Applying mechanical engineering to pharmaceutical research

Conducting research within the field of pharmaceuticals might be the last place you’d expect to find a mechanical engineer but Michael Olsen would prove you wrong.

Mechanical engineering professor Michael Olsen smiles as he poses in front of a wooden door. He is wearing a black collared shirt.
Olsen

Olsen, a professor of mechanical engineering (ME) at Iowa State University, is getting ready to begin his newest research project with his colleague Dennis Vigil, professor of chemical and biological engineering at Iowa State, for the pharmaceutical company Pfizer. For this newest project, which will begin later this year, Olsen, Vigil, and their research team will develop a computer model to assist Pfizer in predicting the behavior of ointment creams under the various manufacturing processes that they undergo, from emulsification in a homogenizer, to transport through pipes and valves in the manufacturing plant, to the packaging process.

“To assist in the development of this model, we will use data obtained by Pfizer on droplet size and population during homogenization as well as data that we will collect in our laboratory for droplet coalescence using a Taylor-Couette reactor,” said Olsen, who is also a researcher with Iowa State’s Center for Multiphase Flow Research and Education.

Olsen and Vigil will utilize various ME concepts and methods in this project including fundamental thermal sciences (fluid mechanics, thermodynamics, heat transfer), computer programming and manufacturing. This project will showcase the diversity of an ME’s skill set, according to Olsen. First, he said, it highlights the importance of the fundamental thermal sciences beyond what are viewed as the “traditional” areas of mechanical engineering (i.e. HVAC, heat exchangers, combustion, refrigeration).

“The fundamental thermal sciences are very important in the biomedical arena, such as pharmaceutical manufacturing, as in this project, medical device design for say artificial heart valves or ventilators, and even physiological processes in the human body, like blood flow and respiration,” said Olsen, adding that the project will help his ME students to understand how they might collaborate with chemical engineers, biomedical engineers and researchers from other fields in the future.

Olsen and Vigil’s research partnership with Pfizer first started about three years ago when Avik Sarkar, a scientist from Pfizer, visited the Iowa State University campus. Sarkar toured their lab and was interested in the multiphase flow research that Olsen and Vigil were conducting, specifically focused on Taylor-Couette flow. Sarkar realized that the work the Iowa State researchers were doing could be adapted to investigate the emulsions that make up topical ointment creams.

Dennis Vigil, professor of chemical and biological engineering, poses while wearing a blue collared shirt and a dark suit jacket.
Vigil

For their first collaboration the researchers investigated the effects of strain rate and temperature on phase separation in a petrolatum based topical ointment cream. The ointment consisted primarily of petrolatum (the main component in Vasoline) and polyproline glycol droplets that contain the pharmaceutical agent.  Pfizer wanted to know about the conditions under which this emulsion would break down into its individual components, a phenomenon known as phase separation, rendering the ointment useless, according to Olsen.

“We designed a temperature-controlled Taylor-Couette flow cell that would allow us to carefully control the strain rate and temperature imparted on the ointment and developed imaging techniques to visualize the onset of phase separation,” Olsen said.

Taylor-Couette flow is the flow generated in the annulus between two concentric cylinders when one or both of the cylinders are rotated. In their experiments, the inner cylinder was rotated.

“Because the Taylor-Couette reactor that we constructed has a very narrow annulus between the cylinders, the resulting flow has a nearly uniform shear strain rate, allowing us to easily investigate the effect of strain rate on the phase separation,” said Olsen. “From these experiments, we were able to determine the conditions under which the ointment was in danger of undergoing phase separation.”

In a second project, Iowa State and Pfizer utilized some of the same techniques they used in their first experiment to study phase separation in a mineral oil-based ointment. The success of these first two projects is what led them to come together for this newest effort. Olsen also acknowledged the work of two of his former graduate students, Hannan Nadeem and Arya Haghighat, for their contributions to these efforts.

The experimental and modelling techniques that the researchers are developing for this project could eventually be extended to other ointment formulations. Olsen said they might also apply the computer model they developed to future projects to perform droplet breakup and coalescence measurements at constant temperatures and strain rates in a Taylor-Couette reactor designed explicitly for this purpose.