Particle-Filter-Based Fault Diagnosis for the Startup Process of an Open-Cycle Liquid-Propellant Rocket Engine.

This study introduces a fault diagnosis algorithm based on particle filtering for open-cycle liquid-propellant rocket engines (LPREs). The algorithm serves as a model-based method for the startup process, accounting for more than 30% of engine failures. Similar to the previous fault detection and diagnosis (FDD) algorithm for the startup process, the algorithm in this study is composed of a nonlinear filter to generate residuals, a residual analysis, and a multiple-model (MM) approach to detect and diagnose faults from the residuals. In contrast to the previous study, this study makes use of the modified cumulative sum (CUSUM) algorithm, widely used in change-detection monitoring, and a particle filter (PF), which is theoretically the most accurate nonlinear filter. The algorithm is confirmed numerically using the CUSUM and MM methods. Subsequently, the FDD algorithm is compared with an algorithm from a previous study using a Monte Carlo simulation. Through a comparative analysis of algorithmic performance, this study demonstrates that the current PF-based FDD algorithm outperforms the algorithm based on other nonlinear filters.

Investigation of Flame Structures of Double-Base Propellant and Modified Double-Base Propellant Containing Nitramine Using OH-PLIF and Kinetic Simulation.

The combustion behavior of various propellant samples, including double-base propellants, pressed nitramine powders, and modified double-base propellants containing nitramine, was examined using OH-PLIF technology. The combustion process took place within a combustion chamber, and images capturing the flame at the moment of stable combustion were selected for further analysis. The distribution and production rate of OH radicals in both the double-base propellant and the nitramine-modified double-base propellant were simulated using Chemkin-17.0 software. The outcomes from both the experimental and simulation studies revealed that the concentration of OH radicals increased with a higher content of NG in the double-base propellant. In the modified double-base propellant containing RDX, the OH radical concentration decreased as the RDX content increased, with these tendencies of change aligning closely with the simulation results.

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Controlled Release of Diborane from Alkali Metal Borohydride using Ionic Liquid-Based Lewis Acids.

Alkali metal borohydrides present a rich source of energy dense materials of boron and hydrogen, however their potential in propellants has been hitherto untapped. Potassium borohydride is a promising fuel with high gravimetric energy density and relatively low sensitivity to air and moisture. Problems arise due to the dehydrogenation of the borohydride on heating with minimal energy release. Common methods to extract both boron and hydrogen by means of borane species involve direct reaction of boron trifluoride species with alkali borohydrides. However, these methods face storage and safety issues due to rapid release of diborane on mixing the reactants. We propose a method of diborane release through controlled release of boron trifluoride by means of a tetrafluoroborate based ionic liquid. The trifluoride is released from the ionic liquid at elevated temperatures and enables safe mixture of the reactants at room temperature. It was found that the reaction between borohydride and boron trifluoride proceeds well above room temperature with potassium borohydride releasing diborane and potassium fluoride. The reaction pathway shows a primary reaction releasing diborane and potassium fluoride and a second less energy efficient step leading to the formation of potassium tetrafluoroborate. A 3D printed propellant formulation was also tested.

Relative bioavailability of budesonide/glycopyrrolate/formoterol fumarate triple therapy delivered using next generation propellants with low global warming potential.

