When to Choose a Metastable Crystal Structure for Development?

Question

Accepted Answer

• The solubility and bioavailability of stable crystals are too low

• A fast-release agent with a high dissolution rate is required

• Polycrystalline forms also exhibit different mechanical properties, such as hardness, powder fluidity, compressibility, and bonding strength. A well-known example is Acetaminophen, where the thermodynamically stable form (monoclinic form 1) cannot be pressed into a stable tablet. In contrast, metastable form 11 (orthorhombic form) can be pressed because it exhibits more favorable properties in terms of plastic deformation. In rare cases, this may lead to a decision to develop metastable forms.

• Manufacturing difficulty

• IP issues

• Chemical instability of thermodynamically stabilized crystals due to topological chemical factors