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Sample records for dry powder aerosols

  1. Liposomal dry powders as aerosols for pulmonary delivery of proteins.

    PubMed

    Lu, Dongmei; Hickey, Anthony J

    2005-12-21

    The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. Beta-glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7:3) was selected as the liposome composition. The lyophilization of liposomes, micronization of the powders, aerosolization using a dry powder inhaler (DPI), and in vitro aerodynamic fine particle fraction upon collection in a twin-stage liquid impinger were evaluated. After lyophilization and jet-milling, the total amount of GUS and its activity, representing encapsulation efficiency and stability, were evaluated. The GUS amount and activity were measured and compared with freshly-prepared liposomes in the presence of mannitol, 43% of initial GUS amount, 29% of GUS activity after lyophilization and 36% of GUS amount, 22% of activity after micronization were obtained. Emitted doses from dry powder inhaler were 53%, 58%, 66%, and 73% for liposome powder:mannitol carrier ratios of 1:0, 1:4, 1:9, and 1:19. Fifteen percent of the liposome particles were less than 6.4 mum in aerodynamic diameter. The results demonstrate that milled liposome powders containing protein molecules can be aerosolized effectively at a fixed flow rate. Influences of different cryoprotectants on lyophilization of protein liposome formulations are reported. The feasibility of using liposomal dry powder aerosols for protein delivery has been demonstrated but further optimization is required in the context of specific therapeutic proteins.

  2. Improving aerosolization of drug powders by reducing powder intrinsic cohesion via a mechanical dry coating approach.

    PubMed

    Zhou, Qi Tony; Qu, Li; Larson, Ian; Stewart, Peter J; Morton, David A V

    2010-07-15

    The aim of this study was to investigate the effect of coating on the aerosolization of three model micronized powders. Three model powder materials (salbutamol sulphate, salmeterol xinafoate, triamcinolone acetonide) were chosen not only for their different chemical properties but also for their different physical properties such as shape and size distribution. Each powder was coated with 5% (w/w) magnesium stearate using two different dry mechanofusion approaches. After mechanofusion, both poured and tapped densities for all three model drug powders significantly increased. There were significant improvements in aerosolization behavior from an inhaler device for all model powders after mechanofusion. Such improvements in aerosolization were attributed to the reduction in agglomerate strength caused by decreasing powder intrinsic cohesion via surface modification. The work also indicated that the effect of the coating was dependant on the initial particle properties.

  3. Nifedipine Nanoparticle Agglomeration as a Dry Powder Aerosol Formulation Strategy

    PubMed Central

    Plumley, Carl; Gorman, Eric M.; Munson, Eric J.; Berkland, Cory

    2009-01-01

    Efficient administration of drugs represents a leading challenge in pulmonary medicine. Dry powder aerosols are of great interest compared to traditional aerosolized liquid formulations in that they may offer improved stability, ease of administration, and simple device design. Particles 1–5 µm in size typically facilitate lung deposition. Nanoparticles may be exhaled as a result of their small size; however, they are desired to enhance the dissolution rate of poorly soluble drugs. Nanoparticles of the hypertension drug nifedipine were co-precipitated with stearic acid to form a colloid exhibiting negative surface charge. Nifedipine nanoparticle colloids were destabilized by using sodium chloride to disrupt the electrostatic repulsion between particles as a means to achieve the agglomerated nanoparticles of a controlled size. The aerodynamic performance of agglomerated nanoparticles was determined by cascade impaction. The powders were found to be well suited for pulmonary delivery. In addition, nanoparticle agglomerates revealed enhanced dissolution of the drug species suggesting the value of this formulation approach for poorly water soluble pulmonary medicines. Ultimately, nifedipine powders are envisioned as an approach to treat pulmonary hypertension. PMID:19015016

  4. Pulmonary Delivery of Vancomycin Dry Powder Aerosol to Intubated Rabbits.

    PubMed

    Sullivan, Bradley P; El-Gendy, Nashwa; Kuehl, Christopher; Berkland, Cory

    2015-08-03

    Antibiotic multiresistant pneumonia is a risk associated with long-term mechanical ventilation. Vancomycin is commonly prescribed for methicillin-resistant Staphylococcus aureus infections; however, current formulations of vancomycin are only given intravenously. High doses of vancomycin have been associated with severe renal toxicity. In this study, we characterized dry powder vancomyin as a potential inhaled therapeutic aerosol and compared pharmacokinetic profiles of iv and pulmonary administered vancomycin in intubated rabbits through an endotracheal tube system. Cascade impaction studies indicated that using an endotracheal tube, which bypasses deposition in the mouth and throat, increased the amount of drug entering the lung. Bypassing the endotracheal tube with a catheter further enhanced drug deposition in the lung. Interestingly, intubated rabbits administered 1 mg/kg vancomycin via inhalation had similar AUC to rabbits that were administered 1 mg/kg vancomycin via a single bolus iv infusion; however, inhalation of vancomycin reduced Cmax and increased Tmax, indicating that inhaled vancomycin resulted in more sustained pulmonary levels of vancomycin. Collectively, these results suggested that dry powder vancomycin can successfully be delivered by pulmonary inhalation in intubated patients. Furthermore, as inhaled vancomycin is delivered locally to the site of pulmonary infection, this delivery route could reduce the total dose required for therapeutic efficacy and simultaneously reduce the risk of renal toxicity by eliminating the high levels of systemic drug exposure required to push the pulmonary dose to therapeutic thresholds during iv administration.

  5. Pulmonary delivery of vancomycin dry powder aerosol to intubated rabbits

    PubMed Central

    Sullivan, Bradley P.; El-Gendy, Nashwa; Kuehl, Christopher; Berkland, Cory

    2016-01-01

    Antibiotic multi-resistant pneumonia is a risk associated with long term mechanical ventilation. Vancomycin is commonly prescribed for methicillin-resistant staphylococcus aureus infections; however, current formulations of vancomycin are only given intravenously. High doses of vancomycin have been associated with severe renal toxicity. In this study we characterized dry powder vancomyin as a potential inhaled therapeutic aerosol and compared pharmacokinetic profiles of i.v. and pulmonary administered vancomycin in intubated rabbits using a novel endotracheal tube catheter system. Cascade Impaction studies indicated that using an endotracheal tube, which bypasses deposition the mouth and throat, increased the amount of drug entering the lung. Drug deposition in the lung was further enhanced by using an endotracheal tube catheter, which did not alter the aerosol fine particle fraction. Interestingly, intubated rabbits administered 1 mg/kg vancomycin via inhalation had similar AUC to rabbits that were administered 1 mg/kg vancomycin via a single bolus i.v. infusion; however, inhalation of vancomycin reduced Cmax and increased Tmax, suggesting that inhaled vancomycin resulted in more sustained pulmonary levels of vancomycin. Collectively, these results suggested that dry powder vancomycin can successfully be delivered by pulmonary inhalation in intubated patients. Furthermore, as inhaled vancomycin is delivered locally to the site of pulmonary infection, this delivery route could reduce the total dose required for therapeutic efficacy and simultaneously reduce the risk of renal toxicity by eliminating the high levels of systemic drug exposure required to push the pulmonary dose to therapeutic thresholds during i.v. administration. PMID:25915095

  6. Moving from CFC aerosol to HFA aerosol or dry powder inhalers: what do patients think?

    PubMed

    Hartung, Thomas K; Allbutt, Helen; Dewar, Maria; Innes, J Alastair; Crompton, Graham K

    2002-01-01

    Environmentally friendly hydrofluoroalkane (HFA) pressurised metered-dose inhalers are currently being marketed to replace chlorofluorocarbon (CFC)-driven devices. It is uncertain whether these new formulations with different properties are acceptable to patients. Similarly, switching a patient to a dry powder inhaler (DPI) carries the risk of non-acceptance. One hundred patients with obstructive airway disease on regular CFC aerosol inhaler medication underwent a standardised, structured interview. During the interview patients were asked to use a new HFA aerosol inhaler and three DPIs in random order. Patients' notions were recorded. Most patients (96) agreed to change from their CFC to the HFA inhaler, of those, only 12 did so with some reservation. Properties (taste, user-friendliness, design) of the HFA inhaler were rated favourably. DPIs represented an acceptable alternative to aerosol inhalers. In fact, 57 patients preferred a DPI over the HFA inhaler. Not all powder devices were equally acceptable. Replacing the CFC inhaler with patients' preferred alternative devices resulted in a more than 3-fold increase in costs. Concerns about the acceptability of reformulated CFC-free aerosol inhalers are ill founded. However, if given the choice, many patients prefer a DPI over the HFA inhaler. The transition offers an opportunity to review patients' current treatment and the proficiency of their inhaling technique. Moving to CFC-free inhalers will have revenue implications. Copyright 2002 S. Karger AG, Basel

  7. Design, Characterization, and Aerosol Dispersion Performance Modeling of Advanced Spray-Dried Microparticulate/Nanoparticulate Mannitol Powders for Targeted Pulmonary Delivery as Dry Powder Inhalers

    PubMed Central

    Li, Xiaojian; Vogt, Frederick G.; Hayes, Don

    2014-01-01

    Abstract Background: The purpose was to design and characterize inhalable microparticulate/nanoparticulate dry powders of mannitol with essential particle properties for targeted dry powder delivery for cystic fibrosis mucolytic treatment by dilute organic solution spray drying, and, in addition, to tailor and correlate aerosol dispersion performance delivered as dry powder inhalers based on spray-drying conditions and solid-state physicochemical properties. Methods: Organic solution advanced spray drying from dilute solution followed by comprehensive solid-state physicochemical characterization and in vitro dry powder aerosolization were used. Results: The particle size distribution of the spray-dried (SD) powders was narrow, unimodal, and in the range of ∼500 nm to 2.0 μm. The particles possessed spherical particle morphology, relatively smooth surface morphology, low water content and vapor sorption (crystallization occurred at exposure above 65% relative humidity), and retention of crystallinity by polymorphic interconversion. The emitted dose, fine particle fraction (FPF), and respirable fraction (RF) were all relatively high. The mass median aerodynamic diameters were below 4 μm for all SD mannitol aerosols. Conclusion: The in vitro aerosol deposition stage patterns could be tailored based on spray-drying pump rate. Positive linear correlation was observed between both FPF and RF values with spray-drying pump rates. The interplay between various spray-drying conditions, particle physicochemical properties, and aerosol dispersion performance was observed and examined, which enabled tailoring and modeling of high aerosol deposition patterns. PMID:24502451

  8. Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

    PubMed Central

    Wu, Xiao; Zhang, Weifen; Hayes, Don; Mansour, Heidi M

    2013-01-01

    In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug – cyclosporine A – for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero- 3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters. PMID:23569375

  9. Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery.

    PubMed

    Wu, Xiao; Zhang, Weifen; Hayes, Don; Mansour, Heidi M

    2013-01-01

    In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug - cyclosporine A - for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero- 3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters.

  10. Nanoparticle agglomerates of fluticasone propionate in combination with albuterol sulfate as dry powder aerosols

    PubMed Central

    El-Gendy, Nashwa; Pornputtapitak, Warangkana; Berkland, Cory

    2015-01-01

    Particle engineering strategies remain at the forefront of aerosol research for localized treatment of lung diseases and represent an alternative for systemic drug therapy. With the hastily growing popularity and complexity of inhalation therapy, there is a rising demand for tailor-made inhalable drug particles capable of affording the most proficient delivery to the lungs and the most advantageous therapeutic outcomes. To address this formulation demand, nanoparticle agglomeration was used to develop aerosols of the asthma therapeutics, fluticasone or albuterol. In addition, a combination aerosol was formed by drying agglomerates of fluticasone nanoparticles in the presence of albuterol in solution. Powders of the single drug nanoparticle agglomerates or of the combined therapeutics possessed desirable aerodynamic properties for inhalation. Powders were efficiently aerosolized (~75% deposition determined by cascade impaction) with high fine particle fraction and rapid dissolution. Nanoparticle agglomeration offers a unique approach to obtain high performance aerosols from combinations of asthma therapeutics. PMID:21964203

  11. Dry powder antibiotic aerosol product development: inhaled therapy for tuberculosis.

    PubMed

    Hickey, Anthony J; Misra, Amit; Fourie, P Bernard

    2013-11-01

    Inhaled therapies offer a unique approach to the treatment of tuberculosis (TB) using a relevant target organ system as a route of administration. The number of research reports on this topic has been increasing exponentially in the last decade but studies of clinical efficacy have been rare in recent times. The challenge is to take many research findings and translate them into a strategy for product development. Dry powder inhalers are the dominant drug product under consideration by those interested in the inhaled therapy for TB. A range of factors including candidate drug, formulation, device selection, drug product testing for proof of concept, and preclinical and clinical purposes all demand different considerations. The following review is intended to raise awareness of a growing body of evidence, suggesting that inhaled therapy for TB is possible and desirable. In addition, it is intended to outline key elements of the product-development activity for this particular application that has not been discussed elsewhere in the literature. Hopefully, this will encourage those with development expertise to seriously contemplate the steps required to bring such products forward. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols.

    PubMed

    Park, Chun-Woong; Li, Xiaojian; Vogt, Frederick G; Hayes, Don; Zwischenberger, Joseph B; Park, Eun-Seok; Mansour, Heidi M

    2013-10-15

    Respirable microparticles/nanoparticles of the antibiotics vancomycin (VCM) and clarithromycin (CLM) were successfully designed and developed by novel organic solution advanced spray drying from methanol solution. Formulation optimization was achieved through statistical experimental design of pump feeding rates of 25% (Low P), 50% (Medium P) and 75% (High P). Systematic and comprehensive physicochemical characterization and imaging were carried out using scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Karl Fischer titration (KFT), laser size diffraction (LSD), gravimetric vapor sorption (GVS), confocal Raman microscopy (CRM) and spectroscopy for chemical imaging mapping. These novel spray-dried (SD) microparticulate/nanoparticulate dry powders displayed excellent aerosol dispersion performance as dry powder inhalers (DPIs) with high values in emitted dose (ED), respirable fraction (RF), and fine particle fraction (FPF). VCM DPIs displayed better aerosol dispersion performance compared to CLM DPIs which was related to differences in the physicochemical and particle properties of VCM and CLM. In addition, organic solution advanced co-spray drying particle engineering design was employed to successfully produce co-spray-dried (co-SD) multifunctional microparticulate/nanoparticulate aerosol powder formulations of VCM and CLM with the essential lung surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPC), for controlled release pulmonary nanomedicine delivery as inhalable dry powder aerosols. Formulation optimization was achieved through statistical experimental design of molar ratios of co-SD VCM:DPPC and co-SD CLM:DPPC. XRPD and DSC confirmed that the phospholipid bilayer structure in the solid-state was preserved following spray drying. Co-SD VCM:DPPC and co-SD CLM:DPPC dry powder aerosols demonstrated controlled release of antibiotic drug that was fitted to various

  13. Aerosolization properties, surface composition and physical state of spray-dried protein powders.

    PubMed

    Bosquillon, Cynthia; Rouxhet, Paul G; Ahimou, François; Simon, Denis; Culot, Christine; Préat, Véronique; Vanbever, Rita

    2004-10-19

    Powder aerosols made of albumin, dipalmitoylphosphatidylcholine (DPPC) and a protein stabilizer (lactose, trehalose or mannitol) were prepared by spray-drying and analyzed for aerodynamic behavior, surface composition and physical state. The powders exited a Spinhaler inhaler as particle aggregates, the size of which depending on composition, spray-drying parameters and airflow rate. However, due to low bulk powder tap density (<0.15 g/cm3), the aerodynamic size of a large fraction of aggregates remained respirable (<5 microm). Fine particle fractions ranged between 21% and 41% in an Andersen cascade impactor operated at 28.3 l/min, with mannitol and lactose providing the most cohesive and free-flowing powders, respectively. Particle surface analysis by X-ray photoelectron spectroscopy (XPS) revealed a surface enrichment with DPPC relative to albumin for powders prepared under certain spray-drying conditions. DPPC self-organized in a gel phase in the particle and no sugar or mannitol crystals were detected by X-ray diffraction. Water sorption isotherms showed that albumin protected lactose from moisture-induced crystallization. In conclusion, a proper combination of composition and spray-drying parameters allowed to obtain dry powders with elevated fine particle fractions (FPFs) and a physical environment favorable to protein stability.

  14. Influence of formulation and preparation process on ambroxol hydrochloride dry powder inhalation characteristics and aerosolization properties.

    PubMed

    Ren, Yachao; Yu, Chaoqun; Meng, Kangkang; Tang, Xing

    2008-09-01

    The objective of this study is to evaluate the influence of formulation and preparation process on ambroxol hydrochloride (AH) dry powder inhalation (DPI) characteristics and aerosolization properties. Spray-dried samples of AH, AH/leucine, and AH/leucine/mannitol were prepared from their corresponding water solutions under the same conditions to study the influence of the composition, and the AH/leucine/mannitol (2.5/0.5/1 by weight) formulation was used for investigation of the effect of the preparation process. Following spray-drying, the resulting powders were characterized using scanning electron microscopy, laser diffraction, tapped density, and angle of repose measurements, and the aerosolization performance was determined using a twin-stage liquid impinger. AH/leucine/mannitol (2.5/0.5/1 by weight) obtained by cospray-drying improved the AH aerosolization properties. The AH/leucine/mannitol (2.5/0.5/1 by weight) preparation exhibited the following properties: 62.34% yield, 0.34 g/cm(3) tap density, 2.71 microm d(ae), 33.45 degrees angle of repose, and 30.93% respirable fraction. The influence of the preparation process on DPI characteristics and aerosolization properties was relatively small, but the influence of the composition was relatively large. Optimization of DPI can be achieved by selecting the most appropriate formulation and preparation process.

  15. Spray-freeze-dried liposomal ciprofloxacin powder for inhaled aerosol drug delivery.

    PubMed

    Sweeney, Lyle G; Wang, Zhaolin; Loebenberg, Raimar; Wong, Jonathan P; Lange, Carlos F; Finlay, Warren H

    2005-11-23

    Spray-freeze drying was utilized to manufacture a liposomal powder formulation containing ciprofloxacin as a model active component. The powder forms liposomally encapsulated ciprofloxacin when wetted. Aerosol properties of this formulation were assessed using a new passive inhaler, in which the powder was entrained at a flow rate of 60l/min. A mass median aerodynamic diameter (MMAD) of 2.8 microm was achieved for this formulation. Using the experimental dispersion testing data, ciprofloxacin concentration in the airway surface liquid (ASL) was calculated using a Lagrangian deposition model. The reconstitution of the powder in various aqueous media gave drug encapsulation efficiencies as follows: 50% in water, 93.5% in isotonic saline, 80% in bovine mucin, 75% in porcine mucus and 73% in five-fold-diluted ex vivo human cystic fibrosis patient sputum.

  16. A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge

    PubMed Central

    Klas, S.D.; Petrie, C.R.; Warwood, S.J.; Williams, M.S.; Olds, C.L.; Stenz, J.P.; Cheff, A.M.; Hinchcliffe, M.; Richardson, C.; Wimer, S.

    2009-01-01

    Here we confirm that intranasal (IN) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. The optimum dose of rPA in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150 μg and therefore was chosen as the target dose for all subsequent experiments. Rabbits received a single dose of either 150 μg rPA, 150 μg rPA + 150 μg of a conjugated 10-mer peptide representing the B. anthracis capsule (conj), or 150 μg of conj alone. All dry powder formulations contained MPL and chitosan (ChiSys®). Significant anti-rPA titers and anthrax lethal toxin neutralizing antibody (TNA) levels were seen with both rPA containing vaccines, although rPA-specific IgG and TNA levels were reduced in rabbits immunized with rPA plus conj. Nine weeks after immunization, rabbits were exposed to a mean aerosol challenge dose of 278 LD50 of Ames spores. Groups immunized with rPA or with rPA + conj had significant increases in survivor proportions compared to the negative control group by Logrank test (p = 0.0001 and 0.003, respectively), and survival was not statistically different for the rPA and rPA + conj immunized groups (p = 0.63). These data demonstrate that a single immunization with our dry powder anthrax vaccine can protect against a lethal aerosol spore challenge 9 weeks later. PMID:18703110

  17. Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried microparticulate/nanoparticulate antibiotic dry powders of tobramycin and azithromycin for pulmonary inhalation aerosol delivery.

    PubMed

    Li, Xiaojian; Vogt, Frederick G; Hayes, Don; Mansour, Heidi M

    2014-02-14

    The purpose of this study was to systematically design pure antibiotic drug dry powder inhalers (DPIs) for targeted antibiotic pulmonary delivery in the treatment of pulmonary infections and comprehensively correlate the physicochemical properties in the solid-state and spray-drying conditions effects on aerosol dispersion performance as dry powder inhalers (DPIs). The two rationally chosen model antibiotic drugs, tobramycin (TOB) and azithromycin (AZI), represent two different antibiotic drug classes of aminoglycosides and macrolides, respectively. The particle size distributions were narrow, unimodal, and in the microparticulate/nanoparticulate size range. The SD particles possessed relatively spherical particle morphology, smooth surface morphology, low residual water content, and the absence of long-range molecular order. The emitted dose (ED%), fine particle fraction (FPF%) and respirable fraction (RF%) were all excellent. The MMAD values were in the inhalable range (<10 μm) with smaller MMAD values for SD AZI powders in contrast to SD TOB powders. Positive linear correlations were observed between the aerosol dispersion performance parameter of FPF with increasing spray-drying pump rates and also with the difference between thermal parameters expressed as Tg-To (i.e. the difference between the glass transition temperature and outlet temperature) for SD AZI powders. The aerosol dispersion performance for SD TOB appeared to be influenced by its high water vapor sorption behavior (hygroscopicity) and pump rates or To. Aerosol dispersion performance of SD powders were distinct for both antibiotic drug aerosol systems and also between different pump rates for each system. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. CFD analysis of the aerosolization of carrier-based dry powder inhaler formulations

    NASA Astrophysics Data System (ADS)

    Zhou, Qi (Tony); Tong, Zhenbo; Tang, Patricia; Yang, Runyu; Chan, Hak-Kim

    2013-06-01

    This study applied computational fluid dynamics (CFD) analysis to investigate the role of device design on the aerosolization of a carrier-based dry powder inhaler (DPI). The inhaler device was modified by reducing the inlet size, decreasing the mouthpiece length and increasing the mesh grid voidage. The flow patterns in the inhaler device were examined. It was observed that there was no significant influence on the aerosol performance with the reduced mouthpiece. When the inlet size was reduced to one third of the original one, the fine particle fraction (FPF), defined as mount of inhalable fine particles below 5μm in the aerosol, was improved significantly from 17.7% to 24.3%. The CFD analysis indicated that the increase in FPF was due to increasing air velocity for the smaller inlet. No significant difference was shown in FPF when the grid voidage was increased, but more drugs deposited in the mouthpiece and throat.

  19. Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery

    PubMed Central

    Duan, Jinghua; Vogt, Frederick G; Li, Xiaojian; Hayes, Don; Mansour, Heidi M

    2013-01-01

    The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders. PMID:24092972

  20. Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler

    PubMed Central

    Golshahi, Laleh; Behara, Srinivas R.B.; Tian, Geng; Farkas, Dale R.; Hindle, Michael

    2015-01-01

    Abstract Purpose: Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy. Methods: The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region. Results: The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5–2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%. Conclusions: The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy. PMID:25192072

  1. Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler.

    PubMed

    Longest, P Worth; Golshahi, Laleh; Behara, Srinivas R B; Tian, Geng; Farkas, Dale R; Hindle, Michael

    2015-06-01

    Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy. The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region. The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5-2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%. The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy.

  2. Dry powder aerosols to co-deliver antibiotics and nutrient dispersion compounds for enhanced bacterial biofilm eradication.

    PubMed

    Sommerfeld Ross, S; Gharse, S; Sanchez, L; Fiegel, J

    2017-08-04

    The purpose of this study was to formulate a dry powder for inhalation containing a combination treatment for eradication of Pseudomonas aeruginosa bacterial biofilms. Dry powders containing an antibiotic (ciprofloxacin hydrochloride, CH) and nutrient dispersion compound (glutamic acid, GA) at a ratio determined to eliminate the biofilms were generated by spray drying. Leucine was added to the spray dried formulation to aid powder flowability. A central composite design of experiments was performed to determine the effects of solution and processing parameters on powder yield and aerodynamic properties. Combinations of CH and GA eradicated bacterial biofilms at lower antibiotic concentrations compared to CH alone. Spray dried powders were produced with yields up to 43% and mass mean aerodynamic diameters (MMAD) in the respirable range. Powder yield was primarily affected by variables that determine cyclone efficiency, i.e. atomizer and solution flow rates and solution concentration; while MMAD was mainly determined by solution concentration. Fine particle fractions (FPF)<4.46μm and <2.82μm of the powders ranged from 56 to 70% and 35 to 46%, respectively. This study demonstrates that dry powder aerosols containing high concentrations of a combination treatment effective against P. aeruginosa biofilms could be developed with high yield, aerodynamic properties appropriate for inhalation, and no loss of potency. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. L-Leucine as an excipient against moisture on in vitro aerosolization performances of highly hygroscopic spray-dried powders.

    PubMed

    Li, Liang; Sun, Siping; Parumasivam, Thaigarajan; Denman, John A; Gengenbach, Thomas; Tang, Patricia; Mao, Shirui; Chan, Hak-Kim

    2016-05-01

    L-Leucine (LL) has been widely used to enhance the dispersion performance of powders for inhalation. LL can also protect powders against moisture, but this effect is much less studied. The aim of this study was to investigate whether LL could prevent moisture-induced deterioration in in vitro aerosolization performances of highly hygroscopic spray-dried powders. Disodium cromoglycate (DSCG) was chosen as a model drug and different amounts of LL (2-40% w/w) were added to the formulation, with the aim to explore the relationship between powder dispersion, moisture protection and physicochemical properties of the powders. The powder formulations were prepared by spray drying of aqueous solutions containing known concentrations of DSCG and LL. The particle sizes were measured by laser diffraction. The physicochemical properties of fine particles were characterized by X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic vapor sorption (DVS). The surface morphology and chemistry of fine particles were analyzed by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performances were evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH), and 25°C for 24h. Spray-dried (SD) DSCG powders were amorphous and absorbed 30-45% (w/w) water at 70-80% RH, resulting in deterioration in the aerosolization performance of the powders. LL did not decrease the water uptake of DSCG powders, but it could significantly reduce the effect of moisture on aerosolization performances. This is due to enrichment of crystalline LL on the surface of the composite particles. The effect was directly related to the percentage of LL coverage on the surface of particles. Formulations having 61-73% (molar percent) of LL on the particle surface (which correspond to 10-20% (w

  4. Investigation on the aerosol performance of dry powder inhalation hypromellose capsules with different lubricant levels.

    PubMed

    Saleem, I Y; Diez, F; Jones, B E; Kayali, N; Polo, L

    2015-08-15

    HPMC capsules are made by a dipping process and a surface lubricant for the mould pins is an essential processing aid for removing dried capsules shells. For the purpose of this study, the level was determined by quantifying methyloleate (MO) a component found in the lubricant but not in the hypromellose capsules. Here we investigated the influence of the lubricant, low (10.81 μg/capsule=60 mg/kg MO), medium (15.97 μg/capsule=90 mg/kg MO) and high (23.23 μg/capsule=127 mg/kg MO) content on powder (binary mixture of salbutamol: lactose, 1:50 w/w) aerosolization properties was investigated. Results indicated significantly lower emitted dose from capsules with 60 mg/kg MO. Furthermore, the 90 and 127 mg/kg MO level of lubricant capsules produced almost double the Fine Particle Dose & Fine Particle Fraction compared with the low level of lubricant. The data indicates that lubricant level within capsules has an influence on deposition profiles and amount of drug remaining in capsule and inhaler device after actuation. It is suggested lubricant levels greater than 60 mg/kg MO per capsule are required to minimise powder retention within capsules and maximise deposition profiles. AFM (atomic force microscopy) data suggest that internal surface roughness may be related with this phenomena. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Aerodynamic and electrostatic properties of model dry powder aerosols: a comprehensive study of formulation factors.

    PubMed

    Telko, M J; Hickey, A J

    2014-12-01

    The impact of formulation variables on aerodynamic and electrostatic properties of dry powder aerosol particles is of great importance to the development of efficient and reproducible inhaler products. Systematic evaluation requires a well-designed series of experiments using appropriate methods. A factorial experimental design was employed. In broad terms, the conditions considered were two drugs, albuterol and budesonide, in combination with different excipients, drug concentrations, delivered doses, and metering system (capsule composition) and sampled under different flow conditions using standard entrainment tubes. Samples were collected in an electrical low-pressure impactor, to evaluate distribution of electrostatic properties, and an Andersen eight-stage nonviable cascade impactor, to estimate aerodynamic particle size distribution, concurrently. The deposition studies allowed calculation of approximate per particle charge levels for drug. The results showed very high particle charge levels, often in the 1,000-10,000 of elementary charges per particle range, orders of magnitude higher than charge levels predicted by the Boltzmann charge distribution. The charge levels are considerably higher than had previously been estimated (200e per particle).

  6. A dry powder combination of pyrazinoic acid and its n-propyl ester for aerosol administration to animals.

    PubMed

    Durham, P G; Young, E F; Braunstein, M S; Welch, J T; Hickey, A J

    2016-12-05

    Combining the advantage of higher efficacy due to local pulmonary administration of pyrazinoic acid (POA) and potent effect of pyrazinoic acid ester (PAE) delivered as an aerosol would aid in tuberculosis therapy. A combination spray dried dry powder, composed of POA, PAE (n-propyl POA), maltodextrin and leucine, was prepared for aerosol delivery to animals. Solid-state characteristics of morphology (scanning electron microscopy) crystallinity (X-ray powder diffraction), thermal properties (thermogravimetric analysis and differential scanning calorimetry) and moisture content (Karl Fisher) were evaluated. Particle size distributions, by volume (laser diffraction) for the dispersed powder and by mass (inertial impaction) were determined. Efficient delivery of the powder to a nose only animal exposure chamber employed a novel rotating brush/micro-fan apparatus. Spherical, crystalline particles were prepared. The volume median diameter, ∼1.5μm, was smaller than the mass median aerodynamic diameter, ∼3.0μm, indicating modest aggregation. Drug content variations were observed across the particle size distribution and may be explained by PAE evaporative losses. Delivery to the nose-only exposure chamber indicated that boluses could be administered at approximately 3min intervals to avoid aerosol accumulation and effect uniform dose delivery with successive doses suitable for future pharmacokinetic and pharmacodynamic studies.

  7. Characterization and aerosol dispersion performance of advanced spray-dried chemotherapeutic PEGylated phospholipid particles for dry powder inhalation delivery in lung cancer.

    PubMed

    Meenach, Samantha A; Anderson, Kimberly W; Zach Hilt, J; McGarry, Ronald C; Mansour, Heidi M

    2013-07-16

    Pulmonary inhalation chemotherapeutic drug delivery offers many advantages for lung cancer patients in comparison to conventional systemic chemotherapy. Inhalable particles are advantageous in their ability to deliver drug deep in the lung by utilizing optimally sized particles and higher local drug dose delivery. In this work, spray-dried and co-spray dried inhalable lung surfactant-mimic PEGylated lipopolymers as microparticulate/nanoparticulate dry powders containing paclitaxel were rationally designed via organic solution advanced spray drying (no water) in closed-mode from dilute concentration feed solution. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) with varying PEG chain length were mixed with varying amounts of paclitaxel in methanol to produce co-spray dried microparticles and nanoparticles. Scanning electron microscopy showed the spherical particle morphology of the inhalable particles. Thermal analysis and X-ray powder diffraction confirmed the retention of the phospholipid bilayer structure in the solid-state following spray drying, the degree of solid-state molecular order, and solid-state phase transition behavior. The residual water content of the particles was very low as quantified analytically Karl Fisher titration. The amount of paclitaxel loaded into the particles was quantified which indicated high encapsulation efficiencies (43-99%). Dry powder aerosol dispersion performance was measured in vitro using the Next Generation Impactor (NGI) coupled with the Handihaler dry powder inhaler device and showed mass median aerodynamic diameters in the range of 3.4-7 μm. These results demonstrate that this novel microparticulate/nanoparticulate chemotherapeutic PEGylated phospholipid dry powder inhalation aerosol platform has great potential in lung cancer drug delivery.

  8. Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate.

    PubMed

    Xu, Zhen; Mansour, Heidi M; Mulder, Tako; McLean, Richard; Langridge, John; Hickey, Anthony J

    2010-08-01

    The major objective of this study was: discriminatory assessment of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs. Drug/lactose interactive physical mixtures (2%w/w) were prepared. Their properties were measured: solid-state characterization of phase behavior and molecular interactions by differential scanning calorimetry and X-ray powder diffraction; particle morphology and size by scanning electron microscopy and laser diffraction; aerosol generation by SETs and characterization by twin-stage liquid impinger and Andersen cascade impactor operated at 60 L/min. The fine particle fraction (FPF) was correlated with SET shear stress (tau(s)), using a novel powder aerosol deaggregation equation (PADE). Drug particles were <5 microm in volume diameter with narrow unimodal distribution (Span <1). The lowest shear SET (tau(s) = 0.624 N/m(2)) gave a higher emitted dose (ED approximately 84-93%) and lower FPF (FPF(6.4) approximately 7-25%). In contrast, the highest shear SET (tau(s) = 13.143 N/m(2)) gave a lower ED (ED approximately 75-89%) and higher FPF (FPF(6.4) approximately 15-46%). The performance of disodium cromoglycate was superior to albuterol sulfate at given tau(s), as was milled with respect to sieved lactose monohydrate. Excellent correlation was observed (R(2) approximately 0.9804-0.9998) when pulmonary drug particle release from the surface of lactose carriers was interpreted by PADE linear regression for dry powder formulation evaluation and performance prediction. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  9. The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process.

    PubMed

    Poursina, Narges; Vatanara, Alireza; Rouini, Mohammad Reza; Gilani, Kambiz; Najafabadi, Abdolhossein Rouholamini

    2016-06-01

    Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-β-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery) were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween-free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content).

  10. Tuning aerosol performance using the multibreath Orbital® dry powder inhaler device: controlling delivery parameters and aerosol performance via modification of puck orifice geometry.

