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Leveraging Lyophilization Modeling for Reliable Development, Scale-up and Technology Transfer
Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a useful tool in understanding and optimizing of the process, developing an operating design space following the quality-by-design principle, and justifying occasional process deviations during routine manuf...
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Published in: | AAPS PharmSciTech 2019-07, Vol.20 (7), p.263 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a useful tool in understanding and optimizing of the process, developing an operating design space following the quality-by-design principle, and justifying occasional process deviations during routine manufacturing. The steady-state model relies on two critical parameters, namely, the vial heat transfer coefficient,
K
v
, and the cake resistance,
R
p
. The classical gravimetric method used to measure
K
v
is tedious, time- and resource-consuming, and can be challenging and costly for commercial scale dryers. This study proposes a new approach to extract both
K
v
and
R
p
directly from an experimental run (
e.g.
, temperature and Pirani profiles). The new methodology is demonstrated using 5%
w
/
v
mannitol model system. The values of
K
v
obtained using this method are comparable to those measured using the classic gravimetric method. Application of the proposed approach to process scale-up and technology transfer is illustrated using a case study. The new approach makes the steady-state model a simple and reliable tool for model parameterization, thus maximizes its capability and is particularly beneficial for transfer products from lab/pilot to commercial manufacturing. |
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ISSN: | 1530-9932 |
DOI: | 10.1208/s12249-019-1478-9 |