High Resolution Mass Spectrometric Approaches To Study Protein Structure and Environment in Lyophilized Solids

Proteins comprise a growing class of therapeutics that is used to treat various diseases such as diabetes and cancer. However, intrinsic structural features such as the primary sequence and extrinsic factors such as pH, temperature, agitation and metal ions can promote instability that manifests as chemical degradation (e.g. oxidation, deamidation, hydrolysis) and/or physical degradation (aggregation, phase separation). Since several degradation pathways are accelerated by diffusion in solution, proteins are lyophilized to improve stability. The lyophilized formulation may still undergo degradation during manufacture and/or storage. The mechanism of protein aggregation in lyophilized solids is not well understood or predictable by conventional analytical methods such as solid-state Fourier-transform infrared spectroscopy (ssFTIR) and differential scanning calorimetry (DSC) and this poses challenges in rational formulation design.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Industrial and Physical Pharmacy

Year

2015

Author dc:creator

• Iyer, Lavanya

Contributors dc:contributor

• Elizabeth M Topp
• Gregory T Knipp
• Lynne S Taylor
• Steven L Nail

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/1416

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-2632