    PubMed

    Zhu, Bing; Young, Paul M; Ong, Hui Xin; Crapper, John; Flodin, Carina; Qiao, Erin Lin; Phillips, Gary; Traini, Daniela

    2015-07-01

    The current study presents a new approach to tackle high-dose lung delivery using a prototype multibreath Orbital® dry powder inhaler (DPI). One of the key device components is the "puck" (aerosol sample chamber) with precision-engineered outlet orifice(s) that control the dosing rate. The influence of puck orifice geometry and number of orifices on the performance of mannitol aerosols were studied. Pucks with different orifice configurations were filled with 400 mg of spray-dried mannitol and tested in the Orbital® DPI prototype. The emitted dose and overall aerodynamic performance across a number of "breaths" were studied using a multistage liquid impinger. The aerosol performances of the individual actuations were investigated using in-line laser diffraction. The emptying rate of all pucks was linear between 20% and 80% cumulative drug released (R(2) > 0.98), and the amount of formulation released per breath could be controlled such that the device was empty after 2 to 11 breath maneuvers. The puck-emptying rate linearly related to the orifice hole length (R(2) > 0.95). Mass median aerodynamic diameters of the emitted aerosol ranged from 4.03 to 4.62 μm and fine particle fraction (≤6.4 μm) were 50%-66%. Laser diffraction suggested that the aerosol performance and emptying rates were not dependent on breath number, showing consistent size distribution profiles. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Preparation and physicochemical characterization of spray-dried and jet-milled microparticles containing bosentan hydrate for dry powder inhalation aerosols

    PubMed Central

    Lee, Hyo-Jung; Kang, Ji-Hyun; Lee, Hong-Goo; Kim, Dong-Wook; Rhee, Yun-Seok; Kim, Ju-Young; Park, Eun-Seok; Park, Chun-Woong

    2016-01-01

    The objectives of this study were to prepare bosentan hydrate (BST) microparticles as dry powder inhalations (DPIs) via spray drying and jet milling under various parameters, to comprehensively characterize the physicochemical properties of the BST hydrate microparticles, and to evaluate the aerosol dispersion performance and dissolution behavior as DPIs. The BST microparticles were successfully prepared for DPIs by spray drying from feeding solution concentrations of 1%, 3%, and 5% (w/v) and by jet milling at grinding pressures of 2, 3, and 4 MPa. The physicochemical properties of the spray-dried (SD) and jet-milled (JM) microparticles were determined via scanning electron microscopy, atomic force microscopy, dynamic light scattering particle size analysis, Karl Fischer titration, surface analysis, pycnometry, differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The in vitro aerosol dispersion performance and drug dissolution behavior were evaluated using an Anderson cascade impactor and a Franz diffusion cell, respectively. The JM microparticles exhibited an irregular corrugated surface and a crystalline solid state, while the SD microparticles were spherical with a smooth surface and an amorphous solid state. Thus, the in vitro aerosol dispersion performance and dissolution behavior as DPIs were considerably different due to the differences in the physicochemical properties of the SD and JM microparticles. In particular, the highest grinding pressures under jet milling exhibited excellent aerosol dispersion performance with statistically higher values of 56.8%±2.0% of respirable fraction and 33.8%±2.3% of fine particle fraction and lower mass median aerodynamic diameter of 5.0±0.3 μm than the others (P<0.05, analysis of variance/Tukey). The drug dissolution mechanism was also affected by the physicochemical properties that determine the dissolution kinetics of the SD and JM microparticles, which were well

  12. Preparation and physicochemical characterization of spray-dried and jet-milled microparticles containing bosentan hydrate for dry powder inhalation aerosols.

    PubMed

    Lee, Hyo-Jung; Kang, Ji-Hyun; Lee, Hong-Goo; Kim, Dong-Wook; Rhee, Yun-Seok; Kim, Ju-Young; Park, Eun-Seok; Park, Chun-Woong

    2016-01-01

    The objectives of this study were to prepare bosentan hydrate (BST) microparticles as dry powder inhalations (DPIs) via spray drying and jet milling under various parameters, to comprehensively characterize the physicochemical properties of the BST hydrate microparticles, and to evaluate the aerosol dispersion performance and dissolution behavior as DPIs. The BST microparticles were successfully prepared for DPIs by spray drying from feeding solution concentrations of 1%, 3%, and 5% (w/v) and by jet milling at grinding pressures of 2, 3, and 4 MPa. The physicochemical properties of the spray-dried (SD) and jet-milled (JM) microparticles were determined via scanning electron microscopy, atomic force microscopy, dynamic light scattering particle size analysis, Karl Fischer titration, surface analysis, pycnometry, differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The in vitro aerosol dispersion performance and drug dissolution behavior were evaluated using an Anderson cascade impactor and a Franz diffusion cell, respectively. The JM microparticles exhibited an irregular corrugated surface and a crystalline solid state, while the SD microparticles were spherical with a smooth surface and an amorphous solid state. Thus, the in vitro aerosol dispersion performance and dissolution behavior as DPIs were considerably different due to the differences in the physicochemical properties of the SD and JM microparticles. In particular, the highest grinding pressures under jet milling exhibited excellent aerosol dispersion performance with statistically higher values of 56.8%±2.0% of respirable fraction and 33.8%±2.3% of fine particle fraction and lower mass median aerodynamic diameter of 5.0±0.3 μm than the others (P<0.05, analysis of variance/Tukey). The drug dissolution mechanism was also affected by the physicochemical properties that determine the dissolution kinetics of the SD and JM microparticles, which were well

  13. Poly(D,L-lactide-co-glycolide) Nanoparticle Agglomerates as Carriers in Dry Powder Aerosol Formulation of Proteins

    PubMed Central

    Peek, Laura J.; Roberts, Lydia; Berkland, Cory

    2013-01-01

    A dry powder aerosol drug delivery system was designed with both nano- and microstructure to maximize the protein loading via surface adsorption and to facilitate delivery to the deep lung, respectively. Ovalbumin was employed as a model protein to adsorb to and controllably flocculate DOTAP-coated PLG nanoparticles into “nanoclusters” possessing low density microstructure. The mechanism of nanoparticle flocculation was probed by evaluating the effects of ionic strength, shear force, and protein concentration on the geometric and aerodynamic diameters of the nanoclusters as well as the protein adsorption efficiency. Salt ions were found to compete with ovalbumin adsorption to nanoparticles and facilitate flocculation; therefore, formulation of nanoclusters for inhaled drug delivery may require the lowest possible ionic strength to maximize protein adsorption. Additional factors, such as shear force and total protein–particle concentration can be altered to optimize nanocluster size, suggesting the possibility of regional lung delivery. Immediate release of ovalbumin was observed, and native protein structure upon release was confirmed by circular dichroism and fluorescence spectroscopy studies. Controlled flocculation of nanoparticles may provide a useful alternative to spray drying when formulating dry powders for pulmonary or nasal administration of protein therapeutics or antigens. PMID:18680321

  14. Nanoporous mannitol carrier prepared by non-organic solvent spray drying technique to enhance the aerosolization performance for dry powder inhalation

    PubMed Central

    Peng, Tingting; Zhang, Xuejuan; Huang, Ying; Zhao, Ziyu; Liao, Qiuying; Xu, Jing; Huang, Zhengwei; Zhang, Jiwen; Wu, Chuan-yu; Pan, Xin; Wu, Chuanbin

    2017-01-01

    An optimum carrier rugosity is essential to achieve a satisfying drug deposition efficiency for the carrier based dry powder inhalation (DPI). Therefore, a non-organic spray drying technique was firstly used to prepare nanoporous mannitol with small asperities to enhance the DPI aerosolization performance. Ammonium carbonate was used as a pore-forming agent since it decomposed with volatile during preparation. It was found that only the porous structure, and hence the specific surface area and carrier density were changed at different ammonium carbonate concentration. Furthermore, the carrier density was used as an indication of porosity to correlate with drug aerosolization. A good correlation between the carrier density and fine particle fraction (FPF) (r2 = 0.9579) was established, suggesting that the deposition efficiency increased with the decreased carrier density. Nanoporous mannitol with a mean pore size of about 6 nm exhibited 0.24-fold carrier density while 2.16-fold FPF value of the non-porous mannitol. The enhanced deposition efficiency was further confirmed from the pharmacokinetic studies since the nanoporous mannitol exhibited a significantly higher AUC0-8h value than the non-porous mannitol and commercial product Pulmicort. Therefore, surface modification by preparing nanoporous carrier through non-organic spray drying showed to be a facile approach to enhance the DPI aerosolization performance. PMID:28462948

  15. Investigation of the changes in aerosolization behavior between the jet-milled and spray-dried colistin powders through surface energy characterization

    PubMed Central

    Jong, Teresa; Li, Jian; Mortonx, David A.V.; Zhou, Qi (Tony); Larson, Ian

    2016-01-01

    This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared to those produced by jet-milling. Inhalable colistin powder formulations were produced by jet-milling or spray-drying (with or without L-leucine). Scanning electron micrographs showed the jet-milled particles had irregularly angular shapes, while the spray-dried particles were more spherical. Significantly higher fine particle fractions (FPFs) were measured for the spray-dried (43.8-49.6%) vs. the jet-milled formulation (28.4 %) from a Rotahaler at 60L/min; albeit the size distribution of the jet-milled powder was smaller. Surprisingly, addition of L-leucine in the spray drying feed-solution gave no significant improvement in FPF. As measured by inverse gas chromatography, spray-dried formulations had significantly (p<0.001) lower dispersive, specific and total surface energy values and more uniform surface energy distributions than the jet-milled powder. Interestingly, no significant difference was measured in the specific and total surface energy values between the spray-dried formulation with or without L-leucine. Based upon our previous findings in the self-assembling behavior of colistin in aqueous solution and the surface energy data obtained here, we propose the self-assembly of colistin molecules during spray-drying, contributed significantly to the reduction of surface free energy and the superior aerosolization performance. PMID:26886330

  16. Pharmaceutical aerosols deposition patterns from a Dry Powder Inhaler: Euler Lagrangian prediction and validation.

    PubMed

    Ravi Kannan, Ravishekar; Przekwas, A J; Singh, Narender; Delvadia, Renishkumar; Tian, Geng; Walenga, Ross

    2017-04-01

    This study uses Computational Fluid Dynamics (CFD) to predict, analyze and validate the deposition patterns in a human lung for a Budesonide drug delivered from the Novolizer Dry Powder Inhaler device. We used a test case of known deposition patterns to validate our computational Euler Lagrangian-based deposition predictions. Two different lung models are used: (i) a basic ring-less trachea model and (ii) an advanced Human Zygote5 model. Unlike earlier attempts, the current simulations do not include the device in the computational domain. This greatly reduces the computational effort. To mimic the device, we model the inlet particle jet stream from the device as a spray entering the mouth in a conical fashion. Deposition studies in the various lung regions were performed. We were able to computationally predict and then demonstrate the enhanced deposition in the tracheal and first generation rings/ridges. The enhanced vorticity creation due to the ring structure and the geometrical design contributes to larger deposition in the Zygote5 model. These are in accord with existing data, unlike the ring-less model. Our validated results indicate the need to (i) introduce the ridges in the experimental casts and the CFD surface meshes to be anatomically consistent and obtain physiologically consistent depositions; (ii) introduce a factor to account for the recirculating lighter particles in empirical models.

  17. Dry powder inhalers of gentamicin and leucine: formulation parameters, aerosol performance and in vitro toxicity on CuFi1 cells.

    PubMed

    Aquino, R P; Prota, L; Auriemma, G; Santoro, A; Mencherini, T; Colombo, G; Russo, P

    2012-04-15

    The high hygroscopicity of gentamicin (G) as raw material hampers the production of respirable particles during aerosol generation and prevents its direct use as powder for inhalation in patients suffering from cystic fibrosis (CF). Therefore, this research aimed to design a new dry powder formulation of G studying dispersibility properties of an aminoacid, L-leucine (leu), and appropriate process conditions. Spray-dried powders were characterized as to water uptake, particle size distribution, morphology and stability, in correlation with process parameters. Aerodynamic properties were analyzed both by Single Stage Glass Impinger and Andersen Cascade Impactor. Moreover, the potential cytotoxicity on bronchial epithelial cells bearing a CFTR F508/F508 mutant genotype (CuFi1) were tested. Results indicated that leu may improve the aerosol performance of G-dried powders. The maximum fine particle fraction (FPF) of about 58.3% was obtained when water/isopropyl alcohol 7:3 system and 15-20% (w/w) of leu were used, compared to a FPF value of 13.4% for neat G-dried powders. The enhancement of aerosol efficiency was credited both to the improvement of the powder flowability, caused by the dispersibility enhancer (aminoacid), and to the modification of the particle surface due to the influence of the organic co-solvent on drying process. No significant degradation of the dry powder was observed up to 6 months of storage. Moreover, particle engineering did not affect either the cell viability or cell proliferation of CuFi1 over a 24 h period.

  18. Design, characterization, and aerosol dispersion performance modeling of advanced co-spray dried antibiotics with mannitol as respirable microparticles/nanoparticles for targeted pulmonary delivery as dry powder inhalers.

    PubMed

    Li, Xiaojian; Vogt, Frederick G; Hayes, Don; Mansour, Heidi M

    2014-09-01

    Dry powder inhalation aerosols of antibiotic drugs (a first-line aminoglycoside, tobramycin, and a first-line macrolide, azithromycin) and a sugar alcohol mucolytic agent (mannitol) as co-spray dried (co-SD) particles at various molar ratios of drug:mannitol were successfully produced by organic solution advanced co-spray drying from dilute solute concentration. These microparticulate/nanoparticulate aerosols consisting of various antibiotic drug:mannitol molar ratios were rationally designed with a narrow and unimodal primary particle size distribution, spherical particle shape, relatively smooth particle surface, and very low residual water content to minimize the interparticulate interactions and enhance in vitro aerosolization. These microparticulate/nanoparticulate inhalation powders were high-performing aerosols as reflected in the aerosol dispersion performance parameters of emitted dose, fine particle fraction (FPF), respirable fraction (RF), and mass median aerodynamic diameter (MMAD). The glass transition temperature (Tg) values were significantly above room temperature, which indicated that the co-SD powders were all in the amorphous glassy state. The Tg values for co-SD tobramycin:mannitol powders were significantly lower than those for co-SD azithromycin:mannitol powders. The interplay between aerosol dispersion performance parameters and Tg was modeled where higher Tg values (i.e., more ordered glass) were correlated with higher values in FPF and RF and lower values in MMAD.

  19. Dry powder inhalers: physicochemical and aerosolization properties of several size-fractions of a promising alterative carrier, freeze-dried mannitol.

    PubMed

    Kaialy, Waseem; Nokhodchi, Ali

    2015-02-20

    The purpose of this work was to evaluate the physicochemical and inhalation characteristics of different size fractions of a promising carrier, i.e., freeze-dried mannitol (FDM). FDM was prepared and sieved into four size fractions. FDMs were then characterized in terms of micromeritic, solid-state and bulk properties. Dry powder inhaler (DPI) formulations were prepared using salbutamol sulphate (SS) and then evaluated in terms of drug content homogeneity and in vitro aerosolization performance. The results showed that the crystalline state of mannitol was maintained following freeze-drying for all size fractions of FDM. All FDM particles showed elongated morphology and contained mixtures of α-, β- and δ-mannitol. In comparison to small FDM particles, FDMs with larger particle sizes demonstrated narrower size distributions, higher bulk and tap densities, lower porosities and better flowability. Regardless of particle size, all FDMs generated a significantly higher (2.2-2.9-fold increase) fine particle fraction (FPF, 37.5 ± 0.9%-48.6 ± 2.8%) of SS in comparison to commercial mannitol. The FPFs of SS were related to the shape descriptors of FDM particles; however, FPFs did not prove quantitative apparent relationships with either particle size or powder bulk descriptors. Large FDM particles were more favourable than smaller particles because they produced DPI formulations with better flowability, better drug content homogeneity, lower amounts of the drug depositing on the throat and contained lower fine-particle-mannitol. Optimized stable DPI formulations with superior physicochemical and pharmaceutical properties can be achieved using larger particles of freeze-dried mannitol (FDM). Copyright © 2014 Elsevier B.V. All rights reserved.

  20. The influence of crystallization conditions on the morphology of lactose intended for use as a carrier for dry powder aerosols.

    PubMed

    Zeng, X M; Martin, G P; Marriott, C; Pritchard, J

    2000-06-01

    Lactose has been widely used as a carrier for inhalation aerosols. The carrier morphology is believed to affect the delivery of the drug. The aim of this study was to investigate the effects of crystallization conditions on the morphology of alpha-lactose monohydrate intended for use as the carrier for dry powder aerosols. The crystallization of lactose was carried out from aqueous solutions at different supersaturations, temperatures, different stages of crystallization and in the presence of different water-miscible organic solvents. The majority of lactose crystals were found to be either tomahawk-shaped or pyramidal after crystallization at an initial lactose concentration between 33-43% w/w, but these became prismatic if the lactose concentration was increased to 50% w/w. A further increase in the lactose concentration to 60% w/w led to the preparation of elongated cuboidal crystals. Higher initial lactose concentrations tended to result in the crystallization of more elongated particles. Crystallization at 40 degrees C was shown to prepare lactose crystals with a more regular shape and a smoother surface than those crystallized at 0 degrees C. Lactose particles generated during the later stage of crystallization were found to be more regular in shape with a smoother surface than those prepared in the earlier stage. The addition of 10% (v/v) methanol or ethanol or acetone to the mother liquor increased the growth rate of lactose particles whereas addition of propanol or glycerine inhibited the rate of crystal growth. Lactose crystals prepared in the presence of glycerine were more regularly shaped with a smoother surface than those prepared in the presence of ethanol or acetone. All the resultant crystals were shown to comprise alpha-lactose monohydrate. Lactose crystals could be prepared with a precisely defined morphology by means of carefully controlling the crystallization conditions.

  1. Influence of surface characteristics of modified glass beads as model carriers in dry powder inhalers (DPIs) on the aerosolization performance.

    PubMed

    Zellnitz, Sarah; Schroettner, Hartmuth; Urbanetz, Nora Anne

    2015-01-01

    The aim of this work is to investigate the effect of surface characteristics (surface roughness and specific surface area) of surface-modified glass beads as model carriers in dry powder inhalers (DPIs) on the aerosolization, and thus, the in vitro respirable fraction often referred to as fine particle fraction (FPF). By processing glass beads in a ball mill with different grinding materials (quartz and tungsten carbide) and varying grinding time (4 h and 8 h), and by plasma etching for 1 min, glass beads with different shades of surface roughness and increased surface area were prepared. Compared with untreated glass beads, the surface-modified rough glass beads show increased FPFs. The drug detachment from the modified glass beads is also more reproducible than from untreated glass beads indicated by lower standard deviations for the FPFs of the modified glass beads. Moreover, the FPF of the modified glass beads correlates with their surface characteristics. The higher the surface roughness and the higher the specific surface area of the glass beads the higher is the FPF. Thus, surface-modified glass beads make an ideal carrier for tailoring the performance of DPIs in the therapy of asthma and chronically obstructive pulmonary diseases.

  2. Investigation of the Changes in Aerosolization Behavior Between the Jet-Milled and Spray-Dried Colistin Powders Through Surface Energy Characterization.

    PubMed

    Jong, Teresa; Li, Jian; Morton, David A V; Zhou, Qi Tony; Larson, Ian

    2016-03-01

    This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared with those produced by jet milling. Inhalable colistin powder formulations were produced by jet milling or spray drying (with or without l-leucine). Scanning electron micrographs showed the jet-milled particles had irregularly angular shapes, whereas the spray-dried particles were more spherical. Significantly higher fine particle fractions were measured for the spray-dried (43.8%-49.6%) versus the jet-milled formulation (28.4%) from a Rotahaler at 60 L/min; albeit the size distribution of the jet-milled powder was smaller. Surprisingly, addition of l-leucine in the spray drying feed solution gave no significant improvement in fine particle fraction. As measured by inverse gas chromatography, spray-dried formulations had significantly (p < 0.001) lower dispersive, specific, and total surface energy values and more uniform surface energy distributions than the jet-milled powder. Interestingly, no significant difference was measured in the specific and total surface energy values between the spray-dried formulation with or without l-leucine. Based on our previous findings in the self-assembling behavior of colistin in aqueous solution and the surface energy data obtained here, we propose the self-assembly of colistin molecules during spray drying contributed significantly to the reduction of surface free energy and the superior aerosolization performance. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders.

    PubMed

    Yu, Jiaqi; Chan, Hak-Kim; Gengenbach, Thomas; Denman, John A

    2017-10-01

    Inhalable particles containing amorphous form of drugs or excipients may absorb atmospheric moisture, causing powder aggregation and recrystallization, adversely affecting powder dispersion and lung deposition. The present study aims to explore hydrophobic amino acids for protection against moisture in spray-dried amorphous powders, using disodium cromoglycate (DSCG) as a model drug. DSCG powders were produced by co-spray drying with isoleucine (Ile), valine (Val) and methionine (Met) in various concentrations (10, 20 and 40%w/w). Particle size distribution and morphology were measured by laser diffraction and scanning electron microscopy (SEM). Physiochemical properties of the powders were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and dynamic vapor sorption (DVS). Particle surface chemistry was analyzed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performance was evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH) for one month and three months. Ile, Val and Met significantly reduced the deleterious effect of moisture on aerosol performance, depending on the amount of amino acids in the formulation. Formulations containing 10% or 20% of Ile, Val and Met showed notable deterioration in aerosol performance, with fine particle fraction (FPF) reduced by 6-15% after one-month storage at both 60% and 75% RH. However, 40% Ile was able to maintain the aerosol performance of DSCG stored at 75% RH for one month, while the FPF dropped by 7.5% after three months of storage. In contrast, 40% Val or Met were able to maintain the aerosol performance at 60% RH storage but not at 75% RH. At 40%w/w ratio, these formulations had particle surface coverage of 94.5% (molar percent) of Ile, 87.1% of Val and 84.6% of Met, respectively, which may explain their

  4. Humidity-induced changes of the aerodynamic properties of dry powder aerosol formulations containing different carriers.

    PubMed

    Zeng, Xian-Ming; MacRitchie, Helen B; Marriott, Christopher; Martin, Gary P

    2007-03-21

    This paper presents the findings of two related studies. The aim of the first was to study any changes in the aerodynamic properties of salbutamol base powder formulations when different sugars were used as the carriers, after storage at an elevated humidity (75% RH), and whether any such changes (if any) were related to the physical properties of the carriers. The aim of the second was to investigate whether "ageing", i.e. storage of the carrier, drug and blends under desiccation for more than 2 years, affected the aerodynamic properties of salbutamol sulphate powder formulations. Different formulations were prepared, each containing 1.5% (w/w) micronised salbutamol base or sulphate blended with the sieved fraction (63-90 microm) of one of the following sugars: alpha lactose monohydrate, sorbitol, maltose and dextrose. The salbutamol base blends were then stored unprotected at 75% RH (ambient temperature) and salbutamol fine particle fractions (FPFs) were measured by laser diffraction (LD) (% < 5.2 microm) and a multistage liquid impinger (MSLI) (% < 5.3 microm), following aerosolisation at 100 l min(-1) from a model glass inhaler, after storage of each formulation at the elevated conditions for 0, 1 and 6 days. Particle morphology and equilibrium moisture content (EMC) of each formulation prior to and after storage were also evaluated. However, the salbutamol sulphate blends containing either "fresh" or "aged" components were only characterized using LD at 60 l min(-1). Prior to exposure to 75% RH, the lactose blend was found to give the highest FPF of salbutamol (30% by LD and 37% by MSLI), followed by the sorbitol blend (17% by LD and 29% by MSLI), then by the dextrose blend (15% by LD and 25% by MSLI) and finally by the maltose blend (13% by LD and 13% by MSLI). Exposure to 75% RH for 6 days resulted in a small reduction of salbutamol FPF from the lactose blend but drastic diminution of salbutamol FPFs from other blends. After exposure to the high RH, the

  5. Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 2. Ipratropium bromide monohydrate and fluticasone propionate.

    PubMed

    Xu, Zhen; Mansour, Heidi M; Mulder, Tako; McLean, Richard; Langridge, John; Hickey, Anthony J

    2010-08-01

    The objectives of this study were: systematic investigation of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs; mechanistic evaluation of performance data by powder aerosol deaggregation equation (PADE). The drugs (IPB and FP) were prepared in sieved and milled lactose carriers (2% w/w). Aerosol studies were performed using SETs (shear stresses tau(s) = 0.624-13.143 N/m(2)) by twin-stage liquid impinger, operated at 60 L/min. PADE was applied for formulation screening. Excellent correlation was observed when PADE was adopted correlating FPF to tau(s). Higher tau(s) corresponded to higher FPF values followed by a plateau representing invariance of FPF with increasing tau(s). The R(2) values for PADE linear regression were 0.9905-0.9999. Performance described in terms of the maximum FPF (FPF(max): 15.0-37.6%) resulted in a rank order of ML-B/IPB > ML-A/IPB > SV-A/IPB > SV-B/IPB > ML-B/FP > ML-A/FP > SV-B/FP > SV-A/FP. The performance of IPB was superior to FP in all formulations. The difference in lactose monohydrate carriers was less pronounced for the FPF in IPB than in FP formulations. The novel PADE offers a robust method for evaluating aerodynamic performance of dry powder formulations within a defined tau(s) range.

  6. The effects of excipients and particle engineering on the biophysical stability and aerosol performance of parathyroid hormone (1-34) prepared as a dry powder for inhalation.

    PubMed

    Shoyele, Sunday A; Sivadas, Neeraj; Cryan, Sally-Ann

    2011-03-01

    Pulmonary delivery of therapeutic peptides and proteins has many advantages including high relative bioavailability, rapid systemic absorption and onset of action and a non-invasive mode of administration which improves patient compliance. In this study, we investigated the effect of spray-drying (SD) and spray freeze-drying processes on the stability and aerosol performance of parathyroid hormone (PTH) (1-34) microparticles. In this study, the stabilisation effect of trehalose (a non-reducing sugar) and Brij 97 (a non-ionic surfactant) on spray-dried PTH particles was assessed using analytical techniques including circular dichroism (CD), fluorescence spectroscopy, modulated differential scanning calorimetry and an in vitro bioactivity assay. Physical characterisation also included electron microscopy, tap density measurement and laser light diffraction. The aerosol aerodynamic performance of the formulations was assessed using the Andersen cascade impactor. Based on these studies, a formulation for spray freeze-drying was selected and the effects of the two particle engineering techniques on the biophysical stability and aerosol performance of the resulting powders was determined. CD, fluorescence spectroscopy and bioactivity data suggest that trehalose when used alone as a stabilising excipient produces a superior stabilising effect than when used in combination with a non-ionic surfactant. This highlights the utility of CD and fluorescence spectroscopy studies for the prediction of protein bioactivity post-processing. Therefore, a method and formulation suitable for the preparation of PTH as a dry powder was developed based on spray-drying PTH with trehalose as a stabiliser with the bioactivity of SD PTH containing trehalose being equivalent to that of unprocessed PTH.

  7. Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

    PubMed Central

    Meenach, Samantha A; Vogt, Frederick G; Anderson, Kimberly W; Hilt, J Zach; McGarry, Ronald C; Mansour, Heidi M

    2013-01-01

    Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600 nm to 1.2 μm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 μm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the

  8. Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols.

    PubMed

    Meenach, Samantha A; Vogt, Frederick G; Anderson, Kimberly W; Hilt, J Zach; McGarry, Ronald C; Mansour, Heidi M

    2013-01-01

    Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600 nm to 1.2 μm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 μm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the

  9. Formulation Design of Dry Powders for Inhalation.

    PubMed

    Weers, Jeffry G; Miller, Danforth P

    2015-10-01

    Drugs for inhalation are no longer exclusively highly crystalline small molecules. They may also be amorphous small molecules, peptides, antibodies, and myriad types of engineered proteins. The evolution of respiratory therapeutics has created a need for flexible formulation technologies to engineer respirable particles. These technologies have enabled medicinal chemists to focus on molecular design without concern regarding compatibility of physicochemical properties with traditional, blend-based technologies. Therapeutics with diverse physicochemical properties can now be formulated as stable and respirable dry powders. Particle engineering technologies have also driven the deployment of new excipients, giving formulators greater control over particle and powder properties. This plays a key role in enabling efficient delivery of drugs to the lungs. Engineered powder and device combinations enable aerosols that largely bypass the mouth and throat, minimizing the inherent variability among patients that arises from differences in oropharyngeal and airway anatomies and in breathing profiles. This review explores how advances among molecules, particles, and powders have transformed inhaled drug product development. Ultimately, this scientific progress will benefit patients, enabling new classes of therapeutics to be formulated as dry powder aerosols with improved efficacy, reduced variability and side effects, and improved patient adherence. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. An investigation into the effect of fine lactose particles on the fluidization behaviour and aerosolization performance of carrier-based dry powder inhaler formulations.

    PubMed

    Kinnunen, Hanne; Hebbink, Gerald; Peters, Harry; Shur, Jagdeep; Price, Robert

    2014-08-01

    The effect of milled and micronized lactose fines on the fluidization and in vitro aerosolization properties of dry powder inhaler (DPI) formulations was investigated, and the suitability of static and dynamic methods for characterizing general powder flow properties of these blends was assessed. Lactose carrier pre-blends were prepared by adding different lactose fines (Lactohale® (LH) 300, 230 and 210) with coarse carrier lactose (Lactohale100) at 2.5, 5, 10 and 20 wt% concentrations. Powder flow properties of lactose pre-blends were characterized using the Freeman Technology FT4 and Schulze RST-XS ring shear tester. A strong correlation was found between the basic flow energy (BFENorm) measured using the Freeman FT4 Rheometer and the flowability number (ffc) measured on Schulze RST-XS. These data indicate that both static and dynamic methods are suitable for characterizing general powder flow properties of lactose carriers. Increasing concentration of fines corresponded with an increase in the normalized fluidization energy (FENorm). The inclusion of fine particles of lactose resulted in a significant (p < 0.05) increase in fine particle delivery of budesonide and correlated with FENorm. This trend was strongest for lactose containing up to 10 wt% LH300. A similar trend was found for the milled lactose grades LH230 and LH210. However, the increase in FENorm upon addition of milled fines only corresponded to a very slight improvement in the performance. These data suggest that whilst the fluidization energy correlated with fine particle delivery, this relationship is specific to lactose grades of similar particle size.

  11. Formoterol by pressurized metered-dose aerosol or dry powder on airway obstruction and lung hyperinflation in partially reversible COPD.

    PubMed

    Brusasco, Vito; Canonica, G Walter; Dal Negro, Roberto; Scano, Giorgio; Paggiaro, Pierluigi; Fabbri, Leonardo M; Barisione, Giovanni; D'Amato, Gennaro; Varoli, Guido; Baroffio, Michele; Milanese, Manlio; Mereu, Carlo; Crimi, Emanuele

    2011-10-01

    We compared the efficacy and safety of formoterol given by a pressurized metered-dose inhaler (pMDI) (Atimos®, Chiesi Farmaceutici, Italy), using a chlorine-free hydrofluoroalkane (HFA-134a) propellant developed to provide stable and uniform dose delivery (Modulite™, Chiesi Farmaceutici, Italy), with formoterol by dry powder inhaler (DPI) (Foradil® Aerolizer®, Novartis Pharmaceuticals) and placebo, in reducing airflow obstruction and lung hyperinflation, in moderate-to-severe, partially reversible chronic obstructive pulmonary disease (COPD). Forty-eight patients were randomized to a 1-week, double-blind, double-dummy, three-period crossover study with 12 μg b.i.d. of formoterol given by pMDI or DPI, or placebo. Spirometry, specific airway conductance, and lung volumes were measured at the beginning and at the end of each treatment period from predose to 4 h postdose. A 6-min walking test was carried out 4 h after the first and the last dose, with dyspnea assessed by Borg scale. Safety was assessed through adverse events monitoring electrocardiography and vital signs. The two formulations of formoterol were significantly superior to placebo but not different from each other in increasing 1-sec forced expiratory volume, specific airway conductance, inspiratory capacity, and inspiratory-to-total lung capacity ratio. The two active treatments were also equivalent and superior to placebo in reducing dyspnea at rest and on exertion. No differences in terms of safety between the two active forms and placebo were detected. Formoterol given with chlorine-free pMDI was equivalent to DPI in reducing airway obstruction and lung hyperinflation in COPD patients. Both formoterol formulations confirmed the good safety profile similar to placebo.

  12. Dry PMR-15 Resin Powders

    NASA Technical Reports Server (NTRS)

    Vannucci, Raymond D.; Roberts, Gary D.

    1988-01-01

    Shelf lives of PMR-15 polymides lengthened. Procedure involves quenching of monomer reactions by vacuum drying of PRM-15 resin solutions at 70 to 90 degree F immediately after preparation of solutions. Absence of solvent eliminates formation of higher esters and reduces formation of imides to negligible level. Provides fully-formulated dry PMR-15 resin powder readily dissolvable in solvent at room temperature immediately before use. Resins used in variety of aerospace, aeronautical, and commercial applications.

  13. Measles vaccination of macaques by dry powder inhalation.

    PubMed

    de Swart, Rik L; LiCalsi, Cynthia; Quirk, Alan V; van Amerongen, Geert; Nodelman, Vladislav; Alcock, Robert; Yüksel, Selma; Ward, Gary H; Hardy, John G; Vos, Helma; Witham, Clyde L; Grainger, Christopher I; Kuiken, Thijs; Greenspan, Bernard J; Gard, Trevor G; Osterhaus, Albert D M E

    2007-01-26

    Measles vaccination via the aerosol route has proven effective under field conditions, using vaccine reconstituted prior to nebulization. Inhalation of a dry powder aerosol vaccine would have additional benefits, including easier logistics of administration, reduced cold chain dependence and the potential of single dose administration. We have evaluated two candidate dry powder measles vaccine formulations in macaques. Specific immune responses were demonstrated, but levels of immunity were lower than in animals vaccinated by injection or by nebulized aerosol. These studies provide proof of principle that dry powder inhalation is a possible route for measles vaccination, but suggest that either the vaccine formulation or the method of delivery need to be improved for a better immune response.

  14. Wetter for fine dry powder

    DOEpatents

    Hall, James E.; Williams, Everett H.

    1977-01-01

    A system for wetting fine dry powders such as bentonite clay with water or other liquids is described. The system includes a wetting tank for receiving water and a continuous flow of fine powder feed. The wetting tank has a generally square horizontal cross section with a bottom end closure in the shape of an inverted pyramid. Positioned centrally within the wetting tank is a flow control cylinder which is supported from the walls of the wetting tank by means of radially extending inclined baffles. A variable speed motor drives a first larger propeller positioned immediately below the flow control cylinder in a direction which forces liquid filling the tank to flow downward through the flow control cylinder and a second smaller propeller positioned below the larger propeller having a reverse pitch to oppose the flow of liquid being driven downward by the larger propeller.

  15. Investigation of dry powder inhaler (DPI) resistance and aerosol dispersion timing on emitted aerosol aerodynamic particle sizing by multistage cascade impactor when sampled volume is reduced from compendial value of 4 L.

