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Multidrug solids have a potential use to efficiently treat and control a superfluity of medical conditions.
To address the current drawbacks of drug development in R&D, it was targeted to achieve new pharmaceutical solid forms of fenamic acids having improved solubility and thermal stability. Subsequently, five new multicomponent solids consisting of three salt hydrates of trimethoprim (TMP) with mefenamic acid (TMP-MFA-H2O), tolfenamic acid (TMP-TFA-H2O) and flufenamic acid (TMP-FFA-H2O), and two cocrystals of sulfamethazine (SFZ) with flufenamic acid (SFZ-FFA) and niflumic acid (SFZ-NFA) were prepared by liquid assisted grinding. Looking at the structures of active pharmaceutical ingredient (API) molecules, it was quite expected that a wide range of supramolecular synthons would lead to cocrystallization.
New forms were characterized thoroughly by various solid-state techniques, including single crystal X-ray diffraction (SCXRD), which provided details of hydrogen bonding, molecular packing and interactions between drug and coformer. Kinetic solubility at pH 7.4 buffer study has been carried out and a comparison is made with respect to the parent drugs. A significant enhancement of NSAIDs solubility was observed in all salt hydrate systems of TMP. Thus with increasing physicochemical properties such as improved solubility further leads to the enhancement of bioavailability, which has implications to overcoming the formulation related problems of active pharmaceutical ingredients (APIs).
Effect of Tensile Loading and Temperature on the Hydrogen Solubility of Steels at High Gas Pressure
(2023)
The hydrogen solubility in ferritic and martensitic steels is affected by hydrostatic stress, pressure, and temperature. In general, compressive stresses decrease but tensile stresses increase the hydrogen solubility. This important aspect must be considered when qualifying materials for high‐pressure hydrogen applications (e.g., for pipelines or tanks) by using autoclave systems. In this work, a pressure equivalent for compensating the effect of compressive stresses on the hydrogen solubility inside of closed autoclaves is proposed to achieve solubilities that are equivalent to those in pipelines and tanks subjected to tensile stresses. Moreover, it is shown that the temperature effect becomes critical at low temperatures (e.g., under cryogenic conditions for storing liquid hydrogen). Trapping of hydrogen in the microstructure can increase the hydrogen solubility with decreasing temperature, having a solubility minimum at about room temperature. To demonstrate this effect, the generalized law of the hydrogen solubility is parameterized for different steels using measured contents of gaseous hydrogen. The constant parameter sets are verified and critically discussed with respect to the high‐pressure hydrogen experiments.
Die schädigende Alkali-Kieselsäure-Reaktion (AKR) im Beton stellt in Teilbereichen nach wie vor ein Problem bei der Bewertung der Dauerhaftigkeit von Beton dar. Eine der häufigsten Fragestellungen ist immer noch eine schnelle und sichere Beurteilung der Alkaliempfindlichkeit von Gesteinskörnungen für die Betonherstellung. In der Präsentation wird gezeigt, welchen Beitrag die Gesteinskörnung zur AKR im Beton hat. Dabei wird die Alkaliempfindlichkeit von Gesteinskörnungen quantifiziert und die zu erwartende Schädigung des Betons durch die Gesteinskörnung detaillierter als bisher möglich klassifiziert. Im Vordergrund der Präsentation steht dabei das Verständnis der Auflösungsprozesse von Gesteinskörnungen in KOH-Lösungen (pH ≥ 13) bei unterschiedlichen Reaktionsbedingungen.
Anhand von Löseversuchen an den originalen Lieferkörnungen der Gesteinskörnungen bei 40 °C und mit 1,0 M KOH-Lösung ist es möglich, die Reaktivität der Gesteinskörnungen mit den ermittelten SiO2- und Al2O3-Konzentrationen der alkalischen Lösungen zu beschreiben. Durch eine erhöhte Temperatur von 80 °C und eine abgesenkte Konzentration der KOH-Lösung von 0,1 M können innerhalb von 56 Tagen vergleichbare Ergebnisse zu den Resultaten der Löseversuche bei 40 °C und 1,0 M KOH-Lösung erreicht werden.
In der alkalischen Lösung wird ein bestimmter Teil des gelösten SiO2 durch ebenfalls vorhandenes Al2O3 alumosilikatisch gebunden. Der verbleibende Teil des gelösten SiO2 steht für eine AKR zur Verfügung. Aus der zeitabhängigen Darstellung dieser SiO2-Konzentration wird die Lösegeschwindigkeit ermittelt. Dabei werden vier aufeinanderfolgende Phasen dem Dehnungs- und Rissbreitenverlauf der Probekörper des 40 °C-Betonversuchs zugeordnet. Zur Beurteilung der Alkaliempfindlichkeit einer Gesteinskörnung sind die Lösegeschwindigkeiten der letzten drei Phasen entscheidend.
Die Methode bietet eine Möglichkeit, die Alkaliempfindlichkeit einer Gesteinskörnung schnell, sicher und genauer als bisher zu bestimmen. Besonders vorteilhaft sind dabei die direkte Prüfung der Gesteinskörnung an der originalen Korngröße (Lieferkörnung), die zementunabhängige Prüfung, sowie die einfache experimentelle Durchführung und Auswertung.
Processing and cytocompatibility of Cu-doped and undoped fluoride-containing bioactive glasses
(2024)
Sintered or additive-manufactured bioactive glass (BG) scaffolds are highly interesting for bone replacement applications. However, crystallization often limits the high-temperature processability of bioactive glasses (BGs). Thus, the BG composition must combine high bioactivity and processability. In this study, three BGs with nominal molar (%) compositions 54.6SiO2-1.7P2O3-22.1CaO-6.0Na2O-7.9K2O-7.7MgO (13–93), 44.8SiO2-2.5P2O3-36.5CaO-6.6Na2O-6.6K2O-3.0CaF2 (F3) and 44.8SiO2-2.5P2O3-35.5CaO-6.6Na2O-6.6K2O-3.0CaF2-1.0CuO (F3–Cu) were investigated. The dissolution and ion release kinetics were investigated on milled glass powder and crystallized particles (500–600 μm). All glasses showed the precipitation of hydroxyapatite (HAp) crystals after 7 days of immersion in simulated body fluid. No significant differences in ion release from glass and crystalline samples were detected. The influence of surface roughness on cytocompatibility and growth of preosteoblast cells (MC3T3-E1) was investigated on sintered and polished BG pellets. Results showed that sintered BG pellets were cytocompatible, and cells were seen to be well attached and spread on the surface after 5 days of incubation. The results showed an inverse relation of cell viability with the surface roughness of pellets, and cells were seen to attach and spread along the direction of scratches.
The solubility is generally thought to be higher if the solvent effectively solvates solute molecules that are well-separated from each other. The present work suggests, however, that the formation of large solute aggregates does not necessarily imply less effective solvation and lower solubility. Measurements of the solubility of simvastatin (one of the most commonly prescribed antihyperlipidemic drugs) in three solvents with different polarities and protic characters, led to the solubility order acetone > ethyl acetate > ethanol, in the full temperature range covered by the experiments (283–308 K). An analysis of the structures of the different solutions on the basis of molecular dynamics simulation results indicated that this trend seems to be determined by a balance between the solute tendency toward aggregation and the ability of the solvent to efficiently solvate it, by integrating the cluster structures, regardless of their size, and effectively establishing solvent–solute interactions.