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.

Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing.

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.

CO2-Reactive Ionic Liquid Surfactants for the Control of Colloidal Morphology.

This article reports on a new class of stimuli-responsive surfactant generated from commercially available amphiphiles such as dodecyltrimethylammmonium bromide (DTAB) by substitution of the halide counterion with counterions such as 2-cyanopyrrolide, 1,2,3-triazolide, and L-proline that complex reversibly with CO2. Through a combination of small-angle neutron scattering (SANS), electrical conductivity measurements, thermal gravimetric analysis, and molecular dynamics simulations, we show how small changes in charge reorganization and counterion shape and size induced by complexation with CO2 allow for fine-tunability of surfactant properties. We then use these findings to demonstrate a range of potential practical uses, from manipulating microemulsion droplet morphology to controlling micellar and vesicular aggregation. In particular, we focus on the binding of these surfactants to DNA and the reversible compaction of surfactant-DNA complexes upon alternate bubbling of the solution with CO2 and N2.

Understanding and Analyzing Freezing-Point Transitions of Confined Fluids within Nanopores.

Understanding phase transitions of fluids confined within nanopores is important for a wide variety of technological applications. It is well known that fluids confined in nanopores typically demonstrate freezing-point depressions, ΔTf, described by the Gibbs-Thomson (GT) equation. Herein, we highlight and correct several thermodynamic inconsistencies in the conventional use of the GT equation, including the fact that the enthalpy of melting, ΔHm, and the solid-liquid surface energy, γ(SL), are functions of pore diameter, complicating their prediction. We propose a theoretical analysis that employs the Turnbull coefficient, originally derived from metal nucleation theory, and show its consistency as a more reliable quantity for the prediction of ΔTf. This analysis provides a straightforward method to estimate ΔTf of nanoconfined organic fluids. As an example, we apply this technique to ibuprofen, an active pharmaceutical ingredient (API), and show that this theory fits well to the experimental ΔTf of nanoconfined ibuprofen.