    PubMed

    Mohammed, Hlack; Arp, Jan; Chambers, Frank; Copley, Mark; Glaab, Volker; Hammond, Mark; Solomon, Derek; Bradford, Kerry; Russell, Theresa; Sizer, Yvonne; Nichols, Steven C; Roberts, Daryl L; Shelton, Christopher; Greguletz, Roland; Mitchell, Jolyon P

    2014-10-01

    Compendial methods determining dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distribution (APSD) collect a 4-L air sample containing the aerosol bolus, where the flow, which propagates through the cascade impactor (CI) measurement system from the vacuum source, is used to actuate the inhaler. A previous article described outcomes with two CIs (Andersen eight-stage cascade impactor (ACI) and Next-Generation Pharmaceutical Impactor (NGI)) when the air sample volume was ≤4 L with moderate-resistance DPIs. This article extends that work, examining the hypothesis that DPI flow resistance may be a factor in determining outcomes. APSD measurements were made using the same CI systems with inhalers representing low and high flow resistance extremes (Cyclohaler® and HandiHaler® DPIs, respectively). The ratio of sample volume to internal dead space (normalized volume (V*)) was varied from 0.25 to 1.98 (NGI) and from 0.43 to 3.46 (ACI). Inhaler resistance was a contributing factor to the rate of bolus transfer; the higher resistance DPI completing bolus relocation to the NGI pre-separator via the inlet when V* was as small as 0.25, whereas only ca. 50% of the bolus mass was collected at this condition with the Cyclohaler® DPI. Size fractionation of the bolus from either DPI was completed within the ACI at smaller values of V* than within the NGI. Bolus transfer from the Cyclohaler® capsule and from the HandiHaler® to the ACI system were unaffected by the different flow rise time observed in the two different flow controller systems, and the effects the ACI-based on APSD measurements were marginal.

  16. Understanding the influence of powder flowability, fluidization and de-agglomeration characteristics on the aerosolization of pharmaceutical model powders.

    PubMed

    Zhou, Qi Tony; Armstrong, Brian; Larson, Ian; Stewart, Peter J; Morton, David A V

    2010-08-11

    The aim of this study was to investigate the influence of the intrinsic inter-particulate cohesion of model pharmaceutical powders on their aerosolization from a dry powder inhaler. Two cohesive poly-disperse lactose powders with median particle sizes of around 4 and 20 microm were examined. The results showed that after dry coating with magnesium stearate, their flowability, fluidization and de-agglomeration behaviours could be substantially improved, as indicated by powder rheometry, shear testing and laser diffraction aerosol testing. This was achieved by reducing their cohesiveness via surface modification. In contrast to some previous reports, this study demonstrated how powder aerosolization may be improved more significantly and consistently (for widely varying air flow rates) by substantially reducing their inter-particulate cohesive forces. This study contributes to the understanding of the relationship between intrinsic cohesive nature and bulk properties such as flowability, fluidization and de-agglomeration and its impact on their aerosolization, which is fundamental and critical in the optimal design of dry powder inhaler formulations. The intensive mechanical dry coating technique also demonstrated a promising potential to improve aerosolization efficiency of fine cohesive model powders.

  17. Development of high efficiency ventilation bag actuated dry powder inhalers.

    PubMed

    Behara, Srinivas R B; Longest, P Worth; Farkas, Dale R; Hindle, Michael

    2014-04-25

    New active dry powder inhaler systems were developed and tested to efficiently aerosolize a carrier-free formulation. To assess inhaler performance, a challenging case study of aerosol lung delivery during high-flow nasal cannula (HFNC) therapy was selected. The active delivery system consisted of a ventilation bag for actuating the device, the DPI containing a flow control orifice and 3D rod array, and streamlined nasal cannula with separate inlets for the aerosol and HFNC therapy gas. In vitro experiments were conducted to assess deposition in the device, emitted dose (ED) from the nasal cannula, and powder deaggregation. The best performing systems achieved EDs of 70-80% with fine particle fractions <5 μm of 65-85% and mass median aerodynamic diameters of 1.5 μm, which were target conditions for controlled condensational growth aerosol delivery. Decreasing the size of the flow control orifice from 3.6 to 2.3mm reduced the flow rate through the system with manual bag actuations from an average of 35 to 15LPM, while improving ED and aerosolization performance. The new devices can be applied to improve aerosol delivery during mechanical ventilation, nose-to-lung aerosol administration, and to assist patients that cannot reproducibly use passive DPIs. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Dry-powder inhalers in acute asthma.

    PubMed

    Selroos, Olof

    2014-01-01

    An updated literature search was performed to evaluate the efficacy of rapid-acting β2-agonists delivered via dry powder inhalers in the treatment of moderate-to-severe acute asthma. Databases were searched from 1985 up to December 2012. A total of 23 randomized, double-blind or open clinical studies in acute asthma comparing the efficacy of a dry powder inhaler with a pressurized metered-dose inhaler or a nebulizer, and performed under controlled hospital conditions, were identified. This review found that administration of β2-agonist bronchodilators via dry powder inhalers (formoterol, salbutamol, terbutaline and budesonide/formoterol) was effective during severe asthma worsening and acute asthma attacks, and was as effective as established therapies with a pressurized metered-dose inhaler with or without a spacer, or nebulization. These results ensure that patients can rely upon dry powder inhalers equally well as other inhaler devices during episodes of asthma worsening.

  19. Direct lung delivery of a dry powder formulation of DTPA with improved aerosolization properties: effect on lung and systemic decorporation of plutonium.

    PubMed

    Gervelas, C; Serandour, A-L; Geiger, S; Grillon, G; Fritsch, P; Taulelle, C; Le Gall, B; Benech, H; Deverre, J-R; Fattal, E; Tsapis, N

    2007-03-12

    DTPA, an actinide chelating agent, has demonstrated its ability to complex plutonium (Pu) and to facilitate its urinary excretion after internal contamination. This process, known as decorporation is crucial to diminish the burden of Pu in the body. The ability to deliver a chelating agent directly to the alveolar region may increase its local concentration as compared to systemic delivery and therefore increase the extent of decorporation. Second, inhalation offers the potential for needle-free, systemic delivery of small molecules and would be convenient in case of nuclear accident as a first pass emergency treatment. To benefit from the improvement of inhalation technology, we have formulated DTPA into porous particles by spray-drying with dl-Leucine, DPPC and ammonium bicarbonate. The optimized particles possess a volume mean geometric diameter around 4.5 mum and crumpled paper morphology. The in vitro aerodynamic evaluation shows that about 56% of the powder should deposits in the lungs, with about 27% in the alveolar region, an improvement as compared with the micronized powder available with the Spinhaler. After pulmonary administration to rats contaminated with PuO(2), a 3-fold increase of the Pu urinary excretion was observed, but the dissolution of PuO(2) in the lungs was not enhanced.

  20. Combined control of morphology and polymorph in spray drying of mannitol for dry powder inhalation

    NASA Astrophysics Data System (ADS)

    Lyu, Feng; Liu, Jing J.; Zhang, Yang; Wang, Xue Z.

    2017-06-01

    The morphology and polymorphism of mannitol particles were controlled during spray drying with the aim of improving the aerosolization properties of inhalable dry powders. The obtained microparticles were characterized using scanning electron microscopy, infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction and inhaler testing with a next generation impactor. Mannitol particles of varied α-mannitol content and surface roughness were prepared via spray drying by manipulating the concentration of NH4HCO3 in the feed solution. The bubbles produced by NH4HCO3 led to the formation of spheroid particles with a rough surface. Further, the fine particle fraction was increased by the rough surface of carriers and the high α-mannitol content. Inhalable dry powders with a 29.1 ± 2.4% fine particle fraction were obtained by spray-drying using 5% mannitol (w/v)/2% NH4HCO3 (w/v) as the feed solution, proving that this technique is an effective method to engineer particles for dry powder inhalation.

  1. Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhaler.

    PubMed

    Pitcairn, Gary; Reader, Sandie; Pavia, Demetri; Newman, Steve

    2005-01-01

    Fourteen mild-to-moderate asthmatic patients completed a randomized four-way crossover scintigraphic study to determine the lung deposition of 200 microg budesonide inhaled from a Respimat Soft Mist Inhaler (Respimat SMI), 200 microg budesonide inhaled from a Turbuhaler dry powder inhaler (Turbuhaler DPI, used with fast and slow peak inhaled flow rates), and 250 microg beclomethasone dipropionate inhaled from a pressurized metered dose inhaler (Becloforte pMDI). Mean (range) whole lung deposition of drug from the Respimat SMI (51.6 [46-57]% of the metered dose) was significantly (p < 0.001) greater than that from the Turbuhaler DPI used with both fast and slow inhaled flow rates (28.5 [24-33]% and 17.8 [14-22]%, respectively) or from the Becloforte pMDI (8.9 [6-12]%). The deposition pattern within the lungs was more peripheral for Respimat SMI than for Turbuhaler DPI. The results of this study showed that Respimat SMI deposited corticosteroid more efficiently in the lungs than either of two widely used inhaler devices, Turbuhaler DPI or Becloforte pMDI.

  2. Experimental investigation of design parameters on dry powder inhaler performance.

    PubMed

    Ngoc, Nguyen Thi Quynh; Chang, Lusi; Jia, Xinli; Lau, Raymond

    2013-11-30

    The study aims to investigate the impact of various design parameters of a dry powder inhaler on the turbulence intensities generated and the performance of the dry powder inhaler. The flow fields and turbulence intensities in the dry powder inhaler are measured using particle image velocimetry (PIV) techniques. In vitro aerosolization and deposition a blend of budesonide and lactose are measured using an Andersen Cascade Impactor. Design parameters such as inhaler grid hole diameter, grid voidage and chamber length are considered. The experimental results reveal that the hole diameter on the grid has negligible impact on the turbulence intensity generated in the chamber. On the other hand, hole diameters smaller than a critical size can lead to performance degradation due to excessive particle-grid collisions. An increase in grid voidage can improve the inhaler performance but the effect diminishes at high grid voidage. An increase in the chamber length can enhance the turbulence intensity generated but also increases the powder adhesion on the inhaler wall.

  3. LaRC dry powder towpreg process

    NASA Technical Reports Server (NTRS)

    Marchello, Joseph M.; Baucom, Robert M.

    1991-01-01

    The dry powder towpreg process overcomes many of the difficulties associated with melt, solution and slurry prepregging of advanced composite materials. In the process, fluidized powder is deposited on spread tow bundles and melted on the fibers by radiant heating to adhere the polymer to the fiber. Bench scale design and operating data have been correlated for use in process scale up to commercial operation. Powdered towpreg has been woven and molded into preform material of good quality. Cost estimates suggest that processing costs are comparable to those of conventional hot melt prepreg. In the future, from a part fabrication point of view, powder coated prepreg tape, woven broad goods and woven and braided preforms may be considered as options to similar materials made by other methods.

  4. Production of inhalation phage powders using spray freeze drying and spray drying techniques for treatment of respiratory infections

    PubMed Central

    Leung, Sharon S.Y.; Parumasivam, Thaigarajan; Gao, Fiona G.; Carrigy, Nicholas B.; Vehring, Reinhard; Finlay, Warren H.; Morales, Sandra; Britton, Warwick J; Kutter, Elizabeth; Chan, Hak-Kim

    2016-01-01

    Purpose The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders. Method A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1 = 60:20:20 and F2 = 40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed. Results A significant titer loss (~ 2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1 = 13.1 ± 1.7 × 104 pfu and SD-F2 = 11.0 ± 1.4 × 104 pfu) than from their counterpart SFD formulations (SFD-F1 = 8.3 ± 1.8 × 104 pfu and SFD-F2 = 2.1 ± 0.3 × 104 pfu). Conclusion Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2. PMID:26928668

  5. Powder dispersion mechanisms within a dry powder inhaler using microscale particle image velocimetry.

    PubMed

    Kou, Xiang; Wereley, Steven T; Heng, Paul W S; Chan, Lai Wah; Carvajal, M Teresa

    2016-12-05

    The goal of this work was to evaluate the ability of Particle Image Velocimetry (PIV) to visually assess dry powder dispersion within an inhaler. Herein, the study reports particle movement characterization of entrained low-micron particles within an inhaler to further scheme of potential mechanisms. Carrier based DPI formulations were prepared and placed in a transparent model Rotahaler(®) chamber for the aerosolization experiments. Then using the PIV, a high-speed camera, the dried powder dispersion was directly observed and analyzed for all, neat, binary and ternary systems. Powder dispersion mechanisms proposed include drag force, impact with obstacle and particle-particle collision; these different mechanisms depended on the powder flow properties. A revised ratio of aerodynamic response time (τA) to the mean time between collisions (τC) was found to be 6.8 indicating that particle collisions were of strong influence to particle dispersion. With image analysis techniques, visualization of particle flow pattern and collision regions was possible; suggesting that the various mechanisms proposed did govern the powder dispersion. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Effect of sampling volume on dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distributions (APSDs) measured by the Next-Generation Pharmaceutical Impactor (NGI) and the Andersen eight-stage cascade impactor (ACI).

    PubMed

    Mohammed, Hlack; Roberts, Daryl L; Copley, Mark; Hammond, Mark; Nichols, Steven C; Mitchell, Jolyon P

    2012-09-01

    Current pharmacopeial methods for testing dry powder inhalers (DPIs) require that 4.0 L be drawn through the inhaler to quantify aerodynamic particle size distribution of "inhaled" particles. This volume comfortably exceeds the internal dead volume of the Andersen eight-stage cascade impactor (ACI) and Next Generation pharmaceutical Impactor (NGI) as designated multistage cascade impactors. Two DPIs, the second (DPI-B) having similar resistance than the first (DPI-A) were used to evaluate ACI and NGI performance at 60 L/min following the methodology described in the European and United States Pharmacopeias. At sampling times ≥2 s (equivalent to volumes ≥2.0 L), both impactors provided consistent measures of therapeutically important fine particle mass (FPM) from both DPIs, independent of sample duration. At shorter sample times, FPM decreased substantially with the NGI, indicative of incomplete aerosol bolus transfer through the system whose dead space was 2.025 L. However, the ACI provided consistent measures of both variables across the range of sampled volumes evaluated, even when this volume was less than 50% of its internal dead space of 1.155 L. Such behavior may be indicative of maldistribution of the flow profile from the relatively narrow exit of the induction port to the uppermost stage of the impactor at start-up. An explanation of the ACI anomalous behavior from first principles requires resolution of the rapidly changing unsteady flow and pressure conditions at start up, and is the subject of ongoing research by the European Pharmaceutical Aerosol Group. Meanwhile, these experimental findings are provided to advocate a prudent approach by retaining the current pharmacopeial methodology.

  7. Weavability of dry polymer powder towpreg

    NASA Technical Reports Server (NTRS)

    Hugh, Maylene K.; Marchello, Joseph M.; Maiden, Janice R.; Johnston, Norman J.

    1993-01-01

    Carbon fiber yarns (3k, 6k, 12k) were impregnated with LARC (tm) thermoplastic polyimide dry powder. Parameters for weaving these yarns were established. Eight-harness satin fabrics were successfully woven from each of the three classes of yarns and consolidated into test specimens to determine mechanical properties. It was observed that for optimum results warp yarns should have flexural rigidities between 10,000 and 100,000 mg-cm. Tow handling minimization, low tensioning, and tow bundle twisting were used to reduce fiber breakage, the separation of filaments, and tow-to-tow abrasion. No apparent effect of tow size or twist was observed on either tension or compression modulus. However, fiber damage and processing costs favor the use of 12k yarn bundles versus 3k or 6k yarn bundles in the weaving of powder-coated towpreg.

  8. Dry powder segregation and flowability: Experimental and numerical studies

    NASA Astrophysics Data System (ADS)

    Ely, David R.

    Dry powder blending is a very important industrial and physical process used in the production of numerous pharmaceutical dosage forms such as tablets, capsules, and dry powder aerosols. Key aspects of this unit operation are process monitoring and control. Process control is particularly difficult due to the complexity of particle-particle interactions, which arise from the adhesion/cohesion characteristics of interfaces and morphological characteristics such as particle size, shape, and dispersity. The effects of such characteristics need to be understood in detail in order to correlate individual particle properties to bulk powder properties. The present dissertation numerically and experimentally quantifies the mixing process to rationalize particle-particle interactions. In particular, near infrared spectroscopy (NIRS) was used to non-invasively characterize in real-time the blending processes and thus investigate the dynamics of blending under different operating conditions. A novel image analysis technique was developed to quantify the scale of segregation from images obtained non-destructively via near infrared chemical imaging (NIR-CI). Although NIR-CI data acquisition times are too long for real-time data collection, NIR-CI has an advantage, in that it provides the spatial distribution of the drug. Therefore, NIRS and NIR-CI are complementary techniques for investigating the complex process of blending dry powders and assessing end-product quality. Additionally, the discrete element method was used to investigate the effect of powder cohesion on the packing fraction. Simulations indicated an exponential relationship between the random loose packing fraction and cohesive forces. Specifically, the packing fraction decreased asymptotically with increased ratio of cohesive force to particle weight. Thus, increasing this force ratio above a critical value has negligible impact on the packing fraction. Such result directly impacts the Hausner ratio flowability

  9. Alternative sugars as potential carriers for dry powder inhalations.

    PubMed

    Steckel, Hartwig; Bolzen, Nina

    2004-02-11

    Most dry powder inhaler (DPI) formulations rely on lactose monohydrate as a carrier in the drug powder blends. However, lactose cannot be used for compounds that interact with the reducing sugar function of the lactose, such as formoterol, budesonide or peptides and proteins. In this study, alternative carriers like mannitol, glucose, sorbitol, maltitol and xylitol have therefore been evaluated for their potential use in DPI formulations. Raw materials were characterised physico-chemically and blends with the model drug substance budesonide were tested with respect to the aerosolization behaviour of the powders. It was found out that similarly to the problems known for lactose monohydrate, such as supplier variability, variability between different qualities of one supplier, the same difficulties apply to the alternative carriers investigated. Different sources and qualities of mannitol led to significant differences in the fine particle fraction (FPF), varying from 15 to 50% for two different qualities of mannitol. Similar observations were made for the other carrier materials studied. Also, the influence of conditioning the raw material at different relative humidity was found to have substantial influence on the performance of drug/carrier blends which is characterised by a strong decrease in the FPF. In summary, mannitol showed potential as a drug carrier to be used in DPIs whereas the more hygroscopic sugars only showed poor dispersibility.

  10. Nutritional composition of ginger powder prepared using various drying methods.

    PubMed

    Sangwan, A; Kawatra, A; Sehgal, S

    2014-09-01

    A study was undertaken to prepare ginger powder using various drying methods and their nutritional evaluation was carried out. Ginger (Zingiber officinale) was dried using shade, solar, oven and microwave drying methods. All the samples were ground in grinder to make fine powder. Sensory analysis indicated that acceptability of all types of ginger powders were in the range of 'liked very much' to 'liked moderately' by the panelists. The mean score obtained for colour was higher in shade dried ginger powder i.e., 8.20 as compared to oven dried (7.60), solar dried (7.70) and microwave dried ginger powder (7.80). Moisture content ranged from 3.55 % in solar dried ginger powder to 3.78 % in shade dried ginger powder. Slightly higher moisture content was found in shade dried ginger powder. Protein, crude fiber, fat and ash contents ranged from 5.02 to 5.82, 4.97 to 5.61, 0.76 to 0.90 and 3.38 to 3.66 %, respectively. β-carotene and ascorbic acid content was found maximum in shade dried ginger powder i.e., 0.81 mg/100 g and 3.83 mg/100 g, respectively. Polyphenol content was almost similar in all the samples whereas calcium was slightly higher in the shade dried ginger powder i.e., 69.21 mg/100 g. Results have shown that ginger powder prepared from various drying methods had good sensory and nutritional profile.

  11. Aerosol delivery of nanoparticles in uniform mannitol carriers formulated by ultrasonic spray freeze drying.

    PubMed

    D'Addio, Suzanne M; Chan, John Gar Yan; Kwok, Philip Chi Lip; Benson, Bryan R; Prud'homme, Robert K; Chan, Hak-Kim

    2013-11-01

    While most examples of nanoparticle therapeutics have involved parenteral or IV administration, pulmonary delivery is an attractive alternative, especially to target and treat local infections and diseases of the lungs. We describe a successful dry powder formulation which is capable of delivering nanoparticles to the lungs with good aerosolization properties, high loadings of nanoparticles, and limited irreversible aggregation. Aerosolizable mannitol carrier particles that encapsulate nanoparticles with dense PEG coatings were prepared by a combination of ultrasonic atomization and spray freeze drying. This process was contrasted to particle formation by conventional spray drying. Spray freeze drying a solution of nanoparticles and mannitol (2 wt% solids) resulted in particles with an average diameter of 21 ± 1.7 μm, regardless of the fraction of nanoparticles loaded (0-50% of total solids). Spray freeze dried (SFD) powders with a 50% nanoparticle loading had a fine particle fraction (FPF) of 60%. After formulation in a mannitol matrix, nanoparticles redispersed in water to < 1 μm with hand agitation and to < 250 nm with the aid of sonication. Powder production by spray drying was less successful, with low powder yields and extensive, irreversible aggregation of nanoparticles evident upon rehydration. This study reveals the unique advantages of processing by ultrasonic spray freeze drying to produce aerosol dry powders with controlled properties for the delivery of therapeutic nanoparticles to the lungs.

  12. Design and development of dry powder sulfobutylether-β-cyclodextrin complex for pulmonary delivery of fisetin.

    PubMed

    Mohtar, Noratiqah; Taylor, Kevin M G; Sheikh, Khalid; Somavarapu, Satyanarayana

    2017-04-01

    This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyclodextrins to improve its solubility. Sulfobutylether-β-cyclodextrin (SBE-β-CD) showed the highest complexation efficiency while maintaining the in vitro antioxidant activity of fisetin. Addition of 20%v/v ethanol in water improved the amount of solubilized fisetin in the complex 5.9-fold compared to the system containing water alone. Spray drying of fisetin-SBE-β-CD complex solution in the presence of ethanol produced a dry powder with improved aerosolization properties when delivered from a dry powder inhaler, indicated by a 2-fold increase in the fine particle fraction (FPF) compared to the powder produced from the complex solution containing water alone. The pitted morphological surface of these particles suggested a more hollow internal structure, indicating a lighter and less dense powder. Incorporation of 20%w/w leucine improved the particle size distribution of the powder and further increased the FPF by 2.3-fold. This formulation also showed an EC50 value equivalent to fisetin alone in the A549 cell line. In conclusion, an inhalable dry powder containing fisetin-SBE-β-CD complex was successfully engineered with an improved aqueous solubility of fisetin. The dry powder may be useful to deliver high amounts of fisetin to the deep lung region for therapeutic purposes. Copyright © 2016. Published by Elsevier B.V.

  13. Spray-freeze-dried dry powder inhalation of insulin-loaded liposomes for enhanced pulmonary delivery.

    PubMed

    Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

    2008-11-01

    Nowadays, growing attention has been paid to the pulmonary region as a target for the delivery of peptide and protein drugs, especially macromolecules with systemic effect like insulin, since the pulmonary route exhibits numerous benefits to be an alternative for repeated injection. Furthermore, encapsulation of insulin into liposomal carriers is an attractive way to increase drug retention time and control the drug release in the lung; however, its long-term stability during storage in the reservoir and the process of aerosolization might be suspected when practically applied. Thus, the aim of this study was to design and characterize dry powder inhalation of insulin-loaded liposomes prepared by novel spray-freeze-drying method for enhanced pulmonary delivery. Process variables such as compressed air pressure, pump speed, and concentration were optimized for parameters such as mean particle diameter, moisture content, and fine particle fraction of the produced powders. Influence of different kinds and amounts of lyoprotectants was also evaluated for the best preservation of the drug entrapped in the liposome bilayers after the dehydration-rehydration cycle. The in vivo study of intratracheal instillation of insulin-loaded liposomes to diabetic rats showed successful hypoglycemic effect with low blood glucose level and long-lasting period and a relative pharmacological bioavailability as high as 38.38% in the group of 8 IU/kg dosage.

  14. A statistical approach to optimize the spray drying of starch particles: application to dry powder coating.

    PubMed

    Bilancetti, Luca; Poncelet, Denis; Loisel, Catherine; Mazzitelli, Stefania; Nastruzzi, Claudio

    2010-09-01

    This article describes the preparation of starch particles, by spray drying, for possible application to a dry powder coating process. Dry powder coating consists of spraying a fine powder and a plasticizer on particles. The efficiency of the coating is linked to the powder morphological and dimensional characteristics. Different experimental parameters of the spray-drying process were analyzed, including type of solvent, starch concentration, rate of polymer feeding, pressure of the atomizing air, drying air flow, and temperature of drying air. An optimization and screening of the experimental parameters by a design of the experiment (DOE) approach have been done. Finally, the produced spray-dried starch particles were conveniently tested in a dry coating process, in comparison to the commercial initial starch. The obtained results, in terms of coating efficiency, demonstrated that the spray-dried particles led to a sharp increase of coating efficiency value.

  15. Spray-dried respirable powders containing bacteriophages for the treatment of pulmonary infections.

    PubMed

    Matinkhoo, Sadaf; Lynch, Karlene H; Dennis, Jonathan J; Finlay, Warren H; Vehring, Reinhard

    2011-12-01

    Myoviridae bacteriophages were processed into a dry powder inhalable dosage form using a low-temperature spray-drying process. The phages were incorporated into microparticles consisting of trehalose, leucine, and optionally a third excipient (either a surfactant or casein sodium salt). The particles were designed to have high dispersibility and a respirable particle size, and to preserve the phages during processing. Bacteriophages KS4- M, KS14, and cocktails of phages ΦKZ/D3 and ΦKZ/D3/KS4-M were spray-dried with a processing loss ranging from 0.4 to 0.8 log pfu. The aerosol performance of the resulting dry powders as delivered from an Aerolizer® dry powder inhaler (DPI) exceeded the performance of commercially available DPIs; the emitted mass and the in vitro total lung mass of the lead formulation were 82.7% and 69.7% of filled capsule mass, respectively. The total lung mass had a mass median aerodynamic diameter of 2.5-2.8 µm. The total in vitro lung doses of the phages, delivered from a single actuation of the inhaler, ranged from 10(7) to 10(8) pfu, levels that are expected to be efficacious in vivo. Spray drying of bacteriophages into a respirable dry powder was found to be feasible. Copyright © 2011 Wiley-Liss, Inc.

  16. Characterisation of spray dried soy sauce powders made by adding crystalline carbohydrates to drying carrier.

    PubMed

    Wang, Wei; Zhou, Weibiao

    2015-02-01

    This study aimed to reduce stickiness and caking of spray dried soy sauce powders by introducing a new crystalline structure into powder particles. To perform this task, soy sauce powders were formulated by using mixtures of cellulose and maltodextrin or mixtures of waxy starch and maltodextrin as drying carriers, with a fixed carrier addition rate of 30% (w/v) in the feed solution. The microstructure, crystallinity, solubility as well as stickiness and caking strength of all the different powders were analysed and compared. Incorporating crystalline carbohydrates in the drying carrier could significantly reduce the stickiness and caking strength of the powders when the ratio of crystalline carbohydrates to maltodextrin was above 1:5 and 1:2, respectively. X-ray Diffraction (XRD) results showed that adding cellulose or waxy starch could induce the crystallinity of powders. Differential Scanning Calorimetry (DSC) results demonstrated that the native starch added to the soy sauce powders did not fully gelatinize during spray drying.

  17. Low-Flow-Rate Dry-Powder Feeder

    NASA Technical Reports Server (NTRS)

    Ramsey, Keith E.

    1994-01-01

    Apparatus feeds small, precise flow of dry powder through laser beam of optical analyzer measuring patterns of light created by forward scattering (Fraunhofer diffraction) of laser beam from powder particles. From this optical measurement, statistical distribution of sizes of powder particles computed. Rates of flow optimized for measurement of particle-size distributions. Developed for analyzing particle-size distributions of solid-propellant powders. Also adapted to pharmaceutical industry, in manufacture of metal powder, and in other applications where particle-size distributions of materials used to control rates of chemical reactions and/or physical characteristics of processes.

  18. Low-Flow-Rate Dry-Powder Feeder

    NASA Technical Reports Server (NTRS)

    Ramsey, Keith E.

    1994-01-01

    Apparatus feeds small, precise flow of dry powder through laser beam of optical analyzer, measuring patterns of light created by forward scattering (Fraunhofer diffraction) of laser beam from powder particles. From measurement, statistical distribution of sizes of powder particles computed. Developed for analyzing particle-size distributions of solid-propellant powders. Also adapted to use in pharmaceutical industry, in manufacture of metal powder, and in other applications in which particle-size distributions of materials used to control rates of chemical reactions and/or physical characteristics of processes.

  19. Low-Flow-Rate Dry-Powder Feeder

    NASA Technical Reports Server (NTRS)

    Ramsey, Keith E.

    1994-01-01

    Apparatus feeds small, precise flow of dry powder through laser beam of optical analyzer measuring patterns of light created by forward scattering (Fraunhofer diffraction) of laser beam from powder particles. From this optical measurement, statistical distribution of sizes of powder particles computed. Rates of flow optimized for measurement of particle-size distributions. Developed for analyzing particle-size distributions of solid-propellant powders. Also adapted to pharmaceutical industry, in manufacture of metal powder, and in other applications where particle-size distributions of materials used to control rates of chemical reactions and/or physical characteristics of processes.

  20. Low-Flow-Rate Dry-Powder Feeder

    NASA Technical Reports Server (NTRS)

    Ramsey, Keith E.

    1994-01-01

    Apparatus feeds small, precise flow of dry powder through laser beam of optical analyzer, measuring patterns of light created by forward scattering (Fraunhofer diffraction) of laser beam from powder particles. From measurement, statistical distribution of sizes of powder particles computed. Developed for analyzing particle-size distributions of solid-propellant powders. Also adapted to use in pharmaceutical industry, in manufacture of metal powder, and in other applications in which particle-size distributions of materials used to control rates of chemical reactions and/or physical characteristics of processes.

  1. Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying

    PubMed Central

    Okuda, Tomoyuki; Suzuki, Yumiko; Kobayashi, Yuko; Ishii, Takehiko; Uchida, Satoshi; Itaka, Keiji; Kataoka, Kazunori; Okamoto, Hirokazu

    2015-01-01

    In this study, two types of biodegradable polycation (PAsp(DET) homopolymer and PEG-PAsp(DET) copolymer) were applied as vectors for inhalable dry gene powders prepared by spray freeze drying (SFD). The prepared dry gene powders had spherical and porous structures with a 5~10-μm diameter, and the integrity of plasmid DNA could be maintained during powder production. Furthermore, it was clarified that PEG-PAsp(DET)-based dry gene powder could more sufficiently maintain both the physicochemical properties and in vitro gene transfection efficiencies of polyplexes reconstituted after powder production than PAsp(DET)-based dry gene powder. From an in vitro inhalation study using an Andersen cascade impactor, it was demonstrated that the addition of l-leucine could markedly improve the inhalation performance of dry powders prepared by SFD. Following pulmonary delivery to mice, both PAsp(DET)- and PEG-PAsp(DET)-based dry gene powders could achieve higher gene transfection efficiencies in the lungs compared with a chitosan-based dry gene powder previously reported by us. PMID:26343708

  2. The Dry Aerosol Deposition Device (DADD): An Instrument for Depositing Microbial Aerosols onto Surfaces

    DTIC Science & Technology

    2008-12-01

    AFRL-RX-TY-TR-2008-4592 THE DRY AEROSOL DEPOSITION DEVICE (DADD): AN INSTRUMENT FOR DEPOSITING MICROBIAL AEROSOLS ONTO SURFACES...RESPONSIBLE PERSON 19b. TELEPHONE NUMBER (Include area code) 30-NOV-2008 Final Technical Report 01-OCT-2004 -- 02-OCT-2008 The Dry Aerosol Deposition ...Device (DADD): An Instrument for Depositing Microbial Aerosols Onto Surfaces FA4819-07-D-0001 99999F DODT 00 DODT0056 Heimbuch, Brian K.; Kinney

  3. The Dry Aerosol Deposition Device (DADD): An Instrument for Depositing Microbial Aerosols onto Surfaces (PREPRINT)

    DTIC Science & Technology

    2008-12-01

    AFRL-RX-TY-TP-2008-4617 PREPRINT THE DRY AEROSOL DEPOSITION DEVICE (DADD): AN INSTRUMENT FOR DEPOSITING MICROBIAL AEROSOLS ONTO SURFACES... Deposition Device (DADD): 3  An Instrument for Depositing Microbial Aerosols onto Surfaces 4  5  Authors and affiliation 6  7  Heimbuch, B.K., Kinney...footprint, variable loading, etc.). We developed a Dry Aerosol 33  Deposition Device (DADD) that uses impaction rather than settling for loading surfaces

  4. Dry Powder Precursors of Cubic Liquid Crystalline Nanoparticles (cubosomes)

    NASA Astrophysics Data System (ADS)

    Spicer, Patrick T.; Small, William B.; Small, William B.; Lynch, Matthew L.; Burns, Janet L.

    2002-08-01

    Cubosomes are dispersed nanostructured particles of cubic phase liquid crystal that have stimulated significant research interest because of their potential for application in controlled-release and drug delivery. Despite the interest, cubosomes can be difficult to fabricate and stabilize with current methods. Most of the current work is limited to liquid phase processes involving high shear dispersion of bulk cubic liquid crystalline material into sub-micron particles, limiting application flexibility. In this work, two types of dry powder cubosome precursors are produced by spray-drying: (1) starch-encapsulated monoolein is produced by spray-drying a dispersion of cubic liquid crystalline particles in an aqueous starch solution and (2) dextran-encapsulated monoolein is produced by spray-drying an emulsion formed by the ethanol-dextran-monoolein-water system. The encapsulants are used to decrease powder cohesion during drying and to act as a soluble colloidal stabilizer upon hydration of the powders. Both powders are shown to form (on average) 0.6 μm colloidally-stable cubosomes upon addition to water. However, the starch powders have a broader particle size distribution than the dextran powders because of the relative ease of spraying emulsions versus dispersions. The developed processes enable the production of nanostructured cubosomes by end-users rather than just specialized researchers and allow tailoring of the surface state of the cubosomes for broader application.

  5. Dry powder inhalable formulations for anti-tubercular therapy.

    PubMed

    Parumasivam, Thaigarajan; Chang, Rachel Yoon Kyung; Abdelghany, Sharif; Ye, Tian Tian; Britton, Warwick John; Chan, Hak-Kim

    2016-07-01

    Tuberculosis (TB) is an intracellular infectious disease caused by the airborne bacterium, Mycobacterium tuberculosis. Despite considerable research efforts, the treatment of TB continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. The delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or vaccination against TB. Pulmonary delivery is non-invasive, avoids first-pass metabolism in the liver and enables targeting of therapeutic agents to the infection site. Inhaled delivery also potentially reduces the dose requirement and the accompanying side effects. Dry powder is a stable formulation of drug that can be stored without refrigeration compared to liquids and suspensions. The dry powder inhalers are easy to use and suitable for high-dose formulations. This review focuses on the current innovations of inhalable dry powder formulations of drug and vaccine delivery for TB, including the powder production method, preclinical and clinical evaluations of inhaled dry powder over the last decade. Finally, the risks associated with pulmonary therapy are addressed. A novel dry powder formulation with high percentages of respirable particles coupled with a cost effective inhaler device is an appealing platform for TB drug delivery.

