(81e) Imaging and Analysis of Lyophilized Structures By Micro-Computed Tomography

Lyophilization, better known as freeze drying, is a key technology for manufacturing shelf-stable pharmaceuticals such as injectable antibiotics, monoclonal antibodies, antibody-drug conjugates and vaccines. The lyophilization process can be divided into three main phases: freezing, primary drying, and secondary drying. Optimization of the freeze drying process requires a robust understanding of each stage of the process. For instance, the microstructure of the drug product depends on both the drug formulation and freezing process. The product microstructures in turn determine key parameters for both the primary and secondary drying stages, as well as the final appearance and properties of the dried drug product.

Microcomputed tomography (micro-CT) scanning is a powerful imaging technique, used to resolve 3D volumetric structures at resolutions as fine as 0.5μm. This is sufficient resolution to shed light on the microstructures that result from the lyophilization process. However, only a handful of studies have been published which used micro-CT scanning to image lyophilized structures, and few quantitative descriptions of the observed microstructures are given. In this work, I will present a more thorough geometric characterization of lyophilized mannitol and sucrose, including features such as porosity, tortuosity, and pore size distribution. This analysis will be carried out by developing a robust image processing procedure, using open source tools written in the Julia programming language, for the manipulation and analysis of micro-CT scans. The open source nature of the computational tools will make these tools more accessible to other researchers as well.

In future work, geometric parameters of the microstructure may be related to controllable parameters (e.g. freezing process, drug formulation) and useful macroscale parameters (e.g. mass transfer resistance, reconstitution time), allowing effective estimation of macroscale parameters without the need for lengthy process experiments.