Supersaturated State Research Articles

Phase Separation Investigation of Axitinib in Supersaturated Solution

Phase separation is quite common in formulations for hydrophobic active pharmaceutical ingredients (APIs) due to their thermodynamic instability in a supersaturated state during in vitro dissolution or in vivo absorption. Phase separation possibly accompanies the formation of a disordered drug-rich phase, but this is still not thoroughly understood. In this study, the phase separation of supersaturated axitinib (Axi) in media with or without polymers was evaluated via multiple analytical methods, including UV–vis and fluorescence spectroscopy, dynamic light scattering, and microscopy. The phase separation of Axi occurred at an Axi concentration of 25–30 µg/mL in the media, while the addition of quantitative hypromellose acetate succinate (HPMCAS) MG and povidone (PVP) K30 did not alter its phase separation concentration. The second scattering dispersion phase of the system exhibited superior stability and reversibility as the formative filamentous crystalline condensates could disintegrate upon dilution. These disparate analyses consistently detected the phase separation of Axi. This manuscript could provide a better understanding of the supersaturation state of hydrophobic APIs upon pharmaceutical application.

Polymer‐Assisted Nucleation for Stable Single‐Crystal Perovskite Thin Films

AbstractOrganic‐inorganic hybrid perovskite single crystals have emerged as a strong candidate in photovoltaic and general optoelectronic applications. However, the high supersaturation of the precursor solution leads to the rapid formation of a significant number of nuclei and a diminished concentration of perovskite solute. Consequently, the inadequate availability of precursors poses challenges in sustaining the subsequent crystal growth phase, culminating in the development of small‐sized single crystals. In this work, we report a controlled nucleation process to foster the growth of large‐size single crystals. This method through the coordination interaction between polyacrylic acid and Pb2+ ions, and substitution of the coordination with I− ions. This reduces the formation of the Pb‐I6 complex, which promptly emerges in a state of supersaturation and acts as a nucleus, thereby effectively reducing the number of nuclei formed. The single crystals produced using this method exhibit a lateral size exceeding 5 mm, an extended absorption range, a longer carrier lifetime of 10.93 ns, and enhanced stability. These crystals demonstrate the ability to remain stable even after storage in an ambient environment (T=20±5 °C, RH=60±5 %) for a period of 20 days.

Solutions and case studies for thermally driven reactive transport and porosity evolution in geothermal systems (reactive Lauwerier problem)

Abstract. Subsurface non-isothermal fluid injection is a ubiquitous scenario in energy and water resource applications, which can lead to geochemical disequilibrium and thermally driven solubility changes and reactions. Depending on the nature of the solubility of a mineral, the thermal change can lead to either mineral dissolution or precipitation (due to undersaturation or supersaturation conditions). Here, by considering this thermo-hydro-chemical (THC) scenario and by calculating the temperature-dependent solubility using a non-isothermal solution (the so-called Lauwerier solution), thermally driven reactive transport solutions are derived for a confined aquifer. The coupled solutions, hereafter termed the “reactive Lauwerier problem”, are developed for axisymmetric and Cartesian symmetries and additionally provide the porosity evolution in the aquifer. The solutions are then used to study two common cases: (I) hot CO2-rich water injection into a carbonate aquifer and (II) hot silica-rich water injection into a sandstone aquifer, leading to mineral dissolution and precipitation, respectively. We discuss the timescales of such fluid–rock interactions and the changes in hydraulic system properties. The solutions and findings contribute to the understanding and management of subsurface energy and water resources, such as aquifer thermal energy storage, aquifer storage and recovery and reinjection of used geothermal water. The solutions are also useful for developing and benchmarking complex coupled numerical codes.

Enhanced Crystallinity of SrTiO3 Films on a Silicon Carbide Substrate: Structural and Microwave Characterization

Thin films of strontium titanate, which reveal high structure quality and tunable properties prospective for microwave applications at room temperature, were grown on a semi-insulating silicon carbide substrate using magnetron sputtering for the first time. The films’ growth mechanisms were studied using medium-energy ion scattering, and the films’ structures were investigated using X-ray diffraction. The electrical characteristics of planar capacitors based on strontium titanate films were measured at a frequency of 2 GHz using a high-precision resonance technique. It is shown that the tendency to improve the crystalline structure of strontium titanate film with an increase in the substrate temperature is most pronounced for films deposited at elevated working gas pressure under low supersaturation conditions. Planar capacitors formed on the basis of oriented SrTiO3 films on silicon carbide showed tunability n = 36%, with a loss tangent of 0.008–0.009 at a level of slow relaxation of capacitance, which is significantly lower than the data published currently regarding planar tunable ferroelectric elements. This is the first successful attempt to realize a planar SrTiO3 capacitor on a silicon carbide substrate, which exhibits a commutation quality factor more than 2500 at microwaves.

