Composite Dry Powder Research Articles

Analysis of the effectiveness of Mg(OH)2/NH4H2PO4 composite dry powder in suppressing methane explosion

To improve the suppression effect of NH4H2PO4 powder on methane explosion, Mg(OH)2/NH4H2PO4 composite dry powder (CDP) with different quality ratios was prepared, and explosion suppression experiments were performed to determine the explosion suppression effect of the CDP. The explosion suppression mechanism of the CDP was explored by performing a thermal analysis. The results revealed that the CDP markedly reduced the KG, Tmax, and vmax of methane explosion. The different proportions of Mg(OH)2 exhibited different degrees of improvement in the explosion suppression effect of NH4H2PO4. For 8, and 10 vol% methane-air mixtures, the optimal explosion suppression ratios of the CDP were 20:80, and the minimum concentrations required for complete explosion suppression were 0.6 g/L. For 12 vol% methane-air mixtures, the optimal explosion suppression ratio of the CDP was 15:85, and the minimum concentration required for complete explosion suppression was 0.4 g/L. The introduction of 20 mass% Mg(OH)2 could advance the start of the first and second stages of NH4H2PO4 decomposition, and the mass loss temperature changed by 26.94 and 46.63 °C, respectively. The findings indicated that the decomposition products of the CDP substantially enhanced the explosion suppression effect to inhibit the methane explosion chain reaction.

Experimental and numerical simulation research on fire suppression efficiency of dry powder mediums containing molybdenum flame retardant additive

In order to cope with the frequent fire accidents in modern society, it is crucial to develop efficient fire extinguishing agents to stamp out fires in its early stage. In this work, a new composite ultrafine dry powder extinguishing agent containing ammonium molybdate ((NH4)2MoO4) is prepared, and its fire extinguishing efficiency is studied. The cup burner experimental results show that with the increase of the mass fraction of (NH4)2MoO4, the flame temperature drop and flame height variation rate show a trend of increasing and then decreasing, while the MEC and extinguishing time present a trend of a decrease and then an increase. It is indicated that the composite dry powder has the best fire extinguishing efficiency when the mass fraction of (NH4)2MoO4 is 7%. Besides, in terms of the pyrolysis results of TGA and DSC, it is found that the degree of thermal decomposition is significantly promoted under the condition of 7% addition. Based on the gas-solid two-phase flow theory and multiphase flow model, a simplified simulation model of the cup burner is established by the ANSYS-FLUENT software to analyze the variation of temperature and particle motion trajectory. The simulation results demonstrate that the ultra-fine dry powder mediums have a good dispersibility after entering the cup burner. This can achieve a full submerged state at a faster speed, and the flame temperature of the entire fire suppression stage is consistent with the experimental results. This article mainly develops the application of fire extinguishing media in the field of fire protection from the perspective of process safety.

The fire extinguishing mechanism of ultrafine composite dry powder agent containing Mg(OH)2

AbstractCompound dry powder agent containing Mg(OH)2 is an efficient substitute for halon. Magnesium hydroxide and ammonium dihydrogen phosphate play an important role in chemical fire extinguishing substances. The reaction mechanism and thermal decomposition products of ammonium dihydrogen phosphate and magnesium hydroxide simulated by both molecule and cluster model were theoretically studied. Dense functional theory (DFT) was used to optimize the structure of the samples, and the reaction of the samples with free radicals H·, OH· and CH3· was calculated to prevent the combustion process. A fire extinguishing reaction mechanism that consisted of 13 elementary reactions were proposed. The most kinetically favorable mechanistic pathways in extinguishing reactions were identified. The direct reaction of Mg(OH)2 with H· free radical is the main pathway. Similarly, in the H3PO4 phase, the energy barrier of H3PO4 reacting with free radicals is smaller than that of self‐decomposition and the thermal decomposition of intermediates, indicating that the reaction of H3PO4 with free radicals is also the main route. In addition, the intermediate produced by the reaction will also combine with each other to form new fire extinguishing substances, which accelerates the fire extinguishing process. Therefore, the fire extinguishing effect of composite dry powder containing magnesium hydroxide is higher than the single powder extinguishing agent.

