The Impact of Process Parameters on the Lyophilized Porous Micro-structure: A Case Study of Dextran.

Freeze-drying is used to prolong the shelf life of pharmaceutical formulations stored in vials. To achieve this, formulations are first frozen and then dried, yielding a porous product that can in some cases be stored even at ambient conditions. In this work, the effect of different process parameters on the properties of the porous micro-structure obtained when freeze-drying dextran solutions was studied. To characterize the pore sizes, the samples were imaged with scanning electron microscopy (SEM) and the images were manually analyzed to determine the pore size distribution. To study the robustness of such manual pore characterization methodology, a reliability analysis was carried out, which showed that defining a set of guidelines leads to comparable pore size distributions among multiple participants conducting the analysis. The pore characterization methodology was then applied to products that were freeze-dried under different conditions. Higher dextran concentrations and higher cooling rates were found to lead to predominantly smaller pore sizes and longer primary drying. The conclusions of this work complement the existing literature in demonstrating the robustness of the manual pore size analysis and give valuable insight into the link between the micro-structure formed during the freezing of dextran solutions and the drying performance.