INTRODUCTION: The climate crisis poses an immediate threat to human health and well-being, demanding urgent adaptions across sectors, including healthcare. The development of pressurized metered dose inhalers (MDIs) with greater sensitivity to the climate emergency using novel propellants with lower global warming potentials (GWPs), but comparable pharmacokinetic (PK) parameters to currently marketed MDIs, is a vital step toward reducing the impact of healthcare for respiratory disorders on climate change. This study evaluated the relative bioavailabilities of the individual components of a fixed-dose combination of budesonide/glycopyrrolate/formoterol fumarate (BGF) 160/9/4.8 µg per actuation between three different propellant formulations. METHODS: Healthy male participants (aged 18-60 years) were randomized into a single-blind, three-period, single-dose, single-center, crossover study (NCT04600505). The PK and safety and tolerability profiles of BGF MDI formulated with two novel propellants with low GWP (hydrofluoroolefin-1234ze [HFO]; hydrofluorocarbon-152a [HFC]) were compared with BGF MDI formulated with the propellant used in the currently marketed reference product (hydrofluoroalkane-134a [HFA]). The study included a screening period, three treatment periods (with 3- to 7-day washout periods between each dose), and a follow-up. The primary PK parameters assessed were maximum observed plasma concentration (Cmax), area under the plasma concentration curve (AUC) from time zero extrapolated to infinity (AUCinf), and AUC from time zero to the time of the last quantifiable analyte concentration (AUClast). The study was not powered to statistically demonstrate bioequivalence. RESULTS: Forty-seven participants completed the study, and 24 participants were evaluable for PK assessments. Systemic exposure, based on geometric mean ratios (90% confidence interval), to each BGF component from the test propellants delivered in a standard MDI was comparable with the reference propellant for AUClast (HFO vs. HFA: budesonide, 107.30 [94.53, 121.90]; glycopyrrolate, 106.10 [86.18, 130.60]; formoterol, 98.13 [86.44, 111.40]; HFC vs. HFA: budesonide, 98.80 [84.59, 115.40]; glycopyrrolate, 99.71 [80.84, 123.00]; formoterol, 107.00 [88.82, 128.90]); AUCinf (where evaluable) and Cmax followed the same trend. There were no serious adverse events or adverse events leading to treatment discontinuation. No new safety signals were observed. CONCLUSIONS: Systemic BGF component exposure was similar for both test propellants (HFO and HFC) compared with the HFA reference propellant, with an acceptable safety profile in the studied population. Therefore, both novel low GWP propellants show strong potential as candidates for development of MDIs with greater sensitivity to the climate crisis, a vital step toward ameliorating the detrimental impact of healthcare on the environment. Further investigation in larger studies is warranted.

Acute, repeated inhalation toxicity, respiratory system irritation, and mutagenicity studies of 1,1,2,2-tetrafluoroethane (HFC-134) as the impurity in the pharmaceutical propellant 1,1,1,2-tetrafluoroethane (HFA-134a).

HFC-134 is the main impurity of HFA-134a. In order to verify the rationality of HFC-134 limits in HFA-134a and ensure the safety of HFA-134a as propellant in pharmaceutical metered-dose inhalers, acute inhalation toxicity, seven-day repeat dose inhalation irritation study, 21-day repeat dose inhalation toxicity study and reverse mutation assay of HFC-134 were tested to evaluate its inhalation safety. In acute inhalation studies, Sprague-Dawley rats were exposed nose-only to HFC-134 at levels of 100 000, 200 000, 400 000, 600 000, and 800 000 ppm for 4 h. Based on the mortality incidence, the calculated four-hour LC50 value for HFC-134 is 532 069 ppm for males and 502 058 ppm for females and acute inhalation toxicity is manifested as the lung lobes turn dark red. Exposures to 836 ± 67 ppm for 4 hours/day 7 days/week continuously did not induce local irritation of the respiratory system in Sprague-Dawley rats. Sprague-Dawley rats were exposed nose-only to HFC-134 at levels of 0 (control), 203 929 ppm and 394 871 ppm 2 h/day for 21 consecutive days, no significant treatment-related adverse effects was noted. Results from Ames studies demonstrated that HFC-134 was not mutagenic. Although HFC-134 has a very low acute inhalation toxicity, considering that its acute inhalation toxicity is higher than that of HFA-134a, and due to the high frequency of use of MDI by asthma patients, acceptance criteria of HFC-134 as the impurity in aerosol propellant HFA-134a should be lower than 8-h TWA WEEL value of 1000 ppm to ensure the safety of the MDI.

Molecular Simulation Study on the Aging Mechanism of NEPE Propellant Matrix.

Polyethylene glycols (PEG) and toluene diisocyanate (TDI) are often used as the main components of binders and curing agents in solid propellants, and their aging is an important issue in the storage and use of propellants. To study the aging behavior and aging mechanism of nitrate ester plasticized polyether propellant (NEPE) matrix during storage, the transition states of aging reactions of binder and curing agent were optimized at the (U)B3LYP/6-311G(d,p) level of theory, and the rate coefficients over the temperature range of 298-1000 K were calculated by CVT theory. The results showed that there were five kinds of aging reactions for binder, which included decomposition, nitration, H abstraction, oxidation, and crosslinking reactions. Among them, theenergy barriers of oxidation and H abstraction reactions were relatively low (79.3-91.2 kJ·mol-1) and the main reaction types of binder aging. The main aging reaction of curing agent was decomposition. Compared with the aging reactions of binder, the energy barriers of curing agent are higher (196.6-282.7 kJ·mol-1) and the reaction is more difficult to occur. By comparing the energy barriers and rate constants of different reactions, it is found that the aging of NEPE propellant matrix can be divided into two stages. In the first stage, the propellant matrix mainly undergoes H abstraction and oxidation reaction, and as the reaction proceeds, the products crosslink to form -O-O-, -C-C-, and -C-O-C- bonds. At this time, the long chain molecules of the propellant matrix crosslink, and the molecular weight increases. This stage corresponds to the rising stage of mechanical properties in the aging process of the propellant. In the second stage, the propellant matrix mainly undergoes decomposition and nitration, resulting in degradation, the reduction of molecular weights, and the appearance of holes and microcracks in the matrix. This stage corresponds to the decline of mechanical properties in the aging process of the propellant. The above simulation results are in good agreement with the aging experimental phenomena, revealing the microscopic mechanism of the changes in the macroscopic properties of NEPE propellant during the aging process, and providing a theoretical basis for the related research on the aging properties and anti-aging technology of NEPE propellant.

