Online monitoring of dissolution tests using dedicated potentiometric sensors in biorelevant media.

The performance of the Ion-Selective Electrode (ISE) for in vitro dissolution testing using biorelevant media was evaluated in this study. In vitro dissolution was carried out using USP apparatus 2 (paddle method) with classical and with updated biorelevant media to simulate the pre- and postprandial states. The ISE was used as an analytical stand-alone system and in combination with a single-point HPLC-UV measurement. A modified method enabling the use of the ISE for very poorly soluble substances is also proposed. In terms of f(2)-factor, the results acquired using the ISE for the drug diphenhydramine-HCl were found to be very similar to the results obtained by manual sampling followed by HPLC-UV analysis. In Fed State Simulated Gastric Fluid (FeSSGF), a medium containing 50% milk, the ISE is more practical since the need to separate proteins from the analyte prior to HPLC-UV analysis is eliminated. Further work will be needed to establish ISE methodology for Fed State Simulated Intestinal Fluid (FeSSIF) media. In summary, the ISE has promise as an analytical tool for research and development applications.

In situ dissolution testing using potentiometric sensors.

Potentiometric sensors can be used to determine the amount of API dissolved in the dissolution medium in function of time by measuring directly in the dissolution vessel of a Paddle (USP type 2) and Basket (USP type 1) apparatus. The prototype potentiometric sensor instrumentation showed very promising results for a selection of APIs with different physico-chemical properties. The applicability, benefits and limitations of the prototype were explored. The applicability of the measurement technique strongly depends on the log(P) of the API. Here, it is shown that measurements can easily be performed for APIs with a log(P)>4. Electrode performance however decreases with decreasing logP of the APIs due to decreased drug selectivity in comparison to the excipients and ionic strength of the applied dissolution medium. The potentiometric sensors are shown to be insensitive towards undissolved particles and air bubbles as opposed to UV spectrometric measurement where these can lead to severe light scattering. For the tested APIs, the obtained dissolution profiles are very reproducible and show a low variation compared to the measurements using manual sampling and UV or HPLC analysis. The measurements demonstrate that potentiometric sensors are a very promising technology that can become a standard for in situ dissolution measurements.

Comparison of different surface modification techniques for electrodes by means of electrochemistry and micro synchrotron radiation X-ray fluorescence. dimerization of cobalt(II) tetrasulfonated phthalocyanine and its influence on the electrodeposition on gold surfaces.

This paper compares different electrochemical surface modification techniques with special attention to the immobilization of cobalt(II) tetrasulfonated phthalocyanine tetrasodium salt (Co(II)TSPc) on gold electrodes. Electrochemical and synchrotron radiation X-ray fluorescence (SR-XRF) microbeam analysis were performed in order to compare the amount of adsorbed CoTSPc onto the gold electrode and to determine the level of uniformity of the deposited layer. The nondestructive, quantitative characterization of CoTSPc deposition on gold electrodes by means of scanning SR-XRF on the microscopic scale has never been described before. The described methodology can be in general used for thin-film characterization. Depending on the degree of dimerization of the CoTSPc molecules, different electrochemical behavior is observed.