  6. Characterisation of Aronia powders obtained by different drying processes.

    PubMed

    Horszwald, Anna; Julien, Heritier; Andlauer, Wilfried

    2013-12-01

    Nowadays, food industry is facing challenges connected with the preservation of the highest possible quality of fruit products obtained after processing. Attention has been drawn to Aronia fruits due to numerous health promoting properties of their products. However, processing of Aronia, like other berries, leads to difficulties that stem from the preparation process, as well as changes in the composition of bioactive compounds. Consequently, in this study, Aronia commercial juice was subjected to different drying techniques: spray drying, freeze drying and vacuum drying with the temperature range of 40-80 °C. All powders obtained had a high content of total polyphenols. Powders gained by spray drying had the highest values which corresponded to a high content of total flavonoids, total monomeric anthocyanins, cyaniding-3-glucoside and total proanthocyanidins. Analysis of the results exhibited a correlation between selected bioactive compounds and their antioxidant capacity. In conclusion, drying techniques have an impact on selected quality parameters, and different drying techniques cause changes in the content of bioactives analysed. Spray drying can be recommended for preservation of bioactives in Aronia products. Powder quality depends mainly on the process applied and parameters chosen. Therefore, Aronia powders production should be adapted to the requirements and design of the final product. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, I.O.

    1994-12-06

    A free flowing, conformable powder-like mix of silica particles and a phase change material (PCM) is provided. The silica particles have a critical size of about 0.005 to about 0.025 microns and the PCM must be added to the silica in an amount of 75% or less PCM per combined weight of silica and PCM. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and particularly in applications for heat protection for heat sensitive items, such as aircraft flight recorders, and for preventing brake fade in automobiles, buses, trucks and aircraft. 3 figures.

  8. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, Ival O.

    1995-01-01

    A free flowing, conformable powder-like mix of silica particles and a phase change material (PCM) is provided. The silica particles have a critical size of about 0.005 to about 0.025 microns and the PCM must be added to the silica in an amount of 75% or less PCM per combined weight of silica and PCM. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and particularly in applications for heat protection for heat sensitive items, such as aircraft flight recorders, and for preventing brake fade in automobiles, buses, trucks and aircraft.

  9. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, I.O.

    1995-12-26

    A free flowing, conformable powder-like mix of silica particles and a phase change material (PCM) is provided. The silica particles have a critical size of about 0.005 to about 0.025 microns and the PCM must be added to the silica in an amount of 75% or less PCM per combined weight of silica and PCM. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and particularly in applications for heat protection for heat sensitive items, such as aircraft flight recorders, and for preventing brake fade in automobiles, buses, trucks and aircraft. 3 figs.

  10. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, Ival O.

    1994-01-01

    A free flowing, conformable powder-like mix of silica particles and a phase change material (PCM) is provided. The silica particles have a critical size of about 0.005 to about 0.025 microns and the PCM must be added to the silica in an amount of 75% or less PCM per combined weight of silica and PCM. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and particularly in applications for heat protection for heat sensitive items, such as aircraft flight recorders, and for preventing brake fade in automobiles, buses, trucks and aircraft.

  11. Experimental observations of dry powder inhaler dose fluidisation.

    PubMed

    Tuley, Rob; Shrimpton, John; Jones, Matthew D; Price, Rob; Palmer, Mark; Prime, Dave

    2008-06-24

    Dry powder inhalers (DPIs) are widely used to deliver respiratory medication as a fine powder. This study investigates the physical mechanism of DPI operation, assessing the effects of geometry, inhalation and powder type on dose fluidisation. Patient inhalation through an idealised DPI was simulated as a linearly increasing pressure drop across three powder dose reservoir geometries permitting an analysis of shear and normal forces on dose evacuation. Pressure drop gradients of 3.3, 10 and 30 kPa s(-1)were applied to four powder types (glass, aluminium, and lactose 6 and 16% fines) and high speed video of each powder dose fluidisation was recorded and quantitatively analysed. Two distinct mechanisms are identified, labelled 'fracture' and 'erosion'. 'Fracture' mode occurs when the initial evacuation occurs in several large agglomerates whilst 'erosion' mode occurs gradually, with successive layers being evacuated by the high speed gas flow at the bed/gas interface. The mechanism depends on the powder type, and is independent of the reservoir geometries or pressure drop gradients tested. Both lactose powders exhibit fracture characteristics, while aluminium and glass powders fluidise as an erosion. Further analysis of the four powder types by an annular shear cell showed that the fluidisation mechanism cannot be predicted using bulk powder properties.

  12. Spherical agglomerates of pure drug nanoparticles for improved pulmonary delivery in dry powder inhalers

    NASA Astrophysics Data System (ADS)

    Hu, Jun; Dong, Yuancai; Pastorin, Giorgia; Ng, Wai Kiong; Tan, Reginald B. H.

    2013-04-01

    The aim of this study was to produce micron-sized spherical agglomerates of pure drug nanoparticles to achieve improved aerosol performance in dry powder inhalers (DPIs). Sodium cromoglicate was chosen as the model drug. Pure drug nanoparticles were prepared through a bottom-up particle formation process, liquid antisolvent precipitation, and then rapidly agglomerated into porous spherical microparticles by immediate (on-line) spray drying. Nonporous spherical drug microparticles with similar geometric size distribution were prepared by conventional spray drying of the aqueous drug solution, which together with the mechanically micronized drug particles were used as the control samples. The three samples were characterized by field emission scanning electron microscopy, laser diffraction, Brunauer-Emmett-Teller analysis, density measurement, powder X-ray diffraction, and in vitro aerosol deposition measurement with a multistage liquid impinger. It was found that drug nanoparticles with a diameter of 100 nm were precipitated and agglomerated into highly porous spherical microparticles with a volume median diameter ( D 50 %) of 2.25 ± 0.08 μm and a specific surface area of 158.63 ± 3.27 m2/g. In vitro aerosol deposition studies showed the fine particle fraction of such spherical agglomerates of drug nanoparticles was increased by more than 50 % in comparison with the control samples, demonstrating significant improvements in aerosol performance. The results of this study indicated the potential of the combined particle engineering process of liquid antisolvent precipitation followed by immediate (on-line) spray drying in the development of novel DPI drug products with improved aerosol performance.

  13. 30 CFR 75.1101-14 - Installation of dry powder chemical systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Installation of dry powder chemical systems. 75...-14 Installation of dry powder chemical systems. (a) Self-contained dry powder chemical systems shall... fire-control components of each dry powder chemical system shall be a type approved by the...

  14. 30 CFR 75.1101-14 - Installation of dry powder chemical systems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Installation of dry powder chemical systems. 75...-14 Installation of dry powder chemical systems. (a) Self-contained dry powder chemical systems shall... fire-control components of each dry powder chemical system shall be a type approved by the...

  15. 30 CFR 75.1101-14 - Installation of dry powder chemical systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Installation of dry powder chemical systems. 75...-14 Installation of dry powder chemical systems. (a) Self-contained dry powder chemical systems shall... fire-control components of each dry powder chemical system shall be a type approved by the Underwriters...

  16. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, I.O.

    1993-05-18

    Free flowing, conformable powder-like mix of silica particles and a phase change material (p.c.m.) is disclosed. The silica particles have a critical size of about 7[times]10[sup [minus]3] to about 7[times]10[sup [minus]2] microns and the p.c.m. must be added to the silica in an amount of 80 wt. % or less p.c.m. per combined weight of silica and p.c.m. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and in cementitious compositions of the type in which it is beneficial to use a p.c.m. material. The silica-p.c.m. mix can also be admixed with soil to provide a soil warming effect and placed about a tree, flower, or shrub.

  17. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, I.O.

    1993-10-19

    Free flowing, conformable powder-like mix of silica particles and a phase change material (pcm) is disclosed. The silica particles have a critical size of about 7[times]10[sup [minus]3] to about 7[times]10[sup [minus]2] microns and the pcm must be added to the silica in an amount of 80 wt. % or less pcm per combined weight of silica and pcm. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and in cementitious compositions of the type in which it is beneficial to use a pcm material. The silica-pcm mix can also be admixed with soil to provide a soil warming effect and placed about a tree, flower, or shrub. 10 figures.

  18. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, I.O.

    1994-02-01

    Free flowing, conformable powder-like mix of silica particles and a phase change material (PCM) is provided. The silica particles have a critical size of about 0.005 to about 0.025 microns and the PCM must be added to the silica in an amount of 75% or less PCM per combined weight of silica and PCM. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and in cementitious compositions of the type in which it is beneficial to use a PCM material. The silica-PCM mix can also be admixed with soil to provide a soil warming effect and placed about a tree, flower, or shrub. 2 figures.

  19. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, Ival O.

    1992-01-01

    Free flowing, conformable powder-like mix of silica particles and a phase change material (p.c.m.) is disclosed. The silica particles have a critical size of about 7.times.10.sup.-3 to about 7.times.10.sup.-2 microns and the pcm must be added to the silica in an amount of 80 wt. % or less pcm per combined weight of silica and pcm. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and in cementitious compositions of the type in which it is beneficial to use a pcm material. The silica-pcm mix can also be admixed with soil to provide a soil warming effect and placed about a tree, flower, or shrub.

  20. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, Ival O.

    1993-01-01

    Free flowing, conformable powder-like mix of silica particles and a phase change material (p.c.m.) is disclosed. The silica particles have a critical size of about 7.times.10.sup.-3 to about 7.times.10.sup.-2 microns and the pcm must be added to the silica in an amount of 80 wt. % or less pcm per combined weight of silica and pcm. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garmets, quilts and blankets, and in cementitious compositions of the type in which it is beneficial to use a pcm material. The silica-pcm mix can also be admixed with soil to provide a soil warming effect and placed about a tree, flower, or shrub.

  1. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, Ival O.

    1993-01-01

    Free flowing, conformable powder-like mix of silica particles and a phase change material (p.c.m.) is disclosed. The silica particles have a critical size of about 7.times.10.sup.-3 to about 7.times.10.sup.-2 microns and the pcm must be added to the silica in an amount of 80 wt. % or less pcm per combined weight of silica and pcm. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and in cementitious compositions of the type in which it is beneficial to use a pcm material. The silica-pcm mix can also be admixed with soil to provide a soil warming effect and placed about a tree, flower, or shrub.

  2. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, Ival O.

    1994-01-01

    Free flowing, conformable powder-like mix of silica particles and a phase change material (PCM) is provided. The silica particles have a critical size of about 0.005 to about 0.025 microns and the PCM must be added to the silica in an amount of 75% or less PCM per combined weight of silica and PCM. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and in cementitious compositions of the type in which it is beneficial to use a PCM material. The silica-PCM mix can also be admixed with soil to provide a soil warming effect and placed about a tree, flower, or shrub.

  3. Dry powder mixes comprising phase change materials

    DOEpatents

    Salyer, I.O.

    1992-04-21

    A free flowing, conformable powder-like mix of silica particles and a phase change material (p.c.m.) is disclosed. The silica particles have a critical size of about 7 [times] 10[sup [minus]3] to about 7 [times] 10[sup [minus]2] microns and the pcm must be added to the silica in an amount of 80 wt. % or less pcm per combined weight of silica and pcm. The powder-like mix can be used in tableware items, medical wraps, tree wraps, garments, quilts and blankets, and in cementitious compositions of the type in which it is beneficial to use a pcm material. The silica-pcm mix can also be admixed with soil to provide a soil warming effect and placed about a tree, flower, or shrub. 9 figs.

  4. Freeze drying vs microwave drying-methods for synthesis of sinteractive thoria powders

    NASA Astrophysics Data System (ADS)

    Annie, D.; Chandramouli, V.; Anthonysamy, S.; Ghosh, Chanchal; Divakar, R.

    2017-02-01

    Thoria powders were synthesized by oxalate precipitation from an aqueous solution of the nitrate. The filtered precipitates were freeze dried or microwave dried before being calcined at 1073 K. The thoria powders obtained were characterized for crystallite size, specific surface area, bulk density, particle size distribution and residual carbon. Microstructure of the product was studied using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Sinterability of the synthesized powders was studied by measuring the density of the sintered compacts. Powders that can be consolidated and sintered to densities ∼96% theoretical density (TD) at 1773 K were obtained.

  5. Phytohemagglutination Activity in Extruded Dry Bean Powder

    USDA-ARS?s Scientific Manuscript database

    Dry beans are a highly nutritious food. Besides making beans palatable, cooking is required to denature lectin, a protein found in beans. If consumed raw or undercooked, lectin poisoning can occur. Symptoms of lectin poisoning include vomiting, diarrhea, and abdominal pain, and occur within hours of...

  6. Applying a novel electrostatic dry powder coating technology to pellets.

    PubMed

    Yang, Qingliang; Ma, Yingliang; Zhu, Jesse

    2015-11-01

    The present study aimed to apply a novel dry powder technology to coat pellets with different coating materials grounded into fine powders. Piroxicam, a non-steroidal anti-inflammatory drug, was used as the active pharmaceutical ingredient (API). Eudragit® EPO, Eudragit® RS/RL and Acryl EZE were used as the coating materials to achieve immediate release, sustained release and delayed release, respectively. Three steps including preheating, powder adhesion and curing were carried out to form the coating film while liquid plasticizers were used to decrease the glass transition temperature of coating powders and also served to reduce the electrical resistance of pellets. Results of SEM indicated coating film could be better formed by increasing curing temperature or extending curing time. Dissolution tests showed that three different drug release profiles, including immediate release, sustained release and delayed release, were achieved by this coating technology with different coating formulations. And the dry powder coated pellets using this developed technology exhibited an excellent stability with 1 month at 40 °C/75% RH. The coating procedure could be shortened to within 120 min and the use of fluidized hot air was minimized, both cutting down the overall cost dramatically compared to organic solvent coating and aqueous coating. All results demonstrated that the novel electrostatic dry powder coating method is a promising technology in the pharmaceutical coating industry.

  7. Spray dried glyceryl monooleate-magnesium trisilicate dry powder as cubic phase precursor.

    PubMed

    Shah, Manish H; Biradar, Shailesh V; Paradkar, Anant R

    2006-10-12

    Glyceryl monooleate (GMO) is a polar amphiphilic lipid, which forms different sequential lyotropic liquid crystals upon hydration. GMO has been utilized for various delivery systems and routes of administrations. Owing to sticky and waxy nature of GMO, preparation of oral solid dosage form utilizing GMO is still a challenge for pharmaceutical researchers. Therefore, the objective of the present work was to fabricate dry powder precursors using GMO, which upon hydration in situ forms cubic phase and can be wisely used for fabrication of oral solid dosage forms. In addition to this, dry powder precursor was evaluated for drug loading, in vitro release behavior and in vivo performance of model drug diclofenac sodium (DiNa). The dry powder precursor was obtained by spray-drying GMO with DiNa using magnesium trisilicate (MTS) as adsorbent. The percent drug entrapment of various batches of powder precursor was in the range of 84-93% indicating high content uniformity. SEM and image analysis showed that as the amount of MTS in powder precursor was increased, the particle size decreased. Furthermore, the viscosity of powder precursor was function of amount of MTS. The rate of water uptake of powder precursor was higher due to uniform layer of GMO on the MTS surface, which led to faster transformation of lamellar phase into cubic phase. The polarizing light microscopy confirmed that cubic phase was formed upon hydration of powder precursor. The drug released from powder precursor was initially governed by the cubic phase formed and in later stage it depends upon dynamic swelling behavior of hexagonally packed cylindrical aggregates. The drug loaded powder precursor was found to have more effective and prolonged anti-inflammatory and analgesic activity as compared to pure drug. Thus the dry powder precursor of cubic phase was prepared in which drug release was entirely governed by the mesophases formed.

  8. Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design

    PubMed Central

    Farkas, Dale R.; Hindle, Michael; Longest, P. Worth

    2015-01-01

    The objective of this study was to develop a new high-efficiency dry powder inhaler (DPI) that can effectively aerosolize large masses (25–100 mg) of spray dried powder formulations. The DPI was designed to implement a concept similar to a fluidized bed for aerosolization using small mixing balls made of polytetrafluoroethylene (PTFE) along with a larger, hollow dosing sphere filled with the powder. The performance of the fluidized bed DPI was compared, based on emitted dose (ED) and aerosolization efficiency, to other recently developed capsule-based DPIs that were designed to accommodate smaller powder masses (~2–20 mg). The inhalers were tested with spray dried excipient enhanced growth formulations that contained an antibiotic (ciprofloxacin) and hygroscopic excipient (mannitol). The new fluidized bed design produced an ED of 71% along with a mass median aerodynamic diameter (MMAD) of 1.53 µm and fine particle fractions (FPFs) less than 5 µm and 1 µm of 93% and 36%, respectively, when used to deliver a 100 mg loaded mass of EEG powder with the advantage of not requiring multiple capsules. Surprisingly, performance of the device was further improved by removing the mixing balls from the inhaler and only retaining the dose containment sphere. PMID:25986955

  9. Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design.

    PubMed

    Farkas, Dale R; Hindle, Michael; Longest, P Worth

    2015-11-01

    The objective of this study was to develop a new high-efficiency dry powder inhaler (DPI) that can effectively aerosolize large masses (25-100 mg) of spray dried powder formulations. The DPI was designed to implement a concept similar to a fluidized bed for aerosolization using small mixing balls made of polytetrafluoroethylene along with a larger, hollow dosing sphere filled with the powder. The performance of the fluidized bed DPI was compared, based on emitted dose (ED) and aerosolization efficiency, to other recently developed capsule-based DPIs that were designed to accommodate smaller powder masses (~2-20 mg). The inhalers were tested with spray dried excipient enhanced growth (EEG) formulations that contained an antibiotic (ciprofloxacin) and hygroscopic excipient (mannitol). The new fluidized bed design produced an ED of 71% along with a mass median aerodynamic diameter of 1.53 μm and fine particle fractions <5 and 1 μm of 93 and 36%, respectively, when used to deliver a 100 mg loaded mass of EEG powder with the advantage of not requiring multiple capsules. Surprisingly, performance of the device was further improved by removing the mixing balls from the inhaler and only retaining the dose containment sphere.

  10. Effect of compression pressure on inhalation grade lactose as carrier for dry powder inhalations

    PubMed Central

    Raut, Neha Sureshrao; Jamaiwar, Swapnil; Umekar, Milind Janrao; Kotagale, Nandkishor Ramdas

    2016-01-01

    Introduction: This study focused on the potential effects of compression forces experienced during lactose (InhaLac 70, 120, and 230) storage and transport on the flowability and aerosol performance in dry powder inhaler formulation. Materials and Methods: Lactose was subjected to typical compression forces 4, 10, and 20 N/cm2. Powder flowability and particle size distribution analysis of un-compressed and compressed lactose was evaluated by Carr's index, Hausner's ratio, the angle of repose and by laser diffraction method. Aerosol performance of un-compressed and compressed lactose was assessed in dispersion studies using glass twin-stage-liquid-impenger at flow rate 40-80 L/min. Results: At compression forces, the flowability of compressed lactose was observed same or slightly improved. Furthermore, compression of lactose caused a decrease in in vitro aerosol dispersion performance. Conclusion: The present study illustrates that, as carrier size increases, a concurrent decrease in drug aerosolization performance was observed. Thus, the compression of the lactose fines onto the surfaces of the larger lactose particles due to compression pressures was hypothesized to be the cause of these observed performance variations. The simulations of storage and transport in an industrial scale can induce significant variations in formulation performance, and it could be a source of batch-to-batch variations. PMID:27014618

  11. Production of Dry Powder Clots Using Piezoelectric Drop Generator

    SciTech Connect

    Lee, Eric R

    2002-09-05

    We have demonstrated that piezoelectrically driven, squeeze mode, tubular reservoir liquid drop generation, originally developed as a ''drop-on-demand'' method for ejection of microdrops of pure liquid or liquid suspensions of powdered bulk materials, can successfully operate with dry powder. Spherical silver powder with maximum particle diameter of 20 {micro}m (-635 mesh) was loaded into and ejected from a 100 {micro}m orifice glass dropper with flat piezoelectric disk driver. Time of flight experiments were performed to optimize the dropper operation parameters and to determine the size and velocity of the ejected particles. It was found that at certain values of the amplitude, duration, and repetition rate of the voltage pulses applied to the dropper piezoelectric disk, one can produce ejection of powder clots of a stable size, comparable with the dropper orifice diameter. In contrast to the dropper operation with a liquid, in the case of silver powder, a clot is not ejected at each high voltage pulse, but quasi-periodically with an interval corresponding to thousands of pulses. The application of the dry powder clot generation technique for injection of atoms into helium buffer gas at cryogenic temperatures is discussed.

  12. NASA. Langley Research Center dry powder towpreg system

    NASA Technical Reports Server (NTRS)

    Baucom, Robert M.; Marchello, Joseph M.

    1990-01-01

    Dry powder polymer impregnated carbon fiber tows were produced for preform weaving and composite materials molding applications. In the process, fluidized powder is deposited on spread tow bundles and melted on the fibers by radiant heating to adhere the polymer to the fiber. Unit design theory and operating correlations were developed to provide the basis for scale up of the process to commercial operation. Special features of the operation are the pneumatic tow spreader, fluidized bed, resin feeder, and quality control system. Bench scale experiments, at tow speeds up to 50 cm/sec, demonstrated that process variables can be controlled to produce weavable LARC-TPI carbon fiber towpreg. The towpreg made by the dry powder process was formed into unidirectional fiber moldings and was woven and molded into preform material of good quality.

  13. Recent advances in liposomal dry powder formulations: preparation and evaluation.

    PubMed

    Misra, Ambikanandan; Jinturkar, Kaustubh; Patel, Deepa; Lalani, Jigar; Chougule, Mahavir

    2009-01-01

    Liposomal drug dry powder formulations have shown many promising features for pulmonary drug administration, such as selective localization of drug within the lung, controlled drug release, reduced local and systemic toxicities, propellant-free nature, patient compliance, high dose carrying capacity, stability and patent protection. Critical review of the recent developments will provide a balanced view on benefits of liposomal encapsulation while developing dry powder formulations and will help researchers to update themselves and focus their research in more relevant areas. In liposomal dry powder formulations (LDPF), drug encapsulated liposomes are homogenized, dispersed into the carrier and converted into dry powder form by using freeze drying, spray drying and spray freeze drying. Alternatively, LDPF can also be formulated by supercritical fluid technologies. On inhalation with a suitable inhalation device, drug encapsulated liposomes get rehydrated in the lung and release the drug over a period of time. The prepared LDPF are evaluated in vitro and in vivo for lung deposition behavior and drug disposition in the lung using a suitable inhaler device. The most commonly used liposomes are composed of lung surfactants and synthetic lipids. Delivery of anticancer agents for lung cancer, corticosteroids for asthma, immunosuppressants for avoiding lung transplantation rejection, antifungal drugs for lung fungal infections, antibiotics for local pulmonary infections and cystic fibrosis and opioid analgesics for pain management using liposome technology are a few examples. Many liposomal formulations have reached the stage of clinical trials for the treatment of pulmonary distress, cystic fibrosis, lung fungal infection and lung cancer. These formulations have given very promising results in both in vitro and in vivo studies. However, modifications to new therapies for respiratory diseases and systemic delivery will provide new challenges in conducting well

  14. Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery.

    PubMed

    Sinsuebpol, Chutima; Chatchawalsaisin, Jittima; Kulvanich, Poj

    2013-01-01

    The aim of the present study was to prepare inhalable co-spray dried powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs) with mannitol and investigate pulmonary absorption in rats. The sCT-CS-NPs were prepared by the ionic gelation method using sodium tripolyphosphate (TPP) as a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders were characterized with respect to morphology, particle size, powder density, aerodynamic diameter, protein integrity, in vitro release of sCT, and aerosolization. The plasmatic sCT levels following intratracheal administration of sCT-CS-NPs spray dried powders to the rats was also determined. sCT-CS-NPs were able to be incorporated into mannitol forming inhalable microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and spray drying process affected the properties of the microparticles obtained. The conformation of the secondary structures of sCTs was affected by both mannitol content and spray dry inlet temperature. The sCT-CS-NPs were recovered after reconstitution of spray dried powders in an aqueous medium. The sCT release profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS-NPs spray dried powders having promising aerodynamic properties for deposition in the deep lung. Determination of the plasmatic sCT levels following intratracheal administration to rats revealed that the inhalable sCT-CS NPs spray dried powders provided higher protein absorption compared to native sCT powders. The sCT-CS-NPs with mannitol based spray dried powders were prepared to have appropriate aerodynamic properties for pulmonary delivery. The developed system was able to deliver sCT via a pulmonary route into the systemic circulation.

  15. Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery

    PubMed Central

    Sinsuebpol, Chutima; Chatchawalsaisin, Jittima; Kulvanich, Poj

    2013-01-01

    Purpose The aim of the present study was to prepare inhalable co-spray dried powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs) with mannitol and investigate pulmonary absorption in rats. Methods The sCT-CS-NPs were prepared by the ionic gelation method using sodium tripolyphosphate (TPP) as a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders were characterized with respect to morphology, particle size, powder density, aerodynamic diameter, protein integrity, in vitro release of sCT, and aerosolization. The plasmatic sCT levels following intratracheal administration of sCT-CS-NPs spray dried powders to the rats was also determined. Results sCT-CS-NPs were able to be incorporated into mannitol forming inhalable microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and spray drying process affected the properties of the microparticles obtained. The conformation of the secondary structures of sCTs was affected by both mannitol content and spray dry inlet temperature. The sCT-CS-NPs were recovered after reconstitution of spray dried powders in an aqueous medium. The sCT release profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS-NPs spray dried powders having promising aerodynamic properties for deposition in the deep lung. Determination of the plasmatic sCT levels following intratracheal administration to rats revealed that the inhalable sCT-CS NPs spray dried powders provided higher protein absorption compared to native sCT powders. Conclusion The sCT-CS-NPs with mannitol based spray dried powders were prepared to have appropriate aerodynamic properties for pulmonary delivery. The developed system was able to deliver sCT via a pulmonary route into the systemic circulation. PMID:24039397

  16. Nanospray Drying as a Novel Technique for the Manufacturing of Inhalable NSAID Powders

    PubMed Central

    Rita Patrizia, Aquino; Mariateresa, Stigliani; Pasquale, Del Gaudio; Teresa, Mencherini; Francesca, Sansone; Paola, Russo

    2014-01-01

    The aim of this research was to evaluate the potential of the nanospray drier as a novel apparatus for the manufacturing of a dry powder for inhalation containing ketoprofen lysinate, a nonsteroidal anti-inflammatory drug able to control the inflammation in cystic fibrosis patients. We produced several ketoprofen lysinate and leucine powder batches by means of nanospray dryer, studying the influence of process parameters on yield, particle properties (size distribution and morphology), and, mainly, aerodynamic properties of powders. Micronized particles were prepared from different hydroalcoholic solutions (alcohol content from 0 to 30% v/v) using ketoprofen in its lysine salt form and leucine as dispersibility enhancer in different ratios (from 5 to 15% w/w) with a total solid concentration ranging from 1 to 7% w/v. Results indicated that the spray head equipped with a 7 µm nozzle produced powders too big to be inhaled. The reduction of nozzle size from 7 to 4 µm led to smaller particles suitable for inhalation but, at the same time, caused a dramatic increase in process time. The selection of process variables, together with the nozzle pretreatment with a surfactant solution, allowed us to obtain a free flowing powder with satisfying aerosol performance, confirming the usefulness of the nanospray drier in the production of powder for inhalation. PMID:25580462

  17. A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid-polymer hybrid nanoparticles.

    PubMed

    Wang, Yajie; Kho, Katherine; Cheow, Wean Sin; Hadinoto, Kunn

    2012-03-15

    Lipid-polymer hybrid nanoparticles - polymeric nanoparticles enveloped by lipid layers - have emerged as a potent therapeutic nano-carrier alternative to liposomes and polymeric nanoparticles. Herein we perform comparative studies of employing spray drying (SD) and spray freeze drying (SFD) to produce inhalable dry-powder form of drug-loaded lipid-polymer hybrid nanoparticles. Poly(lactic-co-glycolic acid), lecithin, and levofloxacin are employed as the polymer, lipid, and drug models, respectively. The hybrid nanoparticles are transformed into micro-scale nanoparticle aggregates (or nano-aggregates) via SD and SFD, where the effects of (1) different excipients (i.e. mannitol, polyvinyl alcohol (PVA), and leucine), and (2) nanoparticle to excipient ratio on nano-aggregate characteristics (e.g. size, flowability, aqueous reconstitution, aerosolization efficiency) are examined. In both methods, PVA is found more effective than mannitol for aqueous reconstitution, whereas hydrophobic leucineis needed to achieve effective aerosolization as it reduces nano-aggregate agglomeration. Using PVA, both methods are equally capable of producing nano-aggregates having size, density, flowability, yield and reconstitutibility in the range ideal for inhaled delivery. Nevertheless, nano-aggregates produced by SFD are superior to SD in terms of their aerosolization efficiency manifested in the higher emitted dose and fine particle fraction with lower mass median aerodynamic diameter.

  18. Aggregated Nanotransfersomal Dry Powder Inhalation of Itraconazole for Pulmonary Drug Delivery

    PubMed Central

    Hassanpour Aghdam, Mehdi; Ghanbarzadeh, Saeed; Javadzadeh, Yousef; Hamishehkar, Hamed

    2016-01-01

    Purpose: Local therapy is a valuable and strategic approach in the treatment of lung associated diseases and dry powder inhalation (DPI) formulations play the key role in this plan. Transfersome has been introduced as a novel biocompatible vesicular system with potential for administration in pulmonary drug delivery. The present study was designed to prepare Itraconazole-loaded nanotrantransfersomal DPI formulation. Methods: Itraconazole-loaded nanotransfersomes with three different types of surfactant in varying concentrations were prepared and characterized in the point of particle size distribution and morphology by laser light scattering and scanning electron microscopy (SEM) methods. The optimized transferosomal formulations were co-spray dried with mannitol and the aerosolization efficiency and aerodynamic properties of dry powders were determined by next generation impactor using a validated HPLC technique. Results: The volume mean diameter of optimized nanotransfersomal formulation with lecithin:Span® 60 in the ratio of 90:10 was 171 nm with narrow size distribution pattern which increased up to 518 nm after drug loading. Different types of surfactant did not influence the particle size significantly. SEM images confirmed the formation of aggregated nanoparticles in the suitable range (1-5 µm) for the pulmonary drug delivery. Aerosolization evaluation of co-spray dried formulations with different amounts of mannitol indicated that 2:1 ratio of mannitol:transfersome (w:w) showed the best aerosolization efficiency (fine particle fraction (FPF)=37%). Increasing of mannitol significantly decreased the FPF of the optimized formulations. Conclusion: The results of this study was introduced the potential application of nanotransfersomes in the formulation of DPIs for lung delivery of various drugs. PMID:27123418

  19. Development of liposomal salbutamol sulfate dry powder inhaler formulation.

    PubMed

    Huang, Wen-Hua; Yang, Zhi-Jun; Wu, Heng; Wong, Yuen-Fan; Zhao, Zhong-Zhen; Liu, Liang

    2010-01-01

    The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state.

  20. Quality characteristic of spray-drying egg white powders.

    PubMed

    Ma, Shuang; Zhao, Songning; Zhang, Yan; Yu, Yiding; Liu, Jingbo; Xu, Menglei

    2013-10-01

    Spray drying is a useful method for developing egg process and utilization. The objective of this study was to evaluate effects on spray drying condition of egg white. The optimized conditions were spraying flow 22 mL/min, feeding temperature 39.8 °C and inlet-air temperature 178.2 °C. Results of sulfydryl (SH) groups measurement indicated conformation structure have changed resulting in protein molecule occur S-S crosslinking phenomenon when heating. It led to free SH content decreased during spray drying process. There was almost no change of differential scanning calorimetry between fresh egg white and spray-drying egg white powder (EWP). For a given protein, the apparent SH reactivity is in turn influenced by the physico-chemical characteristics of the reactant. The phenomenon illustrated the thermal denaturation of these proteins was unrelated to their free SH contents. Color measurement was used to study browning level. EWP in optimized conditions revealed insignificant brown stain. Swelling capacity and scanning electron micrograph both proved well quality characteristic of spray-drying EWP. Results suggested spray drying under the optimized conditions present suitable and alternative method for egg processing industrial implementation. Egg food industrialization needs new drying method to extend shelf-life. The purpose of the study was to provide optimal process of healthy and nutritional instant spray-drying EWP and study quality characteristic of spray-drying EWP.

  1. Novel budesonide particles for dry powder inhalation (DPI) prepared using a microfluidic reactor coupled with ultrasonic spray freeze drying.

    PubMed

    Saboti, Denis; Maver, Uroš; Chan, Hak-Kim; Planinšek, Odon

    2017-03-09

    Budesonide is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers (MDI), nebulizers and dry powder inhalers (DPI). Inhalable drug particles are conventionally produced by crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations' stability. Other methods involve homogenization or precipitation and often require the use of stabilizers, mostly surfactants. The purpose of this study was therefore to develop a novel method for preparation of fine budesonide particles using a microfluidic reactor coupled with ultrasonic spray freeze drying, and hence avoiding the need of additional homogenization or stabilizer use. A T-junction microfluidic reactor was employed to produce particle suspension (using an ethanol-water, methanol-water and an acetone-water system), which was directly fed into an ultrasonic atomization probe, followed by direct feeding to liquid nitrogen. Freeze drying was the final preparation step. The result were fine crystalline budesonide powders which, when blended with lactose and dispersed in an Aerolizer at 100 L/min, generated fine particle fraction in the range 47.6±2.8% to 54.9±1.8%, thus exhibiting a good aerosol performance. Subsequent sample analysis confirmed the suitability of the developed method to produce inhalable drug particles without additional homogenization or stabilizers. The developed method provides a viable solution for particle isolation in microfluidics in general.

  2. Powder compression mechanics of spray-dried lactose nanocomposites.

    PubMed

    Hellrup, Joel; Nordström, Josefina; Mahlin, Denny

    2017-02-25

    The aim of this study was to investigate the structural impact of the nanofiller incorporation on the powder compression mechanics of spray-dried lactose. The lactose was co-spray-dried with three different nanofillers, that is, cellulose nanocrystals, sodium montmorillonite and fumed silica, which led to lower micron-sized nanocomposite particles with varying structure and morphology. The powder compression mechanics of the nanocomposites and physical mixtures of the neat spray-dried components were evaluated by a rational evaluation method with compression analysis as a tool, using the Kawakita equation and the Shapiro-Konopicky-Heckel equation. Particle rearrangement dominated the initial compression profiles due to the small particle size of the materials. The strong contribution of particle rearrangement in the materials with fumed silica continued throughout the whole compression profile, which prohibited an in-depth material characterization. However, the lactose/cellulose nanocrystals and the lactose/sodium montmorillonite nanocomposites demonstrated high yield pressure compared with the physical mixtures indicating increased particle hardness upon composite formation. This increase has likely to do with a reinforcement of the nanocomposite particles by skeleton formation of the nanoparticles. In summary, the rational evaluation of mechanical properties done by applying powder compression analysis proved to be a valuable tool for mechanical evaluation for this type of spray-dried composite materials, unless they demonstrate particle rearrangement throughout the whole compression profile.

