TY  - JOUR
A1  - Ditzinger, Felix
A1  - Price, Daniel Joseph
A1  - Nair, Anita
A1  - Becker-Baldus, Johanna
A1  - Glaubitz, Clemens
A1  - Dressman, Jennifer B.
A1  - Saal, Christoph
A1  - Kuentz, Martin
T1  - Opportunities for successful stabilization of poor glass-forming drugs: A stability-based comparison of mesoporous silica versus hot melt extrusion technologies
T2  - Pharmaceutics
N2  - 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.
KW  - glass forming ability
KW  - hotmelt extrusion
KW  - mesoporous silica
KW  - amorphous stability
KW  - supersaturation
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51831
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-518317
SN  - 1999-4923
N1  - 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
VL  - 11
IS  - 11, Art. 577
SP  - 1
EP  - 15
PB  - MDPI
CY  - Basel
ER  -