Browsing by Subject "liukeneminen"

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  • Yli-Halla, Markku; Lumme, Ilari (Suomen metsätieteellinen seura, 1987)
  • Kyynäräinen, Kerttu (Helsingfors universitet, 2013)
    In vivo dissolution of drug molecules depends on the conditions in the gastrointestinal tract, like pH, composition of the fluids and hydrodynamics. Weakly basic compounds dissolve rapidly in low pH in stomach but in intestinal conditions forming of supersaturated solution may occur. This unstable state is the driving force either for rapid absorption from small intestine or for possible precipitation of drug. Difference in precipitation and thus in bioavailability between fasted and fed states can be significant. In this study behaviour of three weakly basic drugs, dipyridamole, ketoconazole and compound A, were studied with aid of two-phase microdissolution method. Three clinically relevant doses were used in the studies. In the study both fasted and fed states were tested as well as the effect of different pH in stomach phase and significance of biorelevant solutions over general buffer solutions. Dissolution of the drugs were examined in the media that simulate gastric fluids (SGF pH 1,2, SGF pH 4,0, FaSSGF pH 1,6 and acetate buffer pH 5,0). When biorelevant simulated intestinal fluid (FaSSIF or FeSSIF) was added to the solution to simulate the drug transfer out of stomach into small intestine, precipitation of different doses were analysed. Also the level of supersaturation compared to solubility results was examined. In addition the effects of various mixing speeds (300 rpm and 150 rpm) and scales (USP I and minidissolution) on precipitation were studied. Concentrations were measured directly from dissolution vessels with fibre optic probes. Re-dissolution of the drugs in small intestine and influence of physical properties on dissolution rate were evaluated with flow through dissolution method. In the fed state simulated microdissolution tests even the high doses of the drugs did not precipitate. Instead, in the tests simulating fasted state the effect of dose was clear and the relative part of dissolved drug were the smaller the higher was the dose. The high doses precipitated fast while the small doses remained much supersaturated. When FaSSGF was used the solutions staid longer in supersaturated state. Higher pH in stomach phase had remarkable impairing effect on the dissolved part of the drug in the small intestine phase and no supersaturated solutions were formed. In the microdissolution smaller mixing speed seemed to cause more precipitation and ranges of the results were larger. Different hydrodynamics in different scale dissolution methods as well caused divergent results. The effect of physical properties of precipitate to re-dissolution could be observed with the flow through dissolution tests. According to this study, two-phased dissolution method fit for few milligrams of API and it can be used to evaluate the precipitation potential of basic drugs in fasted and fed states. Also the effect of higher pH in the stomach on dissolved portion of API can be analysed. The method can be used as a risk assessment method for example when you want to know when the dose raises the risk to precipitation or as a tool to be used in early formulation development. As such dissolution tests can be used to get qualitative data of precipitation phenomenon when comparing basic drug compounds. The dissolution, precipitation and re-dissolution parameters will in future be utilised in pharmacokinetic model to evaluate the effect and significance of these phases on the drug absorption in vivo.
  • Asmala, Eero (Suomen ympäristökeskus, 2014)
    Monographs of the Boreal Environment Research No. 45
    The pool of riverine dissolved organic matter (DOM) results from integration of complex catchment processes, and links the terrestrial and coastal systems by transporting organic matter from watersheds to estuaries. In this thesis, field samplings and laboratory experiments were combined to assess the spatio-temporal variation in riverine DOM quantity and quality in three Finnish estuaries discharging to the Baltic Sea. Also, the biogeochemical transformation and removal processes influencing the composition of the DOM pool were studied. Large-scale catchment characteristics were linked to the properties of the riverine DOM. Throughout the work the DOM quality was assessed using multiple analytical approaches: C/N stoichiometry, colored DOM (CDOM) absorption, CDOM fluorescence, molecular weight and iron content. Estuarine DOM was subjected to heterotrophic degradation in factorial experiments to quantify the role of salinity, inorganic nutrients and predegradation to DOM bioavailability. Additionally salt-induced flocculation of DOM was studied by combining field samplings, laboratory experiments and modeling. The selected three study catchments differed markedly in their land-use, and these differences were reflected on the riverine DOM quantity and quality. The experiments provided evidence that increasing proportion of forests and peatlands were linked to the increase of carbon loading from the catchment, and to decreases in the subsequent quantities of bioavailable dissolved organic carbon (DOC) and bacterial growth efficiencies (BGE). A higher proportion of agricultural land in the catchment indicated an increase of the amount and bioavailability of dissolved organic nitrogen (DON) in the DOM pool. A larger proportion of lakes in the catchments were related to decreased bioavailable DON. Replete inorganic nutrients did not influence the DOM bioavailability, although did increase BGE on average from 11 to 40%. Increasing predegradation, i.e. DOM subjected to heterotrophic degradation for varying times before the actual bioassays, decreased BGE from 65 to 25% on average. Flocculation caused deviations from conservative mixing of DOM variables in the study estuaries, and the quantity and quality of flocculated DOM was studied in a laboratory experiment. The maximum deviation from conservative mixing of DOC in estuaries was -16% at salinities between 1 and 2, indicating significant flocculation within a relatively narrow salinity range. Both processes, biodegradation and flocculation, removed riverine DOM before reaching the open sea (so-called marginal filter), but also changed the properties of the remaining DOM pool. Also, both processes increased the humic-like fluorescence and DOC-specific absorbance of the DOM pool, which suggests that the refractory DOM pool reaching the sea is a result of multiple, interacting processes along the hydrological path. All in all, both biodegradation and flocculation remove riverine DOM in estuaries, and also transform the remaining DOM pool that ultimately reaches the open sea. Findings from this thesis show that DOM quality has a pivotal role in the functioning of both of these essential and ubiquitous mechanisms.