The Graphical Design Space for Primary Drying: Sources of Variability in the Dried Product Layer and Resistance and Impact on Cycle Design
Dr. Jayasree Srinivasan is a Research Scientist in the R&D laboratory at Baxter BioPharma Solutions in Bloomington, IN.
Dr. Srinivasan’s expertise includes formulation (solution and lyophilized) and process development of sterile products. When not working on client projects, Jay conducts research in the lyophilization area and has contributed to numerous publications in reputed journals. She has developed and led curricula for lyophilization courses for professional advancement.
An emerging approach to lyophilization process development is to construct a graphical design space for primary drying as an aid to process optimization. The purpose of this investigation is to further challenge the assumption in earlier work that the resistance of dried product layer, Rp, is constant and is independent of process conditions within the design space. Three model formulations of BSA were prepared and a conservative lyophilization cycle was conducted for each formulation to collect mass flow data and individual design spaces was then established. A series of lyophilization cycles was then conducted using process conditions that resided within the individual design space and the resultant product temperatures and Rp values were compared. This presentation discusses the variability in the Rp of the formulations and the relationship between the sublimation rate and Rp.
- Is Rp the same within the design space of a formulation regardless of the process parameters used during primary drying?
- How is Rp impacted by the formulation components?
- How does Rp correlate with sublimation rate during primary drying?