Tracking yeast metabolism and the Crabtree effect in real time via CO2 production using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

In this study, a new approach to measure metabolic activity of yeast via the Crabtree effect is described. BARDS is an analytical technique developed to aid powder and tablet characterisation by monitoring changes in the compressibility of a solvent during solute dissolution. It is a rapid and simple method which utilises a magnetic stir bar to mix added solute and induce the acoustic resonance of a vessel containing a fixed volume of solvent. In this study it is shown that initiation of fermentation in a yeast suspension, in aqueous buffer, is accompanied by reproducible changes in the frequency of induced acoustic resonance. These changes signify increased com-pressibility of the suspension due to CO2release by the yeast. A simple standardised BARDS protocol reveals yeast carbon source preferences and can generate quantitative kinetic data on carbon source metabolism which are characteristic of each yeast strain. The Crawford-Woods equation can be used to quantify total gaseous CO2produced by a given number of viable yeast when supplied with a fixed amount of carbon source. This allows for a value to be calculated for the amount of gaseous CO2produced by each yeast cell. The approach has the potential to transform the way in which yeast metabolism is tracked and potentially provide an orthogonal or surrogate method to determining viability, vitality and attenuation measurements in the future

Tracking cocrystallization of active pharmaceutical ingredients with Bbenzoic acid coformer using Broadband Acoustic resonance Dissolution Spectroscopy (BARDS)

This study investigates the use of Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) as a detection method for the formation of cocrystals. BARDS is a novel approach that uses reproducible changes in the compressibility of a solvent as a sample dissolves to characterize and differentiate between materials and in this case cocrystallization. Two cocrystal systems with a 1:1 stoichiometry were examined, which used benzoic acid as a coformer with isonicotinamide and with theophylline. Cocrystals were prepared using dry and wet milling for periods from 1 to 40 min, and samples were analyzed using infrared spectroscopy, powder X-ray diffraction, and BARDS. Comparison of the BARDS data with the IR and PXRD data cross-validated the BARDS results. This study shows that BARDS can be used to rapidly assess the formation of these cocrystals at-line when milling or as a relatively low cost tool in preformulation product development. The data can also be used to gauge the unique entrained gas and gas volume generation of the cocrystal samples during dissolution and their dissolution kinetics

Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): a rapid test for enteric coating thickness and integrity of controlled release pellet formulations

There are no rapid dissolution based tests for determining coating thickness, integrity and drug concentration in controlled release pellets either during production or post-production. The manufacture of pellets requires several coating steps depending on the formulation. The sub-coating and enteric coating steps typically take up to six hours each followed by additional drying steps. Post production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Also, the amount of drug per unit mass decreases with increasing thickness of the enteric coating. In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by HPLC

Percutaneous absorption of m-xylene vapour in volunteers during pre-steady and steady state

Percutancous absorption of m-xylene (XYL) was determined in volunteers exposed to 29.4 mug cm(-1) XYL vapour on the forearm and hand for 20, 45, 120 and 180 min. The internal exposure was assessed by measuring the concentration of XYL in exhaled air. The systemic kinetics were determined using a reference exposure by inhalation. The dermal permeation rate and the cumulative absorption of XYL as a function of time were calculated using mathematical deconvolution. From these relationships, the average flux into the skin throughout the exposure (J(skin), average) and the maximal flux into the blood (J(bood.max)) were derived. Both fluxes were dependent on the duration of exposure, approaching each other at longer exposure durations. The values of J(skin.average), adjusted to a concentration of 1 mug cm(-3), were 0.091 mug cm(-2) h(-1) during 20-min exposure falling to 0.072, 0.066 and 0.061 mug cm(-2) h(-1) for 45, 120 and 180min, respectively. The values of J(blood, max) showed an opposite trend, gradually increasing from 0.034 mug cm(-2) h(-1) at an exposure duration of 20 min to 0.042, 0.059 and 0.063 mug cm(-2) h(-1) for 45, 120 and 180 min of exposure durations, respectively. (C) 2004 Elsevier Ireland Ltd. All rights reserve

Tracking compression changes in an aqueous electrolyte for real-Time H2 and O2 gas evolution quantification during total water splitting using BARDS

Hydrogen fuel cell technology has the potential for integration with renewable energy sources to produce electricity without the need for fossil fuels. Efforts are being made in producing cheap and effective electrodes from new materials to make hydrogen production more efficient. Gas evolution, in all cases, requires an accurate analysis of electrochemical behaviour of electrodes to quantify efficiency, improvement or stability. Knowing the exact gas volume by any method in real-time during electrochemical water splitting is urgently needed. Taking inspiration from the existing Broadband Acoustic Resonance Dissolution Spectroscopy technique, we demonstrate a new approach to continuously track electrochemical water splitting via gas volume evolution from hydrogen evolution reactions (HER) and oxygen evolution reactions (OER) processes. The technique may be used to unravel the true features of new electrode materials that evolve hydrogen, and correlate material electrochemistry to the true gas volume evolved in real-time

Sounding out falsified medicines from genuine medicines using broadband acoustic resonance dissolution spectroscopy (BARDS)

The trade in falsified medicine has increased significantly and it is estimated that global falsified sales have reached $100 billion in 2020. The EU Falsified Medicines Directive states that falsified medicines do not only reach patients through illegal routes but also via the legal supply chain. Falsified medicines can contain harmful ingredients. They can also contain too little or too much active ingredient or no active ingredient at all. BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy) harnesses an acoustic phenomenon associated with the dissolution of a sample (tablet or powder). The resulting acoustic spectrum is unique and intrinsic to the sample and can be used as an identifier or signature profile. BARDS was evaluated in this study to determine whether a product is falsified or genuine in a rapid manner and at lower cost than many existing technologies. A range of genuine and falsified medicines, including falsified antimalarial tablets from south-east Asia, were tested, and compared to their counterpart genuine products. Significant differences between genuine and falsified doses were found in their acoustic signatures as they disintegrate and dissolve. Principal component analysis was employed to differentiate between the genuine and falsified medicines. This demonstrates that the tablets and capsules included here have intrinsic acoustic signatures which could be used to screen the quality of medicines