Melt-extruded formulations of fenofibrate with various grades of hydrogenated phospholipid exhibit promising in-vitro biopharmaceutical behavior

In the current study, it was demonstrated that three commercially available grades of hydrogenated phospholipids (HPL) differing in their content of phosphatidylcholine may be used as components for hot melt-extruded binary (HPL as sole excipient) or ternary (in combination with copovidone) solid dispersions of fenofibrate (FEN) at mass fractions between 0.5 and 20% (ternary) or 80% (binary). X-ray powder diffraction indicated complete conversion of crystalline fenofibrate into the amorphous state by hot melt extrusion for all ternary blends. In contrast, both the binary blends (HPL- and copovidone-based) contained minor remaining crystallites. Irrespectively, all solid dispersions induced during dissolution studies a supersaturated state of FEN, where the ternary ASDs showed enhanced and more complete release of FEN as compared to the binary blends and, even more pronounced, in comparison to the marketed micronized and nano-milled formulations. In terms of the cumulated amount permeated, there were marginal differences between the various formulations when combined dissolution/permeation was done using FeSSIF as donor medium; with FaSSIF as donor medium, the binary HPL-ASD containing the grade with the highest phosphatidylcholine fraction performed best in terms of permeation, even significantly better than the marketed nano-crystal formulation. Otherwise, no significant differences were seen between the various grades of HPL when FEN dissolution and permeation were analyzed for ternary solid dispersions. In conclusion, the in-vitro biopharmaceutical behaviour of hydrogenated phospholipid-containing blends manufactured by hot melt extrusion appears promising. They can be a viable formulation option for poorly water-soluble and lipophilic drug compounds like FEN.

A Miscibility Study of p(MMA-co-HEMA)-Based Polymer Blends by Thermal Analysis and Solid-State NMR Relaxometry.

Ternary amorphous solid dispersions (ASDs) consist of a multicomponent carrier with the aim of improving physical stability or dissolution performance. A polymer blend as a carrier that combines a water-insoluble and a water-soluble polymer may delay the drug release rate, minimizing the risk of precipitation from the supersaturated state. Different microstructures of the ternary ASD may result in different drug release performances; hence, understanding the phase morphology of the polymer blend is crucial prior to drug incorporation. The objective of this study is to investigate the miscibility of the water-insoluble p(MMA-co-HEMA) and water-soluble polymers such as HPC, HPMC, HPMC-AS, and Soluplus. To prepare the polymer blends, p(MMA-co-HEMA) was spray dried in 80/20 and 90/10 (w/w) ratios with one of the water-soluble polymers. Thermal analysis (mDSC and DMA) and solid-state (ss)NMR relaxometry were applied to study the miscibility of these blends. No conclusions regarding miscibility could be drawn from the Tg measurements by thermal analysis. However, phase-separation could be demonstrated in all blends by ssNMR relaxometry. Moreover, by measuring both the T1ρH and T1H relaxation times, domain sizes between 5 and 50 nm could be estimated. This work shows the importance of using complementary analytical techniques to investigate polymer miscibility.

Beyond gas supersaturation: Dissecting the secondary formation of methane hydrate

Rapid secondary formation of gas hydrate is a critical issue in gas transportation and at the same time has foreseeable potential in future gas storage. Despite the devoted research in the past decade, the intrinsic mechanism of the secondary formation of gas hydrate, is still an on-going subject of debate. Because the secondary formation of gas hydrate is commonly observed under conditions with extraordinarily high content of gas, gas supersaturation is hypothesized as one crucial mechanism. To dissect the gas supersaturation hypothesis, Molecular Dynamics simulations were conducted systematically with hydrate secondary formation in solutions with various gas concentrations covering supersaturation conditions. The effects of key parameters influencing the secondary formation of hydrate, including system temperature and local methane concentration, were explored. The results revealed for the first time a U-shape-like trend in the induction time of hydrate formation with the increase of gas concentration, pinpointing an optimal gas content with the given environmental temperature and pressure. Importantly, the findings highlighted the needed revision of the current gas supersaturation hypothesis in both methane hydrate mitigation and application. This work not only advanced the current understanding of the secondary formation of methane hydrate but also contributed to the fundamental knowledge essential for future gas storage by gas hydrates.

