Experimental research and energy analysis of a new type of dry ice powder pneumatic rock breaking technology

When the traditional drill and blast method is applied to rock crushing projects,it has strong vibration,loud noise and dust pollution,so it cannot be used in densely populated areas such as urban public works.We developed a supercritical CO_(2)true triaxial pneumatic rock-breaking experimental system,and conducted laboratory and field tests of dry ice powder pneumatic rock-breaking.The characteristics of the blast-induced vibration velocity waveform and the evolution of the vibration velocity and frequency with the focal distance were analyzed and discussed.The fracturing mechanism of dry ice powder pneumatic rock breaking is studied.The research results show that:(1)The vibration velocity induced by dry ice powder pneumatic rock breaking decays as a power function with the increase of the focal distance;(2)The vibration frequency caused by dry ice powder pneumatic rock breaking is mainly distributed in 1–120 Hz.Due to the dispersion effect,the dominant frequency of 10–30 Hz appears abnormally attenuated;(3)The traditional CO_(2)phase change fracturing energy calculation formula is also applicable to dry ice pneumatic rock breaking technology,and the trinitrotoluene(TNT)equivalent of fracturing energy is applicable to the Sadovsky formula;(4)Dry ice powder pneumatic rock breaking is shock wave and highenergy gas acting together to fracture rock,which can be divided into three stages,among which the gas wedge action of high-energy gas plays a dominant role in rock mass damage.

Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.

Comparative experimental study on inhibiting gas explosion using ABC dry powder and diatomite powder

Using a 20 L spherical explosion suppressing test system, the largest gas explosion pressure and maximum pressure rising rate with additives of ultra-fine ABC dry powder and diatomite powder were tested and compared, and the explosion suppression effect of the two kinds of powder was analyzed. Experimental results show that both powders can suppress gas ex- plosion and ABC dry powder is superior to diatomite powder. Adding two powders under the same experimental conditions, when methane concentration is 7.0%, the maximum explosion pressure decreased 39% and 4%, respectively, while the rising rate of the maximum pressure decreased 80% and 53%, respectively. When methane concentration is 9.5%, the maximum ex- plosion pressure decreased 14% and 12%, respectively, the rising rate of maximum pressure decreased 62% and 27%, respec- tively, the maximum explosion pressure decreased 23% and 18%, respectively, while the rising rate of the maximum pressure decreased 77% and 70%, respectively. When methane concentration is 12.0%, the explosion suppression effect of ultra-fine ABC dry powder is not affected by the methane concentration, and the explosion suppression effect of diatomite powder under high methane concentrations is more obvious.

Optimizing aerosolization of a high-dose L-arginine powder for pulmonary delivery

In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and excipients.The formulations were evaluated using several analytical methods to assess suitability for further investigation.Several batches had enhanced in vitro aerolization properties.Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.

Studies on the spray dried lactose as carrier for dry powder inhalation

The purpose of this study was to investigate the spray dried lactose as carrier for dry powder inhalation(DPI).The lactose particles were prepared by spray drying,then the particle size,shape and crystal form were characterized by laser diffraction,scanning electron microscopy(SEM),X-ray diffraction(XRD)and differential scanning calorimetry(DSC).The spray dried lactose particles were spherical and amorphous,but would transfer to crystal form when storage humidity was above 32%.Thus,the humidity of the storage environment should be controlled below 30%strictly in order to maintain the amorphous nature of spray dried lactose which is a great benefit to DPI development.

Preparation of Ultra-fine Salbutamol Sulfate Particles by Reactive Precipitation and Characterization of Dry Powder Inhalant

The preparation of ultra-fine particles of salbutamol sulphate （SS） was accomplished with a reactive precipitation pathway, in which salbutamol and sulphuric acid were Used as reactants with the solvents of ethanol.The effects of sulphuric acid concentration, reaction temperature, stirring rate, and reaction time onthesize of the particle were investigated. A binary mixture composed of lactose and SS was prepared to evaluate SS. The results showed that ultra-fine SS particles with controlled diameters ranging between 3 μm and 0.8 μm and with a narrow distribution could be achieved. The morphology consisting of clubbed particles wassuccess.fully obtained. The purity of the particles reached above 98% with-UV detection. The dose- of dry powder inhalation was obtained by blending the particles with recrystallized lactose, which acted as a carrier. The deposition quantity of the drug in breathing tract was estimated using a twin imPinger apparatus. Compared with the Shapuer powder （purchased in the market）, the results showed that SS_particles had more quantifies.subsided in simulative lung.. _

