A comparative study of freeze-drying heat transfer in polymeric vials and glass vials

Abstract

Abstract Implementation of polymeric vials for freeze-dried drug products has been practically non-existent because of unique moisture barrier and thermodynamic technical challenges. Hybrid vials, which combine the benefits of polymer and glass, have been shown to address the challenges of ordinary polymeric vials. Tackling thermodynamic challenges starts with a clear understanding of the heat transfer mechanism. To this end, multi-physics simulations and experimentation were used to compare the heat transfer between hybrid cyclic olefin polymer (COP) vials and borosilicate glass vials during freeze-drying. Parametric models were developed for hybrid COP and glass vials to systematically study the effect of five design parameters based on the arrangement of the vials on a tray inside a lyophilization chamber. Heat transfer in glass vials were dominated by heat conduction with the surrounding vapor, while hybrid COP vials were governed by conduction with the bottom shelf. Furthermore, hybrid COP vials exhibited more consistent heat flow rate and total heat transfer coefficient compared to glass vials, suggesting higher product quality as a result. The distance between adjacent vials and the drug product height were the most important parameters affecting heat transfer irrespective of vial type. Results indicated that hybrid COP vials can be filled to higher fill volumes with higher heat transfer and without the risk of breakage. Results of this study can help design innovative primary packaging systems for freeze drying or optimizing heat transfer for existing glass or hybrid COP vial systems regarding product consistency and drying time.