A microstructural study of water effects in lipid-based pharmaceutical formulations for liquid filling of capsules
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Authors
Machado, Alexandra H.E.
Kokubo, Tohru
Dujovny, Gabriela
Jones, Brian
Scialdone, Claudio
Bravo, Roberto
Author (Corporation)
Publication date
30.07.2016
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Type
01A - Journal article
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Editor (Corporation)
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Parent work
European Journal of Pharmaceutical Sciences
Special issue
DOI of the original publication
Link
Series
Series number
Volume
90
Issue / Number
Pages / Duration
64-75
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
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Practice partner / Client
Abstract
Water is known to exhibit pronounced effects on lipid-based formulations (LBFs) and much research has focused on aqueous dispersion and dilution behavior regarding biopharmaceutical performance. From a product quality perspective, it is also critical to study a range of lower water amounts in formulations with respect to capsule filling. The present work addressed the need for a better understanding of LBF microstructure by taking percolation theory into account. The effects of increasing amounts of water on LBFs were analyzed by conductivity, water activity, time-domain nuclear magnetic resonance, and diffusing wave spectroscopy. Results were interpreted using percolation theory and preliminary mechanical tests were conducted on gelatin and hypromellose (HPMC) capsule shells. For both LBF systems, increasing water amounts led to marked changes in the microstructure of the formulations. Percolation laws could be fitted adequately to the data and thresholds were identified for the formation of continuous water channels (ϕwc~0.02-0.06). A new theoretical model was proposed for water activity. The preliminary shell material studies showed that the threshold for generating water channels in the formulation could be correlated to mechanical changes of the capsule shell that were relatively more pronounced in the case of gelatin. This mechanistic study demonstrated the importance of understanding and monitoring of microstructural changes occurring in LBFs with increasing amounts of water, which will help to design quality into the final dosage form.
Keywords
Colloids, Continuous water channels, Gelatin, HPMC, Hard-shell capsules, Lipid-based formulations, Percolation theory
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ISBN
ISSN
0928-0987
1879-0720
1879-0720
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
Machado, A. H. E., Kokubo, T., Dujovny, G., Jones, B., Scialdone, C., Bravo, R., & Kuentz, M. (2016). A microstructural study of water effects in lipid-based pharmaceutical formulations for liquid filling of capsules. European Journal of Pharmaceutical Sciences, 90, 64–75. https://doi.org/10.1016/j.ejps.2016.04.035