Noncontact Infrared-Mediated Heat Transfer During Continuous Freeze-Drying of Unit Doses

J Pharm Sci. 2017 Jan;106(1):71-82. doi: 10.1016/j.xphs.2016.05.003. Epub 2016 Jun 16.


Recently, an innovative continuous freeze-drying concept for unit doses was proposed, based on spinning the vials during freezing. An efficient heat transfer during drying is essential to continuously process these spin frozen vials. Therefore, the applicability of noncontact infrared (IR) radiation was examined. The impact of several process and formulation variables on the mass of sublimed ice after 15 min of primary drying (i.e., sublimation rate) and the total drying time was examined. Two experimental designs were performed in which electrical power to the IR heaters, distance between the IR heaters and the spin frozen vial, chamber pressure, product layer thickness, and 5 model formulations were included as factors. A near-infrared spectroscopy method was developed to determine the end point of primary and secondary drying. The sublimation rate was mainly influenced by the electrical power to the IR heaters and the distance between the IR heaters and the vial. The layer thickness had the largest effect on total drying time. The chamber pressure and the 5 model formulations had no significant impact on sublimation rate and total drying time, respectively. This study shows that IR radiation is suitable to provide the energy during the continuous processing of spin frozen vials.

Keywords: factorial design; freeze-drying/lyophilization; near-infrared spectroscopy; principal component analysis; process analytical technology.

MeSH terms

  • Algorithms
  • Drug Compounding / instrumentation
  • Drug Compounding / methods
  • Equipment Design
  • Excipients / chemistry
  • Freeze Drying / instrumentation
  • Freeze Drying / methods*
  • Hot Temperature
  • Infrared Rays
  • Thermal Conductivity


  • Excipients