(631b) Measuring the Energetic Heterogeneity of Pharmaceutical Powders and the Effects On Powder Processing and Formulation

Most pharmaceutical solids are energetically heterogeneous.  This heterogeneity could be unintentional due to different crystal facets with different functional groups, co-crystal formation, impurities, defect sites, amorphous regions, or co-processed mixtures of materials.  Additionally, surface energy heterogeneity or homogeneity could be engineered to produce desired powder properties.  Therefore, it is often difficult or even misleading to characterize the surface energy of these materials with a single value.  Recent advances in Inverse Gas Chromatography (IGC) theory and applications have developed new methods for determining surface energy distributions for powders.  This relatively new approach now allows the direct measurement of dispersive surface energy at a specific surface coverage or determination of surface energy profiles over a range of surface coverages. 

EXPERIMENTAL

The current study investigates the surface energetics of various pharmaceutically relevant materials using IGC technology.  Finite concentration IGC experiments allow for the determination of surface energy distributions which more accurately describe the anisotropic surface energy for real materials.  Various materials, including Indomethacin (with different processing routes), mannitol (with different surface treatments), lactose (with different amounts of fines), and aspirin (different milling conditions) were studied.  The surface energy distributions were then correlated to powder performance properties including wet granulation, powder flow and dissolution behavior. 

RESULTS

The affect of processing route on the surface properties of partially amorphous Indomethacin has been investigated.  Quench-cooled, milled, and crystalline Indomethacin exhibited different surface energy profiles.  In particular, amorphous Indomethacin was energetically most heterogeneous.  Additionally, mannitol was studied to relate surface energy distributions to powder flow properties due to changes in surface chemistry. After surface treatment with a silanizing agent, mannitol showed a significantly more homogeneous and hydrophobic surface.  These differences were reflected in their powder flow characteristics and wettability during granulation.  Finally, the affect of milling was studied on aspirin powders.  Milling significantly increased both the average surface energy and surface energy distribution, thus resulting in faster dissolution behavior. 

CONCLUSIONS

Surface energy heterogeneity profiles were measured on a wide range of pharmaceutical materials including excipients and APIs.  Processing route, surface treatment, and milling conditions showed a dramatic affect on the surface energy values for these materials.  These changes in surface energy in turn showed a correlation with bulk power properties like powder flow, dissolution and wet granulation behavior.  Therefore, measuring and controlling surface energy values can be an important characteristic for engineering pharmaceutical powders with desired performance properties.