Lyophilization of Block Copolymer-Based Pharmaceuticals

Interdisciplinary Areas: Engineering-Medicine

Project Description

Block copolymer (BCP) nanoparticle formulations are gaining popularity in pharmaceutical industry because of their versatility, and ease of preparation at scale. In most basic/preclinical research studies in which drug-loaded BCP nanoparticles are explored, as-prepared formulations are used for immediate characterizations. However, for clinical applications, long-term storage is a critical issue. This is especially relevant to systems in which the active pharmaceutical ingredient (API) is a small-molecular drug that can diffuse out of the carrier system over time. A common approach to address this issue is to lyophilize the formulation. Unfortunately, BCP nanoparticles are difficult to successfully lyophilize, because their self-assembled nature makes them susceptible to structural rearrangements during cryogenic processes. Previous approaches to optimize lyophilization processes have been predominantly trial and error. The present project will attempt to unveil hitherto unknown molecular-level mechanisms by which BCP nanoparticles undergo structural changes during the freezing, drying and rehydration processes and thereby develop an understanding of how molecular and process parameters influence the structural behavior of BCP nanoparticles during the lyophilization process. Experimental approaches will be developed and taken to achieve this goal. The Fellow will also be given opportunities to participate in the LyoHUB activities and interact with representatives from pharmaceutical manufacturers.

Start Date


Postdoc Qualifications

Candidates are expected to have educational backgrounds in polymer/materials science, chemical engineering, physical pharmacy and/or related technical fields. Specifically, experiences in polymer synthesis, nanomaterials characterization (electron microscopy and scattering) and/or pharmaceutical formulations are highly desirable. Fluency in written and spoken English is mandatory. The Gilberth Fellow is expected to independently work in Purdue University laboratories with the guidance of the above Co-Advisors.


You-Yeon Won, Professor, Davidson School of Chemical Engineering, College of Engineering, Email:
Alina A. Alexeenko, Professor, School of Aeronautics & Astronautics, College of Engineering, Email:
External Collaborator
Qi (Tony) Zhou, Associate Professor, Department of Industrial & Physical Pharmacy, College of Pharmacy, Email:
A. P. Patel, C. R. Schorr, D. Viswanath, K. Sarkar, N. J. Streb, V. J. Pizzuti, R. Misra, J. Lee, Y.-Y. Won, "Pilot-Scale Optimization of the Solvent Exchange Production and Lyophilization Processing of PEG-PLA Block Copolymer-Encapsulated CaWO4 Radioluminescent Nanoparticles for Theranostic Applications", Industrial & Engineering Chemistry Research 60(19), 7081-7096, 2021 (DOI: 10.1021/acs.iecr.0c05852).
H. C. Kim, M. V.  Suresh, V. V. Singh, D. Q. Arick, D. A. Machado-Aranda, K. Raghavendran, Y.-Y. Won, "Polymer Lung Surfactants", ACS Applied Bio Materials 1(3), 581-592, 2018 (DOI: 10.1021/acsabm.8b00061).
JM Srinivasan, GA Sacha, V Kshirsagar, A Alexeenko, SL Nail, "Equipment Capability Measurement of Laboratory Freeze-Dryers: a Comparison of Two Methods", AAPS PharmSciTech 22(1), 1-6, 2021.
N Adhikari, T Zhu, F Jameel, T Tharp, S Shang, A Alexeenko, "Sensitivity Study to Assess the Robustness of Primary Drying Process in Pharmaceutical Lyophilization", Journal of Pharmaceutical Sciences 109 (2), 1043-1049, 2020.
TT Mutukuri, NE Wilson, LS Taylor, EM Topp, QT Zhou, Effects of drying method and excipient on the structure and physical stability of protein solids: Freeze drying vs. spray freeze drying", International Journal of Pharmaceutics 594, 120169, 2021.