Crystal Growth and Color Tuning of Large Mn(PO3OH)·3H2O Crystals via an Evaporation-Assisted Aqueous Route at Room Temperature.

Large Mn(PO3OH)·3H2O crystals have been prepared from aqueous solutions containing MnCl2 and (NH4)2HPO4 by an evaporation-induced crystal growth technique. The slow solvent evaporation at room temperature maintained the supersaturation of the precursor solution for a long time, resulting in the continuous growth of Mn(PO3OH)·3H2O crystals. The addition of citric acid as a chelating agent and increasing the total volume of the precursor solutions helped to maintain the mild supersaturation conditions for a longer time period, and transparent, unbranched Mn(PO3OH)·3H2O crystals above 2 mm in size were produced by aging for 8 weeks. The large Mn(PO3OH)·3H2O single crystals exhibited a pink color, and the color became stronger by doping with Co2+ ions.

Concentration and crystallization of Microbial Xylitol from oil palm empty fruit bunch (OPEFB) using submerged direct contact membrane distillation (DCMD)

Xylitol possess high solubility in water and increase viscosity at high temperature, making the concentration process become challenging. This study demonstrated the applicability of Membrane Distillation (MD) in concentrating xylitol solutions and evaluates its performance at different conditions and feed compositions. MD was capable of concentrating pure xylitol solution to reach the supersaturated condition. However, when Oil Palm Empty Fruit Bunch (OPEFB) hydrolysate fermentation broth was used, fouling was observed due to the presence of impurities, despite the application of feed agitation. The batch crystallization of xylitol were conducted at 5 °C with a seed addition of 0.5–0.8%-wt. Higher seed concentrations were required to induce crystallization in OPEFB hydrolysate due to lower xylitol concentrations and impurity presence. Furthermore, impurities influenced the quality of the crystals, resulting in crystal purities of 98.98% and 94.56% in the synthetic solution and OPEFB hydrolysate, respectively. These findings indicated notable impact of crystallization temperature, seed addition, and impurity on xylitol crystallization.

Formation temperature of microcrystalline dolomite in oil-rich black shale: Implications for hydrocarbon accumulation in a volcanic-lacustrine rift basin

Lacustrine microcrystalline dolostones in the ancient records have been commonly interpreted as of an evaporitic origin, on the basis of their numerous occurrences in modern evaporative shallow lakes. This interpretation obscures the forming mechanisms of dolostones formed in a deep lacustrine setting, where dolostones interbedded with shale become a focus of hydrocarbon source rocks in recent years. In this study, an alternative non-evaporitic origin of dolomite is interpreted for a Permian lacustrine laminated dolostone. The dolostones are thinly intercalated with tuffaceous shales and composed mainly of volumetrically abundant, low-ordered, subhedral to euhedral, microcrystalline dolomites with a variable amount of pyroclastics. Evidence for evaporation (e.g., the presence of halite, gypsum and shrinkage cracks) and typical methanogenic microfossils is absent. Instead, our dolostones are unevenly and locally distributed as thin beds or lenses and intercalated with tuffaceous shale and have a formation temperature ranging from 31.4 to 73.8 °C, as estimated from dolomite clumped oxygen? isotope thermometry. In addition, the dolostones have a87Sr/86Sr ratio similar to that of the mantle (0.705154 on average) and extremely negative δ18O (−2.9‰ to −24‰) and positive δ13C (5.1‰–10.8‰) values. A lateral trend of increasing formation temperature of the dolostone toward the volcanic center correlates with the trends of: 1) an increasing amount of pyroclastics, euhedral dolomite crystals, Fe, and TOC, and an increasingly positive δEu value, and 2) decreasing values of 87Sr/86Sr and δ18O. The correlation suggests that a local temperature increase and frequent elemental (Fe and Mg) cycling between the conditions of dolomite supersaturation and undersaturation, which are controlled by episodic volcanic-hydrothermal activities are the causes for dolomite nucleation and growth, resulting in the formation of massive dolostone during deposition and shallow burial. The process also affected organic matter accumulation and local transformation to immature or early mature hydrocarbon during deposition and early burial. The results establish a volcanism-controlled temperature range for primary dolomite nucleation and growth, as well as hydrocarbon generation in a deep lake environment during the period of deposition and early burial, and provide insights on shale oil exploration in petroliferous rift basins.

