| 1. |
- Vertzoni, Maria, et al.
(författare)
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Biorelevant media to simulate fluids in the ascending colon of humans and their usefulness in predicting intracolonic drug solubility
- 2010
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 27:10, s. 2187-2196
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Vertzoni, Maria, et al.
(författare)
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Characterization of the ascending colon fluids in ulcerative colitis
- 2010
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 27:8, s. 1620-1626
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To characterize the fluid composition in ascending colon of fasted adults with ulcerative colitis in relapse and in remission with a view to predicting variations on dosage form performance in the lower inflamed gut. Methods: Twelve patients participated in a two-phase, crossover study. Enrolment to the relapse phase (Phase A) and designation of the remission state for the second colonoscopy (Phase B) were based on Clinical Rachmilewicz Index values. Samples were analyzed for pH and buffer capacity immediately upon collection. After ultracentrifugation, osmolality, surface tension, soluble protein, soluble carbohydrates, and the levels of ten bile acids, seven short-chain fatty acids (SCFAs), three long-chain fatty acids, triglycerides, diglycerides, monoglycerides, phosphatidylcholine, and cholesterol were measured. Results: Total SCFAs are significantly decreased in relapse, but pH remains unaffected. Regardless of remission/relapse status, pH and isobutyric acid levels are lower than in healthy adults. Buffer capacity, osmolality, and soluble protein are higher than in healthy adults. Treatment with prednisolone increases the volume of intracolonic contents. Conclusion: Variations in fluid composition of the ascending colon with activity and severity of ulcerative colitis may have an impact on the performance of orally administered products that are targeted to release the therapeutic agent in the colon.
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| 3. |
- Vertzoni, Maria, et al.
(författare)
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Degradation kinetics of metronidazole and olsalazine by bacteria in ascending colon and in feces of healthy adults
- 2011
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 413:1-2, s. 81-86
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To compare the degradation kinetics of metronidazole and olsalazine by the bacteria of ascending colon and the bacteria of feces of healthy adults. METHODS Contents of the ascending colon of seven healthy adults were collected under conditions simulating the bioavailability/bioequivalence studies in the fasted and in the fed states on a crossover basis. Material from the contents of the ascending colon was prepared by ultracentrifuging and diluting the precipitate with a volume of normal saline equivalent to that of the supernatant. Fecal material was prepared from feces of three healthy adults collected at two occasions that were separated by at least 6 months. Ex vivo drug degradation kinetics were evaluated under anaerobic conditions. RESULTS Mean half-lives of metronidazole degradation in material from the contents of the ascending colon collected in the fasted state and in fecal material were 16.1 and 2.4 min, respectively (p<0.001). The corresponding numbers for olsalazine were 57.8 and 9.2 min, respectively (p<0.001). Both compounds were stable in material from the contents of ascending colon collected in the fed state. CONCLUSIONS Compared with data in fecal material, degradation of metronidazole and olsalazine in material from the contents of the ascending colon is significantly slower and it becomes non-significant during the arrival of fresh food remnants in the region.
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