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000893390 0247_ $$2doi$$a10.1016/j.jcis.2021.06.089
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000893390 041__ $$aEnglish
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000893390 1001_ $$0P:(DE-HGF)0$$aHirlak, Ozan$$b0
000893390 245__ $$aPolymer-mediated drug supersaturation – A spotlight on the interplay between phase-separated amorphous drug colloids and dissolved molecules
000893390 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2021
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000893390 520__ $$aHypothesisColloidal aggregation phenomena have been found responsible for the supersaturation of poorly water-soluble drugs, potentially leading to bioavailability enhancements. Unlike coarse precipitates, phase separation in the form of colloids, is expected to enhance drug supersaturation performance. Therefore, a high proportion of these colloids should correlate with the extent and the kinetics of supersaturation. The prime objective of the current study is to provide a mechanistic understanding on supersaturation for the model drug albendazole (ALB) in combination with twelve polymers.ExperimentsSpecies separated after a pH-shift were characterized by dynamic light scattering (DLS), freeze-fracture electron microscopy (FF-EM) and transmission X-ray diffraction (XRD). Laser diffraction (LD) in a liquid cell was introduced for a relative quantification of the colloidally separated species, described as colloid fraction. The pH-dependent supersaturation was assessed online using a miniaturized dissolution assay.FindingsHere, a measure of the extent of amorphous colloidal phase separation was established, and its impact on supersaturation was evaluated. As a result, a correlation was found between the extent of supersaturation and the colloid fraction. This confirmed the dependence of polymer-mediated enabling and preservation of supersaturation on the ability of polymers to stabilize colloid fractions. Furthermore, a fixed ratio was suggested between the dissolved drug and colloidally separated drug as the kinetic profiles of both species showed similar trajectories. In conclusion, colloid fractions were identified to be responsible for dissolved and potentially bioavailable drug molecules.
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000893390 7001_ $$0P:(DE-Juel1)128807$$aDieluweit, Sabine$$b1
000893390 7001_ $$0P:(DE-Juel1)128833$$aMerkel, Rudolf$$b2
000893390 7001_ $$0P:(DE-HGF)0$$aWagner, Karl G.$$b3$$eCorresponding author
000893390 773__ $$0PERI:(DE-600)1469021-4$$a10.1016/j.jcis.2021.06.089$$gVol. 603, p. 370 - 379$$p370 - 379$$tJournal of colloid and interface science$$v603$$x0021-9797$$y2021
000893390 8564_ $$uhttps://juser.fz-juelich.de/record/893390/files/Manuscript%20in%20press%20%20pre-proof.pdf$$yPublished on 2021-06-17. Available in OpenAccess from 2022-06-17.
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