Traditional vs. Energetic and Perchlorate vs. "Green": A Comparative Study of the Choice of Binders and Oxidising Agents.

The aim of this article is to compare rocket propellants containing a traditional binder (hydroxyl-terminated polybutadiene) and an energetic binder (glycidyl azide polymer), as well as a perchlorate oxidising agent and a "green" one, i.e., ammonium perchlorate and phase-stabilised ammonium nitrate. We have outlined the effects of individual substances on the sensitivity parameters and decomposition temperature of the produced solid propellants. The linear combustion velocity was determined using electrical methods. Heats of combustion for the propellant samples and the thermal decomposition features of the utilised binders were investigated via differential scanning calorimetry (DSC). Activation energy values for the energetic decomposition of the propellants were determined via the Kissinger method, based on DSC measurements at varied heating rates.

Research Progress of Bonding Agents and Their Performance Evaluation Methods.

Bonding agents are an important type of additive that are used to increase the interfacial interaction in propellants. A suitable bonding agent can prevent the dewetting between the oxidant and binder, and thus effectively improve the mechanical properties of the propellant. In the current paper, the bonding mechanisms and research progress of different types of bonding agents such as alcohol amine bonding agents, borate ester bonding agents, aziridine bonding agents, hydantoin bonding agents, neutral polymer bonding agents, and so on, are reviewed and discussed. The evaluation methods of their bonding performances including molecular dynamic simulation, contact angle method, in situ loading SEM, characterization analysis, and mechanical analysis are summarized to provide design ideas and reference for future studies.

3D Electron-Rich ZIF-67 Coordination Compounds Based on 2-Methylimidazole: Synthesis, Characterization and Effect on Thermal Decomposition of RDX, HMX, CL-20, DAP-4 and AP.

ZIF-67 is a three-dimensional zeolite imidazole ester framework material with a porous rhombic dodecahedral structure, a large specific surface area and excellent thermal stability. In this paper, the catalytic effect of ZIF-67 on five kinds of energetic materials, including RDX, HMX, CL-20, AP and the new heat-resistant energetic compound DAP-4, was investigated. It was found that when the mass fraction of ZIF-67 was 2%, it showed excellent performance in catalyzing the said compounds. Specifically, ZIF-67 reduced the thermal decomposition peak temperatures of RDX, HMX, CL-20 and DAP-4 by 22.3 °C, 18.8 °C, 4.7 °C and 10.5 °C, respectively. In addition, ZIF-67 lowered the low-temperature and high-temperature thermal decomposition peak temperatures of AP by 27.1 °C and 82.3 °C, respectively. Excitingly, after the addition of ZIF-67, the thermal decomposition temperature of the new heat-resistant high explosive DAP-4 declined by approximately 10.5 °C. In addition, the kinetic parameters of the RDX+ZIF-67, HMX+ZIF-67, CL-20+ZIF-67 and DAP-4+ZIF-67 compounds were analyzed. After the addition of the ZIF-67 catalyst, the activation energy of the four energetic materials decreased, especially HMX+ZIF-67, whose activation energy was approximately 190 kJ·mol-1 lower than that reported previously for HMX. Finally, the catalytic mechanism of ZIF-67 was summarized. ZIF-67 is a potential lead-free, green, insensitive and universal EMOFs-based energetic burning rate catalyst with a bright prospect for application in solid propellants in the future.

Wear Diagnostics of the Thrust Bearing of NK-33 Turbo-Pump Unit on the Basis of Single-Coil Eddy Current Sensors.