Production of fast-dissolving low-density powders for improved lung deposition by spray drying of a nanosuspension

We combined high-energy wet media milling and spray drying to engineer dry powders for inhalation consisting of geometrically large, low-density particles with superior aerodynamic properties and fast dissolution. Peclet number proved to be a useful instrument to guide choice of the additives and process conditions for generating low-density powders by spray drying. Composite dry powders consisted of milled and stabilized budesonide nanoparticles, leucine or albumin as matrix formers, and ammonium carbonate as a pore former. Powders of different composition showed fairly large and comparable geometric particle sizes (de,50 > 4.4 µm) with effective densities strongly depending on the present matrix former. Powders with lowest density reached an aerosol performance of up to 60%, which is well above most commercial, carrier-based products. It was also demonstrated that the nanomilling step was indispensable to yield such good aerosol performance. Dissolution of aerodynamically classified particle fractions showed a very fast onset and was largely completed within 30 min irrespective of the formulation and the impactor stage. Mathematical kinetic modeling was used to deduce the API dissolution rate coefficient from the results obtained using a modified USP 2 apparatus. Dissolution rate was found to be determined by the properties of the API nanoparticles rather than those of the composite particles. The employment of industrially established, solely water-based processes allows introducing the presented approach as a platform technology for the development of well-performing pulmonary formulations.

Preparation of micrometric powders of parathyroid hormone (PTH1–34)-loaded chitosan oligosaccharide by supercritical fluid assisted atomization

Parathyroid hormone (PTH1–34)-loaded dry powders were fabricated from aqueous solution for pulmonary administration using supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM). Herein, chitosan oligosaccharide (CSO) was selected as a carrier in an effort to enhance transmucosal absorption of the drug. Well-defined, separated and spherical PTH(1–34)/CSO composite microparticles were obtained, and the particles size could be well controlled with narrow distribution. Aerodynamic performance was determined using next generation impactor (NGI), and the mass median aerodynamic diameter (MMAD) ranged strictly 1–5 μm range with fine particle fraction (FPF) up to 63.51%. The structural integrity of coprecipitated PTH(1–34) was validated by HPLC, FT-IR and circular dichroism, and a high loading efficiency up to 92.8% was obtained. TGA analyses revealed its thermal stability was preserved and XRD patterns showed amorphous structure of particles. The SAA-HCM process is proposed as a green technique for preparation of inhalable protein/polymer composite dry powders without use of any organic solvents.

Manipulation of spray-drying conditions to develop dry powder particles with surfaces enriched in hydrophobic material to achieve high aerosolization of a hygroscopic drug

This study aimed to develop dry powder particles with surfaces enriched in hydrophobic material by manipulation of spray-drying conditions and to investigate the effect of hydrophobic surface enrichment on aerosolization of hygroscopic drug.The composite dry powder formulations of kanamycin (hygroscopic drug) and rifampicin (hydrophobic drug) were produced by systematically (23 full factorial design) varying the drug ratio, co-solvent composition and inlet temperature using Buchi B-290 Mini Spray-Dryer. All the composite powder particles were inhalable in size (3.1–3.9 µm), wrinkled, flake-shaped and amorphous. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry showed that hydrophobic surface enrichment was significantly affected by co-solvent composition. Complete hydrophobic surface enrichment was achieved in one formulation (F7). The aerosolization efficiency by next generation impactor (NGI) showed that the composite formulations had higher fine particle fraction (FPF: >48.0%) than kanamycin-only formulation (FPF: 27.6%). Increase in hydrophobic surface enrichment (from 80.8 to 100%) decreased the powder density and increased FPF (from 48.0 to 77.2%).This is the first systematic study reporting the manipulation of spray-drying conditions for hydrophobic surface enrichment in composite dry powder particles and its effect on aerosolization. The high aerosolization efficiency of the combination formulations may be useful to deliver high doses of these drugs to treat lung infections.

Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections

Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying. Powder composition and process conditions were selected after in depth formulation studies aimed at selecting the 5-FC/HA/mannitol formulation with convenient aerosolization properties and drug release profile in simulated lung fluids. The optimized 5-FC/HA/mannitol powder for inhalation (HyaMan_FC#3) was effectively delivered from different breath-activated dry powder inhalers (DPI) already available to CF patients. Nevertheless, the aerodynamic assessment of fine particles suggested that the developed formulation well fit with a low-resistance DPI. HyaMan_FC#3 inhibited the growth of the fungus Candida albicans and the production of the virulence factor pyoverdine by P. aeruginosa at 5-FC concentrations that did not affect the viability of both wild type (16HBE14o-) and CF (CFBE41o-) human bronchial epithelial cells. Finally, pharmacokinetics of HyaMan_FC#3 inhalation powder and 5-FC solution after intratracheal administration in rats were compared. In vivo results clearly demonstrated that, when formulated as dry powder, 5-FC levels in both bronchoalveolar lavage fluid and lung tissue were significantly higher and sustained over time as compared to those obtained with the 5-FC solution. Of note, when the same 5-FC amount was administered intravenously, no significant drug amount was found in the lung at each time point from the injection. To realize a 5-FC lung concentration similar to that obtained by using HyaMan_FC#3, a 6-fold higher dose of 5-FC should be administered intravenously. Taken together, our data demonstrate the feasibility to deliver 5-FC by the pulmonary route likely avoiding/reducing the well-known side effects associated to the high systemic 5-FC doses currently used in humans. Furthermore, our results highlight that an appropriate formulation design can improve the persistence of the drug at lungs, where microorganisms causing severe infections are located.

Formulation of insulin-loaded N-trimethyl chitosan microparticles with improved efficacy for inhalation by supercritical fluid assisted atomization

Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was proposed as a green technique to fabricate insulin-loaded dry powders for inhalation administration. N-trimethyl chitosan (TMC), a polymeric mucoadhesive absorption enhancer, was synthesized and successfully micronized from aqueous solution using SAA-HCM. The prepared well-defined spherical TMC microparticles with preserved structure and thermal stability were potential carriers for delivery of proteins. Then, insulin-loaded TMC microparticles with high loading efficiency were coprecipitated from aqueous solutions using SAA-HCM without use of any organic solvents. The polymer/protein ratio revealed to be a factor influencing the particle morphology, and non-coalescing composite microparticles in amorphous state mainly ranging from 1μm to 5μm could be obtained in this work. Aerodynamic properties were assessed by next generation impactor (NGI) and the mass median aerodynamic diameter (MMAD) lied inside the inhalable range of 1–5μm, while fine particle fraction (FPF) reached above 60%. The structural integrity of encapsulated insulin was confirmed by HPLC, circular dichroism and fluorescence spectroscopy. In vivo study demonstrated that TMC could enhance the absorption and bioavailability of the pulmonarily administered insulin formulation for SD rats. These results suggest that TMC microparticles could be efficiently prepared as a promising vehicle for drug delivery, and SAA-HCM is a promising technique to prepare inhalable polymer/protein composite dry powders.

