Massachusetts Institute of Technology
Department of Chemical Engineering





Continuous Pharmaceutical Manufacturing
Stabilization and Formulation of Biopharmaceuticals
Nucleation and Crystallization
Molecular Computational Methods for Reactive Processes in Complex Systems

Continuous Pharmaceutical Manufacturing

Currently, pharmaceutical products are manufactured primarily using batch processes, as has been the industry standard from the beginning.  There is, however, tremendous potential to transform the entire industry by producing these products via continuous manufacturing. Moving to continuous has the potential for huge increases in efficiency, flexibility, and quality. As part of the Novartis-MIT Center for Continuous Manufacturing, a major effort in the Trout Group, together with the Hatton Group, focuses on the development of new technologies to effect continuous pharmaceutical manufacturing.  These include continuous crystallization processes together with a variety of novel separations and final finishing processes that have the potential to transform pharmaceutical manufacturing.
The students and post-docs working on projects in continuous manufacturing include, Manju Sharma, Li Xi, Haitao Zhang, Nikhil Padhye, Sina Bonyadi, and Vibha Puri.

wide pipe

Stabilization and Formulation of Biopharmaceuticals

Biopharmaceutical, including antibodies constitute the most rapidly growing class of human therapeutics for the treatment of numerous indications, including cancer, chronic inflammatory diseases and infectious diseases.  One of the major problems encountered in biopharmaceutical therapies is the inherent instability of biopharmaceuticals to degradation processes, such as aggregation, oxidation, hydrolysis, and deamidation.  Our group has a major effort in developing a mechanistic and quantitative understanding of these processes, leading to new approaches to stabilizing biopharmaceuticals.
Part of our work involves developing a mechanistic understanding how therapeutic antibodies aggregate during long-term storage.  We employ molecular simulation tools in collaboration with experimental techniques to elucidate aggregation mechanisms and determine molecular engineering strategies for antibody stabilization. Lab members working in this area include Veysel Kayser, Neeraj Agrawal, Timothy Lauer, Fabienne Courtois, and Geoffrey Wood.

Nucleation and Crystallization

Solution crystallization is a commonly used technique in the pharmaceutical industry to separate and purify API’s (Active Pharmaceutical Ingredients).  Understanding of crystallization together with nucleation is primarily based on heuristics and rough macroscopic models.  We aim to better control these processes via the development of molecular-based understanding.  Such understanding has the potential to make rational the solvent selection process and design of crystallization processes and therein streamline pharmaceutical development.
Lab members working on crystallization include Haitao Zhang, Vilmali Lopez Mejias and Manju Sharma.  We are also collaborating with Prof. Allan Myerson, Department of Chemical Engineering, MIT.

  Malonic Acid Polymorph Transformation from α to ß form at 95 °C


Methodology Development

The Molecular Engineering Laboratory at MIT was founded to develop cutting edge molecular computational methods and apply these methods to address important industrial problems.  Thus, a major aspect of the work in the Trout Group involves new molecular computational approaches based on statistical mechanics and quantum mechanics.  We are pursuing a number of new approaches to find reaction coordinates in complex systems, including the ones described above.
Students and Post-docs working in this area include Michael Bellucci Geoffrey Wood.

We are also collaborating with Prof. Eric Vanden-Eijnden, Department of Mathematics and the Courant Institute at NYU and Prof. Giovanni Ciccotti, Department of Physics, University of Rome “La Sapienza.”

Last Updated: September 25, 2012