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@ARTICLE{Mller:905082,
author = {Müller, Martin and Platten, Florian and Dulle, Martin and
Fischer, Björn and Hoheisel, Werner and Serno, Peter and
Egelhaaf, Stefan and Breitkreutz, Jörg},
title = {{P}recipitation from amorphous solid dispersions in
biorelevant dissolution testing: {T}he polymorphism of
regorafenib},
journal = {International journal of pharmaceutics},
volume = {603},
issn = {0378-5173},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2022-00381},
pages = {120716 -},
year = {2021},
note = {post-print leider nicht verfügbar},
abstract = {AbstractAmorphous Solid Dispersions (ASDs) are a major drug
formulation technique to achieve higher bioavailability for
poorly water-soluble active pharmaceutical ingredients. So
far, dissolution tailoring and supersaturation enhancement
have been studied in detail, whereas less is known about the
importance of formed precipitates with amorphous or
crystalline states at the site of drug
absorption.Regorafenib monohydrate (RGF MH), a multikinase
inhibitor drug categorized as Biopharmaceutics
Classification System (BCS) class II compound, was
formulated with povidone K25 and hypromellose acetate
succinate (HPMCAS) as an ASD. Here, for the first time, the
RGF precipitation process as well as the physicochemical
properties of the arising precipitates are investigated. The
formed precipitates from biorelevant dissolution showed
varying drug content and were analyzed offline by scanning
electron microscopy (SEM), differential scanning calorimetry
(DSC), confocal Raman microscopy (CRM), X-ray powder
diffraction (XRPD), and small angle X-ray scattering (SAXS).
In addition to different crystalline RGF precipitates, an
amorphous co-precipitate of RGF and HPMCAS was identified,
which was suppressed in the presence of PVP. Wide angle
X-ray scattering (WAXS) and isothermal calorimetry (ITC)
were used to track the precipitation process of RGF in-situ.
From calorimetric data, the precipitation profile was
calculated. RGF forms precipitates in multiple polymorphic
states dependent on the environmental conditions, i.e.,
dissolution media composition and chosen excipients. The
engineered formation of defined amorphous structures in-vivo
may be a promising future drug formulation strategy.},
cin = {IBI-4},
ddc = {610},
cid = {I:(DE-Juel1)IBI-4-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {34015382},
UT = {WOS:000663093900004},
doi = {10.1016/j.ijpharm.2021.120716},
url = {https://juser.fz-juelich.de/record/905082},
}