Excipient phase behavior in the freeze-concentrate

Abstract

Development of robust protein formulations is of paramount importance to the pharmaceutical industry. Traditionally, the development of such products has been an empirical exercise. Efforts should be taken to transition lyophilization R&D away from an empirical exercise and towards an evidence-based science. This thesis will (i) document the pH shift in frozen buffer (sodium phosphate) - sugar (sucrose or trehalose) systems at different buffer and sugar concentrations, (ii) evaluate solute crystallization in these frozen systems using synchrotron radiation, (iii) investigate the thermal behavior (glass transitions) by differential scanning calorimetry with the goal of identifying the two freeze concentrate populations and, (iv) use IR spectroscopy to characterize the two populations and specifically the complexation between trehalose and the buffer components in the two populations.