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000905082 0247_ $$2doi$$a10.1016/j.ijpharm.2021.120716
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000905082 1001_ $$0P:(DE-HGF)0$$aMüller, Martin$$b0
000905082 245__ $$aPrecipitation from amorphous solid dispersions in biorelevant dissolution testing: The polymorphism of regorafenib
000905082 260__ $$aNew York, NY [u.a.]$$bElsevier$$c2021
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000905082 520__ $$aAbstractAmorphous 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.
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000905082 7001_ $$0P:(DE-Juel1)180761$$aPlatten, Florian$$b1$$ufzj
000905082 7001_ $$0P:(DE-Juel1)172746$$aDulle, Martin$$b2$$ufzj
000905082 7001_ $$0P:(DE-HGF)0$$aFischer, Björn$$b3
000905082 7001_ $$0P:(DE-HGF)0$$aHoheisel, Werner$$b4
000905082 7001_ $$0P:(DE-HGF)0$$aSerno, Peter$$b5
000905082 7001_ $$0P:(DE-HGF)0$$aEgelhaaf, Stefan$$b6
000905082 7001_ $$0P:(DE-HGF)0$$aBreitkreutz, Jörg$$b7$$eCorresponding author
000905082 773__ $$0PERI:(DE-600)1484643-3$$a10.1016/j.ijpharm.2021.120716$$gVol. 603, p. 120716 -$$p120716 -$$tInternational journal of pharmaceutics$$v603$$x0378-5173$$y2021
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