Evaluation of spin freezing versus conventional freezing as part of a continuous pharmaceutical freeze-drying concept for unit doses

Abstract

ABSTRACT:16 17Spin-freezing as alternative freezing approach was evaluated as part of an innovative 18 continuous pharmaceutical freeze-drying concept for unit doses. The aim of this paper 19 was to compare the sublimation rate of spin-frozen vials versus traditionally frozen vials 20 in a batch freeze-dryer, and its impact on total drying time. 21Five different formulations, each having a different dry cake resistance, were tested. 23After freezing, the traditionally frozen vials were placed on the shelves while the spin-24 frozen vials were placed in aluminium vial holders providing radial energy supply during 25 drying. Different primary drying conditions and chamber pressures were evaluated. 26After two hours of primary drying, the amount of sublimed ice was determined in each 27 vial. Each formulation was monitored in-line using NIR spectroscopy during drying to

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

“…Due to suboptimal contact between the stainless steel shelf and the aluminium vial holder and between this vial holder and the spin frozen vial, the conduction heat flux is enhanced with the increase in the amount of gas molecules between these surfaces. Hence, the higher heat transfer is responsible for the increased sublimation rate observed at a higher pressure 15 . This phenomenon is also extensively described in batch freeze-drying: poor contact between the shelf and the bottom of the glass vials yields a higher heat transfer coefficient when the chamber pressure is increased 3,26 .…”

“…Increasing the electrical power which resulted in the insignificant impact of the chamber pressure on the sublimation rate. However, when the energy transfer to spin frozen vials is provided by conduction, the chamber pressure does have a significant impact on the sublimation rate 15 . As opposed to heat transfer by radiation, direct contact is required for conductive heat transfer.…”

“…Similar to solid dosage forms, continuous manufacturing is also of major importance for biopharmaceutical products 1,13 . Recently, an innovative continuous freeze-drying concept was proposed which tackles the higher outlined disadvantages associated with the traditional lyophilisation process 14,15 . A major difference compared to conventional batch freeze-drying concerns the freezing step: each vial is rotated along the longitudinal axis while a flow of a cold, inert and sterile gas is used to induce ice nucleation (spin freezing).…”

“…Due to the increase of the surface available for sublimation and the corresponding reduction of the layer thickness, the primary and secondary drying efficiency can be highly improved compared to batch freeze-drying 15 . To achieve a homogeneous and efficient drying behaviour, the thin product layer requires an adequate and uniform heat transfer towards the entire vial wall.…”

“…This way it is not necessary to envelop processed vials by heatable pockets and this eases the monitoring of the drying progress at the level of each individual vial. Additionally, several vial types can be processed without the need to adapt the heatable pockets to obtain a homogeneous energy transfer 15 .…”