Title: The genesis of content non-uniformity in high-shear wet granulation
Abstract: In this seminar, we present and discuss findings with the overall aim of moving toward a more predictive understanding of multi-component high shear wet granulation processes (HSWG) via an integrated experimental and computational study. While a large body of work in the literature has focused on single component granulation, there is very limited fundamental experimental analyses and granulation theory on the key physics that occur in multi-component systems. Moreover, the granulation/processing of multiple components offer several unique challenges compared to that of a single component system, and as a result, several of the complex mechanisms that need to be better understood are not applicable in single component systems (e.g. preferential wetting, segregation, drug migration – all of which lead to content non-uniformity in granules which in turn significantly affects product quality). To further understand the reasons and origins of content non-uniformity, three possible hypotheses were first postulated and then studied, that could be the underlying physical basis of content non-uniformity. Hypothesis 1: Preferential wetting of one formulation component by the binder during the wetting/nucleation stage due to different inter-facial properties of binder with formulation components. Hypothesis 2: Particle segregation during the dry mixing stage which would result in the enrichment of the powder bed surface by one component due to preferential contact with the binder. Hypothesis 3: drug migration due to the drug solubilizing in the binder fluid and leaching to the surface upon drying, followed by attrition during drying/sieving to the finer size fractions. The expected outcome of this work is to be able to decouple and quantify the effects of these underlying causes of content non-uniformity.
Dr. Ramachandran is currently Associate Professor and Chancellor’s Scholar at the Department of Chemical & Biochemical Engineering, Rutgers University, USA. He received his PhD in Chemical Engineering from Imperial College London which was followed by a postdoctoral position at MIT. Since then, he has established an independent and integrated research and educational program, at the interface of Particle Technology and Process Systems Engineering (PSE) whereby his group is developing efficient multi-scale mechanistic models, novel numerical/computational techniques and integrated control/sensing techniques to solve, simulate and control complex particulate processes across the particle – unit operation – flowsheet level, focusing on pharmaceutical, chemical and bioprocessing applications. He has published over 91 journal papers and has received the prestigious National Science Foundation CAREER award and two NIPTE Young Investigator awards. He was also awarded the 2015 Chemical Engineering Outstanding Faculty Award, the 2017 Rutgers New Brunswick Chancellor-Scholar Award and the 2018 Rutgers Board of Trustees award, which recognizes truly outstanding and highly promising scholars at the Associate Professor level. He was also recently awarded the AIChE PD2M Quality by Design for drug product award for contributions in the particle technology area toward drug product pharmaceutical manufacturing.