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@ARTICLE{Hirlak:893390,
      author       = {Hirlak, Ozan and Dieluweit, Sabine and Merkel, Rudolf and
                      Wagner, Karl G.},
      title        = {{P}olymer-mediated drug supersaturation – {A} spotlight
                      on the interplay between phase-separated amorphous drug
                      colloids and dissolved molecules},
      journal      = {Journal of colloid and interface science},
      volume       = {603},
      issn         = {0021-9797},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {FZJ-2021-02731},
      pages        = {370 - 379},
      year         = {2021},
      abstract     = {HypothesisColloidal aggregation phenomena have been found
                      responsible for the supersaturation of poorly water-soluble
                      drugs, potentially leading to bioavailability enhancements.
                      Unlike coarse precipitates, phase separation in the form of
                      colloids, is expected to enhance drug supersaturation
                      performance. Therefore, a high proportion of these colloids
                      should correlate with the extent and the kinetics of
                      supersaturation. The prime objective of the current study is
                      to provide a mechanistic understanding on supersaturation
                      for the model drug albendazole (ALB) in combination with
                      twelve polymers.ExperimentsSpecies separated after a
                      pH-shift were characterized by dynamic light scattering
                      (DLS), freeze-fracture electron microscopy (FF-EM) and
                      transmission X-ray diffraction (XRD). Laser diffraction (LD)
                      in a liquid cell was introduced for a relative
                      quantification of the colloidally separated species,
                      described as colloid fraction. The pH-dependent
                      supersaturation was assessed online using a miniaturized
                      dissolution assay.FindingsHere, a measure of the extent of
                      amorphous colloidal phase separation was established, and
                      its impact on supersaturation was evaluated. As a result, a
                      correlation was found between the extent of supersaturation
                      and the colloid fraction. This confirmed the dependence of
                      polymer-mediated enabling and preservation of
                      supersaturation on the ability of polymers to stabilize
                      colloid fractions. Furthermore, a fixed ratio was suggested
                      between the dissolved drug and colloidally separated drug as
                      the kinetic profiles of both species showed similar
                      trajectories. In conclusion, colloid fractions were
                      identified to be responsible for dissolved and potentially
                      bioavailable drug molecules.},
      cin          = {IBI-2},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IBI-2-20200312},
      pnm          = {5241 - Molecular Information Processing in Cellular Systems
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5241},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {34197986},
      UT           = {WOS:000703595700007},
      doi          = {10.1016/j.jcis.2021.06.089},
      url          = {https://juser.fz-juelich.de/record/893390},
}