| The effects of food on the dissolution of poorly soluble drugs in human and in model small intestinal fluids. | |
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MedLine Citation:
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PMID: 16247711 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: This study was conducted to determine the effect of food on drug solubility and dissolution rate in simulated and real human intestinal fluids (HIF). METHODS: Dissolution rate obtained via the rotating disk method and saturation solubility studies were carried out in fed and fasted state HIF, fed dog (DIF), and simulated (FeSSIF) intestinal fluid for six aprotic low solubility drugs. The intestinal fluids were characterized with respect to physical-chemical characteristics and contents. RESULTS: Fed HIF provided a 3.5- to 30-times higher solubility compared to fasted HIF and FeSSIF, whereas fed DIF corresponded well (difference of less than 30%) to fed HIF. The increased solubility of food could mainly be attributed to dietary lipids and bile acids. The dissolution rate was also 2 to 7 times higher in fed HIF than fasted HIF. This was well predicted by both DIF and FeSSIF (difference of less than 30%). CONCLUSIONS: Intestinal solubility is higher in fed state compared to fasted state. However, the dissolution rate does not increase to the same extent. Dog seems to be a good model for man with respect to dissolution in the small intestine after intake of a meal, whereas FeSSIF is a poorer means of determining intestinal saturation solubility in the fed state. |
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Authors:
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Eva M Persson; Ann-Sofie Gustafsson; Anders S Carlsson; Ralf G Nilsson; Lars Knutson; Patrick Forsell; Gunilla Hanisch; Hans Lennernäs; Bertil Abrahamsson |
Publication Detail:
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Type: Journal Article Date: 2005-10-30 |
Journal Detail:
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Title: Pharmaceutical research Volume: 22 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-12-20 Completed Date: 2006-03-09 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: United States |
Other Details:
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Languages: eng Pagination: 2141-51 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, Uppsala University, Box 580, S-751 23, Uppsala, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Body Fluids / chemistry* Chemistry, Physical Chromatography, High Pressure Liquid Dogs Female Food-Drug Interactions* Humans Intestines / chemistry, metabolism Kinetics Lipids / chemistry Male Molecular Weight Pharmaceutical Preparations / chemistry* Physicochemical Phenomena Solubility Thermodynamics |
| Chemical | |
Reg. No./Substance:
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0/Lipids; 0/Pharmaceutical Preparations |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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