Mechanistic Modeling and Analysis of Thermal Radiation in Conventional, Microwave-assisted, and Hybrid Freeze Drying for Biopharmaceutical Manufacturing

TL;DR

This paper introduces a comprehensive mechanistic model for thermal radiation in various freeze drying methods, enabling accurate prediction and optimization of drying processes for biopharmaceutical manufacturing.

Contribution

It presents a novel diffuse gray surface and radiation network model that accurately predicts thermal radiation effects across different freeze dryer configurations.

Findings

Model accurately predicts drying times for all vial positions.

Thermal radiation significantly affects drying uniformity.

Model facilitates design optimization of freeze dryers.

Abstract

In freeze drying, thermal radiation has a significant effect on the drying process of vials located near the corner and edge of the trays, resulting in non-uniformity of the products. Understanding and being able to predict the impact of thermal radiation are therefore critical to accurate determination of the drying process endpoint given the variation in heat transfer of each vial. This article presents a new mechanistic model that describes complex thermal radiation during primary drying in conventional, microwave-assisted, and hybrid freeze drying. Modeling of thermal radiation employs the diffuse gray surface model and radiation network approach, which systematically and accurately incorporates simultaneous radiation exchange between every surface including the chamber wall and vials, allowing the framework to be seamlessly applied for analyzing various freeze-dryer designs. Model validation with data from the literature shows accurate prediction of the drying times for all vials, including inner, edge, and corner vials. The validated model is demonstrated for thermal radiation analysis and parametric studies to guide the design and optimization of freeze dryers.