Cross-Nucleation between d-Mannitol Polymorphs in Seeded Crystallization

Seeding the liquid of d-mannitol with its polymorphs (α, β, and δ) revealed several cases of cross-nucleation between polymorphs. Only seeds of the α polymorph (the structure of the intermediate thermodynamic stability and the fastest growth rate) yielded the same polymorph in new growth. Seeds of the δ polymorph yielded the α polymorph in new growth. Seeds of the β polymorph yielded the β polymorph in new growth at small undercoolings (a few degrees below its melting point); at lower temperatures, the α polymorph nucleated on β seeds and its amount in the product increased with decreasing temperature. Seeding with single crystals of the β polymorph (rods elongated along c) showed that the orientation of the seed crystal affected how much the seed polymorph could grow before cross-nucleation occurred. Cross-nucleation makes seeding ineffective for achieving polymorphic selectivity but is sometimes avoidable by choosing suitable crystallization conditions.