The Influence of Local Microstructure Inhomogeneities on Local Drying Kinetics during Freeze-Drying

Pharmaceutics. 2022 Oct 7;14(10):2132. doi: 10.3390/pharmaceutics14102132.

Abstract

Freeze-drying is a gentle drying technique to dry high value products, such as pharmaceuticals, without impacting the quality of the product. However, this method is very time and cost intensive. It is known that larger pores reduce the duration of primary drying due to facilitated mass transport. However, next to the pore size, other structural parameters exist whose influence on drying kinetics is still unknown. Therefore, the aim of this article is to investigate the influence of the microstructure (pore size, shape and orientation) on local primary drying kinetics. In the study, freeze-drying experiments on maltodextrin and sucrose solutions (c1 = 0.05 and c2 = 0.15 w/w) were carried out in a lyomicroscope. Two-dimensional images were recorded during the whole drying process and in the dry state and analyzed on the movement of the sublimation front, pore size, orientation and shape. Different microstructures were created by using different freezing parameters, namely two different cooling rates and solid concentrations. It could be shown that for pores with a high aspect ratio, the pore orientation was more important for the drying kinetics than the pore size, while for pores with a lower aspect ratio the pore size was the decisive parameter.

Keywords: drying kinetics; freeze-drying; image analysis; lyomicroscope; maltodextrin; microstructure; sucrose.