Biorelevant media to simulate fluids in the ascending colon of humans and their usefulness in predicting intracolonic drug solubility

• Purpose To develop media simulating human colonic fluids(HCFs), to evaluate their use in predicting intracolonic solubilityof ketoconazole, danazol and felodipine and to comparesolubilities in HCFs with previously determined solubilities ingastric (HGFs) and small intestinal (HIFs) fluids. Methods Fasted state simulated colonic fluid (FaSSCoF) andfed state simulated colonic fluid (FeSSCoF) were designed toreflect fluids previously collected from the ascending colon inhealthy adults. Solubilities of the three model compounds weredetermined in HCFs, simulated HCFs, and plain buffers. Results For ketoconazole, solubilities in FaSSCoF and FeS-SCoF were closer than those in the corresponding plain buffersto the solubility in HCFs. For danazol and felodipine, solubilitiesin FaSSCoF and FeSSCoF predicted solubilities in HCFs. In thefasted state, solubilities of danazol and felodipine in HCFs werehigher than or similar to in HGFs or HIFs, while theketoconazole solubility was lower. In the fed state, solubilities of all three model compounds in HCFs were lower than inHGFs or HIFs. Conclusions FaSSCoF and FeSSCoF more closely predictsolubility of poorly soluble compounds in HCFs than plainbuffers. In most cases, solubility in HCFs differs from those inHGFs and HIFs.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

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PHARMACY

FARMACI

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