The Purdue College of Pharmacy is pleased to honor and recognize the outstanding research and scholarship generated by our faculty each month. This month we highlight Drs. Elizabeth Topp, Professor of Industrial Pharmacy and Tony Zhou, Assistant Professor of Industrial and Physical Pharmacy. Their recent publication, “Effects of drying method and excipient on structure and stability of protein solids using solid-state hydrogen/deuterium exchange mass spectrometry (ssHDX-MS)”, can be read in International Journal of Pharmaceutics (August, 2019; DOI: 10.1016/j.ijpharm.2019.118470). The study was conducted with PhD student in IPPH, Nathan Wilson.
Almost half of the pharmaceutical biological products are formulated into solids to improve their stability. Producing these solids via traditional freeze drying has many disadvantages including long cycle time (>48 hours), batch processing and low energy efficiency. Innovative technologies such as spray drying have been explored for producing solid powder forms of biologicals. These include Exubera, an inhalable insulin product, and Raplixa, a blend of thrombin and fibrinogen powders. Spray drying is a continuous process with high throughput of tons per hour. In addition, it enables a degree of particle to generate powders with improved flowability, dissolution and drug delivery performance. In this study, we examined the effects of drying method (freeze drying vs. spray drying) and excipient type on the physical stability of solid powders containing various proteins. The results showed that the stability of the protein is both process- and formulation-dependent. Solid-state hydrogen/deuterium exchange mass spectrometry (ssHDX-MS), a novel analytical method for proteins in solid powders, was shown to be able to detect subtle differences in protein structure between different formulations, which enabled prediction of long-term physical stability.
“When ssHDX-MS was first developed in the Topp lab, it was applied to look at freeze-dried formulations of protein drugs. We wanted to understand how the excipients interacted with the protein and how that in turn affected stability. This work represents an application of ssHDX-MS to spray-dried protein solids, a particular interest of the Zhou lab. Results reported in this article provide a fundamental understanding in physical stability of spray-dried protein products.”