The effect of ethanol on the habit and in vitro aerodynamic results of dry powder inhalation formulations containing ciprofloxacin hydrochloride

In the case of dry powder inhalation systems(DPIs),the development of carrierfree formulations has gained increased attention.Thereby,spray-drying is a promising technology and is widely used to produce carrier-free DPIs.Numerous works have been published about the co-spray-drying of active ingredients with various solid excipients and their effect on the physicochemical characteristics and aerodynamic properties of the formulations.However,only a few studies have been reported about the role of the solvents used in the stock solutions of spray-dried formulations.In the present work,DPI microcomposites containing ciprofloxacin hydrochloride were prepared by spray-drying in the presence of different ethanol concentrations.The work expresses the roughness,depth and width of the dimples for particle size as a novel calculation possibility,and as a correlation between the MMAD/D_(0.5)ratio and correlating it with cohesion work,these new terms and correlations have not been published–to the best of our knowledge–which has resulted in gap-filling findings.As a result,different proportions of solvent mixtures could be interpreted and placed in a new perspective,in which the influence of different concentrations of ethanol on the habit of the DPI formulations,and thus on in vitro aerodynamic results.Based on these,it became clear why we obtained the best in vitro aerodynamic results for DPI formulation containing 30%ethanol in the stock solution.

Practical,regulatory and clinical considerations for development of inhalation drug products

The formulation and device collectively constitute an inhalation drug product.Development of inhaled drugs must consider the compatibility between formulation and device in order to achieve the intended pharmaceutical performance and usability of the product to improve patient compliance with treatment instruction.From the points of formulation,device and patient use,this article summarizes the inhalation drugs,including pressurized metered dose inhaler(pMDI),dry powder inhaler(DPI),and nebulizer that are currently available in the US and UK markets.It also discusses the practical considerations for the development of inhalers and provides an update on the corresponding regulations of the FDA(U.S.Food and Drug Administration)and the EMA(European Medicines Agency).

Influence of Aloe Gel Enrichment on the Physicochemical, Textural and Sensory Characteristics of Dahi

Aloe gel, derived from Aloe vera plant is well known for its nutraceutical potential, It is available commercially as a juice with poor sensory quality. The therapeutic benefits of Aloe gel could be extended to food products concomitantly improving its acceptability. Dahi/curd is an Asian fermented dairy product that enjoys tremendous mass appeal. The objective of the present study was to formulate dahi enriched with Aloe gel （AG） as a functional ingredient and to study its effect on the quality of dahi. Plain dahi was prepared by addition of 2.5% skimmed milk powder （SMP） and suitable starter to milk. For the preparation of AG enriched dahi, SMP was replaced by AG at different levels （0.1-0.25%）. The products were evaluated for moisture, pH, titrable acidity （TA）, whey syneresis （WS）, total solid content （TS）, water holding capacity （WHC）, total yield （TY）, whiteness index （WI）, and viscosity. Microbial analysis and sensory evaluation were also carried out. Enrichment of dahi with AG was found to improve its quality characteristics by causing a significant reduction in WS and an increase in TA, TS, WHC, TY, WI and viscosity. AG dahi recorded good sensory acceptability. Storage study also indicated AG dahi to perform better in terms of the various parameters studied. The present investigation suggests the feasibility of adding Aloe gel powder as a functional ingredient to dahi to enhance product quality as well as its nutritional and therapeutic potency. It could be commercially exploited as a novel product.

Inhalable microparticles as drug delivery systems to the lungs in a dry powder formulations

Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution,leading to a more effective therapy with reduced required doses and side effects.On the other hand,there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical,aerodynamic and biological properties,which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result.Therefore,we focused on powders consisting of polysaccharides,lipids,proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers.We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms.This review article addresses the most common manufacturing methods with novel modifications,pros and cons of different materials,drug loading capacities with release profiles,and biological properties such as cytocompatibility,bactericidal or anticancer properties.