Responsive hydrogel nanoparticles for pulmonary delivery

Nanoparticles represent one of the most widely studied classes of advanced drug delivery platforms in recent years due to a wide range of unique properties and capabilities that can be utilized to improve upon traditional drug administration. Conversely, hydrogel nanoparticles (HNPs) – also called nanogels – represent a unique class of materials that combine the intrinsic advantages of nanotechnology with the inherent capabilities of hydrogels. Responsive hydrogels pose a particularly interesting class of materials that can sense and respond to external stimuli and previous reports of inhalable hydrogel particles have highlighted their potential in pulmonary delivery. Here, we synthesized two different pH-responsive HNPs, designated HNP120 and HNP270, by incorporating functional monomers with a common crosslinker and characterized their physicochemical properties. One of the HNP systems was selected for incorporation into a composite dry powder by spray drying, and the aerodynamic performance of the resulting powder was evaluated. The HNP120s displayed a hydrodynamic diameter of approximately 120 nm in their fully swollen state and a minimal diameter of around 80 nm while the HNP270s were approximately 270 nm and 115 nm, respectively. Electron microscopy confirmed particle size- and morphological uniformity of the HNPs. The HNP120s were spray dried into composite dry powders for inhalation and cascade impaction studies showed good aerosol performance with a mass median aerodynamic diameter (MMAD) of 4.82 ± 0.37 and a fine particle fraction > 30%. The HNPs released from the spray dried composites retained their responsive behavior thereby illustrating the potential for these materials as intelligent drug delivery systems that combine the advantages of nanotechnology, lung targeting through pulmonary delivery, and stimuli-responsive hydrogels.

Formulation and characterization of inhalable magnetic nanocomposite microparticles (MnMs) for targeted pulmonary delivery via spray drying

Targeted pulmonary delivery facilitates the direct application of bioactive materials to the lungs in a controlled manner and provides an exciting platform for targeting magnetic nanoparticles (MNPs) to the lungs. Iron oxide MNPs remotely heat in the presence of an alternating magnetic field (AMF) providing unique opportunities for therapeutic applications such as hyperthermia. In this study, spray drying was used to formulate magnetic nanocomposite microparticles (MnMs) consisting of iron oxide MNPs and d-mannitol. The physicochemical properties of these MnMs were evaluated and the in vitro aerosol dispersion performance of the dry powders was measured by the Next Generation Impactor®. For all powders, the mass median aerosol diameter (MMAD) was <5μm and deposition patterns revealed that MnMs could deposit throughout the lungs. Heating studies with a custom AMF showed that MNPs retain excellent thermal properties after spray drying into composite dry powders, with specific absorption ratios (SAR)>200W/g, and in vitro studies on a human lung cell line indicated moderate cytotoxicity of these materials. These inhalable composites present a class of materials with many potential applications and pose a promising approach for thermal treatment of the lungs through targeted pulmonary administration of MNPs.

Experimental Evaluation on Performance of Open Kitchen Fire Suppression Systems

Experiments with burning cooking oil in open kitchen fires are reported in this paper. Heat release rate, flame temperature, burning duration and heat fluxes of cooking oil fires were measured. Performances of water mist and gas-solid composite dry powders in suppressing cooking oil fires were evaluated by experiments. Reduction in gas temperature distributions, changes in heat fluxes and suppression time were then measured. Experimental data will provide necessary information for hazard assessment of open kitchen in the residential units of tall buildings.

Biokinetics of gold nanoparticles in the rat

Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was proposed as a green technique to fabricate insulin-loaded dry powders for inhalation administration. N-trimethyl chitosan (TMC), a polymeric mucoadhesive absorption enhancer, was synthesized and successfully micronized from aqueous solution using SAA-HCM. The prepared well-defined spherical TMC microparticles with preserved structure and thermal stability were potential carriers for delivery of proteins. Then, insulin-loaded TMC microparticles with high loading efficiency were coprecipitated from aqueous solutions using SAA-HCM without use of any organic solvents. The polymer/protein ratio revealed to be a factor influencing the particle morphology, and non-coalescing composite microparticles in amorphous state mainly ranging from 1 μm to 5 μm could be obtained in this work. Aerodynamic properties were assessed by next generation impactor (NGI) and the mass median aerodynamic diameter (MMAD) lied inside the inhalable range of 1–5 μm, while fine particle fraction (FPF) reached above 60%. The structural integrity of encapsulated insulin was confirmed by HPLC, circular dichroism and fluorescence spectroscopy. In vivo study demonstrated that TMC could enhance the absorption and bioavailability of the pulmonarily administered insulin formulation for SD rats. These results suggest that TMC microparticles could be efficiently prepared as a promising vehicle for drug delivery, and SAA-HCM is a promising technique to prepare inhalable polymer/protein composite dry powders.