Nucleation of One Polymorph by Another Lian Yu, School of Pharmacy and Dept of Chemistry, University of Wisconsin - Madison D-mannitol
δ α
ROY
c 100 μm
c
Contrary to standard view, crystallization is not always defined by the initial nucleation. In each of the systems shown to the left, the fastnucleating structure grows slowly, allowing a fast-growing structure (new polymorph) to nucleate on it and dominate the product. The phenomenon expands the classes of nucleation:
100 μm
Heterogeneous nucleation of a crystalline phase
Carbamazepine/Nicotinamide
10
log J α/δ , s-1m-2
9
Homogeneous nucleation (multiplied by 1x10230)
Cross-nucleation
8
12 11
Primary heterogeneous nucleation
7 6
10 9
Growth-front nucleation
5 104
106
108
110
T , oC
112
Induced by crystals of Induced by partially the same crystals of the composition (e.g., same composition hydrate on anhydrate)
13
8 114
log N , s-1m-3
Phenobarbital
Induced by foreign particles (composition fully different)
and the same phase (e.g., “growth-front nucleation” in polycrystalline growth)
Cross-nucleation has very different kinetics from other types of nucleation. Data shown are for D-mannitol
and a different phase “Cross-nucleation between polymorphs”
Initial phase is growing. New phase must grow faster, can be more or less stable
Initial phase is not growing. New phase must be more stable, can grow at any rate
