(2ij) Innovating Pharmaceutical Technology through Prototyping, Process Analytics and Modeling

My overarching objective is to meaningfully contribute towards the development of science and technology. I believe that actively engaging in the scientific process, and teaching the next generation of scientists and engineers, are two important ways to enable my objective. This serves as my primary motivation to seek out a career in academics.

Previous Work

The title of my PhD was the ‘Modelling of Crystallization Processes: Batch to Continuous’. In the first part, a model was developed and validated to extract the particle size distribution from the Focused Beam Reflectance Measurement probe measured chord length distributions. In the second part, a population balance model-based framework was developed to estimate crystallization kinetic parameters through batch experiments. In the final part, a tanks-in-series based model framework was developed for modelling continuous crystallizers which allowed for tuning mixing behaviour to match the continuous crystallizer considered.

In my first Postdoctoral assignment, I worked on a proof of concept (PoC) project to develop a novel fluidic device as a continuous crystallizer. The research was purely experimental - involving design and manufacture of fluidic devices and testing them as continuous crystallizers. In my second postdoc, I worked on investigating the potential of using a novel fluidic device for the desulfurization of diesel through cavitation. Although the research was outside my focus on pharmaceutical technology, it was a valuable introduction to cavitation, fluidic devices and process intensification. The research was purely computational - involving the development of a first principles phenomenological model to yield fundamental insights about cavitation, and a system level model to capture the physics of desulfurization. In my third postdoc, I was awarded PROCESS - a Marie Skłodowska-Curie COFUND postdoctoral fellowship. The project involved the integrated development of a crystallization, filtration, washing and drying paradigm for the continuous processing of active pharmaceuticals ingredients (APIs) and was both computational and experimental.

Before PhD I also spent a couple of years working as a research assistant to investigate blending water with high energy liquid propellant fuels to reduce the operating temperature for torpedo propulsion. My task was to develop a simulation package to aid the experimentation. Besides my primary work during my postdocs, I was also involved in the design and development of a novel fluidic oscillator device. The research was both computational and experimental - involving the characterization of flow and mixing behavior of the fluidic device.

Ongoing Work

Process analytical technologies (PATs) enable process control through real-time monitoring of critical quality attributes and process parameters. I worked as a part of a team in developing novel PATs to enable real time monitoring and control of drying, milling and blending unit operations - key in the manufacture of solid dosage form pharmaceuticals. I am primarily responsible for experimentation, data analysis and reporting. The work resulted in a Nature Communications publication and three patents have been filed. Continuous crystallization is gaining traction due to several potential benefits over batch crystallization. I am working as part of a team in demonstrating the proof-of-concept of two continuous crystallizer prototypes and am primarily involved in experimentation, data analysis and reporting. Biological pharmaceuticals are often frozen for storage and need to be thawed in a regulated manner prior to use (e.g., for injecting into patients). I worked as part of a team for the automated end point detection of cell thawing and was responsible for experimentation and process control software development.

Future work

Shown in Figure A is my research focus until now and possible areas for further work. Based on my research experience and domain knowledge, I propose the following research projects.

Laser Enabled Monitoring and Control of Pharmaceutical Operations: Online measurement using laser-based techniques enable unexplored opportunities for monitoring and control of pharmaceutical unit operations. Apart from the ease of use, laser-based techniques are also relatively inexpensive, making them extremely viable in pharmaceutical development. As a co-inventor in the original patents, I hope to have the authority to work on this technology further and explore possible collaborations with the original contributors. The project would involve exploring the laser-based techniques for online monitoring, and developing sophisticated control protocols for pharmaceutical unit operations.

Continuous Crystallizer Prototype: One major conclusion of my PhD thesis, obtained through modelling, was that continuous crystallizer with increasingly plug flow like mixing behavior could potentially provide smaller particle sizes, narrower size distributions, and a faster response to step changes (i.e., better for process control). Additionally, plug flow crystallizers also afford the benefits of higher heat transfer rates due to increased surface area to volume ratios. The project itself would involve the crystallizer prototype development, adding functionalities like fouling onset detection and heat transfer, optimizing crystallizer design and developing control protocols.

Heat Transfer Enabled Models for Exothermic Crystallization: In some API systems (e.g., Ibuprofen), crystallization is highly exothermic, which invariably limits the operating space - especially for cooling crystallization. Mitigation strategies include the efficient removal of heat from the system and/or controlling the heat release through milder crystallizing conditions. Design and scale up of such systems would require accurate estimates of heat generation rates to design for efficient heat removal. The project would involve combining heat transfer models which include the thermal inertia of the crystallizer, with the population balance and mass balance equations typically used to model crystallization processes.

Other promising areas of research are ‘Fouling Mechanisms in Crystallizers’ and ‘Extracting Particle size from Image Analysis’. My research experience spans a mix of both modeling and experimentation in the development of pharmaceutical technology. I also have extensive experience in working as part of a team - a skill which I feel is essential in todays multifaceted research environment.

Teaching Interests

The most important direct teaching experience I have had is giving a couple of lectures for a Masters’ level course - Pharmaceutical Engineering, at the Massachusetts Institute of Technology. I also taught a two-day introductory course – “Introduction to Computational Fluid Dynamics using Fluent” at the Vishwakarma Institute of Technology in India. One of the important experiences for learning to teach was the Kaufman Teaching Certificate Program conducted at the Massachusetts Institute of Technology. During the course, they introduced us to various concepts which would make us effective teachers, and included two teaching sessions which were reviewed by the instructor and peers.

Apart from a direct teaching experience, I also have mentored students in their projects. I was responsible for mentoring a graduate student which led to one publication under my supervision. Over the course of my academic career, I have also mentored three Master’s, three undergraduate summer interns and one undergraduate final year project. I was fortunate to be associated with extremely driven and passionate students – a quality from which I often drew inspiration. I have found that students are extremely keen on learning, and the best way to guide them is to ask them or train them to ask important questions, challenge them to find answers and reassure them in their abilities as researchers.

Teaching Philosophy

One of the most important principles to keep in mind the idea of having a growth mindset. Often times students may become demotivated from learning if they feel that they lack the capacity to achieve the learning objectives. This can result from several factors such poor course design, dismissive language and unnecessarily difficult assessments. In such a case it is important to convey to the students, that they are capable of achieving the objectives and laying a good path to enable them in their success.

Another important principle in teaching is scaffolding. In simple terms scaffolding implies introducing complex concepts with a progressive level of difficulty. With adequate scaffolding, the students are able to connect the dots which leaves them with a more enriched experience.

Formative assessments implies that students understanding is tested while they are learning the concepts. Including more formative assessments rather than the conventional route of having one or two major summative assessments (finals, mid-terms) has been shown to improve student’s learning experience. Formative assessments may be enabled through in class participation or through module-based problem sets.

It has been proven through various studies that active learning strategies improve students’ engagement during lectures. Active learning strategies such as think-pair-share, class poll, group discussions or in-class participation foster an enthusiastic learning environment. Additionally, with the technologies now available, implementing active learning strategies is becoming more and more accessible.

Finally, it is important to convey to students that their opportunity to succeed does not depend on factors like race, gender identity, sexual orientation and such. This message of equality should be reinforced by clearly communicating it in the course description and at the start of the course. Another way to promote inclusivity in learning is to introduce students to contributions made from researchers from diverse backgrounds with which they may identify.

Given my background, I am capable and am interested in teaching a wide range of undergraduate and graduate courses. Courses which I would most enjoy teaching would be Chemical Reaction Engineering, Applied Mathematics, Numerical Methods, Mass Transfer, Heat Transfer and Control Theory.