Opportunities for Successful Stabilization of Poor Glass-Forming Drugs: A Stability-Based Comparison of Mesoporous Silica Versus Hot Melt Extrusion Technologies
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Authors
Price, Daniel J.
Nair, Anita
Becker-Baldus, Johanna
Glaubitz, Clemens
Dressman, Jennifer
Saal, Christoph
Author (Corporation)
Publication date
04.11.2019
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Type
01A - Journal article
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Supervisor
Parent work
Pharmaceutics
Special issue
DOI of the original publication
Series
Series number
Volume
11
Issue / Number
11
Pages / Duration
577
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
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Abstract
Amorphous formulation technologies to improve oral absorption of poorly soluble active pharmaceutical ingredients (APIs) have become increasingly prevalent. Currently, polymer-based amorphous formulations manufactured by spray drying, hot melt extrusion (HME), or co-precipitation are most common. However, these technologies have challenges in terms of the successful stabilization of poor glass former compounds in the amorphous form. An alternative approach is mesoporous silica, which stabilizes APIs in non-crystalline form via molecular adsorption inside nano-scale pores. In line with these considerations, two poor glass formers, haloperidol and carbamazepine, were formulated as polymer-based solid dispersion via HME and with mesoporous silica, and their stability was compared under accelerated conditions. Changes were monitored over three months with respect to solid-state form and dissolution. The results were supported by solid-state nuclear magnetic resonance spectroscopy (SS-NMR) and scanning electron microscopy (SEM). It was demonstrated that mesoporous silica was more successful than HME in the stabilization of the selected poor glass formers. While both drugs remained non-crystalline during the study using mesoporous silica, polymer-based HME formulations showed recrystallization after one week. Thus, mesoporous silica represents an attractive technology to extend the formulation toolbox to poorly soluble poor glass formers.
Keywords
glass forming ability, hot melt extrusion, mesoporous silica, amorphous stability, supersaturation
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ISBN
ISSN
0378-5173
1873-3476
1873-3476
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
Ditzinger, F., Price, D. J., Nair, A., Becker-Baldus, J., Glaubitz, C., Dressman, J., Saal, C., & Kuentz, M. (2019). Opportunities for Successful Stabilization of Poor Glass-Forming Drugs: A Stability-Based Comparison of Mesoporous Silica Versus Hot Melt Extrusion Technologies. Pharmaceutics, 11(11), 577. https://doi.org/10.3390/pharmaceutics11110577