Computational support to explore ternary solid dispersions of challenging drugs using coformer and hydroxypropyl cellulose
Author (Corporation)
Publication date
10.10.2024
Typ of student thesis
Course of study
Collections
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Molecular Pharmaceutics
Special issue
DOI of the original publication
Link
Series
Series number
Volume
21
Issue / Number
11
Pages / Duration
5619–5631
Patent number
Publisher / Publishing institution
American Chemical Society
Place of publication / Event location
Edition
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Abstract
A majority of drugs marketed in amorphous formulations have a good glass-forming ability, while compounds less stable in the amorphous state still pose a formulation challenge. This work explores ternary solid dispersions of two model drugs with a polymer (i.e., hydroxypropyl cellulose) and a coformer as stabilizing excipients. The aim was to introduce a computational approach by preselecting additives using solubility parameter intervals (i.e., overlap range of solubility parameter, ORSP) followed by more advanced COSMO-RS theory modeling. Thus, a mapping of calculated mixing enthalpy and melting points is proposed for in silico evaluation prior to hot melt extrusion. Following experimental testing of process feasibility, the selected formulations were tested for their physical stability using conventional bulk analytics and by confocal laser scanning and atomic force microscopy imaging. In line with the in silico screening, dl-malic and l-tartaric acid (20%, w/w) in HPC formulations showed no signs of early drug crystallization after 3 months. However, l-tartaric acid formulations displayed few crystals on the surface, which was likely a humidity-induced surface phenomenon. Although more research is needed, the conclusion is that the proposed computational small-scale extrusion approach of ternary solid dispersion has great potential in the formulation development of challenging drugs.
Keywords
Subject (DDC)
600 - Technik, Medizin, angewandte Wissenschaften
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ISBN
ISSN
1543-8384
1543-8392
1543-8392
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Hybrid
License
Citation
NIEDERQUELL, Andreas, Susanne HERZIG, Monica SCHÖNENBERGER, Edmont STOYANOV und Martin KUENTZ, 2024. Computational support to explore ternary solid dispersions of challenging drugs using coformer and hydroxypropyl cellulose. Molecular Pharmaceutics. 10 Oktober 2024. Bd. 21, Nr. 11, S. 5619–5631. DOI 10.1021/acs.molpharmaceut.4c00592. Verfügbar unter: https://doi.org/10.26041/fhnw-11912