Peter Liljeroth

Micro ring–disk electrode probes for scanning electrochemical microscopy

Abstract The construction and characterisation of ring–disk (RD) microelectrodes suitable for use in scanning electrochemical microscopy (SECM) is reported. Such RD electrodes are proposed as probes for novel generator–collector SECM experiments. In this case, the interaction of both the reactants and products with the substrate under investigation can be followed simultaneously from a single approach curve to the substrate. Examples of such approach curves to conducting and insulating substrates are given to demonstrate the potential of this new mode of SECM operation.

Membrane activity of ionisable drugs - a task for liquid-liquid electrochemistry?

Abstract Structurally related aminoacridine therapeutics (aminacrine, tacrine, velnacrine and proflavine) were studied electrochemically at the interface between two immiscible electrolyte solutions. To assess both their neutral and ionic partition coefficients, cyclic voltammetry was used to obtain the transfer potential as a function of the aqueous phase pH. Subsequently, in order to create a simple model of a biological membrane, a lipid monolayer was deposited at the liquid–liquid interface using the Langmuir–Blodgett technique. Electrochemical impedance spectroscopy was employed to study the interactions between the drug ions and the biomimetic phospholipid monolayer. Using a model incorporating a charge transfer mechanism coupled with potential dependent adsorption steps, the membrane activity of the studied drug ions could be estimated. The results indicate liquid–liquid electrochemistry to be a versatile tool for detecting differences in membrane activity even between structurally very similar drugs.

Dissolution testing of acetylsalicylic acid by a channel flow method—correlation to USP basket and intrinsic dissolution methods

A new modification of the channel flow dissolution method is introduced together with the theoretical basis to extract the solubility and mass transfer parameters from the dissolution experiments. Correlation of drug dissolution profiles in the channel flow apparatus was evaluated with respect to USP basket and intrinsic dissolution methods at pH 1.2 or 6.8. Acetylsalicylic acid (ASA) was studied as a pure drug substance and as three simple tablet compositions with microcrystalline cellulose (MCC) and/or lactose as excipients. The channel flow measurements of 100% ASA tablets correlated well with the results of intrinsic dissolution tests. In the channel flow method as well as in the USP basket method the release of ASA was fastest from the tablet compositions containing lactose, while the slowest dissolution rate was observed with the composition containing MCC as the only excipient. As presumed, the dissolution rate of the weak acid was decreased as the pH of the medium was lowered, which was clearly confirmed also by the three dissolution methods. MCC forms matrix tablets and in the USP basket method the dissolution profiles followed square root of time kinetics indicating that diffusion was the rate-controlling step of ASA dissolution. Also the channel flow results indicated that the dissolution of ASA was controlled by mass transfer. The swelling behaviour of the tablets is different in the channel flow method as compared to the basket method: only one tablet surface is exposed to the dissolution medium in the channel flow system. The contact between the tablet surface and the dissolution medium is more similar between the channel flow and intrinsic dissolution methods.

Channel flow at an immobilised liquid | liquid interface

A novel rectangular channel flow electrochemical cell for the study of liquid | liquid interfaces is presented. The organic phase is immobilised by the use of a gelling agent, while the aqueous phase flows past the interface. This creates an asymmetric setup that allows us to establish diagnostic criteria to determine, for example, the direction of the ion transfer. The effects of varying flow rate and sweep rate have been considered both theoretically and experimentally. By comparison with two-dimensional simulations, it is demonstrated that a simple one-dimensional theory can be used to describe the cyclic voltammetry response of the channel flow cell.

Charge injection and lateral conductivity in monolayers of metallic nanoparticles

Scanning electrochemical microscopy has been used to quantify both the charge injection energetics between a solution redox couple and a monolayer of hexanethiol stabilised gold nanoparticles and the subsequent lateral charge transport in the monolayer.

Lipophilicity of ions electrogenerated at a Pt coated micropipette supported liquid-liquid interface

Abstract A novel method to readily determine the lipophilicity of electrogenerated charged species is reported. This is achieved by local electrolysis at a Pt coated micropipette and, subsequently, driving the electrogenerated species to transfer across the liquid–liquid interface supported at the tip of the micropipette under potential control. The formal potential of ion transfer can then be used to give a measure of its relative lipophilicity. The method proposed is facile and enables the study of potentially unstable charged products of electron transfer reactions.

Membrane activity of biotechnological peptide drugs.

Charged Langmuir-Blodgett monolayers deposited at an immobilised liquid-liquid interface have been used as a simple model for a biological membrane to investigate the membrane activity of biotechnological oligopeptide drugs.

A novel channel flow method in determination of solubility properties and dissolution profiles of theophylline tablets

Abstract A recently developed channel flow dissolution method was applied in the determination of compound solubility and the dissolution profiles of theophylline tablet formulations. As reference methods were used the USP basket and intrinsic dissolution methods. The four tablet compositions studied contained various proportions of lactose, microcrystalline cellulose (MCC), talc and magnesium stearate as pharmaceutical ingredients. The equilibrium constants of the dissolution reaction of theophylline (describing the relation between the dissolution and precipitation rate constants) in the individual tablet formulations, determined by the channel flow method, were similar at pH values of 1.2 and 6.8. The intrinsic dissolution rate of theophylline was slightly increased (from 0.9 to 1.1xa0mg/(cm 2 min)) as the pH of the medium was decreased. There were clear differences between the results of channel flow and USP basket methods. In the channel flow apparatus the two formulations including the highest amounts of MCC liberated the drug substance the slowest, while with the USP basket method the compositions including either MCC alone or the highest amount of lactose liberated the drug substance the slowest. These release profiles were caused by the different disintegration behaviour of the tablets in the two methods. The advantages of the channel flow method include the analysis of solubility properties of the drug substance and, in particular, when compared to the USP basket method, the study of the early stages of the dissolution process.