Decomposition behavior of GaN under solid and ambient N2 pressure

We investigated the decomposition behavior of GaN crystals under high N2 and solid pressures using a belt-type high-pressure apparatus. The decomposition curve of GaN under solid pressure showed a considerably moderate increase compared to that under a N2 pressure. Such difference was attributed to the N2 dissolution in the Ga melt, where a high N2 pressure creates a supersaturated GaN state, which effectively prevent its decomposition. Conversely, under a solid pressure, the increase in the GaN decomposition temperature followed a common change in enthalpy, which is consistent with its typical thermodynamic behavior. The decomposition behavior of GaN under a solid pressure demonstrated its successful high-temperature annealing using a belt-type high-pressure apparatus. Therefore, this study provides valuable insights into the thermodynamic stability of GaN under different pressures, which is critical for optimizing high-performance GaN-based devices.

Aiming the water transport issues of anion exchange membrane fuel cells by introducing hydrophobic carbon nanotube diffusion layer

The gas diffusion layer (GDL) enhances the transport efficiency of reaction gases and facilitates the removal of accumulated liquid water, thereby improving water management in anion exchange membrane fuel cells (AEMFCs). Carbon nanotubes (CNTs) are recognized as one of the promising materials to optimize mass transport within GDLs. In this study, we successfully synthesized an abundance of CNTs on the surface of commercial gas diffusion media. The as-prepared CNT layer exhibits exceptionally high hydrophobic properties and forms a hierarchically hydrophobic structure combined with the gas diffusion media, effectively enhancing the mass transfer of the membrane electrode assembly (MEA) and reducing ohmic impedance. Under supersaturation conditions, the power density of the MEA containing CNTs reaches 1031.7 mW/cm2, significantly higher than the 760.64 mW/cm2 observed for the commercial GDL. Further testing demonstrates that the MEA containing CNTs exhibits a limiting current density of 2507.4 mA/cm2, which is much superior to the benchmark MEA with the commercial GDL (1591 mA/cm2). Electrochemical impedance spectroscopy analysis reveals that the mass transfer resistance of MEAs with CNTs is lower than that of MEAs with the commercial GDL. More importantly, the phase-field modeling is performed to simulate the transport of the liquid water in the hierarchical GDL.

Amorphous Polymer-Phospholipid Solid Dispersions for the Co-Delivery of Curcumin and Piperine Prepared via Hot-Melt Extrusion.

Curcumin and piperine are plant compounds known for their health-promoting properties, but their use in the prevention or treatment of various diseases is limited by their poor solubility. To overcome this drawback, the curcumin-piperine amorphous polymer-phospholipid dispersions were prepared by hot melt extrusion technology. X-ray powder diffraction indicated the formation of amorphous systems. Differential scanning calorimetry confirmed amorphization and provided information on the good miscibility of the active compound-polymer-phospholipid dispersions. Owing to Fourier-transform infrared spectroscopy, the intermolecular interactions in systems were investigated. In the biopharmaceutical properties assessment, the improvement in solubility as well as the maintenance of the supersaturation state were confirmed. Moreover, PAMPA models simulating the gastrointestinal tract and blood-brain barrier showed enhanced permeability of active compounds presented in dispersions compared to the crystalline form of individual compounds. The presented paper suggests that polymer-phospholipid dispersions advantageously impact the bioaccessibility of poorly soluble active compounds.

Investigation of the Solid Solution Hardening Mechanism of Low-Alloyed Copper–Scandium Alloys

The addition of alloying elements is a crucial factor in improving the mechanical properties of pure copper, particularly in terms of enhancing its yield strength and hardness. This study examines the influence of scandium additions (up to 0.27 wt.%) on low-alloyed copper. Following the casting and solution-annealing processes, the alloys were quenched in water to maintain a supersaturated state. The mechanical properties were evaluated by tensile tests to measure the yield strength and the dynamic resonance method to determine the modulus of rigidity. Additionally, X-ray diffraction was utilized to analyze changes in lattice parameters, elucidating the structural modifications induced by scandium. This study dissects the parelastic and dielastic effects underlying the solid solution hardening mechanism, providing insights into how scandium alters copper’s mechanical properties. The findings align with the solid solution hardening theories proposed by Fleischer and Labusch, providing a comprehensive understanding of the observed phenomena.

