Mechanistic modelling of infrared mediated energy transfer during the primary drying step of a continuous freeze-drying process

Abstract

Conventional pharmaceutical freeze-drying is an inefficient and expensive batch-wise process, associated with several disadvantages leading to an uncontrolled end product variability. The proposed continuous alternative, based on spinning the vials during freezing and on optimal energy supply during drying, strongly increases process efficiency and improves product quality (uniformity). The heat transfer during continuous drying of the spin frozen vials is provided via non-contact infrared (IR) radiation. The energy transfer to the spin frozen vials should be optimised to maximise the drying efficiency while avoiding cake collapse. Therefore, a mechanistic model was developed which allows computing the optimal, dynamic IR heater temperature in function of the primary drying progress and which, hence, also allows predicting the primary drying endpoint based on the applied dynamic IR heater temperature. The model was validated by drying spin frozen vials containing the model formulation (3.9mL in 10R vials) according to the computed IR heater temperature profile. In total, 6 validation experiments were conducted. The primary drying endpoint was experimentally determined via in-line near-infrared (NIR) spectroscopy and compared with the endpoint predicted by the model (50min). The mean ratio of the experimental drying time to the predicted value was 0.91, indicating a good agreement between the model predictions and the experimental data. The end product had an elegant product appearance (visual inspection) and an acceptable residual moisture content (Karl Fischer).

Modelling the primary drying step for the determination of the optimal dynamic heating pad temperature in a continuous pharmaceutical freeze-drying process for unit doses

“…An uncertainty analysis will be conducted in the future to explore the influence of the estimated input variables and process parameters on the model output. Similar to this research, Van Bockstal et al described the development of a mechanistic model to determine the dynamic infra-red heater temperature during primary drying in a continuous freeze-drying process [15]. The results of the uncertainty analysis on that mechanistic model will be compared to the results of the uncertainty analysis of the mechanistic model developed in this paper.…”

“…The continuous freeze-drying process is extensively described in previous work [4,14,15]. The most critical parameter during the primary drying step is T i .…”

Recent Progresses in Eco-Friendly Fabrication and Applications of Sustainable Aerogels from Various Waste Materials

“…Moreover, the manufacturing cost of a freeze-dried aerogel is estimated at 42 USD/m 2 at laboratory scale, which is even competitive with the cost of the corresponding scCO 2 -dried aerogel at industrial scale (21–70 USD/m 2 ) [ 129 ]. Besides, conventional batch-wise freeze-drying has many disadvantages such as high time and energy consumption, uncontrolled freezing step, inefficient use if loading below maximum capacity, and sample-to-sample variation due to inhomogeneous energy distribution [ 130 , 131 ]. These drawbacks can be overcome by using continuous freeze-drying.…”

Thermal Imaging as a Noncontact Inline Process Analytical Tool for Product Temperature Monitoring during Continuous Freeze-Drying of Unit Doses

“…Therefore, the accurate determination of R p is essential for the development of the optimal freeze-drying cycle (i.e., the optimal dynamic IR heater temperature prole) for a specic formulation, allowing a maximum primary drying eciency while yielding a decent cake aspect. 22 The dried product mass transfer resistance R p (m/s) is correlated to the ratio of the vapor pressure gradient between the sublimation interface and the drying chamber and the mass ow rate by the following equation:…”