The effects of food on the dissolution of poorly soluble drugs in human and in model small intestinal fluids.
OBJECTIVE
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.
Persson
Eva M
EM
Department of Pharmacy, Uppsala University, Box 580, S-751 23, Uppsala, Sweden.
Gustafsson
Ann-Sofie
AS
Carlsson
Anders S
AS
Nilsson
Ralf G
RG
Knutson
Lars
L
Forsell
Patrick
P
Hanisch
Gunilla
G
Lennernäs
Hans
H
Abrahamsson
Bertil
B
D000328:Adult; D000818:Animals; D001826:Body Fluids / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000737:chemistry; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008297:Male; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics
D008055:Lipids; D004364:Pharmaceutical Preparations