Title: Crystallization kinetics of indomethacin/polyethylene glycol dispersions containing high drug loadings
Authors: Duong, Van Tu
Van Humbeeck, Jan #
Van den Mooter, Guy # ×
Issue Date: 6-Jul-2015
Publisher: American Chemical Society
Series Title: Molecular Pharmaceutics vol:12 issue:7 pages:2493-2504
Abstract: The reproducibility and consistency of physicochemical properties and pharmaceutical performance are major concerns during preparation of solid dispersions. The crystallization kinetics of drug/polyethylene glycol solid dispersions, an important factor that is governed by the properties of both drug and polymer has not been adequately explored, especially in systems containing high drug loadings. In this paper, by using standard and modulated differential scanning calorimetry and X-ray powder diffraction, we describe the influence of drug loading on crystallization behavior of dispersions made up of indomethacin and polyethylene glycol 6000. Higher drug loading increases the amorphicity of the polymer and inhibits the crystallization of PEG. At 52% drug loading, polyethylene glycol was completely transformed to the amorphous state. To the best of our knowledge, this is the first detailed investigation of the solubilization effect of a low molecular weight drug on a semicrystalline polymer in their dispersions. In mixtures containing up to 55% indomethacin, the dispersions exhibited distinct glass transition events resulting from amorphous–amorphous phase separation which generates polymer-rich and drug-rich domains upon the solidification of supercooled polyethylene glycol, whereas samples containing at least 60% drug showed a single amorphous phase during the period in which crystallization normally occurs. The current study demonstrates a wide range in physicochemical properties of drug/polyethylene glycol solid dispersions as a result of the complex nature in crystallization of this system, which should be taken into account during preparation and storage.
ISSN: 1543-8384
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
Surface and Interface Engineered Materials
× corresponding author
# (joint) last author

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