Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/18948
Title: | Thermally Stable Human Type 5 Adenovirus through Spray Drying: Storage Efficacy and Process Optimization |
Authors: | LeClair, Daniel |
Advisor: | Thompson, Michael Cranston, Emily |
Department: | Chemical Engineering |
Keywords: | spray drying;viral vector;vaccine;adenovirus;thermal stabilization;optimization;glass transition;vitrification |
Publication Date: | 2016 |
Abstract: | This thesis investigates enhancing the thermal stabilization of a human type 5 adenoviral vector (AdHu5) through spray drying. The spray drying process was used to dry and effectively immobilize the AdHu5 within a mixture of carbohydrate or amino acid excipients into a powder form, resulting in significantly increased thermal stabilization of the viral vector. Spray dried powders were characterized by scanning electron microscopy, differential scanning calorimetry, Karl Fischer titrations, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) to identify the effects of temperature and atmospheric moisture on the immobilizing matrix. The best performing spray dried powder in terms of thermal stability consisted of an excipient blend of mannitol and dextran. Response surface methodology was employed to optimize production of these mannitol/dextran powders; measured responses were those relevant to industrial processing of a therapeutic material, namely powder yield for maximizing quantity, particle size for maximizing production of inhalation-deliverable powders, and adenoviral vector response for minimizing the loss of therapeutic activity. The spray drying process parameters of inlet temperature, spray gas flow rate, liquid feed rate and solute concentration in the feed were optimized resulting in a powder yield of 90%, percentage of ideally-sized particles of 50% and a near-zero viral vector titre loss of 0.25 log loss median tissue culture infectious dose (TCID50). The spray dried mannitol/dextran powders proved to have exceptional thermal stability during long term storage as minimal viral vector activity loss was observed when stored at 20°C for 90 days at low relative humidity (0.7 ± 0.3 log TCID50) in comparison to the liquid control which exhibited complete activity loss under the same storage conditions. Furthermore, viral activity of mannitol/dextran powders was retained over short term exposure (72 hours) to temperatures as high as 55°C whereas the liquid control expectedly lost all AdHu5 activity after 30 minutes. Overall, this work provides a guideline for the production of thermally stable powders and active biopharmaceuticals, such as AdHu5 vectors for vaccine applications, using the spray drying process. |
URI: | http://hdl.handle.net/11375/18948 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
leclair_daniel_a_201602_masc.pdf | Main article | 3.8 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.