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Title

Sunitinib-eluting beads for chemoembolization: Methods for in vitro evaluation of drug release

Authors
Bize, Pierre E.
Denys, Alban
Published in International Journal of Pharmaceutics. 2015, vol. 482, no. 1-2, p. 68-74
Abstract Drug-eluting microspheres are used for embolization of hypervascular tumors and allow for local controlled drug release. Although the drug release from the microspheres relies on fast ion-exchange, so far only slow-releasing in vitro dissolution methods have been correlated to in vivo data. Three in vitro release methods are assessed in this study for their potential to predict slow in vivo release of sunitinib from chemoembolization spheres to the plasma, and fast local in vivo release obtained in an earlier study in rabbits. Release in an orbital shaker was slow (t50% = 4.5 h, 84% release) compared to fast release in USP 4 flow-through implant cells (t50% = 1 h, 100% release). Release of sunitinib from microspheres in saline in dialysis inserts was prolonged and incomplete (t50% = 9 d, 68% release) due to low drug diffusion through the dialysis membrane. The slow-release profile fitted best to low sunitinib plasma AUC following injection of sunitinib-eluting spheres. Although limited by lack of standardization, release in the orbital shaker fitted best to local in vivo sunitinib concentrations. Drug release in USP flow-through implant cells was too fast to correlate with local concentrations, although this method is preferred to discriminate between different sphere types.
Keywords In vitro drug releaseSunitinibDrug-eluting beadsUSP dissolution apparatus 4ChemoembolizationIn vitro-in vivo correlation
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Research group Biopharmacie
Project DIP
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FUCHS, Katrin et al. Sunitinib-eluting beads for chemoembolization: Methods for in vitro evaluation of drug release. In: International Journal of Pharmaceutics, 2015, vol. 482, n° 1-2, p. 68-74. https://archive-ouverte.unige.ch/unige:75532

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Deposited on : 2015-09-30

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