  3. 30 CFR 75.1101-14 - Installation of dry powder chemical systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... fire-control components of each dry powder chemical system shall be a type approved by the Underwriters' Laboratories, Inc., or Factory Mutual Engineering Corp. (c) The components of each dry powder chemical system...

  4. Dry season aerosol iron solubility in tropical northern Australia

    NASA Astrophysics Data System (ADS)

    Winton, V. Holly L.; Edwards, Ross; Bowie, Andrew R.; Keywood, Melita; Williams, Alistair G.; Chambers, Scott D.; Selleck, Paul W.; Desservettaz, Maximilien; Mallet, Marc D.; Paton-Walsh, Clare

    2016-10-01

    Marine nitrogen fixation is co-limited by the supply of iron (Fe) and phosphorus in large regions of the global ocean. The deposition of soluble aerosol Fe can initiate nitrogen fixation and trigger toxic algal blooms in nitrate-poor tropical waters. We present dry season soluble Fe data from the Savannah Fires in the Early Dry Season (SAFIRED) campaign in northern Australia that reflects coincident dust and biomass burning sources of soluble aerosol Fe. The mean soluble and total aerosol Fe concentrations were 40 and 500 ng m-3 respectively. Our results show that while biomass burning species may not be a direct source of soluble Fe, biomass burning may substantially enhance the solubility of mineral dust. We observed fractional Fe solubility up to 12 % in mixed aerosols. Thus, Fe in dust may be more soluble in the tropics compared to higher latitudes due to higher concentrations of biomass-burning-derived reactive organic species in the atmosphere. In addition, biomass-burning-derived particles can act as a surface for aerosol Fe to bind during atmospheric transport and subsequently be released to the ocean upon deposition. As the aerosol loading is dominated by biomass burning emissions over the tropical waters in the dry season, additions of biomass-burning-derived soluble Fe could have harmful consequences for initiating nitrogen-fixing toxic algal blooms. Future research is required to quantify biomass-burning-derived particle sources of soluble Fe over tropical waters.

  5. A dry powder stump applicator for a feller-buncher.

    SciTech Connect

    Karsky, Richard, J.; Cram Michelle; Thistle, Harold

    1998-07-11

    Karsky, D., M. Cram, and H. Thistle. 1998. A dry powder borax stump applicator for a feller-buncher. Presented at the 1998 ASAE Annual International Meeting at Colorado Springs Resort, Orlando, Florida, July 11-16, 1998. Paper No. 987023. ASAE, 2950 Niles Road, St. Joseph, MI 49085-9659. Annosum root rot affects conifers throughout the Northern Hemisphere, infecting the roots and eventually killing the trees. An applicator attachment has been developed that mounts to the back of a feller-buncher saw head, that can reduce mortality from Heterobasidion annosum. The attachment applies a borax powder to a stump immediately after the tree has been cut. This document provides information on the design, development and testing of an applicator for applying dry borax on tree stumps at the time of harvesting to reduce future losses due to root rot.

  6. Towards the optimisation and adaptation of dry powder inhalers.

    PubMed

    Cui, Y; Schmalfuß, S; Zellnitz, S; Sommerfeld, M; Urbanetz, N

    2014-08-15

    Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. The goal of the project is the development of a drug powder detachment model to be used in numerical computations (CFD, computational fluid dynamics) of fluid flow and carrier particle motion through the inhaler and the resulting efficiency of drug delivery. This programme will be the basis for the optimisation of inhaler geometry and dry powder inhaler formulation. For this purpose a multi-scale approach is adopted. First the flow field through the inhaler is numerically calculated with OpenFOAM(®) and the flow stresses experienced by the carrier particles are recorded. This information is used for micro-scale simulations using the Lattice-Boltzmann method where only one carrier particle covered with drug powder is placed in cubic flow domain and exposed to the relevant flow situations, e.g. plug and shear flow with different Reynolds numbers. Therefrom the fluid forces on the drug particles are obtained. In order to allow the determination of the drug particle detachment possibility by lift-off, sliding or rolling, also measurements by AFM (atomic force microscope) were conducted for different carrier particle surface structures. The contact properties, such as van der Waals force, friction coefficient and adhesion surface energy were used to determine, from a force or moment balance (fluid forces versus contact forces), the detachment probability by the three mechanisms as a function of carrier particle Reynolds number. These results will be used for deriving the drug powder detachment model.

  7. 30 CFR 75.1101-20 - Safeguards for dry powder chemical systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Safeguards for dry powder chemical systems. 75...-20 Safeguards for dry powder chemical systems. Adequate guards shall be provided along all belt conveyors in the vicinity of each dry powder chemical system to protect persons whose vision is...

  8. 30 CFR 75.1101-20 - Safeguards for dry powder chemical systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Safeguards for dry powder chemical systems. 75...-20 Safeguards for dry powder chemical systems. Adequate guards shall be provided along all belt conveyors in the vicinity of each dry powder chemical system to protect persons whose vision is...

  9. 30 CFR 75.1101-20 - Safeguards for dry powder chemical systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Safeguards for dry powder chemical systems. 75...-20 Safeguards for dry powder chemical systems. Adequate guards shall be provided along all belt conveyors in the vicinity of each dry powder chemical system to protect persons whose vision is...

  10. 30 CFR 75.1101-17 - Sealing of dry powder chemical systems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Sealing of dry powder chemical systems. 75.1101-17 Section 75.1101-17 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-17 Sealing of dry powder chemical systems. Each dry powder chemical system shall be adequately...

  11. 30 CFR 75.1101-17 - Sealing of dry powder chemical systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Sealing of dry powder chemical systems. 75.1101-17 Section 75.1101-17 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-17 Sealing of dry powder chemical systems. Each dry powder chemical system shall be adequately...

  12. 30 CFR 75.1101-17 - Sealing of dry powder chemical systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Sealing of dry powder chemical systems. 75.1101-17 Section 75.1101-17 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-17 Sealing of dry powder chemical systems. Each dry powder chemical system shall be adequately...

  13. 30 CFR 75.1101-17 - Sealing of dry powder chemical systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Sealing of dry powder chemical systems. 75.1101-17 Section 75.1101-17 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-17 Sealing of dry powder chemical systems. Each dry powder chemical system shall be adequately...

  14. 30 CFR 75.1101-13 - Dry powder chemical systems; general.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Dry powder chemical systems; general. 75.1101-13 Section 75.1101-13 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-13 Dry powder chemical systems; general. Self-contained dry powder chemical systems may be...

  15. 30 CFR 75.1101-20 - Safeguards for dry powder chemical systems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Safeguards for dry powder chemical systems. 75...-20 Safeguards for dry powder chemical systems. Adequate guards shall be provided along all belt conveyors in the vicinity of each dry powder chemical system to protect persons whose vision is...

  16. 30 CFR 75.1101-13 - Dry powder chemical systems; general.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Dry powder chemical systems; general. 75.1101-13 Section 75.1101-13 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-13 Dry powder chemical systems; general. Self-contained dry powder chemical systems may be...

  17. 30 CFR 75.1101-15 - Construction of dry powder chemical systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Construction of dry powder chemical systems. 75.1101-15 Section 75.1101-15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-15 Construction of dry powder chemical systems. (a) Each self-contained dry powder system shall...

  18. 30 CFR 75.1101-15 - Construction of dry powder chemical systems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Construction of dry powder chemical systems. 75.1101-15 Section 75.1101-15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-15 Construction of dry powder chemical systems. (a) Each self-contained dry powder system shall...

  19. 30 CFR 75.1101-13 - Dry powder chemical systems; general.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Dry powder chemical systems; general. 75.1101-13 Section 75.1101-13 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-13 Dry powder chemical systems; general. Self-contained dry powder chemical systems may be...

  20. 30 CFR 75.1101-13 - Dry powder chemical systems; general.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-13 Dry powder chemical systems; general. Self-contained dry powder chemical systems may be installed to protect main and secondary belt conveyor drives, however, where such systems are employed, they... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Dry powder chemical systems; general. 75.1101...

  1. 30 CFR 75.1101-13 - Dry powder chemical systems; general.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-13 Dry powder chemical systems; general. Self-contained dry powder chemical systems may be installed to protect main and secondary belt conveyor drives, however, where such systems are employed, they... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Dry powder chemical systems; general. 75.1101...

  2. 30 CFR 75.1101-22 - Inspection of dry powder chemical systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Inspection of dry powder chemical systems. 75...-22 Inspection of dry powder chemical systems. (a) Each dry powder chemical system shall be examined weekly and a functional test of the complete system shall be conducted at least once each year. (b)...

  3. 30 CFR 75.1101-22 - Inspection of dry powder chemical systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Inspection of dry powder chemical systems. 75...-22 Inspection of dry powder chemical systems. (a) Each dry powder chemical system shall be examined weekly and a functional test of the complete system shall be conducted at least once each year. (b)...

  4. 30 CFR 75.1101-22 - Inspection of dry powder chemical systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Inspection of dry powder chemical systems. 75...-22 Inspection of dry powder chemical systems. (a) Each dry powder chemical system shall be examined weekly and a functional test of the complete system shall be conducted at least once each year. (b)...

  5. 30 CFR 75.1101-22 - Inspection of dry powder chemical systems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Inspection of dry powder chemical systems. 75...-22 Inspection of dry powder chemical systems. (a) Each dry powder chemical system shall be examined weekly and a functional test of the complete system shall be conducted at least once each year. (b)...

  6. Crystal coating via spray drying to improve powder tabletability.

    PubMed

    Vanhoorne, V; Peeters, E; Van Snick, B; Remon, J P; Vervaet, C

    2014-11-01

    A continuous crystal coating method was developed to improve both flowability and tabletability of powders. The method includes the introduction of solid, dry particles into an atomized spray during spray drying in order to coat and agglomerate individual particles. Paracetamol was used as a model drug as it exhibits poor flowability and high capping tendency upon compaction. The particle size enlargement and flowability were evaluated by the mean median particle size and flow index of the resulting powders. The crystal coating coprocessing method was successful for the production of powders containing 75% paracetamol with excellent tableting properties. However, the extent of agglomeration achieved during coprocessing was limited. Tablets compressed on a rotary tablet press in manual mode showed excellent compression properties without capping tendency. A formulation with 75% paracetamol, 5% PVP and 20% amorphous lactose yielded a tensile strength of 1.9 MPa at a compression pressure of 288 MPa. The friability of tablets compressed at 188 MPa was only 0.6%. The excellent tabletability of this formulation was attributed to the coating of paracetamol crystals with amorphous lactose and PVP through coprocessing and the presence of brittle and plastic components in the formulation. The coprocessing method was also successfully applied for the production of directly compressible lactose showing improved tensile strength and friability in comparison to a spray dried direct compression lactose grade.

  7. Inhaled powder formulation of naked siRNA using spray drying technology with l-leucine as dispersion enhancer.

    PubMed

    Chow, Michael Y T; Qiu, Yingshan; Lo, Fiona F K; Lin, Hinson H S; Chan, Hak-Kim; Kwok, Philip C L; Lam, Jenny K W

    2017-09-15

    Pulmonary delivery of short interfering RNA (siRNA) has been widely studied in both animal and clinical studies to treat various respiratory diseases by gene silencing through RNA interference. Some of these studies showed that the administration of naked siRNA (without the use of any delivery vectors) could achieve satisfactory gene silencing effect, a unique feature to pulmonary delivery. Liquid aerosols were mostly used with very limited studies on the use of powder aerosols for siRNA. In this study, siRNA was co-spray dried with mannitol and l-leucine, the latter being a dispersion enhancer. To the best of our knowledge, this is the first time that siRNA in its naked form was formulated into an inhalable dry powder using spray drying technology. The aerosol performance of the powder was evaluated by Next Generation Impactor (NGI). The presence of l-leucine in the formulation could improve the aerosolization of siRNA-containing powders. Results from the X-ray photoelectron spectroscopy (XPS) suggested that l-leucine was enriched on the particle surface and promote powder dispersion. Among the different siRNA formulations being examined, the one that contained 50% w/w of l-leucine exhibited the best aerodynamic performance, with a high emitted fraction (EF) of around 80% and a modest fine particle fraction (FPF) of 45%. Importantly, the integrity of siRNA was successfully retained as evaluated by gel retardation assay and high performance liquid chromatography (HPLC). Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Dry Powder Formulation of Plasmid DNA and siRNA for Inhalation.

    PubMed

    Chow, Michael Y T; Lam, Jenny K W

    2015-01-01

    Nucleic acid therapeutics has huge potential for the treatment of a wide range of diseases including respiratory diseases. Plasmid DNA (pDNA) and small interfering RNA (siRNA) are the two most widely investigated nucleic acids for therapeutic development. However, efficient and safe delivery of nucleic acids is still a major hurdle in translating nucleic acid therapy into clinical practice. For the treatment of respiratory diseases, administration via inhalation is the most direct and effective way to deliver therapeutic nucleic acids to the lungs. Although liquid aerosol formulation is investigated in most of the studies, it is not desirable in terms of maintaining the stability of nucleic acid especially during long-term storage. This problem could be circumvented by formulating the therapeutic nucleic acids into dry powder for inhalation, and should be considered as the future direction of developing inhalable nucleic acids. In this review, the three major particle engineering methods investigated for the preparation of inhalable pDNA and siRNA formulations, including spray drying (SD), spray freeze drying (SFD) and supercritical fluid (SFC) drying, are discussed and compared. Moreover, common assessment methods and the challenges of evaluating the biological activities of inhalable nucleic acid powders are also reviewed.

  9. Stable Dry Powder Formulation for Nasal Delivery of Anthrax Vaccine

    PubMed Central

    Wang, Sheena H.; Kirwan, Shaun M.; Abraham, Soman N.; Staats, Herman F.; Hickey, Anthony J.

    2013-01-01

    There is a current biodefense interest in protection against Anthrax. Here we developed a new generation of stable and effective anthrax vaccine. We studied the immune response elicited by rPA delivered intranasally with a novel mucosal adjuvant, a mast cell activator Compound 48/80. The vaccine formulation was prepared in a powder form by spray-freeze-drying (SFD) under optimized conditions to produce particles with a target size of D50=25μm, suitable for delivery to the rabbit nasal cavity. Physicochemical properties of the powder vaccines were characterized to assess their delivery and storage potential. Structural stability of rPA was confirmed by CD and ATR-FTIR, while functional stability of rPA and C48/80 was monitored by cell-based assays. Animal study was performed using a unitdose powder device for direct nasal application. Results showed that C48/80 provided effective mucosal adjuvant activity in rabbits. Freshly prepared SFD powder vaccine formulations or powders stored for over two years at room temperature elicited significantly elevated serum PA-specific and lethal toxin neutralization antibody titers that were comparable to that induced by IM immunization with rPA. Nasal delivery of this vaccine formulation may be a viable alternative to the currently licensed vaccine, or an attractive vaccine platform for other mucosally transmitted diseases. PMID:21905034

  10. Aerodynamic properties, solubility and in vitro antibacterial efficacy of dry powders prepared by spray drying: Clarithromycin versus its hydrochloride salt.

    PubMed

    Manniello, Michele Dario; Del Gaudio, Pasquale; Porta, Amalia; Aquino, Rita Patrizia; Russo, Paola

    2016-07-01

    Antibiotic therapy for a direct administration to the lung in cystic fibrosis patients has to provide suitable availability, possibly in the lower respiratory tract, characterized by the presence of thick secretions. One of the crucial steps in the therapeutic management of the respiratory disease could be the drug solubilization directly in this site of action. The aim of the study was to prepare respirable powders of clarithromycin, while improving drug aqueous solubility. With this aim, several batches of micronized particles were prepared by spray drying different feed solutions, varying the solvent composition (water/isopropyl alcohol ratio), the drug concentration and pH of the liquid feeds. Particle size distribution of raw materials and engineered particles was determined using a light-scattering laser granulometer while particle morphology was assessed by scanning electron microscopy. The in vitro deposition of the micronized clarithromycin powders was evaluated by means of a Single-Stage Glass Impinger using the RS01 model7 by Plastiape® as device for the aerosolization. Solubility measurements of raw and spray-dried (SD) drug were carried out at 37°C in phosphate buffer (0.05M, pH 6.8). Results indicate that morphology and aerodynamic properties of SD particles were strongly influenced by organic solvent concentration and pH of the liquid feeds processed, both modifying drug solubility. Spherical particles and crystals were obtained at higher pH and lower organic solvent content, while wrinkled particles with very interesting aerodynamic properties and higher drug solubility were obtained at lower pH values. Thanks to a fine tuning of the process parameters and liquid feed composition, we produced SD powders with good aerodynamic properties, without using any excipients. Furthermore, SD powders of clarithromycin hydrochloric salt showed higher activity against Pseudomonas aeruginosa growth, compared to clarithromycin raw material. Copyright © 2016

  11. Powder Aerosol Delivery through Nasal High-flow System: In Vitro Feasibility and Influence of Process Conditions.

    PubMed

    Okuda, Tomoyuki; Tang, Patricia; Yu, Jiaqi; Finlay, Warren H; Chan, Hak-Kim

    2017-08-19

    We aimed to obtain fundamental information for potential pulmonary delivery of powder aerosols using a clinically-approved nasal high-flow system (AIRVO), with spray-dried mannitol (SD-Man) being a model powder. Compressed air exiting the AIRVO at set 'dispersion' air flow rates dispersed SD-Man loaded in an Osmohaler(®) into a human nasal airway replica (NAR) coupled downstream to a Next Generation Impactor (NGI) running at specific 'inspiratory' flow rates. Increasing the dispersion flow rate from 30 to 60L/min increased powder deposition in the NAR from 50 to 70% of the emitted dose, while decreased the NGI deposition from 50 to 30% of the emitted dose. The inspiratory flow rate did not affect powder deposition in the NAR and NGI. In contrast, as the inspiratory flow rate was increased from 15 to 40L/min, powder recovery, emitted fraction, and fine particle fraction below 5μm (as aerosol performance indices) were increased from 90, 30 and 5% to 97, 45 and 8% of the loaded dose, respectively. The dispersion flow rate did not change the performance indices. Importantly, heating and humidification of dispersion airflow, loaded doses, and nasal cannula sizes did not greatly affect the aerosol characteristics. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo-controlled, crossover study

    PubMed Central

    Houghton, C M; Langley, S J; Singh, S D; Holden, J; Monici Preti, A P; Acerbi, D; Poli, G; Woodcock, A

    2004-01-01

    Background In response to the phasing out of chlorofluorocarbon (CFC) inhalers, a metered dose hydrofluoroalkane (HFA) formulation, Modulite (Chiesi Farmaceutici S.p.A, Parma, Italy), to be delivered with a pressurized metered dose inhaler (pMDI), has been developed. Modulite is a HFA formulation technology that has been designed to provide stable and uniform dose delivery of HFA-based formulations to enable an easy transition from CFC to HFA inhalers. Objectives The aim of this study was to compare the bronchoprotective and bronchodilator effects of a single dose of 12 µg of formoterol from the HFA Modulite inhaler with the Foradil Aerolizer (dry powder inhaler, DPI) and the Foradil CFC inhalers (Novartis Health Consumer, Basel, Switzerland). Methods This was a double blind, double dummy, randomized, placebo-controlled, crossover study conducted in 38 subjects with mild to moderate asthma (mean forced expiratory volume in 1 s [FEV1] 87.5% predicted). The primary endpoint was methacholine challenge provocative dose required for 20% fall in the FEV1 (PD20) 90 min post dose. Bronchodilation was assessed with spirometry (FEV1, FVC, FEF25–75) and impulse oscillometry (resistance at 5 and 20 Hz, reactance at 5 Hz and resonant frequency) over the 90 min post dose. In a subset of 12 subjects formoterol plasma levels, serum potassium and glucose were determined up to 480 min post dose. Results The three formoterol formulations demonstrated significant (P ≤ 0.05) improvements in bronchoprotection compared to placebo and non-inferiority of the HFA preparation compared to the CFC and DPI preparations was demonstrated. Geometric mean PD20 values were 0.51 mg with HFA, 0.62 mg with DPI, 0.62 mg with CFC and 0.2 mg with placebo. The log transformed mean differences in PD20 doubling dose between HFA and (a) DPI was −0.28 (95% CI −0.84–0.29, P = 0.57) (b) CFC was −0.28 (95% CI −0.84–0.28, P = 0.57) and (c) placebo was 1.38 (95% CI 0.82–1.94, P < 0.001). Serum

  13. Designing CAF-adjuvanted dry powder vaccines: spray drying preserves the adjuvant activity of CAF01.

    PubMed

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Mørck; Yang, Mingshi; Foged, Camilla

    2013-05-10

    Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations.

  14. Preparation and characterization of spray-dried inhalable powders containing nanoaggregates for pulmonary delivery of anti-tubercular drugs.

    PubMed

    Kaur, Ranjot; Garg, Tarun; Das Gupta, Umesh; Gupta, Pushpa; Rath, Goutam; Goyal, Amit Kumar

    2016-01-01

    This study aims to prepare spray-dried inhalable powders containing anti-tubercular drugs-loaded HPMC nanoaggregates for sustained delivery of drugs to the lung. Nanoaggregates were prepared by precipitation technique. Results showed that the powders obtained had excellent aerosolization property. High drug encapsulation efficiency was achieved in HPMC nano aggregates, ranging from 60% to 70%. A single pulmonary dose resulted in therapeutic drug concentrations 40% to 60% in the lungs and in other organs (< 5%) for 24 h. From this study, we can conclude that delivering drugs through pulmonary route is advantageous for local action in lungs.

  15. Effect of ethanol as a co-solvent on the aerosol performance and stability of spray-dried lysozyme.

    PubMed

    Ji, Shuying; Thulstrup, Peter Waaben; Mu, Huiling; Hansen, Steen Honoré; van de Weert, Marco; Rantanen, Jukka; Yang, Mingshi

    2016-11-20

    In the spray drying process, organic solvents can be added to facilitate drying, accommodate certain functional excipients, and modify the final particle characteristics. In this study, lysozyme was used as a model pharmaceutical protein to study the effect of ethanol as a co-solvent on the stability and aerosol performance of spray-dried protein. Lysozyme was dissolved in solutions with various ratios of ethanol and water, and subsequently spray-dried. A change from spherical particles into wrinkled and folded particles was observed upon increasing the ratio of ethanol in the feed. The aerosol performance of the spray-dried lysozyme from ethanol-water solution was improved compared to that from pure water. The conformation of lysozyme in the ethanol-water solution and spray dried powder was altered, but the native structure of lysozyme was restored upon reconstitution in water after the spray drying process. The enzymatic activities of the spray-dried lysozyme showed no significant impact of ethanol; however, the lysozyme enzymatic activity was ca. 25% lower compared to the starting material. In conclusion, the addition of ethanol as a co-solvent in the spray drying feed for lysozyme did not compromise the conformation of the protein after drying, while it improved the inhaled aerosol performance. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Soil amendement by green supplement : Dry cowdung powder

    NASA Astrophysics Data System (ADS)

    Barot, N.; Bagla, H.

    2009-04-01

    Soil is a heavenly resource, a living, breathing and ever changing dynamic ecosystem. Retrogression and degradation of soil system is the result of continuous encroachment done by global anthropogenic activities. Mother earth's monition has increased the local concern to explore solution for the healthy sustainability of soil. At this hour of need it is crucial to regain the health of soil by utilizing eco-friendly solution and the promising one is Dry Cow Dung powder. Cow Dung is bio- organic, complex, polymorphic fecal matter of the bovine species, enriched with ‘Humic acid' (HA), ‘Fulvic Acid' etc. The HA in Cow Dung has been extracted using Neutralization Reaction and its presence is confirmed by comparing it with FTIR spectra of Std HA (IHSS). Property of metal ion adsorption of Standard and Extracted HA has been confirmed using ‘Tracer Technique'. Cow Dung is renewable, easy and freely available with least contaminants as the process of Humification takes place during drying stage hence speciation of any type is not required due to its Biological matrix. Any pre or post conditioning of cow dung powder is not required reducing undesired chemical sink in milieu. It will surely contribute in closing the natural nutrient cycle and increase the fertility as well as carbon pool of soil due to abundance of useful microflora. If compared to present day usage of synthetic and semi- synthetic products, employing Dry Cow Dung powder as agrarian booster will be surely a Green solution! It's rightly said that "The nation which destroys its soil, destroys itself!", hence we need to pursue instant remedies to mitigate our self destruction because healthy soil is the only life line for Survival!

  17. Soil Amendement by green supplement: dry cowdung powder

    NASA Astrophysics Data System (ADS)

    Barot, N. S.; Bagla, H.

    2009-04-01

    Soil is a heavenly resource, a living, breathing and ever changing dynamic ecosystem. Retrogression and degradation of soil system is the result of continuous encroachment done by global anthropogenic activities. Mother earth's monition has increased the local concern to explore solution for the healthy sustainability of soil. At this hour of need it is crucial to regain the health of soil by utilizing eco-friendly solution and the promising one is Dry Cow Dung powder. Cow Dung is bio- organic, complex, polymorphic fecal matter of the bovine species, enriched with ‘Humic acid' (HA), ‘Fulvic Acid' etc. The HA in Cow Dung has been extracted using Neutralization Reaction and its presence is confirmed by comparing it with FTIR spectra of Std HA (IHSS). Property of metal ion adsorption of Standard and Extracted HA has been confirmed using ‘Tracer Technique'. Cow Dung is renewable, easy and freely available with least contaminants as the process of Humification takes place during drying stage hence speciation of any type is not required due to its Biological matrix. Any pre or post conditioning of cow dung powder is not required reducing undesired chemical sink in milieu. It will surely contribute in closing the natural nutrient cycle and increase the fertility as well as carbon pool of soil due to abundance of useful microflora. If compared to present day usage of synthetic and semi- synthetic products, employing Dry Cow Dung powder as agrarian booster will be surely a Green solution! It's rightly said that "The nation which destroys its soil, destroys itself!", hence we need to pursue instant remedies to mitigate our self destruction because healthy soil is the only life line for Survival!

  18. A novel continuous powder aerosolizer (CPA) for inhalative administration of highly concentrated recombinant surfactant protein-C (rSP-C) surfactant to preterm neonates.

    PubMed

    Pohlmann, G; Iwatschenko, P; Koch, W; Windt, H; Rast, M; de Abreu, M Gama; Taut, F J H; De Muynck, C

    2013-12-01

    In pulmonary medicine, aerosolization of substances for continuous inhalation is confined to different classes of nebulizers with their inherent limitations. Among the unmet medical needs is the lack of an aerosolized surfactant preparation for inhalation by preterm neonates, to avoid the risks associated with endotracheal intubation and surfactant bolus instillation. In the present report, we describe a high-concentration continuous powder aerosolization system developed for delivery of inhalable surfactant to preterm neonates. The developed device uses a technique that allows efficient aerosolization of dry surfactant powder, generating a surfactant aerosol of high concentration. In a subsequent humidification step, the heated aerosol particles are covered with a surface layer of water. The wet surfactant aerosol is then delivered to the patient interface (e.g., nasal prongs) through a tube. The performance characteristics of the system are given as mass concentration, dose rate, and size distribution of the generated aerosol. Continuous aerosol flows of about 0.84 L/min can be generated from dry recombinant surfactant protein-C surfactant, with concentrations of up to 12 g/m(3) and median particle sizes of the humidified particles in the range of 3 to 3.5 μm at the patient interface. The system has been successfully used in preclinical studies. The device with its continuous high-concentration delivery is promising for noninvasive delivery of surfactant aerosol to neonates and has the potential for becoming a versatile disperser platform closing the gap between continuously operating nebulizers and discontinuously operating dry powder inhaler devices.

  19. 30 CFR 75.1101-20 - Safeguards for dry powder chemical systems.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-20 Safeguards for dry powder chemical systems. Adequate guards shall be provided along all belt conveyors in the vicinity of each dry powder chemical system to protect persons whose vision is restricted... provide assistance to those passing along the conveyor after a powder discharge. ...

  20. Development and Comparison of New High Efficiency Dry Powder Inhalers for Carrier-Free Formulations

    PubMed Central

    Behara, Srinivas R.B.; Longest, P. Worth; Farkas, Dale R.; Hindle, Michael

    2013-01-01

    High efficiency dry powder inhalers (DPIs) were developed and tested for use with carrier-free formulations across a range of different inhalation flow rates. Performance of a previously reported DPI was compared with two new designs in terms of emitted dose (ED) and aerosolization characteristics using in vitro experiments. The two new designs oriented the capsule chamber (CC) at different angles to the main flow passage, which contained a 3D rod array for aerosol deaggregation. Computational fluid dynamics simulations of a previously developed deaggregation parameter, the NDSD, were used to explain device performance. Orienting the CC at 90° to the mouthpiece, the CC90-3D inhaler provided the best performance with an ED=73.4%, fine particle fractions (FPF) less than 5µm and 1µm of 95.1% and 31.4%, respectively, and a MMAD=1.5µm. For the carrier-free formulation, deaggregation was primarily influenced by capsule aperture position and the NDSD parameter. The new CC-3D inhalers reduced the percent difference in FPF and MMAD between low and high flows by 1–2 orders of magnitude compared with current commercial devices. In conclusion, the new CC-3D inhalers produced extremely high quality aerosols with little sensitivity to flow rate and are expected to deliver approximately 95% of the ED to the lungs. PMID:24307605

  1. Murine pharmacokinetics of rifapentine delivered as an inhalable dry powder.

    PubMed

    Chan, John G Y; Tyne, Anneliese S; Pang, Angel; McLachlan, Andrew J; Perera, Vidya; Chan, Joseph C Y; Britton, Warwick J; Chan, Hak Kim; Duke, Colin C; Young, Paul M; Traini, Daniela

    2015-03-01

    A novel inhalable rifapentine dry powder formulation could improve pulmonary rifapentine concentrations resulting in a significantly shorter time to treat tuberculosis infection. The pharmacokinetics of rifapentine (20mg/kg) in healthy mice was compared following intratracheal (IT) and intraperitoneal (IP) administration. Plasma, bronchoalveolar lavage (BAL) and tissue samples were collected and drug levels were quantified at time points up to 24h. Concentration-time data were analysed using a mixed-effects modelling approach to provide model-based estimates of area under the concentration-time curve from time 0 to infinity (AUC0-∞). IT delivery had considerably higher peak rifapentine lung and BAL concentrations and associated AUC0-∞ compared with IP delivery. The plasma AUC0-∞ following IT dry powder delivery was ca. four-fold smaller than the value for IP delivery. Inhaled delivery of rifapentine has the potential to selectively enhance therapeutic efficacy at the pulmonary site of infection whilst minimising systemic exposure and related toxicity.

  2. A method for the aerodynamic design of dry powder inhalers.

    PubMed

    Ertunç, O; Köksoy, C; Wachtel, H; Delgado, A

    2011-09-15

    An inhaler design methodology was developed and then used to design a new dry powder inhaler (DPI) which aimed to fulfill two main performance requirements. The first requirement was that the patient should be able to completely empty the dry powder from the blister in which it is stored by inspiratory effort alone. The second requirement was that the flow resistance of the inhaler should be geared to optimum patient comfort. The emptying of a blister is a two-phase flow problem, whilst the adjustment of the flow resistance is an aerodynamic design problem. The core of the method comprised visualization of fluid and particle flow in upscaled prototypes operated in water. The prototypes and particles were upscaled so that dynamic similarity conditions were approximated as closely as possible. The initial step in the design method was to characterize different blister prototypes by measurements of their flow resistance and particle emptying performance. The blisters were then compared with regard to their aerodynamic performance and their ease of production. Following selection of candidate blisters, the other components such as needle, bypass and mouthpiece were dimensioned on the basis of node-loop operations and validation experiments. The final shape of the inhaler was achieved by experimental iteration. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Synergistic combination dry powders for inhaled antimicrobial therapy

    NASA Astrophysics Data System (ADS)

    Heng, Desmond; Lee, Sie Huey; Teo, Jeanette; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B. H.

    2013-06-01

    Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.

  4. Physicochemical characterization and stability of rifampicin liposome dry powder formulations for inhalation.

    PubMed

    Changsan, Narumon; Chan, Hak-Kim; Separovic, Frances; Srichana, Teerapol

    2009-02-01

    Liposomes were used to encapsulate rifampicin (RIF) as an alternative formulation for delivery to the respiratory tract. Factors affecting the stability of liposomes containing RIF were determined. Four liposome suspensions were prepared, containing different millimole ratios of cholesterol (CH) and soybean L-infinity-phosphatidylcholine (SPC) by the chloroform film method, followed by freeze-drying. Cryo-transmission electron microscopy, photon correlation spectroscopy, (2)H and (31)P solid-state nuclear magnetic resonance were used to characterize the liposome suspensions. Differential scanning calorimetry and X-ray diffraction were used to examine the properties of the powder formulations. The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. The liposomes were a mixture of 200-300 nm unilamellar and multilamellar vesicles. Higher CH content in the liposome formulation resulted in a smaller change in size distribution with time, and higher CH content was associated with an increase in the (2)H NMR splitting, indicative of an increase in order of the lipid acyl chains. Furthermore, the SS-NMR results indicated that RIF was located between the acyl chains of the phospholipid bilayer and associated with CH molecules. Fifty percent encapsulation of RIF was obtained when the lipid content was high (SPC 10 mM: CH 10 mM). Mannitol was found to be a suitable cryoprotectant, which is attributed to its crystallinity, and use of mannitol gave particles with a mass median aerodynamic diameter of less than 5 microm. In terms of chemical stability, RIF in dry powder formulations was considerably more stable when compared to RIF aqueous solutions and RIF liposomal suspensions.

  5. Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

    PubMed Central

    Bauer, K G; Kaik, B; Sertl, K; Kaik, G A

    1993-01-01

    1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI. PMID:12959305

  6. Aerosol dry deposition on canopies of plane obstacles

    NASA Astrophysics Data System (ADS)

    Petroff, A.; Zhang, L.

    2007-12-01

    A new model to describe aerosol transport and dry deposition on vegetative canopies has been proposed recently by Petroff et al. and applied to canopies of cylindrical obstacles such as coniferous forest (Petroff et al., 2007, Aerosol dry deposition on vegetative canopies. Part II: A new modeling approach and applications, submitted to Atmospheric Environment). In the present study, the approach is extended to canopies of plane obstacles such as grass, crop or broadleaf forest. The model takes into account the characteristics of the canopy, the aerosol and the aerodynamics. Deposition terms are modeled following an up-scaling procedure, which is based on the knowledge of collection dynamics on each individual obstacle and on the statistical distribution of these collecting elements. The statistical description applies to geometrical properties such as leaf characteristic length and orientation. Deposition mechanisms considered in this model include Brownian diffusion, interception, inertial impaction, turbulent impaction and gravitational settling. For interception, no adequate parameterisation is available in the literature to describe the collection on individual obstacle. Thus, an original parameterisation is derived for plane obstacle and is based on potential flow theory. Aerosol transport is described in a mono-dimensional configuration and neutral stratification of the atmosphere is assumed. Preliminary results indicate that the present model agrees with existing measurements data obtained both in wind-tunnel and on site.