An integrated approach for characterization of a fractured-rock carbonate aquifer in the Zagros Region of Iran

Karst aquifers typically exhibit a wide range of dissolution effects that include end-members of matrix, fractured-rock, and conduit-dominated types. This study employs an integrated approach involving geological studies, hydrogeological assessments, hydrochemical and isotopic analysis, and dye tracer tests to investigate the Sarvak limestone aquifer (SLA) in the Zagros Region, southwest Iran. Key characteristics of the SLA include numerous stratification boundaries, thin limestone layers with intercalated siliceous and marl impurities, extensive joint and fracture networks, predominant autogenic recharge, and absence of notable point recharge features (e.g., sinkholes, dolines), and the exchange flow with the Bakhtiari River (B-R) has made it a unique aquifer. Numerous pieces of evidence, such as low spatial and temporal changes in groundwater level, insignificant seasonal variations in the hydrochemical and isotopic composition of water samples, and the supersaturation state of groundwater with calcite and dolomite minerals, suggested a slow flow regime in many parts of the SLA. This regime is characterized by low velocity and long residence time of groundwater. The results reveal that despite the high solubility of carbonate rocks, extensive joint networks can limit significant karst development, leading to fluid flow behavior similar to that of fractured-rock aquifers. Therefore, SLA can be considered a fractured-rock and karst aquifer. The identified paths with fast flow in the dam area are unremarkable and cannot provide a large portion of the Pelle Khan Spring discharge.

Characterization and Dissolution Mechanism of Low-Molecular-Weight Organic Acids or Inorganic Mesoporous Particle-Based Piperine Amorphous Solid Dispersions.

The objective of the current study is to prepare amorphous solid dispersions (ASDs) containing piperine (PIP) by utilizing organic acid glycyrrhizic acid (GA) and inorganic disordered mesoporous silica 244FP (MSN/244FP) as carriers and to investigate their dissolution mechanism. The physicochemical properties of ASDs were characterized with scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) and one-dimensional proton nuclear magnetic resonance (1H NMR) studies collectively proved that strong hydrogen-bonding interactions formed between PIP and the carriers in ASDs. Additionally, molecular dynamic (MD) simulation was conducted to simulate and predict the physical stability and dissolution mechanisms of the ASDs. Interestingly, it revealed a significant increase in the dissolution of amorphous PIP in ASDs in in vitro dissolution studies. Rapid dissolution of GA in pH 6.8 medium resulted in the immediate release of PIP drugs into a supersaturated state, acting as a dissolution-control mechanism. This exhibited a high degree of fitting with the pseudo-second-order dynamic model, with an R2 value of 0.9996. Conversely, the silanol groups on the outer surface of the MSN and its porous nanostructures enabled PIP to display a unique two-step drug release curve, indicating a diffusion-controlled mechanism. This curve conformed to the Ritger-Peppas model, with an R2 > 0.9. The results obtained provide a clear evidence of the proposed transition of dissolution mechanism within the same ASD system, induced by changes in the properties of carriers in a solution medium of varying pH levels.

Inter-droplet frosting propagation mechanism on micropillar patterned surfaces under various supersaturation conditions

To address the burgeoning demand for anti-icing applications in various environments, an effective means of retarding inter-droplet frosting with a high degree of environmental adaptability is urgently required. In this study, frosting experiments were performed on Si micropillar arrays with varying pitches under controlled environmental conditions, especially at low temperatures and high supersaturation, which indicate more severe icing possibilities. The results showed that droplet behavior was highly dependent on the environment and surface geometry. The droplet numbers at the bottom sites increased with humidity, whereas those at the top sites decreased and the transition in droplet diameter proved to be opposite. Dimensionless quantity ƞb was proposed to describe droplet distribution under each working condition, and six frost propagation regimes were categorized into two groups: 0 <ƞb< 0.5 and 0.5 <ƞb< 1. For each condition, six pillar pitches resulted in two or three different regimes, and the lowest frost propagation velocity was observed at the turning point of the last regime (optimal ratio of the normalized pillar pitch to the pillar diameter [L/D]). With the reduction of supersaturation, the optimal L/D was 2 at 10 ℃/90 %RH and 50 %RH, optimal L/D was 3 at 10 ℃/20 %RH, and optimal L/D was 4 at − 5 ℃/90 %RH and 50 %RH. This significantly differed from the room-temperature conditions, as the optimal L/D was found to be larger than 4 in previous studies. These findings provide further understanding of the application of patterned surfaces in anti-icing in harsh and variable environments.

