Opportunities for successful stabilization of poor glass-forming drugs: A stability-based comparison of mesoporous silica versus hot melt extrusion technologies

  • 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.

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Author:Felix Ditzinger, Daniel Joseph PriceORCiDGND, Anita NairGND, Johanna Becker-BaldusORCiD, Clemens GlaubitzORCiDGND, Jennifer B. DressmanGND, Christoph Saal, Martin KuentzORCiD
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31689980
Parent Title (English):Pharmaceutics
Place of publication:Basel
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/11/04
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2020/02/10
Tag:glass forming ability; hotmelt extrusion
amorphous stability; mesoporous silica; supersaturation
Issue:11, Art. 577
Page Number:15
First Page:1
Last Page:15
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Biochemie, Chemie und Pharmazie / Pharmazie
Wissenschaftliche Zentren und koordinierte Programme / Zentrum f├╝r Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0