  7. Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.

    PubMed

    Muddle, Joanna; Kirton, Stewart B; Parisini, Irene; Muddle, Andrew; Murnane, Darragh; Ali, Jogoth; Brown, Marc; Page, Clive; Forbes, Ben

    2017-01-01

    Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r(2) values ranged between 0.46 and 0.90 and the secondary OA increased the r(2) values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r(2) 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs.

  8. A STUDY OF INSPIRATORY RESISTANCE OF DRY POWDER INHALER OF AGENTS FOR ASTHMA CONTROL.

    PubMed

    Suda, Shigeaki; Konno, Rio; Kurosawa, Hajime; Tamura, Gen

    2016-07-01

    Because dry powder inhalers (DPI) aerosolize agents by means of inspiration of patients themselves, inspiratory resistance of DPI is an important factor for increasing inhalation efficiency. Therefore, we measured inspiratory resistance of DPI of agents for asthma control. Using Flow/Volume Simulator, when setting flow rates at 6, 30, 60, 90, and 120L/min, we read off suction pressures and find inspiratory resistances by calculation (=suction pressure/flow rate) at each flow rate. In all DPI, inspiratory resistance increases with the increasing flow rate. To maintain flow rate of 60L/min, suction pressure of around 20-cmH2O for Diskus(®) and Ellipta(®), between 35- and 45-cmH2O for Turbuhaler (®), and about 60-cmH2O for Twisthaler(®) were needed. It is suggested that we should instruct patients to inhaler DPI based on inspiratory resistance of the DPI.

  9. Estimating aerosol light-scattering enhancement from dry aerosol optical properties at different sites

    NASA Astrophysics Data System (ADS)

    Titos, Gloria; Jefferson, Anne; Sheridan, Patrick; Andrews, Elisabeth; Lyamani, Hassan; Ogren, John; Alados-Arboledas, Lucas

    2014-05-01

    Microphysical and optical properties of aerosol particles are strongly dependent on the relative humidity (RH). Knowledge of the effect of RH on aerosol optical properties is of great importance for climate forcing calculations and for comparison of in-situ measurements with satellite and remote sensing retrievals. The scattering enhancement factor, f(RH), is defined as the ratio of the scattering coefficient at a high and reference RH. Predictive capability of f(RH) for use in climate models would be enhanced if other aerosol parameters could be used as proxies to estimate hygroscopic growth. Toward this goal, we explore the relationship between aerosol light-scattering enhancement and dry aerosol optical properties such as the single scattering albedo (SSA) and the scattering Ångström exponent (SAE) at multiple sites around the world. The measurements used in this study were conducted by the US Department of Energy at sites where different aerosol types predominate (pristine marine, polluted marine, dust dominated, agricultural and forest environments, among others). In all cases, the scattering enhancement decreases as the SSA decreases, that is, as the contribution of absorbing particles increases. On the other hand, for marine influenced environments the scattering enhancement clearly increases as the contribution of coarse particles increases (SAE decreases), evidence of the influence of hygroscopic coarse sea salt particles. For other aerosol types the relationship between f(RH) and SAE is not so straightforward. Combining all datasets, f(RH) was found to exponentially increase with SSA with a high correlation coefficient.

  10. Effect of drying parameters on physiochemical and sensory properties of fruit powders processed by PGSS-, Vacuum- and Spray-drying.

    PubMed

    Feguš, Urban; Žigon, Uroš; Petermann, Marcus; Knez, Željko

    2015-01-01

    Aim of this experimental work was to investigate the possibility of producing fruit powders without employing drying aid and to investigate the effect of drying temperatures on the final powder characteristics. Raw fruit materials (banana puree, strawberry puree and blueberry concentrate) were processed using three different drying techniques each operating at a different temperature conditions: vacuum-drying (-27-17 °C), Spray-drying (130-160 °C) and PGSS-drying (112-152 °C). Moisture content, total colour difference, antioxidant activity and sensory characteristics of the processed fruit powders were analysed. The results obtained from the experimental work indicate that investigated fruit powders without or with minimal addition of maltodextrin can be produced. Additionally, it was observed that an increase in process temperature results in a higher loss of colour, antioxidant activity and intensity of the flavour profile.

  11. Dry powder inhalation of antibiotics in cystic fibrosis therapy: part 2. Inhalation of a novel colistin dry powder formulation: a feasibility study in healthy volunteers and patients.

    PubMed

    Le Brun, P P H; de Boer, A H; Mannes, G P M; de Fraîture, D M I; Brimicombe, R W; Touw, D J; Vinks, A A; Frijlink, H W; Heijerman, H G M

    2002-07-01

    The aim of the present study was to perform a proof of principle study with a new colistin dry powder inhalation system in six healthy volunteers and five patients with cystic fibrosis. All subjects were asked to inhale 25 mg colistin sulfate dry powder. The patients were also asked to nebulize 160 mg colistin sulfomethate as a solution. Colistin serum concentrations were determined as an indirect parameter to compare both forms of administration. Pulmonary function tests were performed. Peak serum colistin concentrations ranged from 14 to 59 microg/l in volunteers after inhalation of 25 mg as dry powder. In patients, peak concentrations ranged from 18 to 64 microg/l after nebulization of 160 mg colistin sulfomethate solution and from 77 to 159 microg/l after inhalation of 25 mg colistin sulfate dry powder. Pulmonary function tests were not significantly different after inhalation of the dry powder by the volunteers nor after nebulization of the solution by the patients. In some patients a decrease in pulmonary function and moderate to severe cough was observed after inhalation of the dry powder. The new colistin inhaler provides an attractive alternative for nebulized colistin and was highly appreciated by the patients. The decrease in pulmonary function and cough in patients is a drawback, which may be overcome by dose reduction and a further improvement of the new dosage form.

  12. Development of a microparticle-based dry powder inhalation formulation of ciprofloxacin hydrochloride applying the quality by design approach.

    PubMed

    Karimi, Keyhaneh; Pallagi, Edina; Szabó-Révész, Piroska; Csóka, Ildikó; Ambrus, Rita

    2016-01-01

    Pulmonary drug delivery of ciprofloxacin hydrochloride offers effective local antibacterial activity and convenience of easy application. Spray drying is a trustworthy technique for the production of ciprofloxacin hydrochloride microparticles. Quality by design (QbD), an up-to-date regulatory-based quality management method, was used to predict the final quality of the product. According to the QbD-based theoretical preliminary parameter ranking and priority classification, dry powder inhalation formulation tests were successfully performed in practice. When focusing on the critical parameters, the practical development was more effective and was in correlation with our previous findings. Spray drying produced spherical microparticles. The dry powder formulations prepared were examined by particle size analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro drug release and aerodynamic particle size analyses were also performed. These formulations showed an appropriate particle size ranging between 2 and 4 μm and displayed an enhanced aerosol performance with fine particle fraction up to 80%.

  13. Development of a microparticle-based dry powder inhalation formulation of ciprofloxacin hydrochloride applying the quality by design approach

    PubMed Central

    Karimi, Keyhaneh; Pallagi, Edina; Szabó-Révész, Piroska; Csóka, Ildikó; Ambrus, Rita

    2016-01-01

    Pulmonary drug delivery of ciprofloxacin hydrochloride offers effective local antibacterial activity and convenience of easy application. Spray drying is a trustworthy technique for the production of ciprofloxacin hydrochloride microparticles. Quality by design (QbD), an up-to-date regulatory-based quality management method, was used to predict the final quality of the product. According to the QbD-based theoretical preliminary parameter ranking and priority classification, dry powder inhalation formulation tests were successfully performed in practice. When focusing on the critical parameters, the practical development was more effective and was in correlation with our previous findings. Spray drying produced spherical microparticles. The dry powder formulations prepared were examined by particle size analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro drug release and aerodynamic particle size analyses were also performed. These formulations showed an appropriate particle size ranging between 2 and 4 μm and displayed an enhanced aerosol performance with fine particle fraction up to 80%. PMID:27784991

  14. Effect of drying method on volatile compounds, phenolic profile and antioxidant capacity of guava powders.

    PubMed

    Nunes, Juliana C; Lago, Mabel G; Castelo-Branco, Vanessa N; Oliveira, Felipe R; Torres, Alexandre Guedes; Perrone, Daniel; Monteiro, Mariana

    2016-04-15

    We studied the chemical composition of oven and freeze dried guava powders for future use as antioxidant-rich flavour enhancers. Among thirty-one volatiles in guava powders, terpenes were predominant, even after both drying processes. In contrast, esters and aldehydes, volatiles characteristic of fresh guava fruit, appeared to have been decreased by drying. Insoluble phenolics were predominant and among the sixteen compounds identified, quercetin-3-O-rutinoside and naringenin corresponded to 56% of total phenolics. Drying processes decreased total phenolics contents by up to 44%. Oven drying promoted the release of insoluble flavonoids, generating mainly quercetin. Antioxidant capacity also decreased due to both drying processes, but guava powders still presented similar antioxidant capacity in comparison to other tropical fruit powders. Our results suggest that oven drying is a viable option for the production of a functional ingredient that would improve the phenolic content of cereal foods while adding desirable guava flavour.

  15. Optimizing the Entrainment Geometry of a Dry Powder Inhaler: Methodology and Preliminary Results.

    PubMed

    Kopsch, Thomas; Murnane, Darragh; Symons, Digby

    2016-11-01

    For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of aerosol can be determined by the timing of dose emission into the tidal airstream. An optimization algorithm was used to iteratively perform computational fluid dynamic (CFD) simulations of the drug emission of a DPI. The algorithm seeks to improve performance by changing the device geometry. Objectives were to achieve drug emission that was: A) independent of inhalation manoeuvre; B) similar to a target profile. The simulations used complete inhalation flow-rate profiles generated dependent on the device resistance. The CFD solver was OpenFOAM with drug/air flow simulated by the Eulerian-Eulerian method. To demonstrate the method, a 2D geometry was optimized for inhalation independence (comparing two breath profiles) and an early-bolus delivery. Entrainment was both shear-driven and gas-assisted. Optimization for a delay in the bolus delivery was not possible with the chosen geometry. Computational optimization of a DPI geometry for most similar drug delivery has been accomplished for an example entrainment geometry.

  16. A levodopa dry powder inhaler for the treatment of Parkinson's disease patients in off periods.

    PubMed

    Luinstra, Marianne; Grasmeijer, Floris; Hagedoorn, Paul; Moes, Jan Reindert; Frijlink, Henderik W; de Boer, Anne H

    2015-11-01

    Adequate treatment of Parkinson's patients in off periods with orally administered levodopa is hindered by a poor bioavailability and a slow onset of action. Hence, there is a need for a fast and reliable alternative as for instance via pulmonary administration of the drug. We developed a levodopa containing powder formulation for pulmonary delivery by a recently presented high dose dry powder inhaler (Cyclops). The objective was to produce the drug formulation by means of simple techniques such as micronization, either as pure active substance or with a minimum amount of excipients. After an initial screening on dispersion behaviour, the most promising formulation in the Cyclops was characterized in vitro over a range of pressure drops (2-6 kPa) and doses (20, 30 and 40 mg), representative of those to be expected in practice. A co-micronized levodopa formulation with 2% L-leucine appeared to yield the best aerosol properties for inhalation and highest delivered dose reproducibility. The combination of this particular formulation and the Cyclops inhaler seems to meet the basic requirements for satisfactory deposition in the airways. This formulation is therefore expected to be a promising candidate for the treatment of Parkinson's patients in an off period.

  17. The Dry Aerosol Deposition Device (DADD): an instrument for depositing microbial aerosols onto surfaces.

    PubMed

    Heimbuch, B K; Kinney, K; Nichols, B; Wander, J D

    2009-09-01

    Concerns surrounding the contamination of infrastructure and equipment with biowarfare agents have led to the development of antimicrobial surfaces/coatings that are designed to "self-sterilize." Surfaces will likely be contaminated via an aerosol exposure and thus antimicrobial efficacy measurements should also be performed using biological aerosols. Standard methods that use microbial agents suspended in aqueous buffers may provide misleading results that overestimate the performance of the surface. A settling chamber is the most common instrument for applying biological aerosols to surfaces. However, settling chambers have some drawbacks (e.g., slow loading times, large footprint, variable loading, etc.) that make them undesirable for many applications. We have developed a Dry Aerosol Deposition Device (DADD) that uses impaction rather than settling to load surfaces with biological aerosols. The use of impaction allows for rapid and highly reproducible loading of microorganisms onto surfaces. We have demonstrated that the DADD can deliver both Bacillus atrophaeus spores and Staphylococcus aureus vegetative cells to glass coupons at concentrations exceeding 1x10(4) CFU/cm(2). The average coefficient of variation (CV) for sample-to-sample loading within an experiment was 13.6% for spores and 6.1% for S. aureus cells. The DADD is also a relatively simple and inexpensive device that can easily be contained within a 4-foot biological safety cabinet.

  18. How surface composition of high milk proteins powders is influenced by spray-drying temperature.

    PubMed

    Gaiani, C; Morand, M; Sanchez, C; Tehrany, E Arab; Jacquot, M; Schuck, P; Jeantet, R; Scher, J

    2010-01-01

    High milk proteins powders are common ingredients in many food products. The surface composition of these powders is expected to play an essential role during their storage, handling and/or final application. Therefore, an eventual control of the surface composition by modifying the spray-drying temperature could be very useful in the improvement of powder quality and the development of new applications. For this purpose, the influence of five spray-drying temperatures upon the surface composition of the powders was investigated by X-ray photoelectron spectroscopy. The major milk proteins were studied: native micellar casein and native whey, both more or less enriched in lactose. The results show a surface enrichment in lipids for all the powders and in proteins for many powders. Whatever the drying temperature, lipids and proteins are preferentially located near the surface whereas lactose is found in the core. This surface enrichment is also highly affected by the spray-drying temperature. More lipids, more proteins and less lactose are systematically observed at the surface of powders spray-dried at lower outlet air temperatures. The nature of proteins is also found essential; surface enrichment in lipids being much stronger for whey proteins containing powders than for casein containing powders. Additionally, we found a direct correlation between the lipids surface concentration and the wetting ability for the 25 powders studied.

  19. Inhibition by sodium cromoglycate of bronchoconstriction stimulated by respiratory heat loss: comparison of pressurised aerosol and powder.

    PubMed Central

    Latimer, K M; Roberts, R; Morris, M M; Hargreave, F E

    1984-01-01

    The protective effect was examined of three doses (2, 10, and 20 mg) of sodium cromoglycate inhaled from a pressurised metered dose inhaler on the response to isocapnic hyperventilation of cold dry air in 10 asthmatic subjects. This was compared with the effect of cromoglycate powder (20 mg) inhaled from a Spincap and with placebo given on two occasions. The medications were inhaled on separate days, in random order and with the use of a double blind double dummy technique, 20 minutes before isocapnic hyperventilation of two fold increasing volumes of air (-15 degrees C, 0% humidity) to produce a 20% fall in the post-treatment FEV1. The response was expressed as the provocative dose of respiratory heat loss required to cause a fall in FEV1 of 15% (PD15, kcal/min). The mean baseline spirometric indices exceeded 85% of predicted normal values on each test day; both placebo treatments reduced the baseline FEV1 by comparison with all active treatments (p less than 0.0001). Comparison of the PD15 on the two placebo days confirmed excellent reproducibility. All doses of cromoglycate shifted the respiratory heat loss dose-response curve to the right of the placebo curve; PD15 after all active treatments exceeded PD15 after placebo (p less than 0.0001). There was no cromoglycate dose-response relationship between the three doses of aerosol (p greater than 0.05), or between any dose of aerosol and powder (p greater than 0.05). It is concluded that cromoglycate aerosol inhaled from a pressurised inhaler in a dose of 2 mg gives the same magnitude of protection against bronchoconstriction stimulated by airway cooling as 20 mg of pressurised aerosol or powder from a Spincap. PMID:6426073

  20. Aerodynamic factors responsible for the deaggregation of carrier-free drug powders to form micrometer and submicrometer aerosols.

    PubMed

    Longest, P Worth; Son, Yoen-Ju; Holbrook, Landon; Hindle, Michael

    2013-06-01

    To employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform. Eight airflow passages were evaluated for deaggregation of the aerosol including a standard constricted tube, impaction surface, 2D mesh, inward radial jets, and newly proposed 3D grids and rod arrays. CFD simulations were implemented to evaluate existing and new aerodynamic factors for deaggregation and in vitro experiments were used to evaluate performance of each inhaler. For the carrier-free formulation considered, turbulence was determined to be the primary deaggregation mechanism. A strong quantitative correlation was established between the mass median diameter (MMD) and newly proposed non-dimensional specific dissipation (NDSD) factor, which accounts for turbulent energy, inverse of the turbulent length scale, and exposure time. A 3D rod array design with unidirectional elements maximized NDSD and produced the best deaggregation with MMD<1 μm. The new NDSD parameter can be used to develop highly effective dry powder inhalers like the 3D rod array that can efficiently produce submicrometer aerosols for next-generation respiratory drug delivery applications.

  1. Preparation of High-Grade Powders from Tomato Paste Using a Vacuum Foam Drying Method.

    PubMed

    Sramek, Martin; Schweiggert, Ralf Martin; van Kampen, Andreas; Carle, Reinhold; Kohlus, Reinhard

    2015-08-01

    We present a rapid and gentle drying method for the production of high-grade tomato powders from double concentrated tomato paste, comparing results with powders obtained by foam mat air drying and freeze dried powders. The principle of this method consists of drying tomato paste in foamed state at low temperatures in vacuum. The formulations were dried at temperatures of 50, 60, and 70 °C and vacuum of 200 mbar. Foam stability was affected by low serum viscosity and the presence of solid particles in tomato paste. Consequently, serum viscosity was increased by maltodextrin addition, yielding optimum stability at tomato paste:maltodextrin ratio of 2.4:1 (w/w) in dry matter. Material foamability was improved by addition of 0.5% (w/w, fresh weight) egg white. Because of solid particles in tomato paste, foam air filling had to be limited to critical air volume fraction of Φ = 0.7. The paste was first pre-foamed to Φ = 0.2 and subsequently expanded in vacuo. After drying to a moisture content of 5.6% to 7.5% wet base (w.b.), the materials obtained were in glassy state. Qualities of the resulting powders were compared with those produced by freeze and air drying. Total color changes were the least after vacuum drying, whereas air drying resulted in noticeable color changes. Vacuum foam drying at 50 °C led to insignificant carotenoid losses, being equivalent to the time-consuming freeze drying method. In contrast, air drying caused lycopene and β-carotene losses of 18% to 33% and 14% to 19% respectively. Thus, vacuum foam drying enables production of high-grade tomato powders being qualitatively similar to powders obtained by freeze drying. © 2015 Institute of Food Technologists®

  2. Effect of oil droplet size on the oxidative stability of spray-dried flaxseed oil powders.

    PubMed

    Shiga, Hirokazu; Loon Neoh, Tze; Ninomiya, Ai; Adachi, Sae; Pasten, Ignacio Lopez; Adachi, Shuji; Yoshii, Hidefumi

    2017-04-01

    The effect of the size of oil droplets on the oxidative stability of flaxseed oil in spray-dried powders was investigated. Maltodextrin with a dextrose equivalent of 25 was used as a wall material, and sodium caseinate and transglutaminase-polymerized sodium caseinate were used as emulsifiers. The oxidative stability of flaxseed oil encapsulated in the spray-dried powders was evaluated using lipid oxidation and conductometric determination tests at 105 °C. The powders containing larger oil droplets exhibited higher surface oil content after spray drying, and higher peroxide value and conductivity after storage at 105 °C. Removal of the surface oil from the powders by washing with hexane significantly decreased the conductivity. The results indicated that the surface oil of the spray-dried flaxseed oil powders affected the oxidation stability.

  3. Constant size, variable density aerosol particles by ultrasonic spray freeze drying.

    PubMed

    D'Addio, Suzanne M; Chan, John Gar Yan; Kwok, Philip Chi Lip; Prud'homme, Robert K; Chan, Hak-Kim

    2012-05-10

    This work provides a new understanding of critical process parameters involved in the production of inhalation aerosol particles by ultrasonic spray freeze drying to enable precise control over particle size and aerodynamic properties. A series of highly porous mannitol, lysozyme, and bovine serum albumin (BSA) particles were produced, varying only the solute concentration in the liquid feed, c(s), from 1 to 5 wt%. The particle sizes of mannitol, BSA, and lysozyme powders were independent of solute concentration, and depend only on the drop size produced by atomization. Both mannitol and lysozyme formulations showed a linear relationship between the computed Fine Particle Fraction (FPF) and the square root of c(s), which is proportional to the particle density, ρ, given a constant particle size d(g). The FPF decreased with increasing c(s) from 57.0% to 16.6% for mannitol and 44.5% to 17.2% for lysozyme. Due to cohesion, the BSA powder FPF measured by cascade impaction was less than 10% and independent of c(s). Ultrasonic spray freeze drying enables separate control over particle size, d(g), and aerodynamic size, d(a) which has allowed us to make the first experimental demonstration of the widely accepted rule d(a)=d(g)(ρ/ρ(o))(1/2) with particles of constant d(g), but variable density, ρ (ρ(o) is unit density).

  4. [Study on totai flavonoids of Epimedium assisted with soybean polysaccharide spray-drying powder].

    PubMed

    Yan, Hong-mei; Jia, Xiao-bin; Zhang, Zhen-hai; Sun, E; Deng, Jia-hui

    2015-08-01

    In order to evaluate the characteristics of the spray drying of total flavonoids of Epimedium extracts assisted with soybean polysaccharide, a certain percentage of soybean polysaccharide or polyvidone were added to the total flavonoids of Epimedium extract to conduct the spray drying. The effect of soybean polysaccharides against the wall sticking effect of the spray drying was detected, as well as the powder property of total flavonoids of Epimedium spray drying powder and the dissolution in vitro behavior of the effective component. Compared with the total flavonoids of Epimedium spray drying powder, soybean polysaccharide revealed a significant anti-wall sticking effect. The spray drying power which had no notable change in the grain size made a increase in the fluidity, improvement in the moisture absorption and remarkable rise in the dissolution in vitro behavior. It was worth further studying the application of soybean polysaccharide in spray drying power of traditional Chinese medicine.

  5. The effect of water to ethanol feed ratio on physical properties and aerosolization behavior of spray dried cromolyn sodium particles.

    PubMed

    Gilani, Kambiz; Najafabadi, Abdolhossien Rouholamini; Barghi, Mohammadali; Rafiee-Tehrani, Morteza

    2005-05-01

    Cromolyn sodium (CS) was spray dried under constant operation conditions from different water to ethanol feed ratios (50:50-0:100). The spray dried CS samples were characterized for their physicochemical properties including crystallinity, particle size distribution, morphology, density, and water/ethanol content. To determine quantitatively the crystallinity of the powders, an X-ray diffraction (XRD) method was developed using samples with different crystallinity prepared by physical mixing of 100% amorphous and 100% crystalline CS materials. The aerodynamic behavior of the CS samples was determined using an Andersen Cascade Impactor (ACI) with a Spinhaler at an air flow of 60 L/min. Binary mixtures of each spray dried CS powder and Pharmatose 325, a commercial alpha-lactose monohydrate available for DPI formulations, were prepared and in vitro aerosol deposition of the drug from the mixtures was analyzed using ACI to evaluate the effect of carrier on deposition profiles of the spray dried samples. CS spray dried from absolute ethanol exhibited XRD pattern characteristic for crystalline materials and different from patterns of the other samples. The crystallinity of spray dried CS obtained in the presence of water varied from 0% to 28.37%, depending on the ratio of water to ethanol in the feed suspensions. All samples presented different particle size, water/ethanol content, and bulk density values. CS particles spray dried from absolute ethanol presented uniform elongated shape whereas the other samples consisted mainly of particles with irregular shape. Overall, fine particle fraction increased significantly (p < 0.01) with decreasing d50% and water and ethanol content of spray dried CS samples. Significant difference (p < 0.01) in deposition profiles of the drug were observed between corresponding carrier free and carrier blended formulations. The difference in deposition profiles of CS aerosolized from various spray dried samples were described according to

  6. Feasibility of spray drying bacteriophages into respirable powders to combat pulmonary bacterial infections.

    PubMed

    Vandenheuvel, Dieter; Singh, Abhishek; Vandersteegen, Katrien; Klumpp, Jochen; Lavigne, Rob; Van den Mooter, Guy

    2013-08-01

    The use of bacterial viruses for antibacterial treatment (bacteriophage therapy) is currently being reevaluated. In this study, we analyze the potential of processing bacteriophages in a dry powder formulation, using a laboratory spray dryer. The phages were dried in the presence of lactose, trehalose or dextran 35, serving as an excipient to give the resulting powder the necessary bulk mass and offer protection to the delicate phage structure. Out of the three excipients tested, trehalose was found to be the most efficient in protecting the phages from temperature and shear stress throughout the spray drying process. A low inlet air temperature and atomizing force appeared to be the best parameter conditions for phage survival. Pseudomonas podovirus LUZ19 was remarkably stable, suffering less than 1 logarithmic unit reduction in phage titer. The phage titer of Staphyloccus phage Romulus-containing powders, a member of the Myoviridae family, showed more than 2.5 logarithmic units reduction. On the other hand, Romulus-containing powders showed more favorable characteristics for pulmonary delivery, with a high percentage of dry powder particles in the pulmonary deposition fraction (1-5 μm particle diameter). Even though the parameters were not optimized for spray drying all phages, it was demonstrated that spray drying phages with this industrial relevant and scalable set up was possible. The resulting powders had desirable size ranges for pulmonary delivery of phages with dry powder inhalers (DPIs).

  7. Atmospheric freeze drying for the reduction of powder electrostatics of amorphous, low density, high surface area pharmaceutical powders.

    PubMed

    O'Donnell, K P; Cai, Z; Schmerler, P; Williams, R O

    2013-02-01

    Amorphous itraconazole (ITZ) was prepared by Thin Film Freezing (TFF) utilizing 1,4-dioxane as the solvent with subsequent solvent removal via conventional tray lyophilization (ITZ LYO) or atmospheric freeze drying (ITZ AFD). ITZ AFD was prepared under various drying conditions to assess the influence of drying parameters on powder properties. XRD analysis confirmed all products were amorphous and DSC analysis revealed both drying processes resulted in the formation of the nematic mesophase of ITZ. SEM revealed a larger pore size and agglomerate size with fewer fine particles (i.e. less than 10 microns in diameter) for ITZ AFD compared to ITZ LYO. Residual solvent analysis revealed a primary drying temperature of -10°C resulted in residual solvent levels above the acceptable limits set by the International Conference on Harmonization as a result of microcollapse. Primary drying temperatures of less than -10°C resulted in acceptable residual solvent levels. The extent of microcollapse did not alter the macrostructure of the resulting powder. Powder flowability was determined to be similar for ITZ AFD and ITZ LYO based on Carr's index and the Hausner ratio, as well as by dynamic angle of repose. All powders displayed poor flowability. Chargeability measurements demonstrated a lower charge transfer for ITZ AFD powders compared to ITZ LYO due to a combination of factors including differences in residual solvent level, particle size, pore size, surface area, and fine particles content. The reduction in chargeability as a result of AFD is highly desirable because it allows for improved powder handling and use post-production.

  8. Heat-Stable Dry Powder Oxytocin Formulations for Delivery by Oral Inhalation.

    PubMed

    Fabio, Karine; Curley, Kieran; Guarneri, Joseph; Adamo, Benoit; Laurenzi, Brendan; Grant, Marshall; Offord, Robin; Kraft, Kelly; Leone-Bay, Andrea

    2015-12-01

    In this work, heat stable dry powders of oxytocin (OT) suitable for delivery by oral inhalation were prepared. The OT dry powders were prepared by spray drying using excipients chosen to promote OT stability including trehalose, isoleucine, polyvinylpyrrolidone, citrate (sodium citrate and citric acid), and zinc salts (zinc chloride and zinc citrate). Characterization by laser diffraction indicated that the OT dry powders had a median particle size of 2 μm, making them suitable for delivery by inhalation. Aerodynamic performance upon discharge from proprietary dry powder inhalers was evaluated by Andersen cascade impaction (ACI) and in an anatomically correct airway (ACA) model, and confirmed that the powders had excellent aerodynamic performance, with respirable fractions up to 77% (ACI, 30 L/min). Physicochemical characterization demonstrated that the powders were amorphous (X-ray diffraction) with high glass transition temperature (modulated differential scanning calorimetry, MDSC), suggesting the potential for stabilization of the OT in a glassy amorphous matrix. OT assay and impurity profile were conducted by reverse phase HPLC and liquid chromatography-mass spectrometry (LC-MS) after storage up to 32 weeks at 40°C/75%RH. Analysis demonstrated that OT dry powders containing a mixture of citrate and zinc salts retained more than 90% of initial assay after 32 weeks storage and showed significant reduction in dimers and trisulfide formation (up to threefold reduction compared to control).

  9. Effect of cholesterol on the properties of spray-dried lysozyme-loaded liposomal powders.

    PubMed

    Charnvanich, Dusadee; Vardhanabhuti, Nontima; Kulvanich, Poj

    2010-06-01

    The influence of cholesterol (Chol) in the liposomal bilayer on the properties of inhalable protein-loaded liposomal powders prepared by spray-drying technique was investigated. Lysozyme (LSZ) was used as a model protein. Feed solution for spray drying was prepared by direct mixing of aqueous solution of LSZ with mannitol solution and empty liposome dispersions composed of hydrogenated phosphatidylcholine and Chol at various molar ratios. The spray-dried powders were characterized with respect to morphology, thermal property, and crystallinity using scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction, respectively. Most formulations gave slightly aggregated, spherical particles, and percentage yields of the spray-dried powders decreased with increasing Chol content. Degree of particle aggregation depended on the powder composition. The powders spontaneously formed liposomes which efficiently entrapped LSZ after reconstitution with HEPES buffered saline (HBS) at 37 degrees C. Lysozyme entrapment efficiency and size distribution of the reconstituted liposomes were evaluated after the powders were reconstituted with HBS. Increasing Chol content resulted in a decrease in size of the reconstituted liposomes and an increase in entrapment efficiency of LSZ. These results correlated with thermal behaviors of the reconstituted liposomes. Biological activity of LSZ was not affected by the spray-drying process. It was also demonstrated that LSZ-loaded liposomal powders could be produced without the need to preload the LSZ into liposomes prior to spray-drying process.

  10. Effects of extrusion cooking on the chemical composition and functional properties of dry common bean powders.

    PubMed

    Ai, Yongfeng; Cichy, Karen A; Harte, Janice B; Kelly, James D; Ng, Perry K W

    2016-11-15

    The impact of extrusion cooking on the chemical composition and functional properties of bean powders from four common bean varieties was investigated. The raw bean powders were extruded under eight different conditions, and the extrudates were then dried and ground (particle size⩽0.5mm). Compared with corresponding non-extruded (raw) bean powders (particle size⩽0.5mm), the extrusion treatments did not substantially change the protein and starch contents of the bean powders and showed inconsistent effects on the sucrose, raffinose and stachyose contents. The extrusion cooking did cause complete starch gelatinization and protein denaturation of the bean powders and thus changed their pasting properties and solvent-retention capacities. The starch digestibilities of the cooked non-extruded and cooked extruded bean powders were comparable. The extruded bean powders displayed functional properties similar to those of two commercial bean powders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Submicron silicon powder production in an aerosol reactor

    NASA Technical Reports Server (NTRS)

    Wu, J. J.; Flagan, R. C.; Gregory, O. J.

    1986-01-01

    Powder synthesis by thermally induced vapor phase reactions is described. The powder generated by this technique consists of spherical, nonagglomerated particles of high purity. The particles are uniform in size, in the 0.1-0.2-micron size range. Most of the particles are crystalline spheres. A small fraction of the spheres are amorphous. Chain agglomerates account for less than 1 percent of the spherules.

  12. Technical procedure features of nickel dry-powder developer manufacturing by method of plasma-electrolytic dispergating

    NASA Astrophysics Data System (ADS)

    Gumerov, A. Z.; Nasibullin, R. T.; Sarimov, L. R.

    2017-01-01

    The following work describes means of nickel dry-powder developer manufacturing by plasma-electrolytic dispergating. For that purpose, a plasma-electrothermic device was developed that allows to manufacture dry-powders with wide range of parameters. Technical conditions for nickel dry-powder developer manufacturing by method of plasma-electrolytic dispergating were defined. By factorial design method regression equations were obtained, that make it possible to plan the process of dry-powders manufacturing with set average particle size and set manufacturing process rate. The described means allows to manufacture nicol dry-powder developer with a particle size of aprox. 100 nm.

  13. Difference in resistance to humidity between commonly used dry powder inhalers: an in vitro study

    PubMed Central

    Janson, Christer; Lööf, Thomas; Telg, Gunilla; Stratelis, Georgios; Nilsson, Folke

    2016-01-01

    Multi-dose dry powder inhalers (DPIs) are commonly used in asthma and chronic obstructive lung disease (COPD) treatment. A disadvantage is their sensitivity to humidity. In real life, DPIs are periodically exposed to humid conditions, which may affect aerosol characteristics and lung deposition. This study compared DPI aerosol performance after exposure to humidity. Budesonide (BUD) inhalers (Turbuhaler; Novolizer; Easyhaler) and budesonide/formoterol (BUD/FORM) inhalers (Turbuhaler; Spiromax; Easyhaler) were stored in 75% relative humidity (RH) at both ambient temperature and at −0 °C. Delivered dose (DD) and fine-particle dose (FPD) were tested in vitro before and after storage. BUD inhalers: Turbuhaler and Novolizer showed only small decreases (<15%) in FPD in 40 °C/75% RH, whereas FPD for Easyhaler decreased by >60% (P=0.01) after 1.5 months of storage. Easyhaler also decreased significantly after 6 months of storage in ambient/75%RH by 25% and 54% for DD and FPD, respectively, whereas only small decreases were seen for Turbuhaler and Novolizer (<15%). BUD/FORM inhalers: Turbuhaler and Spiromax DD were unchanged in 40 °C/75% RH, whereas Easyhaler showed a small decrease. FPD (budesonide) decreased for Turbuhaler, Spiromax and Easyhaler by 18%, 10% and 68% (all significant), respectively, at 40 °C/75% RH. In ambient/75%RH, DD was unchanged for all inhalers, whereas FPD (budesonide) decreased for Spiromax (7%, P=0.02) and Easyhaler (34%, (P<0.01)). There are significant differences in device performance after exposure to humid conditions. A clinically relevant decrease of more than half FPD was seen for one of the inhalers, a decrease that may affect patients’ clinical outcomes. Prescriber and patient knowledge on device attributes are essential to ensure optimal drug delivery to the lungs. PMID:27853177

  14. High shear treatment of concentrates and drying conditions influence the solubility of milk protein concentrate powders.

