The effects of food on the dissolution of poorly soluble drugs in human and in model small intestinal fluids
2005 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 22, no 12, 2141-2151 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 22, no 12, 2141-2151 p.
bile acids, dissolution rate, food effects, poorly soluble drugs, solubility
IdentifiersURN: urn:nbn:se:uu:diva-75382DOI: 10.1007/s11095-005-8192-xPubMedID: 16247711OAI: oai:DiVA.org:uu-75382DiVA: diva2:103292