Mechanistic modelling of fluid bed granulation, Part II: Eased process development via degree of wetness.

Degree of wetness Fluid bed granulation Particle drying Population balance equation Spray evaporation Zero-dimensional modeling

Journal

International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127

Informations de publication

Date de publication:
15 Dec 2019
Historique:
received: 24 07 2019
revised: 26 10 2019
accepted: 28 10 2019
pubmed: 13 11 2019
medline: 6 5 2020
entrez: 13 11 2019
Statut: ppublish

Résumé

The performance of a fluid bed granulator was investigated through experimental and numerical study to develop a stand-alone fluid bed granulation model. The single-compartment model proposed in part I (for agglomeration modeling) was extended to account for i) evaporation of freely-flowing droplets, and ii) particle drying. This model enables us to predict the granule liquid content and temperature besides the granule size. Accurately, the equations of heat and mass conservation were solved in parallel to the population balance calculation of the agglomeration. In the same manner as for the agglomeration model, the model parameters associated with the drying model were estimated and correlated to the relevant quantities. The analysis of the experimental results revealed the significant contribution of the system "degree of wetness" to the bed performance, i.e., granule size and loss on drying (LoD). As the agglomeration model parameters were partially correlated to LoD in Part I, the presented model was revisited by inclusion of the degree of wetness. The reliability of the developed model in predicting the temporal evolution of granule size, liquid content, and temperature was proven through comparing the bed performance between simulation and experiment. Subsequently, to lowering the costs associated with experimental run, an approach was proposed based on the degree of wetness, aimed at reducing the number of experiments required for the design of experiment (DoE). The results of our simulation using reduced experiments demonstrated that the degree of wetness can be a promising indicator for the performance of the fluid bed granulator as well as for more efficient design of experiment.

Identifiants

pubmed: 31715353
pii: S0378-5173(19)30881-6
doi: 10.1016/j.ijpharm.2019.118836
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

118836

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Auteurs

Maryam Askarishahi (M)

Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz, Austria.

Mohammad-Sadegh Salehi (MS)

Institute of Process and Particle Engineering, Graz University of Technology, Graz, Austria.

Martin Maus (M)

Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany.

Daniela Schröder (D)

Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany.

David Slade (D)

Process Systems Enterprise (PSE), London, United Kingdom.

Dalibor Jajcevic (D)

Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz, Austria. Electronic address: dalibor.jajcevic@rcpe.at.

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Classifications MeSH