    PubMed

    Augustin, Mary Ann; Sanguansri, Peerasak; Williams, Roderick; Andrews, Helen

    2012-11-01

    The solubility of milk protein concentrate (MPC) powders was influenced by the method used for preparing the concentrate, drying conditions, and the type of dryer used. Increasing total solids of the ultrafiltered concentrates (23% total solids, TS) by diafiltration to 25% TS or evaporation to 31% TS decreased the solubility of MPC powders (80-83% protein, w/w dry basis), with ultrafiltration followed by evaporation to higher total solids having the greater detrimental effect on solubility. High shear treatment (homogenisation at 350/100 bar, microfluidisation at 800 bar or ultrasonication at 24 kHz, 600 watts) of ultrafiltered and diafiltered milk protein concentrates prior to spray drying increased the nitrogen solubility of MPC powders (82% protein, w/w dry basis). Of the treatments applied, microfluidisation was the most effective for increasing nitrogen solubility of MPC powders after manufacture and during storage. Manufacture of MPC powders (91% protein, w/w dry basis) prepared on two different pilot-scale dryers (single stage or two stage) from milk protein concentrates (20% TS) resulted in powders with different nitrogen solubility and an altered response to the effects of microfluidisation. Microfluidisation (400, 800 and 1200 bar) of the concentrate prior to drying resulted in increased long term solubility of MPC powders that were prepared on a single stage dryer but not those produced on a two stage spray dryer. This work demonstrates that microfluidisation can be used as a physical intervention for improving MPC powder solubility. Interactions between the method of preparation and treatment of concentrate prior to drying, the drying conditions and dryer type all influence MPC solubility characteristics.

  15. Effects of extrusion cooking on the chemical composition and functional properties of dry bean powders

    USDA-ARS?s Scientific Manuscript database

    This study aimed to investigate the impacts of extrusion cooking on the chemical composition and functional properties of bean powders from four bean varieties. The raw bean powders were extruded under eight different conditions, and the extrudates were then dried and ground (particle size = 0.5 mm)...

  16. The rheology and hydrodynamics of dry powder lubrication

    NASA Technical Reports Server (NTRS)

    Heshmat, Hooshang

    1991-01-01

    This paper conceptualizes a powder lubrication mechanisms which closely resembles that of a hydrodynamic fluid film. Based on the observations of past investigations and on the author's experiments, it is postulated that a layered shearing of the compacted powder generates velocity, density, and temperature profiles akin to fluid film bearings. Thus, a lubricant consisting of a fine powder unserted either deliberately or one generated by the water of the mating surfaces, constitutes a viable lubricant that generates the required flows and pressures to prevent contact between the surfaces.

  17. The rheology and hydrodynamics of dry powder lubrication

    NASA Technical Reports Server (NTRS)

    Heshmat, Hooshang

    1991-01-01

    This paper conceptualizes a powder lubrication mechanisms which closely resembles that of a hydrodynamic fluid film. Based on the observations of past investigations and on the author's experiments, it is postulated that a layered shearing of the compacted powder generates velocity, density, and temperature profiles akin to fluid film bearings. Thus, a lubricant consisting of a fine powder unserted either deliberately or one generated by the water of the mating surfaces, constitutes a viable lubricant that generates the required flows and pressures to prevent contact between the surfaces.

  18. Characteristics of bovine lactoferrin powders produced through spray and freeze drying processes.

    PubMed

    Wang, Bo; Timilsena, Yakindra Prasad; Blanch, Ewan; Adhikari, Benu

    2017-02-01

    Bovine lactoferrin (LFb) powders were produced using spray drying and freeze drying. Industrially obtained fresh liquid-LFb was used as starting material. The antioxidant capacity, solubility in water, moisture sorption behaviour, the extent of denaturation and changes in the secondary structural features of spray-dried (SDLFb) and freeze-dried bovine lactoferrin (FDLFb) powders were determined. The residual moisture content, water activity, particle size and amorphous/crystalline nature of the SDLFb and FDLFb were also measured. Results showed that both SDLFb and FDLFb powders had negligible denaturation and conformation changes compared to the liquid-LFb. Both SDLFb and FDLFb showed type II sorption behaviour with almost identical monolayer moisture content. The SDLFb powders were amorphous in nature with >98% solubility in water. The antioxidant activity of SDLFb was similar to that of the liquid-LFb while it was ∼6% less in FDLFb. Based on the residual moisture content, water activity, solubility and preservation of secondary structure of LFb in resultant powders, a spray drying process with 180°C inlet and 95°C outlet temperature was found to produce similar or better quality LFb powders compared to the ones produced through a freeze drying process. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. The Diskus™: a review of its position among dry powder inhaler devices

    PubMed Central

    Chrystyn, H

    2007-01-01

    The use of dry powder inhalers (DPIs) to administer treatments for respiratory diseases has increased significantly in recent years. There is now a wide range of DPIs available that vary considerably in design, required operational techniques, output characteristics and drug delivery across a range of inhalation patterns. Different patient populations may find individual types of DPI easier to use correctly than others and selecting the right DPI for particular patient requirements will improve compliance with therapy. For example, some DPIs offer a greater resistance against inspirational flow rate than others which affects the total emitted dose and also fine particle mass of the aerosol released. An individual patient may therefore receive different amounts of drug when inhaling from different DPIs. Therefore, it is important that the prescriber is fully aware of the characteristics of the different types of DPI, so that he or she can prescribe the device that is most appropriate to an individual patient's needs. This review explores the characteristics of currently available DPIs and evaluates their efficacy and patient acceptability. The differences in output characteristics, ease of use and patient preferences between available devices is shown to affect treatment efficacy and patient compliance with therapy. Changing the DPI prescribed to a patient to a cheaper or generic device may therefore adversely affect disease control and thereby increase the cost of treatment. PMID:17504364

  20. Inhalable liposomal dry powder of gemcitabine-HCl: Formulation, in vitro characterization and in vivo studies.

    PubMed

    Gandhi, Manit; Pandya, Tosha; Gandhi, Ravi; Patel, Sagar; Mashru, Rajashree; Misra, Ambikanandan; Tandel, Hemal

    2015-12-30

    Pulmonary drug delivery system facilitates local instillation of anticancer drugs to lungs which has proven to be pioneering approach for treatment of lung cancer. This approach led the groundwork for delivering liposomal formulation directly to lungs. Gemcitabine-HCl is currently considered as most effective drug for management of lung cancer. However, its application is limited owing to its metabolism by enzymes present in plasma resulting in reduced efficacy and higher toxicity. In present study, lyophilisation technique was used to convert liposomes into dry powder inhaler, which was formulated using emulsification solvent evaporation technique. The physicochemical properties including size, morphology, entrapment efficiency, loading efficiency etc. of formulated liposomes were evaluated. The prepared liposomal DPI (LDPI) formulations were then examined for solid state characteristics and aerosol performance using cascade impactor. From all the formulations prepared, the LDPI formulated using trehalose as cryoprotectant presented required properties along with desirable deposition pattern. Finally, the optimized formulation was selected for in vitro cell line studies; in vivo studies and stability study. This formulated inhalable particles offers a promising approach for the management of lung cancer through regional chemotherapy.

  1. Lung bioavailability of chlorofluorocarbon free, dry powder and chlorofluorocarbon containing formulations of salbutamol.

    PubMed

    Clark, D J; Lipworth, B J

    1996-03-01

    With the future advent of a world wide ban on chlorofluorocarbon containing aerosols, a study was designed to compare the in vivo lung bioavailability of salbutamol via chlorofluorocarbon-containing metered-dose inhaler (CFC), chlorofluorocarbon-free metered-dose inhaler (CFC-free), and dry powder inhaler (DPI). Twelve healthy male subjects were given 1200 micrograms salbutamol and measurements made of plasma and urinary salbutamol. CFC-free produced significantly higher plasma salbutamol levels (ng ml-1; mean and 95% CI for difference) than either CFC or DPI: Cmax, CFC-free 4.18 vs CFC 3.29 (95% CI 0.10-1.68), vs DPI 3.42 (95% CI -0.03-1.56). The ratio for the difference in Cmax between CFC and CFC-free formulations was 1.32 (95% CI 1.02-1.61). There were no significant differences between CFC and DPI formulations. Urinary salbutamol results did not reveal any significant differences between the three inhalers (micrograms 30 min-1): CFC-free 42.4, CFC 43.8, DPI 45.3. Thus, the lung bioavailability of CFC-free was greater than that of CFC or DPI formulations of salbutamol.

  2. Effect of interactive ternary mixtures on dispersion characteristics of ipratropium bromide in dry powder inhaler formulations.

    PubMed

    Beilmann, Bianca; Kubiak, René; Grab, Peter; Häusler, Heribert; Langguth, Peter

    2007-04-20

    The purpose of this investigation was to evaluate the effect of mixing order and the influence of adding fines on in vitro performance of ipratropium bromide (ITB) dry powder inhaler formulations. Coarse lactose (CL) in varying mass ratio with or without addition of micronized lactose (ML) and ITB in different mixing sequences was used to formulate ternary mixtures. A binary mixture composed of CL and ITP served as control. The in vitro deposition of ITB from these formulations was measured using an Andersen cascade impactor (aerosolization at 39 L/min) employing a HandiHaler as the delivery device. It was observed that mixing order has a significant effect (P < .05) on in vitro deposition of ITB. Formulations with preblending of CL and ITB produced similar deposition profiles as the control, regardless of the added ML. In contrast, formulations without preblending resulted in significantly higher fine particle dose (FPD) as compared with the control. In addition, an increased quantity of ML generally resulted in an increase in drug deposition. The results show that the effect of ML on dispersion of ITB is highly dependent upon the mixing order. The evaluation of atomic force measurement (AFM) to forecast drug detachment and predict the aerodynamic characteristics resulted in similar attraction forces for the different pairs lactose/lactose (42.66 +/- 25.01 nN) and lactose/ITB (46.77 +/- 17.04 nN).

  3. Surface Energy Determined by Inverse Gas Chromatography as a Tool to Investigate Particulate Interactions in Dry Powder Inhalers.

    PubMed

    Das, Shyamal C; Tucker, Ian G; Stewart, Peter J

    2015-01-01

    Dry powder inhalers (DPIs) usually contain drug particles <6 µm which agglomerate and/ or adhere on the surfaces of large carriers particles. The detachment of drug particles from carriers and de-agglomeration of drug particles into primary particles is essential for drug deposition in the deep lung. These processes are influenced by the surface energy of particles. Inverse gas chromatography (IGC) has been used to determine the surface energy of powder particles used in DPI to characterize materials and to understand aerosolization behaviour. Early studies used an infinite dilution technique to determine nonpolar surface energy and free energy of adsorption for polar interactions separately. Although some correlations were observed with the change in nonpolar surface energy before and after micronization, milling and storage, a lack of consistency in the change of free energy of adsorption was common. Moreover, a consistent relationship between complex de-agglomeration behaviour and surface energy has not been established and there are even some examples of negative correlation. In fact, nonpolar surface energy at infinite dilution is an incomplete representation of powder surface characteristics. The techniques for measuring polar surface energy, total surface energy and surface energy distribution have provided more revealing information about surface energetics of powders. Surface energy distributions determined by IGC or surface energy analyser have been successfully used to understand energetic heterogeneity of surfaces, characterize different polymorphs and understand changes due to micronization, structural relaxation, dry coating and storage. Efforts have been made to utilize surface energy distribution data to calculate powder strength distribution and to explain complex de-agglomeration behaviour of DPI formulations.

  4. Development of inhalable dry powder formulation of basic fibroblast growth factor.

    PubMed

    Ibrahim, Basma M; Jun, Seoung Wook; Lee, Mee Yong; Kang, Soo Hyung; Yeo, Yoon

    2010-01-29

    Basic fibroblast growth factor (bFGF) is a promising agent for therapy of asthma or chronic obstructive pulmonary disease. We aim to develop an inhalable powder formulation of bFGF, which may provide a safe, effective, and convenient way of delivering bFGF to the disease-ridden lungs. Development of a bFGF dry powder formulation is constrained by the poor stability of bFGF and the uncertainty in compatibility of the protein with carrier excipients. With these constraints in mind, we prepared dry powders containing bFGF in combinations of albumin, phospholipid, lactose, and/or leucine, by spray drying, and evaluated the aerodynamic properties of the powders and the stability of bFGF loaded in the powders. While an ethanolic solution of phospholipid, albumin, and lactose produced dispersible powder, bFGF was unstable in ethanol. The stability of bFGF was preserved when spray-dried with lactose in an aqueous solution. Leucine was required to obtain dry powder with good dispersibility; however, increase in the leucine content more than 50% (w/w) negatively influenced the bFGF stability with no additional benefit to the aerodynamic properties of the powders. Dry powders containing 20% (w/w) leucine provided desirable aerodynamic properties (fine particle fraction of 25.2+/-5.4% and mass median aerodynamic diameter of 4.7+/-0.9 microm) and 98.1+/-7% recovery of bioactive bFGF. This result warrants further investigation of the biological activity of the inhaled bFGF in a disease model. 2009 Elsevier B.V. All rights reserved.

  5. The impact of using chickpea flour and dried carp fish powder on pizza quality

    PubMed Central

    El-Senousi, Naglaa A.; Ali, Zeinab A.; Omran, Azza A.

    2017-01-01

    Pizza being the most popular food worldwide, quality and sensory appeal are important considerations during its modification effort. This study was aimed to evaluate the quality of pizza made using two different sources of proteins, chickpea (Cicer arietinum) flour and dried carp fish powder (Cyprinus carpio). Analysis indicated nutrients richness specificity of chickpea flour (higher fiber, energy, iron, zinc, linoleic acid and total nonessential amino acids) and dried carp fish powder (higher contents of protein, fats, ash, oleic acid and total essential amino acids) complementing wheat flour to enhance nutritional value of pizza. Total plate count and thiobarbituric acid were increased (P<0.05) in dried carp fish powder after 45 days of storage, but no Coliform were detected. Wheat flour was substituted with 5, 7.5 and 10% chickpea flour or dried carp fish powder and chemical, textural, sensory and storage evaluation parameters of in pizza were investigated. Dried carp fish powder increased (P<0.05) contents of protein, ash, fats, zinc and protein digestibility of pizza. Chickpea flour increased iron and zinc contents of the pizza. Water activity (aw) was decreased in fish powder and chickpea pizza. Pizza firmness and gumminess were significantly (p<0.05) increased at every level of protein source, but cohesiveness was decreased with 10% chickpea flour. Pizza chewiness was the same (P>0.05) across the levels of two protein sources. Springiness was decreased (P<0.05) with high level (10%) dried fish powder and low/intermediate level of chickpea flour. Chickpea and dried carp fish incorporation up to 7.50% in pizza at the expense of wheat flour had no effect (P>0.05) on all sensorial parameters except for odor values. The results could be useful in utilization of chickpea flour and carp fish powder in designing nutritious pizza for consumers. PMID:28873098

  6. The impact of using chickpea flour and dried carp fish powder on pizza quality.

    PubMed

    El-Beltagi, Hossam S; El-Senousi, Naglaa A; Ali, Zeinab A; Omran, Azza A

    2017-01-01

    Pizza being the most popular food worldwide, quality and sensory appeal are important considerations during its modification effort. This study was aimed to evaluate the quality of pizza made using two different sources of proteins, chickpea (Cicer arietinum) flour and dried carp fish powder (Cyprinus carpio). Analysis indicated nutrients richness specificity of chickpea flour (higher fiber, energy, iron, zinc, linoleic acid and total nonessential amino acids) and dried carp fish powder (higher contents of protein, fats, ash, oleic acid and total essential amino acids) complementing wheat flour to enhance nutritional value of pizza. Total plate count and thiobarbituric acid were increased (P<0.05) in dried carp fish powder after 45 days of storage, but no Coliform were detected. Wheat flour was substituted with 5, 7.5 and 10% chickpea flour or dried carp fish powder and chemical, textural, sensory and storage evaluation parameters of in pizza were investigated. Dried carp fish powder increased (P<0.05) contents of protein, ash, fats, zinc and protein digestibility of pizza. Chickpea flour increased iron and zinc contents of the pizza. Water activity (aw) was decreased in fish powder and chickpea pizza. Pizza firmness and gumminess were significantly (p<0.05) increased at every level of protein source, but cohesiveness was decreased with 10% chickpea flour. Pizza chewiness was the same (P>0.05) across the levels of two protein sources. Springiness was decreased (P<0.05) with high level (10%) dried fish powder and low/intermediate level of chickpea flour. Chickpea and dried carp fish incorporation up to 7.50% in pizza at the expense of wheat flour had no effect (P>0.05) on all sensorial parameters except for odor values. The results could be useful in utilization of chickpea flour and carp fish powder in designing nutritious pizza for consumers.

  7. Microparticulate/Nanoparticulate Powders of a Novel Nrf2 Activator and an Aerosol Performance Enhancer for Pulmonary Delivery Targeting the Lung Nrf2/Keap-1 Pathway.

    PubMed

    Muralidharan, Priya; Hayes, Don; Black, Stephen M; Mansour, Heidi M

    2016-01-01

    This systematic and comprehensive study reports for the first time on the successful rational design of advanced inhalable therapeutic dry powders containing dimethyl fumarate, a first-in-class Nrf2 activator drug to treat pulmonary inflammation, using particle engineering design technology for targeted delivery to the lungs as advanced spray dried (SD) one-component DPIs. In addition, two-component co-spray dried (co-SD) DMF:D-Man DPIs with high drug loading were successfully designed for targeted lung delivery as advanced DPIs using organic solution advanced spray drying in closed mode. Regional targeted deposition using design of experiments (DoE) for in vitro predictive lung modeling based on aerodynamic properties was tailored based on composition and spray drying parameters. These findings indicate the significant potential of using D-Man in spray drying to improve particle formation and aerosol performance of small molecule with a relatively low melting point. These respirable microparticles/nanoparticles in the solid-state exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device. Using in vitro predictive lung deposition modeling, the aerosol deposition patterns of these particles show the capability to reach lower airways to treat inflammation in this region in pulmonary diseases such as acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), and pulmonary endothelial disease.

  8. Pharmacokinetic Comparison of a Unit Dose Dry Powder Inhaler with a Multidose Dry Powder Inhaler for Delivery of Fluticasone Furoate.

    PubMed

    Mehta, Rashmi; Moore, Alison; Riddell, Kylie; Joshi, Shashidhar; Chan, Robert

    2017-05-02

    The unit dose dry powder inhaler (UD-DPI) is being considered as an alternative inhaler platform that, if developed, has the potential to improve access to inhaled respiratory medicines in developing countries. This study compared the systemic exposure of fluticasone furoate after delivery from the UD-DPI with that from the ELLIPTA(®) inhaler. This open-label, five-way cross-over, randomized, single-dose study in healthy subjects evaluated fluticasone furoate systemic exposure of three dose strengths (using four inhalations), 4 × 80 μg [320 μg], 4 × 100 μg [400 μg], and 4 × 140 μg [560 μg]), and two percentages of drug in lactose blends (0.6% and 0.8% by weight) after delivery from the UD-DPI compared with systemic exposures from the ELLIPTA inhaler (4 × 100 μg [400 μg] dose, 0.8% lactose blend). The primary treatment comparisons were area under the concentration-time curve from time 0 to 6 hours [AUC0-6] and maximum plasma concentration [Cmax]. After single-dose administration of fluticasone furoate, systemic exposure was lower from all UD-DPI formulations versus the ELLIPTA inhaler in terms of both AUC0-6 [AUC0-6 geometric least squares mean (GLM) ratios confidence interval (90% CI) for: UD-DPI (400 μg 0.8% blend)/ELLIPTA: 0.61 (0.55-0.67) and Cmax GLM (90% CI) for: UD-DPI (400 μg 0.8% blend)/ELLIPTA: 0.56 (0.49-0.64)]. Systemic exposures were ∼10% lower for fluticasone furoate UD-DPI for the 0.8% blend versus the 0.6% blend [GLM ratio (90% CI); 0.90 (0.81-1.00) for AUC0-6 and 0.89 (0.77-1.01) for Cmax], and increasing doses of fluticasone furoate from the UD-DPI showed systemic exposures that were approximately dose proportional. All treatments were well tolerated. Fluticasone furoate systemic exposure was lower from the UD-DPI than from the ELLIPTA inhaler, but the UD-DPI formulations did demonstrate detectable systemic levels and approximate dose proportionality. Together with the good tolerability shown

  9. Comparative Evaluation of Physicochemical Properties of Pine Needle Powders Prepared by Different Drying Methods

    PubMed Central

    Chung, Ha-Sook; Lee, Jun Ho

    2015-01-01

    Systematic study of how different drying methods, namely hot-air drying, vacuum-drying, and freeze-drying, affect color, browning index, degree of rehydration, water solubility, and vitamin C content is critical for utilizing pine needle powders (PNP) as a novel ingredient in functional foods. Samples prepared by vacuum-drying showed a significantly higher L*-value, whereas higher a*- and b*-values were detected in the hot-air dried samples (P<0.05). The browning index was significantly higher in samples prepared by vacuum-drying compared to samples prepared by freeze-drying (P<0.05). Freeze-dried PNP exhibited a significantly higher degree of rehydration than hot-air dried samples (P<0.05). Water solubilities of freeze-dried and hot-air dried samples were significantly higher than that of vacuum-dried sample (P<0.05). Vitamin C was less destroyed during freeze-drying compared to hot-air or vacuum-drying (P<0.05). Freeze-dried samples displayed a clear porous structure and appeared to have a bigger space, whereas hot-air dried samples showed lower porosity than vacuum and freeze-dried samples. PMID:26176003

  10. Preparation, characterization and pulmonary pharmacokinetics of a new inhalable zanamivir dry powder.

    PubMed

    Cai, Xingshi; Yang, Yang; Xie, Xiangyang; Yu, Fanglin; Yang, Yanfang; Yang, Zhenbo; Zhang, Tao; Mei, Xingguo

    2016-07-01

    This work describes a new dry powder for inhalation containing zanamivir, which is less hygroscopic than Relenza®. The powders were prepared via a spray-drying technique using mannitol as the carrier. A 5(3) central composite design was used to optimize the formulations. The final optimized powders, characterized with an angle of repose 37.48°, an aerodynamic diameter of 2.346 μm and in vitro deposition of 58.54%, were obtained by using the predicted variable values. Relenza® absorbed a significant amount of water at 66%, 75% and 85% relative humidity (RH; weight changes of approximately 1.38%, 2.18% and 3.72%, respectively). In contrast, the weight change for the zanamivir dry powder inhalation (DPI) was negligible when the RH was increased to 66%. The in vivo potential for the optimized powders was studied further in rats via the endotracheal administration of an 8.4 mg/kg dose. The bioavailability was 116% relative to Relenza®. Fluorescence imaging monitored the zanamivir dry powder inhalers in rats. The results indicated that the zanamivir DPIs were effectively delivered to the lung. These results indicate that the spray-dried zanamivir DPIs were promising for pulmonary delivery.

  11. Nano-amorphous spray dried powder to improve oral bioavailability of itraconazole.

    PubMed

    Kumar, Sumit; Shen, Jie; Burgess, Diane J

    2014-10-28

    The objective of this study was to formulate nano-amorphous spray-dried powders of itraconazole to enhance its oral bioavailability. A combination approach of solvent-antisolvent precipitation followed by spray drying was used. DoE studies were utilized to understand the critical processing parameters: antisolvent-to-solvent ratio, drug concentration and stabilizer concentration. Particle size was the critical quality attribute. Spray drying of the nano-precipitated formulation was performed with several auxiliary excipients to obtain nano-sized amorphous powder formulations. PLM, DSC and PXRD were utilized to characterize the spray-dried powders. In vitro dissolution and in vivo bioavailability studies of the nano-amorphous powders were performed. The particle size of the nano-formulations was dependent on the drug concentration. The smallest size precipitates were obtained with low drug concentration. All high molecular weight auxiliary excipients and mannitol containing formulations were unstable and crystallized during spray drying. Formulations containing disaccharides were amorphous and non-aggregating. In vitro dissolution testing and in vivo studies showed the superior performance of nano-amorphous formulations compared to melt-quench amorphous and crystalline itraconazole formulations. This study shows superior oral bioavailability of nano-amorphous powders compared to macro-amorphous powders. The nano-amorphous formulation showed similar bioavailability to the nano-crystalline formulation but with a faster absorption profile.

  12. Effect of sucrose on physical properties of spray-dried whole milk powder.

    PubMed

    Ma, U V Lay; Ziegler, G R; Floros, J D

    2008-11-01

    Spray-dried whole milk powders were prepared from whole condensed milk with various sucrose concentrations (0%, 2.5%, 5%, 7.5%, and 10% w/w), and their glass transition temperature and some physical properties of importance in chocolate manufacture were evaluated. In milk powder samples, the glass transition temperature and free-fat content decreased in a nonlinear manner with sucrose addition. Moreover, increasing sucrose concentration reduced the formation of dents on the particle surface. Addition of sucrose in whole condensed milk increased linearly the apparent particle density and in a nonlinear manner the particle size of spray-dried milk powders. The particle size volume distribution of milk powders with the highest sucrose concentration differed from the log-normal distribution of the other samples due to the formation of large agglomerates. Neither vacuole volume, nor the amorphous state of milk powders was affected by sucrose addition.

  13. Physicochemical properties of whole fruit plum powders obtained using different drying technologies.

    PubMed

    Michalska, Anna; Wojdyło, Aneta; Lech, Krzysztof; Łysiak, Grzegorz P; Figiel, Adam

    2016-09-15

    Physicochemical quality parameters of plum powders obtained by applying conventional drying methods and their combination devised to process plums were evaluated. The effect of freeze-drying (FD), vacuum drying (VD), convective drying (CD), microwave-vacuum drying (MVD) and combination of convective pre-drying and microwave finish-drying (CPD-MVFD) affected physical (bulk density, porosity, colour, solubility) and chemical (polyphenolic compounds determined by UPLC and antioxidant capacity by TEAC ABTS and FRAP methods) properties of plum powders. The MVD at 1.2 W g(-1) and a novel combination for plum powders production - CPD-MVFD at 70 °C/1.2 W g(-1) allowed the best preservation of phenolic compounds and increased the efficiency of production. Results obtained support the use of MVD and its combination for better quality of dried plum products. The study proved that the determination of the browning index and HMF level (formed via Maillard reaction) might be good tool for monitoring the thermal processing of plum powders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Suitability of differently formulated dry powder Newcastle disease vaccines for mass vaccination of poultry.

    PubMed

    Huyge, Katrien; Van Reeth, Kristien; De Beer, Thomas; Landman, Wil J M; van Eck, Jo H H; Remon, Jean Paul; Vervaet, Chris

    2012-04-01

    Dry powders containing a live-attenuated Newcastle disease vaccine (LZ58 strain) and intended for mass vaccination of poultry were prepared by spray drying using mannitol in combination with trehalose or inositol, polyvinylpyrrolidone (PVP) and/or bovine serum albumin (BSA) as stabilizers. These powders were evaluated for vaccine stabilizing capacity during production and storage (at 6 °C and 25 °C), moisture content, hygroscopicity and dry powder dispersibility. A mixture design, varying the ratio of mannitol, inositol and BSA, was used to select the stabilizer combination which resulted in the desired powder properties (i.e. good vaccine stability during production and storage, low moisture content and hygroscopicity and good dry dispersibility). Inositol-containing powders had the same vaccine stabilizing capacity as trehalose powders, but were less hygroscopic. Incorporation of BSA enhanced the vaccine stability in the powders compared to PVP-containing formulations. However, increasing the BSA concentration increased the hygroscopicity and reduced the dry dispersibility of the powder. No valid mathematical model could be calculated for vaccine stability during production or storage, but the individual experiments indicated that a formulation combining mannitol, inositol and BSA in a ratio of 73.3:13.3:13.3 (wt/wt) resulted in the lowest vaccine titre loss during production (1.6-2.0 log(10) 50% egg infectious dose (EID(50)) and storage at 6 °C (max. 0.8 log(10) EID(50) after 6 months) in combination with a low moisture content (1.1-1.4%), low hygroscopicity (1.9-2.1% water uptake at 60% relative humidity) and good dry dispersibility properties.

  15. Dry powder inhalation of antibiotics in cystic fibrosis therapy, part 1: development of a powder formulation with colistin sulfate for a special test inhaler with an air classifier as de-agglomeration principle.

    PubMed

    de Boer, A H; Le Brun, P P H; van der Woude, H G; Hagedoorn, P; Heijerman, H G M; Frijlink, H W

    2002-07-01

    The aim of this study was to investigate the pulmonary administration of antibiotics as dry powder to patients with cystic fibrosis (CF), as an alternative for nebulization. This part of the study describes the development of a powder formulation with colistin sulfate as model substance. The aim of the new dosage form was to increase pulmonary deposition, therapeutic efficiency and, by that, compliance by the CF patients. A physical powder mixture of colistin and a size fraction of lactose (106-150 microm) was prepared and the mixture was optimized with respect to colistin content (83.3%) for use in a special test inhaler. A laser diffraction apparatus with special inhaler adapter was applied for analysis of the size distribution of the aerosol cloud from the inhaler. The size distributions of the aerosol clouds from the test inhaler at flow rates between 30 and 60 l/min for the optimized formulation showed nearly the same median diameter as that for the primary drug particles. But the X(100)-value was much lower, because of an effective large particle separation from the inspiratory air by an air classifier in the test inhaler. The results suggest that dry powder inhalation might be a suitable and highly efficient alternative for nebulization of antibiotic drugs in CF therapy.

  16. A study of inter-particle bonds in dry bauxite waste resulting in atmospheric aerosols

    NASA Astrophysics Data System (ADS)

    Wagh, Arun S.; Thompson, Bentley

    1988-02-01

    Bauxite and Alumina production are one of the main activities of several third world countries such as Jamaica, Brazil, India, Guinea, eastern European countries such as Hungary and Rumania and advanced countries such as Australia, West Germany, Japan and the United States. The mining operations lead to dust pollution, but the refining of bauxite to alumina yield large amounts of highly caustic sludge waste, called "Red Mud". Millions of tons of the waste produced in every country are stored in containment dams or natural valleys. This leads to ground water pollution, destruction of plant and bird life and is hazardous to human settlement in earthquake prone regions like Jamaica. As a result several companies have been looking into dry mud stacking which involves thickening the mud in the refining plants and sprying it on the slopes to sun dry it. Typically it involves a drying field of about two hundred acres, which could act as a potential source of caustic dust. In Jamaica one company has started disposing of the mud in this way. The aerosol formation from such areas depends mainly on the integrity of the top dry layers. Presently this is done by studying the approximate parameters such as the friability of the mud. However, following the recent advances in powder technology it has been possible for us to develop an instrument to study the average interparticle forces between the red mud particles. The instrument is based on the principle of a tensometer and a split cell is used to load specimens. A load cell is used to measure the force and a chart recorder is used for plotting separation and the force. The present study reports elemental composition of the dust and its health hazards. It also reports the physical measurement of the average interparticle force as a function of their separation in the Jamaican mud. The effect of ultraviolet radiation on the strength of the material is studied to see the effect of sun-drying of the waste. The five-fold increase

  17. Effect of device design on the in vitro performance and comparability for capsule-based dry powder inhalers.

    PubMed

    Shur, Jagdeep; Lee, Sau; Adams, Wallace; Lionberger, Robert; Tibbatts, James; Price, Robert

    2012-12-01

    This study investigated the effect of modifying the design of the Cyclohaler on its aerosolization performance and comparability to the HandiHaler at multiple flow rates. The Cyclohaler and HandiHaler were designated as model test and reference unit-dose, capsule-based dry powder inhalers (DPIs), respectively. The flow field, pressure drop, and carrier particle trajectories within the Cyclohaler and HandiHaler were modeled via computational fluid dynamics (CFD). With the goal of achieving in vitro comparability to the HandiHaler, the CFD results were used to identify key device attributes and to design two modifications of the Cyclohaler (Mod 1 and Mod 2), which matched the specific resistance of the HandiHaler but exhibited different cyclonic flow conditions in the device. Aerosolization performance of the four DPI devices was evaluated by using the reference product's capsule and formulation (Spiriva capsule) and a multistage cascade impactor. The in vitro data showed that Mod 2 provided a closer match to the HandiHaler than the Cyclohaler and Mod 1 at 20, 39, and 55 l/min. The in vitro and CFD results together suggest that matching the resistance of test and reference DPI devices is not sufficient to attain comparable aerosolization performance, and the improved in vitro comparability of Mod 2 to the HandiHaler may be related to the greater degree of similarities of the flow rate of air through the pierced capsule (Q(c)) and the maximum impact velocity of representative carrier particles (V(n)) in the Cyclohaler-based device. This investigation illustrates the importance of enhanced product understanding, in this case through the CFD modeling and in vitro characterization of aerosolization performance, to enable identification and modification of key design features of a test DPI device for achieving comparable aerosolization performance to the reference DPI device.

  18. Preparation and Evaluation of Surface Modified Lactose Particles for Improved Performance of Fluticasone Propionate Dry Powder Inhaler.

    PubMed

    Singh, Deepak J; Jain, Rajesh R; Soni, P S; Abdul, Samad; Darshana, Hegde; Gaikwad, Rajiv V; Menon, Mala D

    2015-08-01

    Dry powder inhalers (DPI) are generally formulated by mixing micronized drug particles with coarse lactose carrier particles to assist powder handling during the manufacturing and powder aerosol delivery during patient use. In the present study, surface modified lactose (SML) particles were produced using force control agents, and their in vitro performance on dry powder inhaler (DPI) formulation of Fluticasone propionate was studied. With a view to reduce surface passivation of high surface free energy sites on the most commonly used DPI carrier, α- lactose monohydrate, effects of various force control agents such as Pluronic F-68, Cremophor RH 40, glyceryl monostearate, polyethylene glycol 6000, magnesium stearate, and soya lecithin were studied. DPI formulations prepared with SML showed improved flow properties, and atomic force microscopy (AFM) studies revealed decrease in surface roughness. The DSC and X-ray diffraction patterns of SML showed no change in the crystal structure and thermal behavior under the experimental conditions. The fine particle fraction (FPF) values of lactose modified with Pluronic F-68, Cremophor RH 40, glyceryl monostearate were improved, with increase in concentration up to 0.5%. Soya lecithin and PEG 6000 modified lactose showed decrease in FPF value with increase in concentration. Increase in FPF value was observed with increasing concentration of magnesium stearate. Two different DPI devices, Rotahaler(®) and Diskhaler(®), were compared to evaluate the performance of SML formulations. FPF value of all SML formulations were higher using both devices as compared to the same formulations prepared using untreated lactose. One month stability of SML formulations at 40°C/75% RH, in permeable polystyrene tubes did not reveal any significant changes in FPF values. SML particles can help in reducing product development hindrances and improve inhalational properties of DPI.

