POLYMORPHISM

The polymorphic form with the lowest free energy will be the most stable and other polymorphs will
tend to transform into it over time. Phase transformations can cause changes in crystal size in
suspensions and their eventual caking. Crystal growth in creams as a result of phase transformation can
cause the cream to become gritty. Similarly, changes in polymorphic forms of vehicles, such as
theobroma oil used to make suppositories, could cause products with different and unacceptable
melting characteristics.

SOLVATE AND HYDRATES

Crystals that contain solvent of crystallisation are called crystal solvates, or crystal hydrates when water
is the solvent of crystallisation. Crystals that contain no water of crystallisation are termed anhydrates.

With some solvates the solvent plays a key role in holding the crystal together; for example, it may be
part of a hydrogen-bonded network within the crystal structure. These solvates are very stable and are
difficult to desolvate. When these crystals lose their solvent they collapse and recrystallise in a new
crystal form.

AMOURPHOUS

Amorphous solids exhibit a higher energy state than crystalline solids, are inherently less stable and
have the potential for converting to the thermodynamically more stable crystalline form over time. In
addition, because of their higher molecular mobility they often show stronger chemical reactivity and
hence a faster rate of chemical degradation.

CO-CRYSTALS

co-crystals the other molecule is a crystalline solid rather than a liquid as in crystal hydrates. Co-crystals
differ from solid dispersions, which are physical mixtures of drug and a highly water-soluble carrier
molecule in micro-crystalline form; the aim is nevertheless the same to alter the physical properties of
the drug, for example to increase solubility or reduce hygroscopicity.

Co-crystals are designed to have a greater solubility and often lower hygroscopicity than the crystals of
the drug itself, but because they are metastable they may change their crystal form during storage.