crystalline state has a different ground-state free-energy level and a different chemical reactivity. For example, ramified crystals of 5-nitroacetylsalicylic acid are more susceptible to hydrolysis than are column- 

The stability of drugs in their amorphous form is generally lower than that of drugs in their crystalline form, because of the higher free-energy level of the amorphous state. The relationship between degradation rate and crystallinity determined from heats of dissolution for 13-lactam antibiotics such as sodium cefazolin indicates that a drug with low crystallinity tends to have decreased chemical stability.413 

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