The oral bioavailability of a drug substance is strongly related to its aqueous solubility. Only complete dissolution during the GI-passage can maintain an optimal bioavailability. Poor aqueous drug solubility results, according to the Nernst-Brunner equation into a slow dissolution rate, sometimes too slow for complete dissolution in the GI tract. The dissolution rate increases with decreasing particle size and therefore increasing surface area of the drug particles. In consequence,, micronization of the drug is applied to increase oral bioavailability, but often meets with modest success. Recently developed techniques were applied to decrease the particle size into the nanometer range. For some substances, pharmacokinetic parameters could be influenced decisively, e.g. the obviation of a food effect for the drugs aprepitant and fenofibrate. The assessment of a dosage form is investigated by dissolution testing. For a reasonable assessment of such tests, a separation of solid and liquids has to be ensured within an appropriate time frame. For particle sizes of about 150 nm it appears questionable whether such separation can be succeeded by classical techniques, e.g. the use of syringe filters with a pore size of 0.45 μm. The aims of this thesis were to investigate the suitability of various analytical techniques in analysis of dissolution tests containing nanosized drug substance. Furthermore, a suitable analytical tool is applied to establish an in vitro – in vivo correlation of the nanosized drug fenofibrate. At first, several techniques were investigated in theory to assess their ability to ensure a rapid and complete separation of solids and liquids. The classical dialysis, turbidity measurement and UV-measurement via fiber optics were excluded from further investigation due to various reasons, e.g. the speed of separation for dyialisis. The asymmetrical flow field-flow fractionation appeared to be a promising tool, but lack of equipment precluded further investigation. The ultrasonic resonance technology (ResoScan), the microdialysis and the use of centrifugal filter devices have shown to be inappropriate for the analytics of nanosized drugs in dissolution test. The use of syringe filters with various pore sizes and the ionselective electrode (ISE) was promising, so these techniques were examined more intensively. The syringe filters with various filter pore sizes were investigated for their ability to hold back colloidal drug. Fenofibrate was chosen as model drug, since this is commercially available both as micronized and nanosized formulation (Lipidil TerR and Lipidil 145 ONER), enabling direct comparison. The experiments with micronized fenofibrate which contains little or no colloidal fenofibrate yielded similar dissolution profiles, irrespective of filter pore size; f2 was always greater than 65, indicating less than 5% difference between the dissolution profiles in any medium. Using a pore size of 0.1 μm or less, the maximum concentration of drug achieved in solution from the nanosized formulation was commensurate with the saturation solubility of fenofibrate in all tested media. Filtration with a pore size of 0.2 μm or 0.45 μm generated concentrations exceeding the saturation solubility. These results, in combination with higher standard deviations of the analytical results, indicate that the apparent “supersaturation” is caused by colloidal fenofibrate, which is too fine to be held back by these filters. The f2-value of less than 50 when comparing the profiles obtained from 0.1 μm and 0.2 μm filter pore size indicates that the choice of filter pore size is crucial to the interpretation of the dissolution profiles. To separate nanosized drug from molecularly dissolved fenofibrate in Lipidil 145 ONER, a filter pore size of 0.1 μm or less appears to be appropriate. It was observed that the experimental increase of dissolution rate is not congruent with common hypothesis regarding the boundary layer h for decreasing particle sizes and subsequent application of the Nernst-Brunner equation. The initial dissolution rates of both formulations were investigated by using a filter pore size of 0.1 μm. The results were utilized in an in silico model (STELLAc) to correlate the in vitro results with in vivo data (Model A). In the preprandial state a good in correlation was established for the micronized fenofibrate, while for the nanosized fenofibrate the plasma levels were overpredicted. The model was expanded to investigate the impact of an absorption step at the intestinal membrane on the in vitro – in vivo correlation. It was found that even a minor deceleration of absorption results in varied plasma profiles caused by a lagged appearance of drug in the blood. For both formulations the rate determining step was identified: When changing from the micronized to the nanosized formulation, the rate-determining step for absorption may change from completely dissolution-controlled to at least partly permeationcontrolled in the fasted state. In the fed state, gastric emptying appears to be rate-determining for absorption of fenofibrate from both the micronized and the nanosized formulation. Another technique appears to be suitable for analysis of nanosized drugs in dissolution testing. The Ion-selective electrode (ISE) is a recently developed analytical system measuring the changes of the electrochemical potential in solutions. A transformation via the Nikolski – Eisenmann equation results into the concentration of the respective drug in solution. Since only dissolved drug is detected, obviating the need for separation of dissolved from undissolved drug, this system appears to be very promising in the analytics of nanocrystalline drugs. Diphenhydramine_HCl was chosen as model substance for the ISE studies. It was the goal of investigation to test compatibility of the ISE with complex media, e.g. all biorelevant dissolution media. This is done in advance of application of the ISE in these media for nanocrystalline drug substance. The results were compared to manual sampling, filtration and subsequent HPLC-UV analysis. The results demonstrate that the ion-selective electrode is suitable for measurements of diphenhydramine HCl in fasted state biorelevant media (FaSSGF, FaSSIF, FaSSIF-V2) as both a stand-alone system (Method A) and in conjunction with a single point conventional assay (Method B). The results acquired are similar to those obtained by manual sampling and subsequent HPLC-UV analysis. The ISE also delivers satisfactory results in a milk-based medium (FeSSGF), in which it has distinct advantages over manual sampling with HPLC-UV analysis by obviating the need for sample preparation. The application of the ISE in FeSSIF type media will need further study. Finally, as an on-line technology, ISE offers more efficient generation of dissolution profiles than conventional sample-based methods.