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Intestinal solubility and absorption of poorly water soluble compounds: predictions, challenges and solutions
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: 289172612
2015 (English)In: Therapeutic delivery, ISSN 2041-5990, E-ISSN 2041-6008, Vol. 6, no 8, 935-959 p.Article, review/survey (Refereed) Published
Abstract [en]

We have explored for which type of compounds biorelevant dissolution profiling in simulated intestinal fluids would accurately predict solubility in human intestinal fluid. In total, 460 solubility values in simulated and aspirated human intestinal fluid for 78 drugs were compiled and analyzed. Significant solubilization in the colloidal structures was obtained in fasted and fed state fluids for drug compounds with a logD(oct)>3. Highly lipophilic compounds with high melting points (Tm > 200 °C) could also be significantly solubilized, but typically such compounds had solubility values in the lower µg/ml range also in the presence of the colloidal structures. On the basis of our analysis, compounds with a logD(oct)>3 should be explored in biorelevant dissolution media to better predict in vivo performance after oral dosing.

Place, publisher, year, edition, pages
2015. Vol. 6, no 8, 935-959 p.
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-279184DOI: 10.4155/tde.15.45PubMedID: 26316058OAI: oai:DiVA.org:uu-279184DiVA: diva2:907660
Available from: 2016-02-29 Created: 2016-02-29 Last updated: 2017-04-19Bibliographically approved

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Fagerberg, Jonas HBergström, Christel A S

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