Date of Award
January 2015
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Industrial and Physical Pharmacy
First Advisor
Elizabeth M Topp
Committee Member 1
Gregory T Knipp
Committee Member 2
Lynne S Taylor
Committee Member 3
Steven L Nail
Abstract
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.
Recommended Citation
Iyer, Lavanya, "High Resolution Mass Spectrometric Approaches To Study Protein Structure and Environment in Lyophilized Solids" (2015). Open Access Dissertations. 1416.
https://docs.lib.purdue.edu/open_access_dissertations/1416