Applications of the Tunable Diode Laser Absorption Spectroscopy: In-Process Estimation of Primary Drying Heterogeneity and Product Temperature During Lyophilization

The aim of this research was to evaluate the impact of variability in ice sublimation rate (dm/dt) measurement and vial heat transfer coefficient (Kv) on product temperature prediction during the primary drying phase of lyophilization. The mathematical model used for primary drying uses dm/dt and Kv...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2019-01, Vol.108 (1), p.416-430
Main Authors: Sharma, Puneet, Kessler, William J., Bogner, Robin, Thakur, Meena, Pikal, Michael J.
Format: Article
Language:English
Subjects:
Freeze Drying - methods
freeze drying/lyophilization
Lasers, Semiconductor
mathematical model
Models, Theoretical
Pharmaceutical Preparations - chemistry
process analytical technology (PAT)
simulation
Spectrum Analysis - methods
Technology, Pharmaceutical - methods
Temperature
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Summary:The aim of this research was to evaluate the impact of variability in ice sublimation rate (dm/dt) measurement and vial heat transfer coefficient (Kv) on product temperature prediction during the primary drying phase of lyophilization. The mathematical model used for primary drying uses dm/dt and Kv as inputs to predict product temperature. A second-generation tunable diode laser absorption spectroscopy (TDLAS)–based sensor was used to measure dm/dt. In addition, a new approach to calculate drying heterogeneity in a batch during primary drying is described. The TDLAS dm/dt measurements were found to be within 5%-10% of gravimetric measurement for laboratory- and pilot-scale lyophilizers. Intersupplier variability in Kv was high for the same “type” of vials, which can lead to erroneous product temperature prediction if “one value” of vial heat transfer coefficient is used for “all vial types” from different suppliers. Studies conducted in both a laboratory- and a pilot-scale lyophilizer showed TDLAS product temperature to be within ±1°C of average thermocouple temperature during primary drying. Using TDLAS data and calculations to estimate drying heterogeneity (number of vials undergoing primary drying), good agreement was obtained between theoretical and experimental results, demonstrating usefulness of the new approach.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2018.07.031