scholarly journals A NIR-Based Study of Desorption Kinetics during Continuous Spin Freeze-Drying

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2168
Author(s):  
Laurens Leys ◽  
Gust Nuytten ◽  
Joris Lammens ◽  
Pieter-Jan Van Bockstal ◽  
Jos Corver ◽  
...  
Keyword(s):  
Freeze Drying ◽  
Process Analytical Technology ◽  
Thin Layers ◽  
Chamber Pressure ◽  
Drying Rate ◽  
Desorption Kinetics ◽  
Calibration Model ◽  
Desorption Rate ◽  
Continuous Spin ◽  
Secondary Drying

The pharmaceutical industry is progressing toward the development of more continuous manufacturing techniques. At the same time, the industry is striving toward more process understanding and improved process control, which requires the implementation of process analytical technology tools (PAT). For the purpose of drying biopharmaceuticals, a continuous spin freeze-drying technology for unit doses was developed, which is based on creating thin layers of product by spinning the solution during the freezing step. Drying is performed under vacuum using infrared heaters to provide energy for the sublimation process. This approach reduces drying times by more than 90% compared to conventional batch freeze-drying. In this work, a new methodology is presented using near-infrared (NIR) spectroscopy to study the desorption kinetics during the secondary drying step of the continuous spin freeze-drying process. An inline PLS-based NIR calibration model to predict the residual moisture content of a standard formulation (i.e., 10% sucrose) was constructed and validated. This model was then used to evaluate the effect of different process parameters on the desorption rate. Product temperature, which was controlled by a PID feedback mechanism of the IR heaters, had the highest positive impact on the drying rate during secondary drying. Using a higher cooling rate during spin freezing was found to significantly increase the desorption rate as well. A higher filling volume had a smaller negative effect on the drying rate while the chamber pressure during drying was found to have no significant effect in the range between 10 and 30 Pa.

scholarly journals Micro Freeze-Dryer and Infrared-Based PAT: Novel Tools for Primary Drying Design Space Determination of Freeze-Drying Processes

2021 ◽  
Author(s):  
Maitê Harguindeguy ◽  
Davide Fissore
Keyword(s):  
Freeze Drying ◽  
Design Space ◽  
Process Analytical Technology ◽  
Sucrose Solution ◽  
Chamber Pressure ◽  
Transfer Coefficients ◽  
Scale Unit ◽  
Analytical Technology ◽  
Freeze Dryer

Abstract Purpose Present (i) an infrared (IR)-based Process Analytical Technology (PAT) installed in a lab-scale freeze-dryer and (ii) a micro freeze-dryer (MicroFD®) as effective tools for freeze-drying design space calculation of the primary drying stage. Methods The case studies investigated are the freeze-drying of a crystalline (5% mannitol) and of an amorphous (5% sucrose) solution processed in 6R vials. The heat (Kv) and the mass (Rp) transfer coefficients were estimated: tests at 8, 13 and 26 Pa were carried out to assess the chamber pressure effect on Kv. The design space of the primary drying stage was calculated using these parameters and a well-established model-based approach. The results obtained using the proposed tools were compared to the ones in case Kv and Rp were estimated in a lab-scale unit through gravimetric tests and a thermocouple-based method, respectively. Results The IR-based method allows a non-gravimetric estimation of the Kv values while with the micro freeze-dryer gravimetric tests require a very small number of vials. In both cases, the obtained values of Kv and Rp, as well as the resulting design spaces, were all in very good agreement with those obtained in a lab-scale unit through the gravimetric tests (Kv) and the thermocouple-based method (Rp). Conclusions The proposed tools can be effectively used for design space calculation in substitution of other well-spread methods. Their advantages are mainly the less laborious Kv estimation process and, as far as the MicroFD® is concerned, the possibility of saving time and formulation material when evaluating Rp.

