A drug-excipient interaction impurity of bromhexine hydrochloride injection: Structure and formation mechanism elucidation.

A long-term stability study using high performance liquid chromatography (HPLC) revealed an unidentified impurity in the bromhexine hydrochloride injection, which was employed as a mucolytic agent. Investigations into stress degradation and elemental impurities revealed one of the elemental impurities Fe3+ in this injection as the primary generator of these impurities. This impurity, named N-carboxymethyl bromhexine, was a product formed during drug-excipient interaction between bromhexine and tartaric acid with Fe3+. The structure of the impurity was identified through ultra-high-performance liquid chromatography with diode array detector (UHPLC-DAD), liquid chromatograph mass spectrometer (LC-MS). Further, the formation mechanism of the impurity was discussed. Overall, this study elucidates the cause, origin, and mechanism of an unknown impurity in bromhexine hydrochloride injection, providing a basis for quality control for bromhexine hydrochloride injections and drug products containing both amine and tartaric acid.

Preparation of Geopolymers with Nanosilica and Water-in-Air Pickering Emulsion: Mechanisms Underlying Its Rheology, Polymerization, and Strength.

Geopolymers are alkaline-activated aluminosilicate binders recognized as a promising alternative to traditional Portland cement due to their significantly lower greenhouse emissions, energy consumption, and carbon footprint. However, the challenge is meeting or exceeding the strength of Portland cement concrete while being prepared within a desired setting time and possessing workable rheology. A "water-in-air" Pickering emulsion, also called dry water, was prepared by stabilizing water droplets with hydrophobic nano silica and using them to control the geopolymer's strength, setting time, and workability. The mechanisms that underlie the effects of dry water on the rheology, setting, and strength were studied in detail through a combination of rheological, thermal, morphological, chemical, and microstructural assessments. A reduction in the viscosity and yield shear stress manifests in a higher flow diameter, principally due to the particle size coarsening in the precursor and the flowability of hydrophobic nano silica. There was a rapid rise in temperature during the setting process as the dry water temporarily increased the local alkalinity in the mixture, which boosted the dissolution of the precursor and, hence, the reaction. Outcomes from X-ray diffraction, thermogravimetric analysis, and Fourier-transform infrared confirm the highest degree of polycondensation for the principal N-A-S-H framework in mixtures containing dry water. These eventually correspond to a denser microstructure under scanning electron microscopy and, in turn, a superior mechanical strength. Depending on the unique combination of characteristics, including size coarsening, temporary water encapsulation, microfilling effect, and supplementary silica source, dry water resolves the "trade-off" between geopolymer's fresh and hardened properties when introducing nanoparticles.

Application of a new body surface-assisting puncture device in percutaneous transforaminal endoscopic lumbar discectomy.

BACKGROUND: Accurate puncture and localization are critical for percutaneous transforaminal endoscopic lumbar discectomy surgery. However, several punctures are often required, followed by X-ray fluoroscopy, which can increase surgical risk and complications. The aim of this study was to demonstrate a new body surface-assisting puncture device that can be used in percutaneous transforaminal endoscopic lumbar discectomy and to assess its clinical effectiveness. METHODS: Three hundred and forty-four patients were treated with percutaneous transforaminal endoscopic lumbar discectomy surgery in the Spinal Surgery Department of Taian City Central Hospital, China, between January 2020 and February 2022. Of these, 162 patients (the locator group) were punctured using a body surface-assisting puncture device while and 182 patients (the control group) were punctured using the traditional blind puncture method. The number of punctures, radiation dose during X-ray fluoroscopy, operation time, and surgical complications were compared between the two groups. RESULTS: The average number of punctures was 2.15 ± 1.10 in the locator group which was significantly lower than that in the control group (5.30 ± 1.74; P < 0.001). The average X-ray fluoroscopy radiation dose in the locator group was significantly lower at 2.34 ± 0.99 mGy, compared with 5.13 ± 1.29 mGy in the control group (P < 0.001). The mean operation time was also significantly less in locator group (47.06 ± 5.12 vs. 62.47 ± 5.44 min; P = 0.008). No significant differences in surgical complications were found between the two groups (P > 0.05). CONCLUSION: The use of a new body surface-assisting puncture device in percutaneous transforaminal endoscopic lumbar discectomy surgery can significantly reduce the number of punctures and X-ray fluoroscopy radiation dose, as well as shortening the operation time, without increasing surgical complications. This device is cheap, easy to operate, and suitable for all hospitals and spine surgeons, especially for small hospitals, with also no extra costs for patients.

Experimental Characterization and Multi-Factor Modelling to Achieve Desired Flow, Set and Strength of N-A-S-H Geopolymers.

The interaction between compositional ratios, namely, SiO2/Al2O3, Na2O/Al2O3, H2O/Na2O and the liquid-to-solid ratio, triggers mutual sacrifice between workability, setting time and strength for N-A-S-H geopolymers. The present study characterizes the mechanism underlying the effect of these compositional ratios and, in turn, develops guidelines for mixture design that requires a simultaneous and satisfactory delivery of these engineering properties. The experimental results show that an increase in either the SiO2/Al2O3, Na2O/Al2O3 or H2O/Na2O ratio raises the liquid-to-solid ratio, which in turn improves the workability of fresh mixtures. A continuous increase beyond 2.8 for the SiO2/Al2O3 ratio boosts its strength, but also significantly extends its final set. Lowering the Na2O/Al2O3 ratio from 1.3 to 0.75 raises the compressive strength significantly, while the shortest final set was seen at the median value, 1.0. A H2O/Na2O ratio of 9~10 yields the highest strength and the fastest final set simultaneously, due to the maximized degree of geopolymerization. Moreover, the accompanying sensitivity analysis indicates that the workability depends chiefly upon the H2O/Na2O ratio, the final setting time on the SiO2/Al2O3 ratio and, that the compressive strength relies on both of them. Also, this study proposes an optimal range of 2.8~3.6 for SiO2/Al2O3, 0.75~1.0 for Na2O/Al2O3 and 9~10 for H2O/Na2O to guarantee high strength, together with high flow and within the allowable final setting time. Furthermore, multi-factor predictive models are established with acceptable accuracy for practitioners to regulate oxide compositions in N-A-S-H geopolymers, which will guide future mixture design.