Pharmaceuticals nucleation temperature

J Searles, J Carpenter, T Randolph. The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature-controlled shelf Journal of Pharmaceutical Sciences 90 860-871, 2001. 

The chemical and physical stability of amorphous pharmaceutical materials is controlled by the same basic factors as for crystalline materials [i.e., molecular structure (chemistry), purity (absence of catalysts, chemical reactants, or nucleating agents), molecular orientation (physical form), and molecular mobility (related to temperature)]. For any sample of a given molecular structure and purity, there will be more possible molecular orientations that occur in an amorphous sample than in a crystalline sample. Thus... 

The bioavailabihty, stability, solubility, and morphology of the pharmaceutical products are very influenced by polymorphs [2-7], therefore the control of the polymorphic crystalhzation is very important. The crystallization process of polymorphs and solvated crystals is composed of competitive nucleation, growth, and transformation from a meta-stable form to a stable form [4], Furthermore, the crystallization behavior is influenced by various controlling factors such as temperature, supersaturation, additives and solvents [8], In order to perform the selective crystallization of the polymorphs, the mechanism of each elementary step in the crystallization process and the key controlhng factor needs to be elucidated [8], On the other hand, we reported for L-Glutamic acid and L-Histidine system previously... 

Problems caused by polymorphism appear in many fields such as fine chemicals in industries (pharmaceuticals(7,2), foods, etc.), optical electronic materials(i), clathrate compounds(4) and biominerals(5). In crystallizations of these materials the crystallization behavior of the polymorphs is controlled first by basic operational conditions such as temperature, supersaturation degree, stirring rates. In addition to these basic factors, solvents, additives and guest molecules (in clathrate compounds) should be also considered as the important factors((5,7). The crystallization process of the polymorphs is composed of comp)etitive nucleation, competitive growth of polymorphs and transformation from metastable to stable form. Accordingly individual step should be investigated to clarify the crystallization mechanism of polymorphs. 

Hancock B, Shamblin S, Zografl G (1995) Molecular mobflity of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res 12(6) 799-806 James PF (1985) Kinetics of crystal nucleation in silicate glasses. J Non-Crystalline Solids 73(1-3) 517-540... 

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