UV-visible absorption spectroscopy for in-line API concentration measurement in nanoparticle production process using controlled expansion of supercritical solutions (CESS®).

Most new small drug molecules in pharmaceutical development require improvement of solubility. The controlled expansion of supercritical solutions (CESS®) process is a nanoparticle production technology, dedicated to enhancing the dissolution rate of active pharmaceutical ingredients (APIs) suffering from poor solubility and enabling novel drug delivery opportunities. In this process, the API is dissolved in supercritical carbon dioxide (scCO2) and nanoparticles are formed through controlled pressure reduction. To improve process visibility and control, ultraviolet-visible (UV-Vis) spectroscopy was incorporated into CESS® process as a process analytical technology (PAT) tool. The tool quantifies the amount of API dissolved in scCO2 during the solubilization phase of the process. Sample interfacing of the UV-Vis spectrometer was done with a custom-made pressure and temperature rated transmission flow-through cell. In-process calibration was developed to correlate the UV-Vis absorption spectra to the API concentration. Due to the density-dependent molar absorption coefficient of API in scCO2, the calibration was done for each combination of temperature and pressure. The developed PAT tool provides insight into the process enabling real-time API quantity estimation. It also facilitates process development through Quality by Design (QbD) and offers a system for enhanced process control and troubleshooting. For instance, the in-line API concentration data allows one to study the solubilization behavior of the API in the process and to optimize the process parameters in order to maximize throughput.

Ultrasonic actuation of a fine-needle improves biopsy yield.

Despite the ubiquitous use over the past 150 years, the functions of the current medical needle are facilitated only by mechanical shear and cutting by the needle tip, i.e. the lancet. In this study, we demonstrate how nonlinear ultrasonics (NLU) extends the functionality of the medical needle far beyond its present capability. The NLU actions were found to be localized to the proximity of the needle tip, the SonoLancet, but the effects extend to several millimeters from the physical needle boundary. The observed nonlinear phenomena, transient cavitation, fluid streams, translation of micro- and nanoparticles and atomization, were quantitatively characterized. In the fine-needle biopsy application, the SonoLancet contributed to obtaining tissue cores with an increase in tissue yield by 3-6× in different tissue types compared to conventional needle biopsy technique using the same 21G needle. In conclusion, the SonoLancet could be of interest to several other medical applications, including drug or gene delivery, cell modulation, and minimally invasive surgical procedures.

Controlling oleogel crystallization using ultrasonic standing waves.

Oleogels are lipid-based soft materials composed of large fractions of oil (> 85%) developed as saturated and hydrogenated fat substitutes to reduce cardiovascular diseases caused by obesity. Promising oleogels are unstable during storage, and to improve their stability careful control of the crystalline network is necessary. However, this is unattainable with state-of-the-art technologies. We employ ultrasonic standing wave (USSW) fields to modify oleogel structure. During crystallization, the growing crystals move towards the US-SW nodal planes. Homogeneous, dense bands of microcrystals form independently of oleogelator type, concentration, and cooling rate. The thickness of these bands is proportional to the USSW wavelength. These new structures act as physical barriers in reducing the migration kinetics of a liposoluble colorant compared to statically crystallized oleogels. These results may extend beyond oleogels to potentially be used wherever careful control of the crystallization process and final structure of a system is needed, such as in the cosmetics, pharmaceutical, chemical, and food industries.

Practical realization of a sub-λ/2 acoustic jet.

Studies in optics and acoustics have employed metamaterial lenses to achieve sub-wavelength localization, e.g. a recently introduced concept called 'acoustojet' which in simulations localizes acoustic energy to a spot smaller than λ/2. However previous experimental results on the acoustojet have barely reached λ/2-wide localization. Here we show, by simulations and experiments, that a sub-λ/2 wide localization can be achieved by translating the concept of a photonic jet into the acoustic realm. We performed nano- to macroscale molecular dynamics (MD) and finite element method (FEM) simulations as well as macroscale experiments. We demonstrated that by choosing a suitable size cylindrical lens, and by selecting the speed-of-sound ratio between the lens material(s) and the surrounding medium, an acoustic jet ('acoustic sheet') is formed with a full width at half maximum (FWHM) less than λ/2. The results show, that the acoustojet approach can be experimentally realized with easy-to-manufacture acoustic lenses at the macroscale. MD simulations demonstrate that the concept can be extended to coherent phonons at nanoscale. Finally, our FEM simulations identify some micrometer size structures that could be realized in practice. Our results may contribute to starting a new era of super resolution acoustic imaging: We foresee that jet generating constructs can be readily manufactured, since suitable material combinations can be found from nanoscale to macroscale. Tight focusing of mechanical energy is highly desirable in e.g. electronics, materials science, medicine, biosciences, and energy harvesting.