The problem of early wear diagnostics of the combined journal-and-thrust bearing of the turbo-pump unit (TPU) of the liquid-propellant rocket engine NK-33 is considered. A feature of the problem is the significant restriction on modifications of the power plant's design. The original solution based on replacing the standard induction sensors of the turbo-pump rotational speed currently used in TPU by single-coil eddy current sensors (SCECS) with sensitive elements in the form of a segment of a linear conductor is proposed. The SCECS provide the monitoring of the axial displacement of the shaft in the thrust bearing, which characterizes the state of the unit and increases with the bearing wear. The function of the TPU shaft's rotational speed measuring also remains. The article describes the proposed approach as well as a laboratory prototype of the system for early detection of the TPU thrust bearing's wear. The results of the prototype research that confirm the feasibility of the proposed approach are analyzed.

Synthesis of a Series of Dual-Functional Chelated Titanate Bonding Agents and Their Application Performances in Composite Solid Propellants.

Titanate-based bonding agents are a class of efficient bonding agents for improving the mechanical properties of composite solid propellants, a kind of special composite material. However, high solid contents often deteriorate the rheological properties of propellant slurry, which limits the application of bonding agents. To solve this problem, a series of long-chain alkyl chelated titanate binders, N-n-octyl-N, N-dihydroxyethyl-lactic acid-titanate (DLT-8), N-n-dodecyl-N, N-dihydroxyethyl-lactic acid-titanate (DLT-12), N-n-hexadecyl-N, N-Dihydroxyethyl-lactic acid-titanate (DLT-16), were designed and synthesized in the present work. The infrared absorption spectral changes of solid propellants caused by binder coating and adhesion degrees of the bonding agents on the oxidant surface were determined by micro-infrared microscopy (MIR) and X-ray photoelectron spectroscopy (XPS), respectively, to characterize the interaction properties of the bonding agents with oxidants, ammonium perchlorate (AP) and hexogen (RDX), in solid propellants. The further application tests suggest that the bonding agents can effectively interact with the oxidants and effectively improve the mechanical and rheological properties of the four-component hydroxyl-terminated polybutadiene (HTPB) composite solid propellants containing AP and RDX. The agent with longer bond chain length can improve the rheological properties of the propellant slurry more significantly, and the propellant of the best mechanical properties was obtained with DLT-12, consistent with the conclusion obtained in the interfacial interaction study. Our work has provided a new method for simultaneously improving the processing performance and rheological properties of propellants and offered an important guidance for the bonding agent design.

Experimental Study of Pyrolysis and Laser Ignition of Low-Vulnerability Propellants Based on RDX.

Low-vulnerability propellants are propellants designed to resist unintended stimuli to increase safety during transport, storage and handling. The substitution of usual nitrocellulose-based gun propellants with these new materials allows maintaining interior ballistics performances while increasing the safety. In this paper, the pyrolysis, ignition and combustion of such propellants are investigated in order to study conditions leading to a safe and reproducible ignition. Low-vulnerability propellants studied are made of different ratios of hexogen (RDX) and nitrocellulose (NC). Three compositions are studied by varying weight percentages of RDX and NC: 95-5, 90-10 and 85-15 for respective weight percentages of RDX-NC. Pyrolysis of these propellants is studied with two different experimental setups: a flash pyrolysis device linked to a gas chromatograph coupled to a mass spectrometer (Py-GC-MS) and a closed-volume reactor coupled to a mass spectrometer. Different molecules, like NO2, CO, CH3COCH3 or CH2NCH2NCH2, are obtained during the decomposition of these propellants. Laser ignition of these propellants is studied in a cylindrical closed-volume reactor using a laser diode. Several combustion characteristics, such as ignition delays, maximal overpressures and combustion rates are given for the three propellants using the pressure signals. Moreover, ignition energies are also investigated. Obtained results are compared to the few available literature data. A particular behavior is noticed for the 90-10 propellant. The experimental data collected should serve in the future to have a better understanding of the chemical reactions driving the combustion process of these low-vulnerability propellants.

IL6Rα function in myeloid cells modulates the inflammatory response during irritant contact dermatitis.

