(752d) Effect of Nanosmearing On the Rate of Nanostructure Formation in Individual Grains and Tablet Manufacturing

The influence of mixing order, flowing agent formulation, and compaction on tablet hardness, hydrophobicity, coating uniformity, extent of coating, micoporosity, mesoporosity, and nanoporosity was studied to understand how nanostructures affect bio-availability of the active pharmaceutical ingredient (API).  Multiple pharmaceutical formulations of both lubricated and un-lubricated blends were prepared and mixed in a v-blender under fixed shear and strain conditions to characterize the formation of microstructures and nanostructures on the API.  The changes in powder properties and surface topography throughout the various blends can be attributed to these formations of nanostructures, which was the focus of our study.  These nanostructures were characterized using gas absorption and Scanning Electron Microscopy (SEM) with Electron Dispersive Spectroscopy (EDS) mapping.  While the uniformity and extent of coverage on the API particle interface controls the powder flowability, only a fraction of the MgSt lubricant used in the flowing agent formulation coats the API surface and forms the nanostructure.  The powder flowability of the blends was quantified in a gravitational displacement rheometer (GDR), which showed that the flow index did improve when the extent of the coating area was increased.  However, the extent of coating for the Cab-O-Sil was non-uniformly distributed on the API and much weaker than MgSt, which can be attributed to the interaction between the coating and the API particle surface.  When tablets were produced on a rotary tablet press, mercury intrusion, gas absorption, and SEM imaging analysis software were used to characterize the size and distribution of the nanostructures formed.  The best flow properties in a blend were exhibited with a formulation consisting of 1% MgSt and 0.5% Cab-O-Sil.  The distribution or presence of Cab-O-Sil was seen to enhance the distribution and smearing of MgSt on the particle surface only when the Cab-O-Sil concentration did not exceed 0.5% of the formulation.  The variations in uniformity, extent of coating, and characteristic nanostructure formation in the powders are key parameters that influence tablet performance and bioavailability, which has wide applications for bio-medicine manufacturing.