hydrate

Sometimes water becomes a permanent guest inside a crystal rather than just clinging to its surface. A hydrate is a crystalline solid in which water molecules are built into the lattice at defined positions and ratios — for example a monohydrate has one water per drug molecule, a dihydrate two. The water is part of the structure, not just dampness.

Because that water occupies the lattice, the hydrate is a genuinely different solid from the dry (anhydrous) form, with its own melting behavior, density, X-ray powder diffraction pattern and, importantly, its own solubility and dissolution rate. Often the hydrate is more thermodynamically stable in water and dissolves more slowly than the anhydrous form, which can subtly change a product's release.

Hydrates form and convert depending on humidity and water activity, so a drug can interconvert between anhydrous and hydrated forms during wet granulation, drying, storage in humid climates, or even within a dissolving tablet. A hydrate is a type of pseudopolymorph (a solvate where the solvent happens to be water), and which hydration state is manufactured and maintained must be controlled and specified just like a polymorph.