Biorelevant media to simulate fluids in the ascending colon of humans and their usefulness in predicting intracolonic drug solubility.
OBJECTIVE
To develop media simulating human colonic fluids (HCFs), to evaluate their use in predicting intracolonic solubility of ketoconazole, danazol and felodipine and to compare solubilities in HCFs with previously determined solubilities in gastric (HGFs) and small intestinal (HIFs) fluids.


METHODS
Fasted state simulated colonic fluid (FaSSCoF) and fed state simulated colonic fluid (FeSSCoF) were designed to reflect fluids previously collected from the ascending colon in healthy adults. Solubilities of the three model compounds were determined in HCFs, simulated HCFs, and plain buffers.


RESULTS
For ketoconazole, solubilities in FaSSCoF and FeSSCoF were closer than those in the corresponding plain buffers to the solubility in HCFs. For danazol and felodipine, solubilities in FaSSCoF and FeSSCoF predicted solubilities in HCFs. In the fasted state, solubilities of danazol and felodipine in HCFs were higher than or similar to in HGFs or HIFs, while the ketoconazole solubility was lower. In the fed state, solubilities of all three model compounds in HCFs were lower than in HGFs or HIFs.


CONCLUSIONS
FaSSCoF and FeSSCoF more closely predict solubility of poorly soluble compounds in HCFs than plain buffers. In most cases, solubility in HCFs differs from those in HGFs and HIFs.
Vertzoni
Maria
M
Laboratory of Biopharmaceutics and Pharmacokinetics, National and Kapodistrian University of Athens, Athens, Greece.
Diakidou
Amalia
A
Chatzilias
Manos
M
Söderlind
Erik
E
Abrahamsson
Bertil
B
Dressman
Jennifer B
JB
Reppas
Christos
C
D000328:Adult; D001682:Biological Availability; D001826:Body Fluids / Q000737:chemistry* / Q000378:metabolism; D002021:Buffers; D044682:Colon, Ascending / Q000378:metabolism*; D018592:Cross-Over Studies; D003613:Danazol / Q000737:chemistry* / Q000493:pharmacokinetics; D005215:Fasting; D015736:Felodipine / Q000737:chemistry* / Q000493:pharmacokinetics; D005766:Gastrointestinal Contents / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007654:Ketoconazole / Q000737:chemistry* / Q000493:pharmacokinetics; D008954:Models, Biological; D009994:Osmolar Concentration; D011237:Predictive Value of Tests; D012995:Solubility
D002021:Buffers; D003613:Danazol; D015736:Felodipine; D007654:Ketoconazole