Supercritical carbon dioxide spray drying for the production of stable dried protein formulations

The main goals of this thesis are to understand the supercritical carbon dioxide (scCO2) spray drying mechanisms and parameters that influence the stability of proteins, to evaluate the excipients to stabilize protein formulations during scCO2 spray drying, and to study the scalability of the scCO2 spray drying process. For this study, lysozyme and myoglobin were used as model proteins. More specifically, the detailed aims are as follows: 1) to study the scCO2 spray drying parameters (i.e., pressure, protein solution and CO2 flow rate, feed volume) without the use of organic solvents, in order to produce dried protein formulations with minimal residual water content in a single drying step, 2) to evaluate the scalability of the scCO2 spray drying process, 3) To gain fundamental insight into the effect of the CO2 spray drying parameters at sub- and supercritical conditions (65-130bar and 25-50°C) on the stability of myoglobin, 4) to understand the effect of the CO2/water interface and pH shift on heme destabilization and aggregation in myoglobin solutions using a gas bubbling method at atmospheric conditions, 5) to evaluate the influence of pharmaceutical excipients on the stability of myoglobin in terms of heme binding and aggregation during scCO2 spray drying.The Royal Thai Government ScholarshipDrug Delivery Technolog