Study on a Combination Drying Technique of Shrimp

2012 ◽  
Vol 260-261 ◽  
pp. 804-807
Author(s):  
Ya Xiang Bai ◽  
Yu Cai Hu ◽  
Qiang Huang
Keyword(s):  
Freeze Drying ◽  
Sensory Properties ◽  
Drying Rate ◽  
Rehydration Ratio ◽  
Drying Time ◽  
Air Drying ◽  
Combined Process ◽  
Highly Efficient ◽  
Sensory Qualities

In order to develop a highly efficient drying technique for shrimp, a combination of air drying (AD) and vacuum freeze drying (FD) is examined. The drying rate of combination drying, the shrinkage, rehydration ratio, and sensory properties, such as the color and trimness, of the dried product in the AD–FD method are measured. Compared with FD, the combined process consumes less drying time, compared with AD drying alone. Also the product processed by combined drying displays lower shrinkage, higher rehydration rate and better sensory qualities.

Understanding and optimization of the secondary drying step of a freeze-drying process: a case study

2020 ◽  
pp. 1-15 ◽  
Author(s):  
Getachew Assegehegn ◽  
Edmundo Brito-de la Fuente ◽  
José M. Franco ◽  
Críspulo Gallegos
Keyword(s):  
Freeze Drying ◽  
Drying Process ◽  
Secondary Drying

Potential of Near-Infrared Chemical Imaging as Process Analytical Technology Tool for Continuous Freeze-Drying

2018 ◽  
Vol 90 (7) ◽  
pp. 4354-4362 ◽  
Author(s):  
Davinia Brouckaert ◽  
Laurens De Meyer ◽  
Brecht Vanbillemont ◽  
Pieter-Jan Van Bockstal ◽  
Joris Lammens ◽  
...  
Keyword(s):  
Freeze Drying ◽  
Near Infrared ◽  
Process Analytical Technology ◽  
Chemical Imaging ◽  
Technology Tool ◽  
Analytical Technology

scholarly journals Model-Based Optimisation and Control Strategy for the Primary Drying Phase of a Lyophilisation Process

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 181 ◽  
Author(s):  
Brecht Vanbillemont ◽  
Niels Nicolaï ◽  
Laurens Leys ◽  
Thomas De Beer
Keyword(s):  
Real Time ◽  
Control Strategy ◽  
Freeze Drying ◽  
Fixed Time ◽  
Chamber Pressure ◽  
Interface Temperature ◽  
Real Time Control ◽  
Choked Flow ◽  
Model Based ◽  
Time Control

The standard operation of a batch freeze-dryer is protocol driven. All freeze-drying phases (i.e., freezing, primary and secondary drying) are programmed sequentially at fixed time points and within each phase critical process parameters (CPPs) are typically kept constant or linearly interpolated between two setpoints. This way of operating batch freeze-dryers is shown to be time consuming and inefficient. A model-based optimisation and real-time control strategy that includes model output uncertainty could help in accelerating the primary drying phase while controlling the risk of failure of the critical quality attributes (CQAs). In each iteration of the real-time control strategy, a design space is computed to select an optimal set of CPPs. The aim of the control strategy is to avoid product structure loss, which occurs when the sublimation interface temperature ( T i ) exceeds the the collapse temperature ( T c ) common during unexpected disturbances, while preventing the choked flow conditions leading to a loss of pressure control. The proposed methodology was experimentally verified when the chamber pressure and shelf fluid system were intentionally subjected to moderate process disturbances. Moreover, the end of the primary drying phase was predicted using both uncertainty analysis and a comparative pressure measurement technique. Both the prediction of T i and end of primary drying were in agreement with the experimental data. Hence, it was confirmed that the proposed real-time control strategy is capable of mitigating the effect of moderate disturbances during batch freeze-drying.

Monitoring of the Secondary Drying in Freeze-Drying of Pharmaceuticals

2011 ◽  
Vol 100 (2) ◽  
pp. 732-742 ◽  
Author(s):  
Davide Fissore ◽  
Roberto Pisano ◽  
Antonello A. Barresi
Keyword(s):  
Freeze Drying ◽  
Secondary Drying
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