Swirling flow and capillary diameter effect on the performance of an active dry powder inhalers

For patients with lung disease,dry powder inhalers(DPI)are profoundly beneficial.The current study introduces and develops a series of dry powder inhalers(DPIs).A capsule-based(size 0)active DPI was considered.The study aims to investigate whether swirling flow and outlet capillary diameter(dc_out)affect the percentage of emitted doses(ED)released from the capsule.Spiral vanes were added to the capillary inlet to produce a swirling flow.Computational fluid dynamics(CFD)was applied to simulate the problem.The results were compared with previous in vitro and numerical studies to validate the results.Based on the derived results,the small swirl parameter(SP)enhances the secondary flow and recirculation zone.It increases the central jet flow,which increases the ED value by about 5–20%compared to no-swirl flow.However,as the airflow rate increases,the recirculation zone enlarges,vorticities become dominant,and asymmetrical flow patterns emerge.Consequently,ED%drops significantly(more than 50%).As d_(c_out)decreases,the vorticities around the outlet capillary become more potent,which is undesirable.Indeed,the emptying of the capsule does not happen ideally.The research provides a perspective on the device's design and DPI performance.

Preparation of baicalin colon-targeted granules and its intervention effect on ulcerative colitis in rats

Baicalin(BA)is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi with excellent antioxidant and anti-inflammatory biological activities.In this study,Eudragit S100 was used as the colonic target material to prepare BA colonic targeting granules(EBCGs)based on plasticizer dry powder coating technology to improve the targeting transportation performance of BA.In vitro studies showed that EBCGs with pH-sensitive properties were successfully prepared by plasticizer dry powder coating,and in vivo animal imaging studies showed that EBCGs could deliver BA to the colon and inhibit the release of BA in the upper gastrointestinal tract(GIT).In vivo studies showed that EBCGs had good therapeutic effects in colitis,which reduced expression levels of tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)and increased superoxide dismutase(SOD)activities in the colonic tissues of rats with colitis.In conclusion,Eudragit S100 could be used for the preparation of multi-unit oral colon-targeted formulations by plasticizer dry powder coating technology,and our prepared EBCGs had good colon-targeting properties,which could improve the therapeutic effect and provide a potential application for ulcerative colitis(UC).

Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler(LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.

Dry powder platform for pulmonary drug delivery

The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmonary drug delivery with references to fluidization research, in particular, studies on Geldart group C powders. Dry powder inhaler device-formulation combination has been shown to be an effective method for delivering drugs to the lung for treatment of asthma, chronic obstructive pulmonary disease and cystic fibrosis. Even with advanced designs, however, delivery efficiency is still poor mainly due to powder dispersion problems which cause poor lung deposition and high dose variability. Drug particles used in current inhalers must be 1–5 μm in diameter for effective deposition in small-diameter airways and alveoli. These powders are very cohesive, have poor flowability, and are difficult to disperse into aerosol due to cohesion arising from van der Waals attraction. These problems are well known in fluidization research, much of which is highly relevant to pulmonary drug delivery.

Three-dimensional DEM-CFD analysis of air-flow-induced detachment of API particles from carrier particles in dry powder inhalers

Air flow and particle-particle/wall impacts are considered as two primary dispersion mechanisms for dry powder inhalers(DPIs).Hence,an understanding of these mechanisms is critical for the development of DPIs.In this study,a coupled DEM-CFD(discrete element method-computational fluid dynamics)is employed to investigate the influence of air flow on the dispersion performance of the carrier-based DPI formulations.A carrier-based agglomerate is initially formed and then dispersed in a uniformed air flow.It is found that air flow can drag API particles away from the carrier and those in the downstream air flow regions are prone to be dispersed.Furthermore,the influence of the air velocity and work of adhesion are also examined.It is shown that the dispersion number(i.e.,the number of API particles detached from the carrier)increases with increasing air velocity,and decreases with increasing the work of adhesion,indicating that the DPI performance is controlled by the balance of the removal and adhesive forces.It is also shown that the cumulative Weibull distribution function can be used to describe the DPI performance,which is governed by the ratio of the fluid drag force to the pull-off force.

Development of ciclesonide dry powder inhalers and the anti-asthmatic efficacy in guinea pigs

