A primary drying model-based comparison of conventional batch freeze-drying to continuous spin-freeze-drying for unit doses

Eur J Pharm Biopharm. 2020 Dec;157:97-107. doi: 10.1016/j.ejpb.2020.09.009. Epub 2020 Oct 11.

Abstract

An innovative continuous spin-freeze-drying technology for unit doses was recently developed. For this technology, a mechanistic primary drying model was developed allowing the calculation of the optimal dynamic drying trajectory for spin-frozen formulations. In this work, a model-based and experimentally verified comparison was made between conventional batch freeze-drying and spin-freeze-drying by analyzing the outputs (i.e., primary drying endpoint, optimal shelf temperature/power heater and product temperature profile) of both primary drying models. Input parameters such as dried product layer resistance (Rp) and heat input parameters (Kv,Ptot) were experimentally determined for both freeze-drying methods and compared. In addition, optimal dynamic process parameters were calculated for 3 model formulations by using both mechanistic models. Finally, model predictions were validated by measuring the product temperature and primary drying endpoint. It was observed that, when considering the same layer thickness, Rp was generally lower for continuous spin-frozen formulations compared to vials frozen in a conventional batch freeze-dryer. This observation contributes to the short primary drying times of spin-frozen formulations. In addition, as spin-freezing drastically increases the surface area of the product and lowers the dried layer thickness, drying times can be reduced even further while an excellent cake structure and appearance can still be obtained. The primary drying model for spin-frozen formulations proved to be equally accurate for the prediction of the primary drying endpoint and product temperature compared to the batch freeze-drying model.

Keywords: Continuous freeze-drying; Continuous manufacturing; Freeze-drying; Mathematical modelling; Mechanistic modelling.

Publication types

  • Comparative Study

MeSH terms

  • Drug Compounding
  • Freeze Drying*
  • Models, Theoretical*
  • Technology, Pharmaceutical / methods*
  • Temperature
  • Time Factors
  • Vapor Pressure