I&EC 39 |
| A large number of substances, including high-value added pharmaceutical products, crystallize in more than one distinct crystal structure. These structures termed polymorphs, display different physical properties (solubility, dissolution rate, crystal form, density, compressibility, etc.) and consequently pharmacological activities. Regulatory pressure for the development of consistent production processes, dictates the need for a better understanding of all the crystallization steps involved in the process. Primary nucleation has been appreciably clarified since Ostwald advanced his “Rule of Stages” more than a hundred years ago, which stated that the stable morph has the lowest solubility and yet the form of higher solubility nucleates spontaneously first. Various works have showed that this rule does not apply to all systems and why it does not. The picture, however, is not as clear for the case of Secondary Nucleation. This work will attempt to clarify it. The work involves two stages: an experimental and a modeling one. The experimental part utilizes the polymorphic L-glutamic acid, which has two morphs: the stable beta morph and the unstable alpha morph. Solutions of L-glutamic acid were prepared at different supersaturations These solutions were not nucleating spontaneously. However, when seeds were introduced secondary nucleation was observed. The morphicity of the resulting new crystals was determined and was compared with that of the seed. The results were sometimes unexpected. The objective of the modeling part is to explain those results. The current models of secondary nucleation, i.e. Contact Secondary Nucleation (CSN) and Embryos Coagulation Secondary Nucleation (ECSN), which have been developed for single systems, were extended to supersaturated solutions of polymorphic systems. Independent embryo size distributions for each morph in a polymorphic system were identified. As the supersaturation increases, the distributions of embryos of the different morphs shift, affecting thus the outcome of the secondary nucleation. |
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Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix
IEC Poster Session
Division of Industrial & Engineering Chemistry |