Nonclassical Crystallization of the L‑Tartrate Salt of Cyamemazine.

This study investigates the nonclassical crystallization of cyamemazine L-tartrate, a kryptoracemic salt of the antipsychotic drug cyamemazine. The crystallization pathway was studied via slurry conversion of a suspension of cyamemazine and L-tartaric acid in 2-propanol to the salt. Notably, the system transitioned through an intermediate droplet phase, which subsequently coalesced to form a dense phase.

Characterization of Solid-State Complexities in Pharmaceutical Materials via Stimulated Raman Scattering Microscopy.

In this study, we employed stimulated Raman scattering (SRS) microscopy, augmented with sum frequency generation, to characterize complex solid-state mixtures, containing many solid-state forms of the same compound, for the first time. Five crystalline forms and one amorphous form of lactose were characterized and resolved, including two more recently defined anhydrous solid-state forms. Additionally, the complex solid-state character of several commercially available pharmaceutical tableting and inhalation grades of lactose was profiled.

Nuclear envelope-associated lipid droplets are enriched in cholesteryl esters and increase during inflammatory signaling.

Cholesteryl esters (CEs) and triacylglycerols (TAGs) are stored in lipid droplets (LDs), but their compartmentalisation is not well understood. Here, we established a hyperspectral stimulated Raman scattering microscopy system to identify and quantitatively assess CEs and TAGs in individual LDs of human cells. We found that nuclear envelope-associated lipid droplets (NE-LDs) were enriched in cholesteryl esters compared to lipid droplets in the cytoplasm.

Chemically Specific Coherent Raman Imaging of Liquid-Liquid Phase Separation and Its Sequelae.

Liquid-liquid phase separation (LLPS) plays a pivotal role in processes ranging from cellular structure reorganization to the formation of crystalline structures in materials science. In the pharmaceutical field, it has been demonstrated to impact drug crystallization and delivery. To date, characterization of LLPS has been limited to nonspatially resolved or nonchemically resolved analyses.

Understanding the complexity of near-infrared quantification of highly porous patient-tailored drug products by utilizing chemometrics and stimulated Raman imaging.

Additively manufactured drug products, typically produced using small-scale, on-demand batch mode, require rapid and non-destructive quantification methods. A tunable modular design (TMD) approach combining porous polymeric freeze-dried modules and an additive manufacturing method, inkjet printing, was proposed in an earlier study to fabricate accurate and patient-tailored doses of an antidepressant citalopram hydrobromide. This approach addresses the unmet medical needs associated with antidepressant tapering.

Dynamic Phase Behavior of Amorphous Solid Dispersions Revealed with Stimulated Raman Scattering Microscopy.

This study reports the application of stimulated Raman scattering (SRS) microscopy for real-time chemically specific imaging of dynamic phase phenomena in amorphous solid dispersions (ASDs). Using binary ritonavir and poly(vinylpyrrolidone-vinyl acetate) films with different drug loadings (0-100% w/w) as model systems, we employed SRS microscopy with fast spectral focusing to analyze ASD behavior upon contact with a dissolution medium. Multivariate unmixing of the SRS spectra allowed changes in the distributions of the drug, polymer, and water to be (semi)quantitatively imaged in real time, both in the film and the adjacent dissolution medium.

Use of dairy industry side-stream lactose for tablet manufacturing - proof of concept study.

During recent years there have been shortages of certain drugs due to problems in raw material supply. These are often related to active ingredients but could also affect excipients. Lactose is one of the most used excipients in tableting and comes in two anomeric and several solid-state forms.

Rheological insights into 3D printing of drug products: Drug nanocrystal-poloxamer gels for semisolid extrusion.

The importance of ink rheology to the outcome of 3D printing is well recognized. However, rheological properties of printing inks containing drug nanocrystals have not been widely investigated. Therefore, the objective of this study was to establish a correlation between the composition of nanocrystal printing ink, the ink rheology, and the entire printing process.

Radiocarbon dioxide detection using cantilever-enhanced photoacoustic spectroscopy.

In this Letter, we report on the sub-parts-per-billion-level radiocarbon dioxide detection using cantilever-enhanced photoacoustic spectroscopy. The / ratio of samples is measured by targeting a absorption line with minimal interference from other isotopes. Using a quantum cascade laser as a light source allows for a compact experimental setup.

Broadband Laser-Based Infrared Detector for Gas Chromatography.

Cantilever-enhanced photoacoustic spectroscopy coupled with gas chromatography is used to quantitatively analyze a mixture of alcohols in a quasi-online manner. A full identification and quantification of all analytes are achieved based on their spectral fingerprints using a widely tunable continuous-wave laser as a light source. This can be done even in the case of interfering column/septum bleed or simultaneously eluted peaks.

Broadband photoacoustic spectroscopy of CH14 with a high-power mid-infrared optical frequency comb.

We report a photoacoustic spectroscopy setup with a high-power mid-infrared frequency comb as the light source. The setup is used in broadband spectroscopy of radiocarbon methane. Owing to the high sensitivity of a cantilever-enhanced photoacoustic cell and the high-power light source, we can reach a detection limit below 100 ppb in a broadband measurement with a sample volume of only a few milliliters.

Cavity-enhanced cantilever-enhanced photo-acoustic spectroscopy.

We have improved the sensitivity of a state-of-the-art cantilever-enhanced photo-acoustic trace gas sensor by combining it with an optical power build-up cavity. The build-up cavity enhances the photo-acoustic signal by a factor of ∼100, resulting in an exceptionally good normalised noise equivalent absorption (NNEA) value of 1.75 × 10-12 W cm-1 Hz-1/2.

Sub-parts-per-trillion level sensitivity in trace gas detection by cantilever-enhanced photo-acoustic spectroscopy.

An exceptional property of photo-acoustic spectroscopy is the zero-background in wavelength modulation configuration while the signal varies linearly as a function of absorbed laser power. Here, we make use of this property by combining a highly sensitive cantilever-enhanced photo-acoustic detector, a particularly stable high-power narrow-linewidth mid-infrared continuous-wave optical parametric oscillator, and a strong absorption cross-section of hydrogen fluoride to demonstrate the ability of cantilever-enhanced photo-acoustic spectroscopy to reach sub-parts-per-trillion level sensitivity in trace gas detection. The high stability of the experimental setup allows long averaging times.

Spectroscopic thermometry for long-distance surveying.

Electronic distance meters are routinely used to accurately determine the distance between two points. To reach relative measurement uncertainties of 10, the average temperature along the beam has to be known within 100 mK since it is a key component in determining the refractive index of air. Temperature measurements at this level are extremely challenging over long distances and especially in an outdoor environment.