11:15 - 12:15 |
Understanding polymorph selection in nabumentone thin films at surfaces
Abstract: Polymorphs have a strong influence on many different properties including thermodynamic and chemical stability, processibility or dissolution which is turn directly impact pharmaceutical formulation and therapeutic actions. As such the preparation of specific polymorphs as well as their reproducibility is of crucial importance. In this work the polymorphic phase behaviour of nabumetone is studied. This model substance is a non-steroidal anti- inflammatory drug which has two known polymorphs. By employing various thin film fabrication techniques like spin coating, drop casting or dip coating homogenous layers form at substrate surfaces. Nabumetone was dissolved in different solutions like ethanol, toluene and tetrahydrofuran (THF) at different amounts. For sake of increase of surface area, nabumetone is processed together with a matrix forming substance, polystyrene. The thin film properties were examined using microscopy and X-ray diffraction.
The experimental results show that often form I results when films are prepared using slow techniques while spin coating induced the form II more frequently. Nevertheless, the substrate surface in unable to stabilize the form II of nabumentone so that a solid – solid phase transition into form I over time take place. In many cases the thin film formation results in the presence of the two form simultaneously which also is reflected in the morphological appearance consisting of spherulites and clusters.
In matrix co-processed samples a homogenous mixture of the two species is achieved while at relatively larger nabumetone content a phase separation exists. Here form II is developing only in small crystals while form I seems to be less affected. The results allow now draw conclusion on the polymorph selection during thin film fabrication as well as being hosted in a matrix which will be further investigated towards application relevant surfaces and matrices.