Synergistic effect of polymers in stabilizing amorphous pretomanid through high drug loaded amorphous solid dispersion.

Pretomanid (PTM), an oral antibiotic used in the treatment of adults with pulmonary extensively drug-resistant, nonresponsive multidrug-resistant tuberculosis (MDR-TB). It is a poor glass former, that shows high recrystallization tendency from the amorphous and supersaturated state, resulting in low aqueous solubility and suboptimal absorption through the gastrointestinal tract. The present investigation aimed to develop high drug loaded ternary amorphous solid dispersions (ASDs) of PTM with improved stability and enhanced biopharmaceutical performance by utilizing a combination of polymers. The polymers were comprehensively screened based on drug-polymer miscibility and saturation solubility analysis. A combination of Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS-HF) and Polyvinylpyrrolidone K-30 (PVP K-30) showed synergism in drug-polymer miscibility as evidenced through pronounced depression in the melting endotherm of PTM. The Powder X-ray Diffraction (P-XRD) diffractograms of 30% w/w PTM loaded ternary ASDs displayed the halo pattern, contrary to the binary ASDs. Drug-polymer interactions (hydrophobic forces) involved between PTM and polymers were detected through Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance Spectroscopy (13C-NMR) which contributed to the synergistic enhancement in solubility and dissolution of ternary ASDs with sustained release over 12h. Ternary ASDs demonstrated better in-vivo performance compared to the binary ASDs, showing a 4.63-fold increase in maximum plasma concentration. All ASDs remained stable and resisted phase separation during short-term stability studies for 3 months at ambient conditions. It was concluded that the hydrophobic and hydrophilic polymeric combination (HPMCAS-HF and PVP K-30, respectively) effectively prevented the crystallization and ensured sustained drug release with improved in-vivo absorption of PTM.

Lipid-based systems with precipitation inhibitors as formulation approach to improve the drug bioavailability and/or lower its dose: a review.

Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (m/m). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.

Variability in the properties of the distribution of the relative humidity with respect to ice: implications for contrail formation

Abstract. Relative humidity with respect to ice (RHi) is a key variable in the formation of cirrus clouds and contrails. We document its probability density function (PDF) using long-term Measurements of Ozone, Water Vapour, Carbon Monoxide and Nitrogen Oxides by In-Service Airbus Aircraft (MOZAIC) and the In-service Aircraft for a Global Observing System (IAGOS) observations over the period 1995–2022 in the upper troposphere (UT) and the lower stratosphere (LS) between 325 and 175 hPa. The characteristics of the RHi PDF differ in the UT and in the LS of the high-latitude regions (HLs) and mid-latitude regions (MLs) of the Northern Hemisphere. In the LS, this PDF decreases exponentially with increasing RHi. In the UT, it first increases exponentially in subsaturated conditions and then decreases exponentially in supersaturated conditions. Because of these different behaviors, the PDF for the combined UT and LS is bimodal. In contrast to the HLs and the MLs, the RHi PDF in the tropical troposphere decreases exponentially with increasing RHi. The different forms of PDF, in the tropics and in the higher-latitude regions, lead to a global PDF of RHi in subsaturated tropospheric conditions that is almost uniform. These findings invite caution when using MOZAIC and IAGOS measurements to calibrate large-scale simulations of RHi. The variability in RHi properties associated with that of temperature also has implications for the formation of contrails. We examined the impact of switching fuel (from kerosene to bioethanol or liquid hydrogen) on the frequency of contrail formation using the Schmidt–Appleman criterion. We show that bioethanol and, to a larger extent, liquid hydrogen would produce more contrails. The impact of a potential change from kerosene to these alternative fuels decreases with decreasing pressure but increases when moving from the higher latitudes of the Northern Hemisphere to the tropics. Finally, we emphasize that investigations of the impact on contrail occurrence frequency as a result of switching from fossil kerosene to more sustainable fuels must be carried out in various meteorological conditions.