Irritant contact dermatitis (ICD) is characterized by epidermal hyperplasia, infiltration of leucocytes into lesional skin and inflammatory cytokine release. The cellular infiltrate during ICD comprises primarily cells of the myeloid lineage. Our group has previously shown that the cytokine IL-6 confers a protective effect to lesional skin during ICD. How IL-6Rα function in myeloid cells is involved in the inflammatory response during ICD is, however, unknown. In the present study, utilizing a chemical model of ICD, it is shown that mice with a myeloid-specific knockout of the IL-6Rα (IL-6RαΔmyeloid ) display an exaggerated inflammatory response to benzalkonium chloride (BKC) and Jet propellant-8 (JP8) fuel, two well-characterized irritants relative to littermate control. Results from immunohistochemical and flow cytometric analyses revealed that IL-6RαΔmyeloid mouse skin displayed increased epidermal hyperplasia and inflammatory monocyte influx into lesional skin but lower numbers of resident macrophages relative to littermate controls after irritant exposure. Multiplex immunoassay revealed significantly higher levels of pro-inflammatory cytokines IL-1α and TNF-α, but reduced expression of chemokine proteins including CCL2-5, CCL7, CCL11, CXCL1 and CXCL10 in IL-6RαΔmyeloid mouse skin relative to littermate control following irritant exposure. These results highlight a previously unknown role of IL-6Rα function in myeloid cells in modulating the inflammatory response and myeloid population dynamics during ICD.

Non-Propellant Foams of Green Nano-Silver and Sulfadiazine: Development and In Vivo Evaluation for Burn Wounds.

PURPOSE: A non-propellant based foam (NPF) system was developed incorporating the antibiotics, pectin capped green nano-silver and sulfadiazine (SD) for the topical treatment of burn wounds as a convenient alternative to the existing therapies. METHODS: NPF were prepared using various surfactants and oils forming a nanoemulsion. Anti-microbial studies by resazurin microtitre assay, ex vivo diffusion, in vivo skin permeation and deposition studies, and acute irritation studies were carried out. NPF was applied onto secondary thermal wounds manifested on mice models followed by macroscopic and histological examinations. RESULTS: NPF had an average globule size of <75 nm. The viscosity was ~10 cP indicating the feasibility of expulsion from the container upon actuation. With no skin irritation, the foams showed a higher skin deposition of SD. A high contraction and an evident regeneration of the skin tissue upon treatment with NPF indicated a good recovery from the thermal injury was apparent from the histology studies. CONCLUSION: NPF represents an alternative topical formulation that can be employed as a safe and effective treatment modality for superficial second degree (partial thickness) burn wounds. With a minimal requirement of mechanical force, the no-touch application of NPF makes it suitable for sensitive and irritant skin surfaces.

Glycidyl Azide Polymer and its Derivatives-Versatile Binders for Explosives and Pyrotechnics: Tutorial Review of Recent Progress.

Glycidyl azide polymer (GAP), an energetic binder, is the focus of this review. We briefly introduce the key properties of this well-known polymer, the difference between energetic and non-energetic binders in propellant and explosive formulations, the fundamentals for producing GAP and its copolymers, as well as for curing GAP using different types of curing agents. We use recent works as examples to illustrate the general approaches to curing GAP and its derivatives, while indicating a number of recently investigated curing agents. Next, we demonstrate that the properties of GAP can be modified either through internal (structural) alterations or through the introduction of external (plasticizers) additives and provide a summary of recent progress in this area, tying it in with studies on the properties of such modifications of GAP. Further on, we discuss relevant works dedicated to the applications of GAP as a binder for propellants and plastic-bonded explosives. Lastly, we indicate other, emerging applications of GAP and provide a summary of its mechanical and energetic properties.

Modal Propellant Gauging: High-resolution and non-invasive gauging of both settled and unsettled liquids in reduced gravity.

The modal response of a liquid-filled tank to external acoustic excitation can be used to infer with high resolution the mass of contained liquid, the mass flow rate of liquids into and out of the tank, and changes in tank pressure. Both contained liquid mass and internal ullage pressure affect the modal response of the tank walls through fluid mass-loading of the tank walls and pressure-induced wall stiffening, respectively. Modal Propellant Gauging refers to the technology that exploits these shifts in modal frequencies to infer the mass of propellant in a tank. MPG is a non-invasive gauging technology that has demonstrated gauging resolutions of 1% for settled propellants and 2-3% for unsettled, sloshing propellants. Extensive parabolic flight testing of the MPG system on model tanks has been conducted to validate the technology in reduced gravity. MPG testing on a qualification tank for the Orion Program's European Service Module has also been conducted and is reported here. Finite element modeling of the Orion ESM ″upper" tank is discussed and compared with measurement data. Three computational approaches to mass determination, Peak Tracking, Point Sensor, and Spectral Density methods, are described here. Use cases are defined and analyzed in the context of the Orion ESM Qualification tank data, and an implementation scheme for continuous mass gauging on the Orion ESM is discussed.

