Institute of Solid State Physics
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SS22 WS22 SS23 WS23 SS24 WS24 Guidelines for Master Students
Crystallization of active pharmaceutical ingredients in thin films Utilizing surfaces for nucleation and growth is often adopted as a mean to enhance crystallization. Certain surfaces can accelerate crystallization while other prevent it. On the other hand, constrains induced by the surface can trigger crystal growth on well-defined contact planes and thus along specific crystallographic directions i.e. texture or epitaxial growth can result. It has also been shown that surfaces can increase the crystallization rate when compared to the bulk. Furthermore, it has been shown for several organic semiconductors (organic molecules deposited on flat solid substrates as thin films a hundred of nm thick) that new polymorphs could be stabilized only close to the substrate (called “substrate induced polymorphs or SSPs). In this presentation, we report two cases of crystallization of active pharmaceutical ingredients (APIs) showing the ability of a solid surface to drastically change the outcome of the crystallization and thus modify the properties of the API. The first example concerns pyrazinamide (PZA), an API used in the treatment of tuberculosis, which possesses 4 polymorphic forms. Here, thin film deposition of PZA alone or with an additive (dimethyl urea –DMU-) shows the long-time stabilization of a metastable polymorph. The second example pertains to ketoprofen (an non-steroidal anti-inflammatory) for which amorphous solid dispersions could be achieved upon thin film co-deposition with polyethylene oxide. Film thickness and relative humidity proved to significantly influence the stability of those amorphous solid dispersions. |
