2008 NSTI Nanotechnology Conference and Trade Show - Nanotech 2008 - 11th Annual

Partnering Events:

TechConnect Summit
Clean Technology 2008

Nanoscale Aspects of Pharmaceutical Materials

Y. Yang, P. Schields, L. Brostrom, P. Tishmack, R. McClurg, I. Ivanisevic, S. Bates, J-O. Henck, D. Engers
SSCI, An Aptuit Company, US

Keywords:
nanoscale, pharmaceutical materials, drug, characterization

Abstract:
It is estimated that 40% of the drug candidates currently in development pipelines and approximately 60% of the new compounds identified in discovery by approaches such as high-throughput screening are poorly water soluble. These compounds often require non-conventional formulation, processing and control strategies, and are frequently abandoned early in discovery. Nanoparticles and amorphous solid dispersions with microstructure formed by each component are good examples of enabling technologies for successful development of these compounds. At SSCI, a broad range of characterization techniques, such as light scattering, a range of microscopy techniques, x-ray diffraction, thermal analysis, solid-state nuclear magnetic resonance spectroscopy, and vibrational spectroscopy, are applied to facilitate understanding of the solid-state properties of crystalline polymorphs, salts, co-crystals, amorphous and disordered crystalline materials. This understanding and the experiments performed to generate these materials are used to identify materials with improved properties, including increased solubility. Regardless of the composition or intended use, materials with nanoscale attributes (e.g., particle size and microstructure) have the potential to display dramatically different and potentially useful chemical and physical properties imparted by surface interactions rather than by the macroscopic properties of the bulk. To better understand these material properties, we have coupled experimental and computational approaches to assist clients in reaching developability decisions earlier and with less material available. Building from the molecular scale, nanoparticles can be described as clusters of a few hundred to a few thousand molecules within a nanometer-sized solid, and in some cases, can be obtained by careful control of a solidification process. Alternatively, comminution, jet- or wet-milling techniques are used to reduce larger micron-sized solids to the nanoscale. Though the desired outcome of the later is the reduction of particle size to dramatically increase the surface area for dissolution, these processes can introduce defects into the solid structure. Analysis of the physical attributes, such as crystallite size, by Rietveld refinement of x-ray powder diffraction (XRPD) data can be used to compliment particle size determined by light scattering and electron microscopy. In the case of amorphous dispersions, there is growing interest in the relationship between the local order formed when drug and polymer molecules are mixed and the physical stability of these high-energy systems. For instance, a single glass-transition temperature determined by DSC for mixtures of two amorphous components has been interpreted as evidence that the two components are intimately mixed. However, recent analysis by XRPD has refuted this notion reinforcing the limits of sensitivity for making such claims and inferring that the length-scale of the domains of the individual components may have important physical stability implications. To this end, this presentation compares conventional and novel approaches for characterizing the physical properties of nanoscale pharmaceutically-relevant materials.


Nanotech 2008 Conference Program Abstract