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Title: Phase behaviour analysis of solid dispersions of loperamide and two structurally related compounds with the polymers PVP-K30 and PVP-VA64
Authors: Weuts, Ilse ×
Kempen, Dieter
Decorte, Annelies
Verreck, Geert
Peeters, J
Brewster, Marcus
Van den Mooter, Guy #
Issue Date: Aug-2004
Series Title: European Journal of Pharmaceutical Sciences vol:22 issue:5 pages:375-385
Abstract: The purpose of the present study was to investigate the influence of the structure of a poorly water soluble model drug (loperamide) on the phase behaviour in solid dispersions with PVP-K30. Dispersions with PVP-VA64, a less hydrophilic polymer, were investigated as well in order to study the influence of differences in polymer structure and water content of the samples. The solid dispersions of PVP-K30 or PVP-VA64 with loperamide as well as with two fragments of this molecule were prepared by spray drying. The amount of residual solvents and water was determined with GC and thermogravimetric analysis (TGA). The drug loading of the dispersions was determined using high performance liquid chromatography (HPLC). The solid state properties were evaluated using powder-XRD, IR-spectroscopy and MT-DSC. All mixtures containing loperamide proved to be completely amorphous, whereas the dispersions containing the fragments are only amorphous in case the polymer content is high. The phase diagrams that were constructed clearly show that loperamide exhibits a different behaviour in the solid dispersions than its two building blocks. They also point to the presence of specific intermolecular compound--polymer interactions in the dispersions of one of the fragments with the two polymers. This was confirmed by the IR-results. Despite structural similarities, interactions in dispersions containing loperamide are far less important. In dispersions containing high concentrations of the other fragment, the DSC curves give indications for polymorphism whereas IR and XRD-spectra point towards inclusion of solvent in these samples.
ISSN: 0928-0987
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
× corresponding author
# (joint) last author

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