Ciclesonide is a new corticosteroid currently in clinical development for the treatment of asthma by oral inhalation. The objectives of the present study were to develop ciclesonide dry powder inhalers （DPIs, 80 μg） and investigate the anti-asthmatic effect in animals. For preparing a ciclesonide capsule-type DPI, sphere-shaped lactose was used as a diluent carrier, mixed with micronized ciclesonide, and filled into a capsule, and then put into a dry powder inhaler for oral inhalation. The asthmatic model was established with guinea pigs, and the therapeutic efficacy of ciclesonide was performed on the asthmatic guinea pig model. Results showed that the pulmonary deposition ratio of ciclesonide DPIs was approximately 26% and their content uniformity met the requirements of China Pharmacopoeia. The established pathological model exhibited the typical features of asthma with a widened pulmonary alveolar interval, narrowed alveolar space and detached bronchial mucosal epithelium with topical necrosis, goblet cell hyperplasia, and inflammatory cell infiltration. After treating with ciclesonide, the impaired indicators in asthmatic guinea pigs were significantly recovered or alleviated, exhibiting decreased total cells, decreased eosinophils and a decreased IL-5 level while there was an increased IFN-γ level in the bronchoalveolar lavage fluid （BALF）. This study develops a new pulmonary ciclesonide delivery system for treating asthma, and proves the therapeutic efficacy in asthmatic guinea pigs.

DEM analysis of the effect of electrostatic interaction on particle mixing for carrier-based dry powder inhaler formulations

Particle interactions play a significant role in controlling the performance of dry powder inhalers （DPIs）, which mainly arise through van der Waals potentials, electrostatic interactions, and capillary forces. Our aim is to investigate the influence of electrostatic charge on the performance of DPIs as a basis for improv- ing the formulation of the particle ingredients. The mixing process of carrier and active pharmaceutical ingredient （API） particles in a vibrating container is investigated using a discrete element method （DEM）. The number of APl particles attaching to the carrier particle （i.e., contact number） increases with increas- ing charge and decreases with increasing container size. The contact number decreases with increasing vibrational velocity amplitude and frequency. Moreover, a mechanism governed by the electrostatic force is proposed for the mixing process. This mechanism is different from that previously proposed for the mixing process governed by van der Waals forces, indicating that long-range and short-range adhesive forces can result in different mixing behaviours.

基于高凝集素亲和性载体的抗生素吸入粉雾剂用于高效治疗细菌生物膜相关肺部感染

多重耐药细菌引发的肺部感染对人类健康构成了严重威胁.细菌生物膜加剧了肺部感染的持续和复发,限制了抗生素的可及性和有效性.基于凝集素竞争策略和颗粒表面修饰策略,本研究设计了一种硫酸多粘菌素B(PMBS)的吸入粉雾剂(DPI)用于治疗肺部感染.该制剂的载体是具有高凝集素亲和性(HLA)的小分子糖(如棉子糖),可靶向细菌凝集素,限制生物膜的扩展.该制剂的粒径约为3μm,其表面褶皱程度和药物与载体的比例有关.处方F_(5)(PMBS:棉子糖=10:90)表现出最高的微细粒子分数(FPF=64.86%),表明其具备显著增强的肺部药物递送效率.通过添加棉子糖,制剂在抑制生物膜形成和清除成熟生物膜方面的效果显著提高.在急性和慢性肺部感染的大鼠模型中,相较于喷雾干燥的PMBS,处方F_(5)表现出更强的抗菌效果,并引起更低炎症反应.综上,基于HLA载体的抗生素DPI具有治疗细菌生物膜相关肺部感染的良好前景.

Electroconductivity,a regenerative engineering approach to reverse rotator cuff muscle degeneration

Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution,leading to a more effective therapy with reduced required doses and side effects.On the other hand,there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical,aerodynamic and biological properties,which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result.Therefore,we focused on powders consisting of polysaccharides,lipids,proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers.We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms.This review article addresses the most common manufacturing methods with novel modifications,pros and cons of different materials,drug loading capacities with release profiles,and biological properties such as cytocompatibility,bactericidal or anticancer properties.

A homogenous nanoporous pulmonary drug delivery system based on metal-organic frameworks with fine aerosolization performance and good compatibility

Pulmonary drug delivery has attracted increasing attention in biomedicine,and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs.However,the existing methods for preparing porous particles using porogens have several drawbacks,such as the inhomogeneous and uncontrollable pores,drug leakage,and high risk of fragmentation.In this study,a series of cyclodextrin-based metal-organic framework(CD-MOF)particles containing homogenous nanopores were delicately engineered without porogens.Compared with commercial inhalation carrier,CDMOF showed excellent aerosolization performance because of the homogenous nanoporous structure.The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments,including cytotoxicity assay,hemolysis ratio test,lung function evaluation,in vivo lung injury markers measurement,and histological analysis.The results of ex vivo fluorescence imaging showed the high deposition rate of CD-MOF in lungs.Therefore,all results demonstrated that CD-MOF was a promising carrier for pulmonary drug delivery.This study may throw light on the nanoporous particles for effective pulmonary administration.