(671e) Nanostructural Interfaces of Additives on the API Surfaces Influencing Process Performance

The objective of this research is to detect and quantify the % extent of nanosmearing distribution of hydrophobic functional groups on multiple pharmaceutical particle surfaces during high shear mixing conditions of pharmaceutical formulations affecting the critical blend flow properties. Two sets of pharmaceutical blends were prepared by mixing 90% fast flo lactose as excipient, 9% micronized acetaminophen (Acetyl Para Amino Phenol - APAP) as Active Pharmaceutical Ingredient (API) and 1% hydrophobic Magnesium Stearate (MgSt) as lubricant at two shear rates of 100 rpm and 500 rpm in a v-blender. In the first stage, APAP particles from the two blend samples were studied under Raman Spectroscopy to detect and confirm the presence of hydrophobic functional groups of MgSt nanosmears and then to map the nanosmeared area distribution on the surface of multiple APAP particles. In the second stage, using Image-J histogram analysis, the Raman images of MgSt mapping on APAP particles were analyzed and the % nanosmeared area covered by the hydrophobic MgSt nanosmears on multiple APAP particles were quantified. For the first time in the field of particle technology, Raman Spectroscopy Mapping method was employed on the organic particulate matter to develop a novel methodology to quantify the presence and % extent of nanosmeared area distribution of hydrophobic MgSt additive on multiple particles. The results indicated that the applied process shear has a significant effect on the percentage area covered by MgSt nanosmears. The % nanosmeared area of MgSt on multiple APAP particles increased from 22% to 41% as the applied process shear during mixing increased from 100 rpm to 500 rpm. The increased nanosmeared area improved the powder blend flow properties. The nanosmears on APAP particles were found to be non-uniform and partially coated. A direct correlation between % nanosmearing area with applied process shear and powder cohesion was found.