A Simple and Rapid Method for Deposition and Measurement of Drug Transport Across Air Interface Respiratory Epithelia.

The purpose of this study was to present a novel and simple drug deposition method to evaluate drug transport of aerosol microparticles across airway epithelial cells. Microparticles containing ciprofloxacin HCl (Cip) and doxycycline (Dox), alone or in a 50:50% w/w ratio, were spray dried and suspended using 2H, 3H-perfluoropentane, model propellant. The suspension was then used to assess deposition, and transport of these drug microparticles across sub-bronchial epithelial Calu-3 cells was also studied. In comparison with other methods of depositing microparticles, this proposed method, using drug suspended in HPFP, provides control over the amount of drugs applied on the surface of the cells. Therefore, cell permeability studies could be conducted with considerably smaller and more reproducible doses, without the physicochemical characteristics of the drugs being compromised or the use of modified pharmacopeia impactors. The suspension of microparticles in HPFP as presented in this study has provided a non-toxic, simple, and reproducible novel method to deliver and study the permeability of specific quantity of drugs across respiratory epithelial cells in vitro.

Nitrato-Functionalized Task-Specific Ionic Liquids as Attractive Hypergolic Rocket Fuels.

Hypergolic ionic liquids (HILs) as potential replacements for hydrazine derivatives have attracted increasing interest over the last decade. Previous studies on HILs have mostly concentrated on the anionic innovations of ionic liquids to shorten the ignition delay (ID) time, but little attention has been paid to cationic modifications and their structure-property relationships. In this work, we present a new strategy of cationic functionalization by introducing the energetic nitrato group into the cationic units of HILs. Interestingly, the introduction of oxygen-rich nitrato groups into the cationic structure significantly improved the combustion performance of HILs with larger flame diameters and duration times. The density-specific impulse (ρIsp ) of these novel HILs are all above 279.0 s g cm-3 , much higher than that of UDMH (215.7 s g cm-3 ). In addition, the densities of these HILs are in the range of 1.22-1.39 g cm-3 , which is much higher than that of UDMH (0.79 g cm-3 ), showing their higher loading capacity than hydrazine-derived fuels in a propellant tank. This promising strategy of introducing nitrato groups into the cationic structures has provided a new platform for developing high-performing HILs with improved combustion properties.

Comparison of Formoterol, Glycopyrrolate, and Beclomethasone Dipropionate Pharmacokinetic Profile after Inhaled Administration as pMDI Using HFA134a or HFA152a Propellant: Preclinical Assessment of Drug Exposure in Sprague-Dawley Rat Model.

Background: A fixed combination of formoterol, glycopyrrolate, and beclomethasone dipropionate is approved in some geographic areas as pressurized metered dose inhaler (pMDI) formulation for the treatment of asthma and chronic obstructive pulmonary disease. Current pMDIs use hydrofluoroalkanes (HFAs) as a propellant, such as 1,1,1,2-tetrafluoroethane (HFA134a), that have a high global warming potential (GWP), but their use is being progressively lowered to reduce impact on climate. One option to reduce the carbon footprint of the pMDI products while preserving pMDIs as a therapeutic option is reformulating the current pMDIs using low GWP propellants, such as 1,1-difluoroethane (HFA152a). Nevertheless, pharmaceutical, clinical, and regulatory challenges need to be considered when reformulating a pMDI. A nonclinical study in rodents has been performed to support the formulation work and optimize the design of the bioequivalence study in humans. Methods: A fixed combination of formoterol, glycopyrrolate, and beclomethasone dipropionate (BDP) as pMDI with the two propellants HFA134a or HFA152a was administered by inhalation to Sprague-Dawley rats, using inhalation tower, to assess the impact of the propellant on the PK profile of the active components. After administration, serial blood samples were taken from each rat, and plasma aliquots were analyzed by HPLC-MS/MS. Results: Inhalation administration to rats of the fixed triple combination as pMDI showed similar PK profile for formoterol, glycopyrrolate, and BDP with the two propellants. Exposure parameters Cmax and AUClast of the three active ingredients were compared, showing no statistically significant differences in the systemic exposure between the two treatment groups. Higher interanimal variability was observed for the metabolite beclomethasone 17-monopropionate, likely due to individual differences in the metabolite generation. Conclusions: Considering these data, it was possible to conclude that replacing propellant HFA134a with HFA152a in a newly developed formulation had no significant impact on the plasmatic PK profile of formoterol, glycopyrrolate, and BDP in rats after inhalation administration using inhalation towers.