polymorphs

Polymorphs are different crystalline forms of the same chemical substance. They share identical chemical composition but differ in the arrangement of molecules within the crystal lattice, producing distinct physical properties such as solubility, melting point, and stability. Polymorphism is distinct from allotropy (different structural forms of an element, such as graphite and diamond) and from stereoisomerism (different connectivity within molecules).

Polymorphs arise when molecules pack in alternative ways during crystallization or phase changes. The thermodynamic stability of forms depends on temperature and pressure; the most stable form at a given condition is the thermodynamically stable polymorph, while others are metastable. Metastable forms can persist because of kinetic barriers. Transformations may be triggered by heating, pressure, solvent changes, and often proceed by nucleation and growth of a new crystal.

In practice, polymorphism matters in materials science and pharmaceuticals. Different forms can have markedly different solubility and dissolution rates, affecting performance and bioavailability. They influence manufacturability, stability, and patent protection. Screening for all polymorphs during development and controlling crystallization are standard tasks; some forms may interconvert during storage, posing stability challenges for products and regulators require thorough characterization of known forms.

Examples include silica polymorphs such as quartz, cristobalite, and tridymite; ice polymorphs such as ice Ih; and pharmaceutical cases like ritonavir and carbamazepine where a new form prompted reformulation.

Analytical techniques used to study polymorphs include X-ray diffraction (single-crystal and powder), differential scanning calorimetry, thermogravimetric analysis, solid-state NMR, and vibrational spectroscopy, often combined with microscopy and computational modeling to predict stability and transformation pathways.