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.

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.

Scattering And Absorption of Light in Planetary Regoliths.

Theoretical, numerical, and experimental methods are presented for multiple scattering of light in macroscopic discrete random media of densely-packed microscopic particles. The theoretical and numerical methods constitute a framework of Radiative Transfer with Reciprocal Transactions (R2T2). The R2T2 framework entails Monte Carlo order-of-scattering tracing of interactions in the frequency space, assuming that the fundamental scatterers and absorbers are wavelength-scale volume elements composed of large numbers of randomly distributed particles. The discrete random media are fully packed with the volume elements. For spherical and nonspherical particles, the interactions within the volume elements are computed exactly using the Superposition T-Matrix Method (STMM) and the Volume Integral Equation Method (VIEM), respectively. For both particle types, the interactions between different volume elements are computed exactly using the STMM. As the tracing takes place within the discrete random media, incoherent electromagnetic fields are utilized, that is, the coherent field of the volume elements is removed from the interactions. The experimental methods are based on acoustic levitation of the samples for non-contact, non-destructive scattering measurements. The levitation entails full ultrasonic control of the sample position and orientation, that is, six degrees of freedom. The light source is a laser-driven white-light source with a monochromator and polarizer. The detector is a mini-photomultiplier tube on a rotating wheel, equipped with polarizers. The R2T2 is validated using measurements for a mm-scale spherical sample of densely-packed spherical silica particles. After validation, the methods are applied to interpret astronomical observations for asteroid (4) Vesta and comet 67P/Churyumov-Gerasimenko (Figure 1) recently visited by the NASA Dawn mission and the ESA Rosetta mission, respectively.