Investigation of Design Space for Freeze-Drying: Use of Modeling for Primary Drying Segment of a Freeze-Drying Cycle

AbstractThis study explores the use of a statistical model to build a design space for freeze-drying two formulations with ibuprofen. A 2 × 3 factorial experimental design was used to evaluate independent variables (filling volume and annealing time) and responses as residual moisture content, specific surface area and reconstitution time. A statistical model and response surface plots were generated to define the interactions among the selected variables. The models constructed for both formulations suggest that 1 mL of filled volume and no annealing should be used to achieve optimal residual moisture content, specific surface area and reconstitution time. The proposed models were validated with additional experiments, in which the responses observed were mainly in close agreement with the predicted ones. Additionally, the established models demonstrate the reliability of the evaluation procedure in predicting the selected responses.

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Quality by design: optimization of a freeze-drying cycle via design space in case of heterogeneous drying behavior and influence of the freezing protocol

Pharmaceutical Development and Technology ◽

10.3109/10837450.2012.734512 ◽

2012 ◽

Vol 18 (1) ◽

pp. 280-295 ◽

Cited By ~ 51

Author(s):

Roberto Pisano ◽

Davide Fissore ◽

Antonello A. Barresi ◽

Philippe Brayard ◽

Pierre Chouvenc ◽

...

Keyword(s):

Design Optimization ◽

Freeze Drying ◽

Quality By Design ◽

Design Space ◽

Drying Behavior

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Impact of Ice Morphology on Design Space of Pharmaceutical Freeze-Drying

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2016.04.001 ◽

2016 ◽

Vol 105 (6) ◽

pp. 1920-1933 ◽

Cited By ~ 24

Author(s):

Hiroshika Goshima ◽

Gabsoo Do ◽

Kyuya Nakagawa

Keyword(s):

Freeze Drying ◽

Design Space ◽

Ice Morphology

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Design Space Estimation in the Freeze-drying of Instant Soup Product

Japan Journal of Food Engineering ◽

10.11301/jsfe.17494 ◽

2017 ◽

Vol 18 (2) ◽

pp. 115-123

Author(s):

Kyuya NAKAGAWA ◽

Takaaki OCHIAI

Keyword(s):

Freeze Drying ◽

Design Space

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Using mathematical modeling to optimize secondary drying stage of lyophilization technology

10.33920/med-13-2001-03 ◽

2020 ◽

pp. 33-42

Author(s):

Konstantin Alekseyev ◽

Evgeniya Blynskaya ◽

Sergey Tishkov

Keyword(s):

Mathematical Modeling ◽

Heat Transfer ◽

Mathematical Model ◽

Freeze Drying ◽

Design Space ◽

Heat Transfer Fluid ◽

Drying Process ◽

Residual Moisture ◽

Secondary Drying ◽

Temperature And Pressure

During lyophilization frozen water and moisture associated with dissolved substances are removed, desorption occurs in the process of secondary drying. This stage is one of the main stages of the technological process in terms of duration comparable with primary freeze drying and is of paramount importance for the further storage of lyophilisates. Mathematical modeling of secondary drying and the use of these methods in calculating design space of the process are described in the presented article. The equations for calculating the rate of secondary drying, residual moisture, and other conditions on the basis of values of the temperature of the heat-transfer fluid and pressure in the freezedrying chamber are shown. Possibilities for determining design space boundaries on the basis of the composition of lyophilisate, required values of residual moisture and drying kinetics are demonstrated. The proposed mathematical model makes it possible to estimate the duration of the secondary drying process for various values of temperature and pressure in the chamber within the design space.

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