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Lipiodol-based emulsions used for transarterial chemoembolization and drug delivery: Effects of composition on stability and product quality
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.ORCID iD: 0000-0003-4318-6039
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2019 (English)In: Journal of Drug Delivery Science and Technology, ISSN 1773-2247, Vol. 53, article id UNSP 101143Article in journal (Refereed) Published
Abstract [en]

Transarterial chemoembolization with emulsion-based formulations using doxorubicin hydrochloride (DOX) and Lipiodol (R) is the golden standard for the loco-regional treatment of unresectable hepatocellular carcinoma (HCC). However, from a pharmaceutical quality perspective these emulsions are poorly characterized. In this study, clinically relevant Lipiodol (R)-based emulsions were characterized in terms of emulsion stability, continuous phase classification and droplet-size distribution. Also, the solubility of DOX in the different emulsion components and the distribution of DOX to the lipid phase were investigated. These are key features to investigate due to the claimed tumor-seeking properties of Lipiodol (R). The in vitro release of DOX was studied in a miniaturized dialysis method and an empirical release model was applied to adjust for the passage of DOX across the dialysis membrane. The most stable emulsion ( > 72 h) was classified as water-in-oil (w/o), had the highest distribution of DOX to the lipid phase (20%) and an aqueous-to-lipid phase ratio of 1:4. The composition of the aqueous phase was a mixture (v/v) of iohexol (85%) and water (15%). Emulsions containing iohexol and a high aqueousto-lipid phase ratio (1:2-1:4) displayed prolonged in vitro release profiles of DOX. This study further emphasizes the medical need to standardize these emulsion-based drug delivery systems.

Place, publisher, year, edition, pages
ELSEVIER , 2019. Vol. 53, article id UNSP 101143
Keywords [en]
Emulsion, Lipiodol (R), Miniaturized dialysis method, In vitro release, Pharmaceutical quality, Liver cancer
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-395729DOI: 10.1016/j.jddst.2019.101143ISI: 000487963600044OAI: oai:DiVA.org:uu-395729DiVA, id: diva2:1365247
Funder
Swedish Research Council, 521-2011-373Available from: 2019-10-24 Created: 2019-10-24 Last updated: 2019-10-24Bibliographically approved

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Ahnfelt, EmelieDegerstedt, OliverLilienberg, ElsaSjögren, ErikHansson, PerLennernäs, Hans
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