Prediction of product morphology of lyophilized drugs in the case of Vacuum Induced Surface Freezing

[Display omitted] •A dynamic, mechanistic model is developed to describe freezing of pharmaceutical solutions in dosage form.•Vacuum Induced Surface Freezing is used as model protocol.•Simulations were validated for two formulations and various freezing conditions.•Simulations gave accurate predicti...

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Bibliographic Details
Published inChemical engineering research & design Vol. 125; pp. 119 - 129
Main Authors Pisano, Roberto, Capozzi, Luigi C.
Format Journal Article
LanguageEnglish
Published Rugby Elsevier B.V 01.09.2017
Elsevier Science Ltd
Subjects
Computer simulation
Control
Electron microscopy
Formulations
Freeze-drying
Freezing
Mannitol
Modelling
Morphology
Nucleation
Pharmaceutical industry
Pharmaceuticals
Scanning electron microscopy
Shipping
Studies
Sucrose
Vacuum Induced Surface Freezing
Vacuum Induced Surface Freezing
Control
Modelling
Freezing
Freeze-drying
Pharmaceuticals
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Summary:[Display omitted] •A dynamic, mechanistic model is developed to describe freezing of pharmaceutical solutions in dosage form.•Vacuum Induced Surface Freezing is used as model protocol.•Simulations were validated for two formulations and various freezing conditions.•Simulations gave accurate predictions of the average pore size and its distribution within lyophilized samples.•The developed model gives insight into the relationship between product morphology and freezing conditions. In pharmaceutical industry, freeze-drying is often used to produce protein therapeutics that are stable during shipping and long-term storage. The design of adequate freezing process is a crucial aspect to be considered as influences the final morphology and, hence, physicochemical properties of the lyophilized product. In this study, a mechanistic model is developed for better understanding the relationship between morphology of lyophilized samples and freezing conditions. More specifically, we focus on Vacuum Induced Surface Freezing that is a recent, promising technology that allows a precise control of temperature of nucleation. Model simulations were validated by comparison with the lyophilized product morphology as observed by Scanning Electron Microscopy. The model was found to give accurate results for two liquid formulations, containing mannitol and sucrose, and varying nucleation temperature.
ISSN:0263-8762
1744-3563
DOI:10.1016/j.cherd.2017.07.004