Date of Award
Master of Science in Engineering
Chemical and Paper Engineering
Dr. Kalyana Pingali
Dr. Andrew Kline
Dr. Brian Young
Dr. Raja Aravamuthan
Nanosmearing, ordered mixing, processshear, pharmaceuticals, tablet dissolution
Masters Thesis-Open Access
In the pharmaceutical manufacturing process, it is well known that flowing agents such as MgSt and Cab-O-Sil widely affect critical flow properties that influence the finished product performance of oral dosage tablets. Though the effects of flowing agents are beneficial to some extent, the sensitivity of the pharmaceutical formulation to process shearing of flowing agents during blending can be catastrophic which often results in product and batch failures. Hence it is essential to study the concentration of flowing agents and chemical nature of active pharmaceutical ingredients (API) with respect to applied process shear on formulations. Previous studies have shown that new nanostructures form as a result of mechanical stress, which alter the intermediate powder properties such as hydrophobicity, powder flow, and electrostatics. These in turn influence critical properties such as the tablet hardness, friability, and drug release. While the robust nature of formulation is determined by its ability to match standard processing speeds during compression, defects and batch failures are often mistakenly linked to a lack of a particular flowing agent in the blend. The greatest unknown during the processing of pharmaceutical powders is how the uniformity, extent, and amount of nanostructures formed at contact surfaces on the API and carrier particles influence critical properties. The primary aim is to address this gap in a systematic fashion by focusing on the shear and scale dependence of lubrication and its impact critical blend performance. In the first stage of the research, the investigation sought to understand whether the formation of nanostructures was due to applied process shear. In the second stage, the incorporation of nanocharacterization techniques to characterize whether the change in flowing agent concentration affected the rate of formation of new nanostructures. Subsequently in the third stage, the focus sought to correlate how nanodeposits influence powder density, particle porosity, and flow. Statistical analysis of the identified process input variables in correlation to key responses measured by pharmaceutical companies, in terms of product performance validation. This analysis was used to identify significant interactions and effects that may help scientists better understand the mechanistic rate behind the formation of nanosmears at contact particle surfaces during blending of pharmaceutical ingredients with flowing agents.
Kick, Casey F., "The Design of Nanostructures from the Blending of Flowing Agents Influencing Critical Properties of a Pharmaceutical Formulation" (2015). Master's Theses. 624.