Measuring and predicting pore size distribution of freeze-dried solutions

ABSTRACT

In this work, a novel procedure is presented for the measurement and prediction of pore size distribution of freeze-dried solutions in vials. A method based on segmentation is proposed for determining the size of the pores left by ice crystals, using images obtained by scanning electron microscopy. The original ice crystal size distribution is also predicted using a mathematical model based on balance equations. The model predictions and the results of the segmentation technique show a fairly good agreement. The proposed procedure could be used to efficiently estimate the resistance to mass transfer during drying and hence optimize the freeze-drying process.

KEYWORDS:

• Freeze drying
• image analysis
• mathematical modeling
• pore structure

Abbreviations::

• GIMP: GNU Image Manipulation Program
• GMP: Good Manufacturing Practice

Acknowledgments

This work summarizes and extends the two papers presented in the Proceedings of 6th European Drying Conference – EuroDrying’2017, Liège, Belgium, 19–21 June 2017: Arsiccio et al., Prediction of ice crystal size distribution during freezing of a pharmaceutical solution; Sparavigna et al., Measuring the size of pores by the segmentation of images from scanning electron microscopy.