Size Exclusion PEGylation Reaction Chromatography Modelling
Kapadi, A. N. (2006). Size Exclusion PEGylation Reaction Chromatography Modelling (Thesis, Master of Engineering (ME)). The University of Waikato, Hamilton, New Zealand. Retrieved from http://hdl.handle.net/10289/2504
Permanent Research Commons link: http://hdl.handle.net/10289/2504
Size exclusion PEGylation reaction chromatography was investigated using a modeldeveloped by Fee (2005). Column dispersion was neglected and the PEGylationreaction was modelled as second order. The model allowed up to four PEG groups tobe attached to a protein and accounted for succinic acid hydrolysis from activatedPEG. The model was adapted to simulate a-lactalbumin PEGylation and succinicacid hydrolysis from activated PEG in a batch stirred tank so rate parameters fromstirred tank kinetic experiments could be obtained and the model verified. The modelwas solved using finite differences and simulations run in Matlab. The effect ofreaction parameters such as timing, length and concentration of PEG and proteininjection, reaction rates, and model resolution on model simulation results wasexplored.In the size exclusion PEGylation simulations it was found that increasing proteinconcentration increased MonoPEG concentrations and increased the ratio ofMonoPEG to starting protein feed concentration. Increasing PEG pulse length andstarting PEG concentration initially increased MonoPEG concentration and productratio until all protein had been PEGylated at which point MonoPEG concentration theproduct ratio levelled out. Increasing PEG hydrolysis rates did not affect the amountof MonoPEG produced but reduced the activated PEG concentration and increasedsuccinic acid concentration. Optimal conditions for producing MonoPEG were foundto be equal concentrations of PEG and protein, with the PEG injection length twice aslong as the protein injection, and the PEG injection done immediately after the proteininjection.
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