  19. Comparison of particle sizing techniques in the case of inhalation dry powders.

    PubMed

    Bosquillon, C; Lombry, C; Preat, V; Vanbever, R

    2001-12-01

    The objectives of this work were (i) to validate electrical zone sensing and laser diffraction for the analysis of primary particle size in the case of inhalation dry powders and (ii) to study the influence of the aggregation state of the powder on the sizing techniques. Free-flowing dry powders were prepared by spray-drying with a combination of albumin, lactose, and dipalmitoylphosphatidylcholine. The replacement of lactose by mannitol, the removal of albumin, and the atomization at high relative humidity all increased powder cohesion. Automated measurements were compared with primary particle sizes collected by light and electron microscopy. The mass mode obtained by electrical zone sensing and the mass median diameter measured by laser diffraction following dispersion with compressed air at a pressure of 3 bar or following suspension in water and ultrasonic dispersion at a power of 60 W for 30 s each provided primary particle sizes close to microscopy measurements. However, these conditions only applied in the case of slightly to moderately aggregated powders. For strongly agglomerated powders, an exact measurement of the size was only collected by laser diffraction in the wet state combined with ultrasonic dispersion. Our study underlies how measurement of primary particle size highly depends on both powder material and proper particle dispersion.

  20. Effect of drying treatments and storage stability on quality characteristics of bael powder.

    PubMed

    Sagar, V R; Kumar, Rajesh

    2014-09-01

    Dehydration of bael pulp in to powder form is a challenging operation, mainly due to the sticky issue of bael pulp and caking of powder during handling and storage. To overcome on this problem maltodextrin MD (drying aid) and tricalcium phosphate, TCP (anti caking agent) were added to the bael pulp at four levels along with control and dried in a mechanical drier into thin layer at 58 ± 2 °C for 12 h, to obtain a moisture content of 4-5 % in dehydrated pulp. The dehydrated bael pulp was grounded in a laboratory powder mill and sieve with 30 mesh sieve. The powder was packed in 150gauge PP, 400gauge LDPE and 200gauge HDPE pouches and was stored at low temperature (7 °C) and ambient condition (18-35 °C) up to 6 months for storage study. The powder was evaluated for its quality characteristics in respect of acidity, sugars, antioxidant, phenol, ascorbic acid, non- enzymatic browning (NEB) before packaging and during storage. The amount of MD and TCP required to reduce powder stickiness and caking were optimized on the powder properties. The amount of MD (0.25 kg per kg dry bael solids) and TCP (0.15 kg per kg dry bael solids) with the values of degree of caking (19.24 %) and stickiness point temperature (45.4 °C) were found to be optimum for reducing the powder stickiness, caking and nutritional parameters. The adsorption isotherm of bael powder was found to be type-II sigmoid and 200 g HDPE as packaging material followed by storage at low temperature were selected as best process.

  1. Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.

    PubMed

    Yang, Yue; Cheow, Wean Sin; Hadinoto, Kunn

    2012-09-15

    Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers of therapeutics as they combine the attractive characteristics of liposomes and polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as the polymer and lipid constituents, respectively. The hybrid nanoparticles are transformed into inhalable microscale nanocomposite structures by a novel technique based on electrostatically-driven adsorption of nanoparticles onto polysaccharide carrier particles, which eliminates the drawbacks of conventional techniques based on controlled drying (e.g. nanoparticle-specific formulation, low yield). First, we engineer polysaccharide carrier particles made up of chitosan cross-linked with tripolyphosphate and dextran sulphate to exhibit the desired aerosolization characteristics and physical robustness. Second, we investigate the effects of nanoparticle to carrier mass ratio and salt inclusion on the adsorption efficiency, in terms of the nanoparticle loading and yield, from which the optimal formulation is determined. Desorption of the nanoparticles from the carrier particles in phosphate buffer saline is also examined. Lastly, we characterize aerosolization efficiency of the nanocomposite product in vitro, where the emitted dose and respirable fraction are found to be comparable to the values of conventional DPI formulations.

  2. Adherence logger for a dry powder inhaler: a new device for medical adherence research.

    PubMed

    Bogen, Daniel; Apter, Andrea J

    2004-10-01

    Adherence to inhaled steroid regimens is frequently poor. Finding ways to improve adherence depends on the ability to measure time and date of inhaler use reliably and to detect deliberate dose dumping. There is no such monitor for the popular new dry powder inhalers. To develop and test an electronic monitor for a dry powder inhaler that will provide information on the time and date of use. An electronic adherence monitor for the Advair Diskus dry powder inhaler was developed and tested. In this device, inhaler use is determined by detecting and recording the motion of the drug delivery lever in the inhaler with a magnetic sensor. An additional electronic interface and software were also developed to allow the adherence data to be uploaded to a computer for display and analysis. System and reliability tests involving multiple-day and repeated-use tests of the adherence monitor demonstrate the overall performance and reliability of the device, and specifically its ability to record the time and date of dose delivery. In the repeated-use test, 300 successive actuations of the dose delivery lever were correctly sensed and recorded without error. The simple-to-use, low-cost, reusable adherence monitor accurately records time and date of inhaler use and thus allows clinical monitoring and adherence studies in patients using the Advair Diskus dry powder inhaler. The same technology should be adaptable to other dry powder inhalers, including the Pulmicort Tubuhaler and the Symbicort Tubuhaler.

  3. Standardization of spray-dried powder of Piper betle hot water extract.

    PubMed

    Arawwawala, Liyanage Dona Ashanthi Menuka; Hewageegana, Horadugoda Gamage Sujatha Pushpakanthi; Arambewela, Lakshmi Sriyani Rajapaksha; Ariyawansa, Hettiarachchige Sami

    2011-04-01

    The leaves of Piper betle Linn. (Family: Piperaceae) possess several bioactivities and are used in the Traditional Medical systems of Sri Lanka. The present investigation was carried out to standardize the spray-dried powder of P. betle by (a) determination of physicochemical parameters, presence or absence of heavy metals, and microbial contamination; (b) screening for phytochemicals; and (c) development of High Pressure Liquid Chromatography (HPLC) fingerprint and densitogram. The percentages of moisture content, total ash, acid insoluble ash, water-soluble ash, and ethanol extractable matter of spray-dried powder of P. betle were 2.2-2.5, 6.8-7.0, 0.003-0.005, 4.1-4.3, and 15.8-16.2, respectively. The concentrations of all the tested heavy metals were below the WHO acceptable limits and bacterial species, such as Escherichia coli, Salmonella spp, Staphylococcus aureus, and Pseudomonas aeroginosa were not present in the P. betle spray-dried powder. Phenolic compounds, tannins, flavonoids steroids, and alkaloids were found to be present in the spray-dried powder of P. betle and HPLC fingerprint and densitogram clearly demonstrated the proportional differences of these chemical constituents. In conclusion, the results obtained from this study can be used to standardize the spray-dried powder of P. betle.

  4. Development of New Formulation Dry Powder for Pulmonary Delivery Using Amino Acids to Improve Stability.

    PubMed

    Suzuki, Yumiko; Okuda, Tomoyuki; Okamoto, Hirokazu

    2016-01-01

    Cationic polymers are being studied as non-viral gene delivery vectors. Poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PAsp(DET)) and their block copolymers with poly(ethylene glycol), PEG-PAsp(DET), have been reported as efficient biodegradable non-viral vectors which form a polyplex with plasmid DNA (pDNA). However, the polyplexes are not stable because PAsp(DET) and PEG-PAsp(DET) are easily subjected to hydrolysis; therefore, they need to be prepared on site. In this study, using the biodegradable polycations as non-viral vectors, PAsp(DET) and PEG-PAsp(DET), we investigated the effects of L-leucine (Leu) on the polyplex. We prepared solutions and dry powders with and without Leu. Both dry powders had large and porous particles and Leu acted as a dispersing agent. The transfection activity of the sample solutions decreased within a month. However, the decrease in the transfection activity was partially suppressed by the dry powder with Leu at 5 and 25°C at 3 months. Furthermore, transfection experiments revealed that Leu exhibited a pDNA-stabilizing effect in the solution and dry powder. Similar results were observed for pDNA integrity, where a polyplex was formed in the dry powder. The results suggest that Leu is a candidate stabilizer to protect pDNA from degradation.

  5. Cubic phase-forming dry powders for controlled drug delivery on mucosal surfaces.

    PubMed

    Moebus, K; Siepmann, J; Bodmeier, R

    2012-01-30

    The purpose of this study was to prepare and physicochemically characterize protein-loaded, glycerol monooleate (GMO)-based dry powder systems, which can be used for the controlled mucosal delivery of macromolecules (e.g., nasal, buccal, pulmonary). Bovine serum albumin (BSA)-loaded powders were prepared by spray-drying, freeze-drying and/or spray-freezing using different types of carrier materials, including mannitol, polyvinyl pyrrolidone (PVP 25) and polyethylene glycols (PEGs). The systems were characterized by optical and polarized light microscopy, X-ray powder diffraction, gel electrophoresis and diffusion studies. The type of carrier material strongly affected the resulting particle size and shape. The presence of GMO effectively slowed down BSA release. Importantly, broad ranges of release patterns could be achieved by varying the type of preparation method and composition of the dry powders. In all cases, the primary structure of the BSA remained intact. GMO, which is a wax solid at room temperature, has been successfully converted into dry powder formulations that offer potential for the controlled mucosal delivery of proteins.

  6. Standardization of spray-dried powder of Piper betle hot water extract

    PubMed Central

    Arawwawala, Liyanage Dona Ashanthi Menuka; Hewageegana, Horadugoda Gamage Sujatha Pushpakanthi; Arambewela, Lakshmi Sriyani Rajapaksha; Ariyawansa, Hettiarachchige Sami

    2011-01-01

    The leaves of Piper betle Linn. (Family: Piperaceae) possess several bioactivities and are used in the Traditional Medical systems of Sri Lanka. The present investigation was carried out to standardize the spray-dried powder of P. betle by (a) determination of physicochemical parameters, presence or absence of heavy metals, and microbial contamination; (b) screening for phytochemicals; and (c) development of High Pressure Liquid Chromatography (HPLC) fingerprint and densitogram. The percentages of moisture content, total ash, acid insoluble ash, water-soluble ash, and ethanol extractable matter of spray-dried powder of P. betle were 2.2-2.5, 6.8-7.0, 0.003-0.005, 4.1-4.3, and 15.8-16.2, respectively. The concentrations of all the tested heavy metals were below the WHO acceptable limits and bacterial species, such as Escherichia coli, Salmonella spp, Staphylococcus aureus, and Pseudomonas aeroginosa were not present in the P. betle spray-dried powder. Phenolic compounds, tannins, flavonoids steroids, and alkaloids were found to be present in the spray-dried powder of P. betle and HPLC fingerprint and densitogram clearly demonstrated the proportional differences of these chemical constituents. In conclusion, the results obtained from this study can be used to standardize the spray-dried powder of P. betle. PMID:21716924

  7. Rapid formation of phase-clean 110 K (Bi-2223) powders derived via freeze-drying process

    DOEpatents

    Balachandran, U.

    1996-06-04

    A process for the preparation of amorphous precursor powders for Pb-doped Bi{sub 2}Sr{sub 2} Ca{sub 2}Cu{sub 3}O{sub x} (2223) includes a freeze-drying process incorporating a splat-freezing step. The process generally includes splat freezing a nitrate solution of Bi, Pb, Sr, Ca, and Cu to form flakes of the solution without any phase separation; grinding the frozen flakes to form a powder; freeze-drying the frozen powder; heating the dried powder to form a dry green precursor powders; denitrating the green-powders; heating the denitrated powders to form phase-clean Bi-2223 powders. The grain boundaries of the 2223 grains appear to be clean, leading to good intergrain contact between 2223 grains. 11 figs.

  8. Rapid formation of phase-clean 110 K (Bi-2223) powders derived via freeze-drying process

    DOEpatents

    Balachandran, Uthamalingam

    1996-01-01

    A process for the preparation of amorphous precursor powders for Pb-doped Bi.sub.2 Sr.sub.2 Ca.sub.2 Cu.sub.3 O.sub.x (2223) includes a freeze-drying process incorporating a splat-freezing step. The process generally includes splat freezing a nitrate solution of Bi, Pb, Sr, Ca, and Cu to form flakes of the solution without any phase separation; grinding the frozen flakes to form a powder; freeze-drying the frozen powder; heating the dried powder to form a dry green precursor powders; denitrating the green-powders; heating the denitrated powders to form phase-clean Bi-2223 powders. The grain boundaries of the 2223 grains appear to be clean, leading to good intergrain contact between 2223 grains.

  9. Multifunctional graded dielectrics fabricated using dry powder printing

    NASA Astrophysics Data System (ADS)

    Good, Austin J.; Roper, David; Good, Brandon; Yarlagadda, Shridhar; Mirotznik, Mark S.

    2017-09-01

    The ability to fabricate multifunctional devices that combine good structural properties with embedded electromagnetic functionality has many practical applications, including antireflective surfaces for structural radomes, load bearing conformal antennas, integrated RF transmission lines and passive beam forming networks. We describe here a custom made 3D printer that can print high dielectric constant ceramic powders within a low-loss structural composite substrate to produce mechanically robust parts with integrated graded dielectric properties. We fabricated a number of these parts and evaluated their anisotropic dielectric properties by determining the complete permittivity tensor of the printed samples as a function of local powder weight. This data was then experimentally validated using two practical examples: a Chebyshev antireflective stack and a 2D passive beamsteering network. The results of both electromagnetic systems displayed acceptable agreement between the simulated and measured results. This agreement shows that powder printing is a potential approach for fabricating spatially graded dielectric electromagnetic systems. This paper was submitted for review on 15 February 2017. The project is funded by the Office of Naval Research, Code 331.

  10. Formation of highly porous aerosol particles by atmospheric freeze-drying in ice clouds.

    PubMed

    Adler, Gabriela; Koop, Thomas; Haspel, Carynelisa; Taraniuk, Ilya; Moise, Tamar; Koren, Ilan; Heiblum, Reuven H; Rudich, Yinon

    2013-12-17

    The cycling of atmospheric aerosols through clouds can change their chemical and physical properties and thus modify how aerosols affect cloud microphysics and, subsequently, precipitation and climate. Current knowledge about aerosol processing by clouds is rather limited to chemical reactions within water droplets in warm low-altitude clouds. However, in cold high-altitude cirrus clouds and anvils of high convective clouds in the tropics and midlatitudes, humidified aerosols freeze to form ice, which upon exposure to subsaturation conditions with respect to ice can sublimate, leaving behind residual modified aerosols. This freeze-drying process can occur in various types of clouds. Here we simulate an atmospheric freeze-drying cycle of aerosols in laboratory experiments using proxies for atmospheric aerosols. We find that aerosols that contain organic material that undergo such a process can form highly porous aerosol particles with a larger diameter and a lower density than the initial homogeneous aerosol. We attribute this morphology change to phase separation upon freezing followed by a glass transition of the organic material that can preserve a porous structure after ice sublimation. A porous structure may explain the previously observed enhancement in ice nucleation efficiency of glassy organic particles. We find that highly porous aerosol particles scatter solar light less efficiently than nonporous aerosol particles. Using a combination of satellite and radiosonde data, we show that highly porous aerosol formation can readily occur in highly convective clouds, which are widespread in the tropics and midlatitudes. These observations may have implications for subsequent cloud formation cycles and aerosol albedo near cloud edges.

  11. Formation of highly porous aerosol particles by atmospheric freeze-drying in ice clouds

    PubMed Central

    Adler, Gabriela; Koop, Thomas; Haspel, Carynelisa; Taraniuk, Ilya; Moise, Tamar; Koren, Ilan; Heiblum, Reuven H.; Rudich, Yinon

    2013-01-01

    The cycling of atmospheric aerosols through clouds can change their chemical and physical properties and thus modify how aerosols affect cloud microphysics and, subsequently, precipitation and climate. Current knowledge about aerosol processing by clouds is rather limited to chemical reactions within water droplets in warm low-altitude clouds. However, in cold high-altitude cirrus clouds and anvils of high convective clouds in the tropics and midlatitudes, humidified aerosols freeze to form ice, which upon exposure to subsaturation conditions with respect to ice can sublimate, leaving behind residual modified aerosols. This freeze-drying process can occur in various types of clouds. Here we simulate an atmospheric freeze-drying cycle of aerosols in laboratory experiments using proxies for atmospheric aerosols. We find that aerosols that contain organic material that undergo such a process can form highly porous aerosol particles with a larger diameter and a lower density than the initial homogeneous aerosol. We attribute this morphology change to phase separation upon freezing followed by a glass transition of the organic material that can preserve a porous structure after ice sublimation. A porous structure may explain the previously observed enhancement in ice nucleation efficiency of glassy organic particles. We find that highly porous aerosol particles scatter solar light less efficiently than nonporous aerosol particles. Using a combination of satellite and radiosonde data, we show that highly porous aerosol formation can readily occur in highly convective clouds, which are widespread in the tropics and midlatitudes. These observations may have implications for subsequent cloud formation cycles and aerosol albedo near cloud edges. PMID:24297908

  12. Instability of bacteriophages in spray-dried trehalose powders is caused by crystallization of the matrix.

    PubMed

    Vandenheuvel, Dieter; Meeus, Joke; Lavigne, Rob; Van den Mooter, Guy

    2014-09-10

    Spray drying is a valuable technique in pharmaceutical dosage formulation, capable of producing amorphous, spherical powders, suitable for pulmonary deposition and further downstream processing. In this study, we show that spray drying bacteriophages together with trehalose results in an amorphous powder matrix with high glass transition temperature (between 116 and 118°C), typical for amorphous trehalose. These powders are stable at low temperatures (4°C) and relative humidity (0%). However, high humidity causes crystallization of the amorphous matrix, destroying the embedded phages. Furthermore, storage at higher temperature (25°C) causes thermal instability of the embedded phages. The results show that storage conditions are important parameters to take into account in phage therapy development. The resulting particles are hollow spheres, with suitable aerodynamic diameters for deposition into the deep lungs. This opens possibilities to use these phage-containing powder formulations to tackle pulmonary infectious diseases, especially caused by antibiotic resistant pathogens.

  13. Development of dry salbutamol sulfate powder with high inhalation performance independent of inhalation patterns.

    PubMed

    Hira, Daiki; Okuda, Tomoyuki; Ichihashi, Mika; Kojima, Haruyoshi; Okamoto, Hirokazu

    2012-01-01

    While dry powder inhalations are commonly used to treat pulmonary diseases, their clinical performance depends on patient inspiratory flow patterns. The purpose of this study was to develop a new powder with high and stable therapeutic performance for various patients. We applied the supercritical antisolvent (SCF) method to salbutamol sulfate (SS) to prepare a bulky SS particle (SS-SCF). Tests of in vitro inhalation performance with a human inspiratory flow simulator revealed SS-SCF to be less susceptible to inspiratory flow patterns than milled SS. When inspired, the unique structure seemed to be broken resulting in small fragments that could be delivered to the lungs. However, stability tests under physical stress showed tolerance for transportation and handling. In addition, optimization of the concentration of the SS solution applied to SCF method improved the in vitro inhalation performance of SS-SCF. These results indicated that a unique bulky SS powder prepared by the SCF method was useful for dry powder inhalation.

  14. Needle-Free Inhalable Vaccine and Antibiotic Powder Aerosols

    DTIC Science & Technology

    2004-11-15

    carbon dioxide processing • Needle-free delivery of respirable vaccines (e.g., measles), antibiotics, and pharmaceuticals • Nanoparticle and... delivery into • lungs (1-3 microns), or into nasal passages (10-30 microns) • Stabilize in glassy sugar matrices, then micronize and desolvate -Avoid...collected and packaged. CAN-BD Mixing Tee Drying Temperature: 1°C to 60°C Drug Solution or Suspension Near-critical or Supercritical CO2 (80 to 100 bars

  15. Model Calculations of Regional Deposition and Disposition for Single Doses of Inhaled Liposomal and Dry Powder Ciprofloxacin.

    PubMed

    Martin, Andrew R; Finlay, Warren H

    2017-07-14

    Model predictions of regional deposition in the respiratory tract are useful in assessing factors that influence the effectiveness of aerosol delivery. Regional deposition models have previously been coupled with models of mucous production and clearance to estimate initial concentrations of drug deposited in the airway surface liquid (ASL) lining tracheobronchial airways. Established models of regional deposition and ASL volumes were used to provide input to a new model evaluating the disposition of drug resulting from dissolution or release, absorption, and mucociliary clearance. Additional modeling of oral absorption, distribution, and elimination allowed prediction of systemic exposure. Herein, predicted ASL and plasma concentrations of free (dissolved or unencapsulated) ciprofloxacin over time are reported for a healthy, adult lung model following inhalation of single doses of nebulized liposomal (6 mL of liposomal ciprofloxacin for inhalation, 50 mg/mL, or 6 mL of Pulmaquin, 210 mg; Aradigm) and dry powder (32.5 and 65 mg doses; Bayer) formulations. Over a range of mucous production rates and tracheal clearance velocities, peak ASL concentrations of free ciprofloxacin were consistently greater for Pulmaquin than for other formulations investigated, owing to the presence of free drug in the nebulized Pulmaquin formulation. The time that ASL concentrations of free drug remained above the minimum inhibitory concentration for Pseudomonas aeruginosa was similar for all four formulations. Predicted plasma ciprofloxacin concentration profiles were in good agreement with available data from Phase I trials in healthy volunteers. Predictions of ASL drug concentrations over time are valuable in elucidating the roles of deposition, drug release or dissolution, and disposition on the effectiveness of inhaled aerosol therapies. For inhaled ciprofloxacin, the present results predict similar ASL concentrations of free drug over time following single doses of

  16. Dry powder preparation of inulin fructotransferase from Arthrobacter aurescens SK 8.001 fermented liquor.

    PubMed

    Hang, Hua; Li, Yungao; Zhao, Meng; Jiang, Bo; Miao, Ming; Mu, Wanmeng; Zhang, Tao

    2013-06-20

    Difructosan anhydrides III (DFA III) are usually obtained by inulin conversion with inulin fructotransferase (IFTase). IFTase liquor is difficult to store for a long time, which could greatly restrict its application and DFA III production. To meet DFA III scale-up preparation, this work was explored to research dry powder preparation of IFTase from Arthrobacter aurescens SK 8.001 fermented liquor by ultrafiltration concentration, ammonium sulfate precipitation and freeze drying. IFTase powder (10.2g) was obtained from IFTase precipitation (126.4 g) and its specific activity determined was 16.4 U/mg. Dry powder of IFTase could maintain over 120 days at different temperatures. These results showed that it is easy to scale up DFA III preparation for industrial capacity.

  17. Measurement techniques in dry-powdered processing of spent nuclear fuels.

    SciTech Connect

    Bowers, D. L.; Hong, J.-S.; Kim, H.-D.; Persiani, P. J.; Wolf, S. F.

    1999-07-21

    High-performance liquid chromatography (HPLC) with inductively coupled plasma mass spectrometry (ICPMS) detection, {alpha}-spectrometry ({alpha}-S), and {gamma}-spectrometry ({gamma}-S) were used for the determination of nuclide content in five samples excised from a high-burnup fuel rod taken from a pressurized water reactor (PWR). The samples were prepared for analysis by dissolution of dry-powdered samples. The measurement techniques required no separation of the plutonium, uranium, and fission products. The sample preparation and analysis techniques showed promise for in-line analysis of highly-irradiated spent fuels in a dry-powdered process. The analytical results allowed the determination of fuel burnup based on {sup 148}Nd, Pu, and U content. A goal of this effort is to develop the HPLC-ICPMS method for direct fissile material accountancy in the dry-powdered processing of spent nuclear fuel.

  18. Aerosol Particle Monitoring and Dry Deposition Modeling at a Dry Plateau Site at Colorado

    NASA Astrophysics Data System (ADS)

    Luo, H.; Loescher, H. W.; Neff, J.; Fernandez, D.

    2009-12-01

    Dust and elemental inputs from dry deposition affect ecosystem-level biogeochemistry, ecohydrology, energy balance and ultimately productivity and biodiversity, particularly at high altitude mountain areas. Given its important ecological impacts, the long-term estimates (seasonal-to-annual-to decadal scales) of the deposition, fate and transport of the dust regionally are of great interest. We evaluated automated instrumentation to fulfill this goal. A side by side comparison of different type sensors was conducted in semi-arid grasslands 24 Km north of Boulder, CO from July to the end of September in 2009. We measured the concentration of different particle sizes and modeled deposition velocity for particle size <=2.5 micron, <=10 micron and Total Suspended Particulate (TSP). We compared the estimates from the i) PQ200 from BGI Inc. and ii) Bam-1020 from Met One Inc. (Both are EPA designated Federal Equivalent Method (FEM) for PM10 and PM2.5 particulate monitoring), iii) the TSP mass flow-controlled high volume air sampler, which is made by Thermo Fisher Scientific Inc. and commonly used in monitoring TSP in the air and elemental analysis for aerosol particles, and iv) a new laser photometer DustTrak DRX Aerosol Monitor from TSI Inc., which is able to measure size-segregated mass fraction concentration corresponding to PM1, PM2.5, respirable, PM10 and TSP simultaneously. Data from a 3D sonic anemometer were used to model the velocity of dry deposition to the ground surface. Particle concentrations obtained from different samplers tracked well and captured large events (i.e. fires, dust storms, etc) at the same fraction and magnitude. Besides the agreement with other mature (or standard) methods with the corresponding particle fraction, DustTrak DRX demonstrated a faster response to a changing environment (scale of minutes compared to hours). The similar performance found in laser device compared to the tradition FEM methodology indicated that the new laser

  19. Influence of coating material on the flowability and dissolution of dry-coated fine ibuprofen powders.

    PubMed

    Qu, Li; Zhou, Qi Tony; Denman, John A; Stewart, Peter J; Hapgood, Karen P; Morton, David A V

    2015-10-12

    This study investigates the effects of a variety of coating materials on the flowability and dissolution of dry-coated cohesive ibuprofen powders, with the ultimate aim to use these in oral dosage forms. A mechanofusion approach was employed to apply a 1% (w/w) dry coating onto ibuprofen powder with coating materials including magnesium stearate (MgSt), L-leucine, sodium stearyl fumarate (SSF) and silica-R972. No significant difference in particle size or shape was measured following mechanofusion with any material. Powder flow behaviours characterised by the Freeman FT4 system indicated coatings of MgSt, L-leucine and silica-R972 produced a notable surface modification and substantially improved flow compared to the unprocessed and SSF-mechanofused powders. ToF-SIMS provided a qualitative measure of coating extent, and indicated a near-complete layer on the drug particle surface after dry coating with MgSt or silica-R972. Of particular note, the dissolution rates of all mechanofused powders were enhanced even with a coating of a highly hydrophobic material such as magnesium stearate. This surprising increase in dissolution rate of the mechanofused powders was attributed to the lower cohesion and the reduced agglomeration after mechanical coating. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Optimization of spray drying process for developing seabuckthorn fruit juice powder using response surface methodology.

    PubMed

    Selvamuthukumaran, Meenakshisundaram; Khanum, Farhath

    2014-12-01

    The response surface methodology was used to optimize the spray drying process for development of seabuckthorn fruit juice powder. The independent variables were different levels of inlet air temperature and maltodextrin concentration. The responses were moisture, solubility, dispersibility, vitamin C and overall color difference value. Statistical analysis revealed that independent variables significantly affected all the responses. The Inlet air temperature showed maximum influence on moisture and vitamin C content, while the maltodextrin concentration showed similar influence on solubility, dispersibility and overall color difference value. Contour plots for each response were used to generate an optimum area by superimposition. The seabuckthorn fruit juice powder was developed using the derived optimum processing conditions to check the validity of the second order polynomial model. The experimental values were found to be in close agreement to the predicted values and were within the acceptable limits indicating the suitability of the model in predicting quality attributes of seabuckthorn fruit juice powder. The recommended optimum spray drying conditions for drying 100 g fruit juice slurry were inlet air temperature and maltodextrin concentration of 162.5 °C and 25 g, respectively. The spray dried juice powder contains higher amounts of antioxidants viz., vitamin C, vitamin E, total carotenoids, total anthocyanins and total phenols when compared to commercial fruit juice powders and they are also found to be free flowing without any physical alterations such as caking, stickiness, collapse and crystallization by exhibiting greater glass transition temperature.

  1. A Dry Powder Process for Preparing Uni-Tape Prepreg from Polymer Powder Coated Filamentary Towpregs

    NASA Technical Reports Server (NTRS)

    Wilkinson, Steven P. (Inventor); Johnston, Norman J. (Inventor); Marchello, Joseph M. (Inventor)

    1995-01-01

    A process for preparing uni-tape prepreg from polymer powder coated filamentary towpregs is provided. A plurality of polymer powder coated filamentary towpregs are provided. The towpregs are collimated so that each towpreg is parallel. The sandwich is heated to a temperature wherein the polymer flows and intimately contacts the filaments and pressure is repeatedly applied perpendicularly to the sandwich with a longitudinal oscillating action wherein the filaments move apart and the polymer wets the filaments forming a uni-tape prepreg. The uni-tape prepreg is subsequently cooled.

  2. Dry powder process for preparing uni-tape prepreg from polymer powder coated filamentary towpregs

    NASA Technical Reports Server (NTRS)

    Wilkinson, Steven P. (Inventor); Johnston, Norman J. (Inventor); Marchello, Joseph M. (Inventor)

    1997-01-01

    A process for preparing uni-tape prepreg from polymer powder coated filamentary towpregs is provided. A plurality of polymer powder coated filamentary towpregs are provided. The towpregs are collimated so that each towpreg is parallel. A material is applied to each side of the towpreg to form a sandwich. The sandwich is heated to a temperature wherein the polymer flows and intimately contacts the filaments and pressure is repeatedly applied perpendicularly to the sandwich with a longitudinal oscillating action wherein the filaments move apart and the polymer wets the filaments forming a uni-tape prepreg. The uni-tape prepreg is subsequently cooled.

  3. Volatile composition and sensory characteristics of onion powders prepared by convective drying.

    PubMed

    Choi, So Mang; Lee, Dong-Jin; Kim, Jong-Yea; Lim, Seung-Taik

    2017-09-15

    Volatile composition and sensory characteristics of onion powders prepared by convective drying at different temperatures (50, 70, and 90°C) were investigated. Dipropyl disulfide was the major volatile compound in fresh onion (77.70% of total volatile compounds). However it was considerably lost during drying, reaching 6.93-32.25µg/g solids. Dipropyl disulfide showed a positive correlation with green sensory attribute perceived by descriptive sensory analysis. Thiophenes, which were responsible for caramel and sweet attributes, were produced by drying especially when the drying temperature was high. Aldehydes, another type of volatile compound found in fresh onion, showed a positive correlation with humidity. The aldehyde content in dried onion was the highest at the lowest drying temperature, possibly because the aldehydes were produced by the residual enzymes in fresh onion. Using a low temperature for drying was ideal to retain the aroma of fresh onion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Bend strengths of reaction bonded silicon nitride prepared from dry attrition milled silicon powder

    NASA Technical Reports Server (NTRS)

    Herbell, T. P.; Glasgow, T. K.

    1979-01-01

    Dry attrition milled silicon powder was compacted, sintered in helium, and reaction bonded in nitrogen-4 volume percent hydrogen. Bend strengths of bars with as-nitrided surfaces averaged as high as 210 MPa at room temperature and 220 MPa at 1400 C. Bars prepared from the milled powder were stronger than those prepared from as-received powder at both room temperature and at 1400 C. Room temperature strength decreased with increased milling time and 1400 C strength increased with increased milling time.

  5. Toward intradermal vaccination: preparation of powder formulations by collapse freeze-drying.

    PubMed

    Etzl, Elsa E; Winter, Gerhard; Engert, Julia

    2014-03-01

    Intradermal powder immunization is an emerging technique in vaccine delivery. The purpose of this study was to generate powder particles for intradermal injection by freeze-drying and subsequent cryo-milling. Two different freeze-drying protocols were compared, a moderate freeze-drying cycle and an aggressive freeze-drying cycle, which induced a controlled collapse of the sugar matrix. Ovalbumin served as model antigen. The influence of collapse drying and cryo-milling on particle morphology and protein stability was investigated. Cryo-milling generated irregularly shaped particles of size 20-70 µm. The recovery of soluble monomer of ovalbumin was not changed during freeze-drying and after cryo-milling, or after 12 months of storage at 2-8 °C. A slight increase in higher molecular weight aggregates was found in formulations containing the polymer dextran after 12 months of storage at 50 °C. Light obscuration measurements showed an increase in cumulative particle counts after cryo-milling that did not further increase during storage at 2-8 °C for 12 months. The applicability of the cryo-milling process to other therapeutic proteins was shown using recombinant human granulocyte-colony stimulating factor. Collapse freeze-drying and subsequent cryo-milling allows the generation of particles suitable for intradermal powder injection.

  6. A novel aerosol generator for homogenous distribution of powder over the lungs after pulmonary administration to small laboratory animals.

    PubMed

    Tonnis, Wouter F; Bagerman, Marieke; Weij, Michel; Sjollema, Jelmer; Frijlink, Henderik W; Hinrichs, Wouter L J; de Boer, Anne H

    2014-11-01

    To evaluate powder formulations for pulmonary administration in pre-clinic research, the powder should be administered to the lungs of small laboratory animals. To do so properly, a device is needed that generates particles small enough to reach deep into the lungs. In this study a newly developed aerosol generator was tested for pulmonary administration of powder to the lungs of mice and its performance was compared to the only currently available device, the Penn-Century insufflator. Results showed that both devices generated powder particles of approximately the same size distribution, but the fine particle fraction needed for deep lung administration was strongly improved when the aerosol generator was used.Imaging studies in mice showed that powder particles from the aerosol generator deposited into the deep lung, where powder from the Penn-Century insufflator did not reach further than the conducting airways.Furthermore, powder administered by using the aerosol generator was more homogenously distributed over the five individual lungs lobes than powder administrated by using the Penn-Century insufflator.

  7. Single-step Coprocessing of Cohesive Powder via Mechanical Dry Coating for Direct Tablet Compression.

    PubMed

    Qu, Li; Stewart, Peter J; Hapgood, Karen P; Lakio, Satu; Morton, David A V; Zhou, Qi Tony

    2017-01-01

    This study aims at testing the feasibility of a single-step coating process to produce a powder formulation of active and inactive ingredients for direct compression. A cohesive ibuprofen powder was coprocessed with a coating material, a binder (polyvinylpyrrolidone K25), and a superdisintegrant (crospovidone). Magnesium stearate (MgSt), l-leucine, and silica were selected as coating materials (1% w/w). A coprocessed powder without any coating material was employed as a control. Coating with MgSt, l-leucine, or silica produced significantly improved powder flow in comparison to the control batch. Robust tablets were produced from the processed powders for each coating material. The tablets compacted using the coated powders with MgSt or l-leucine also exhibited significantly lower tablet ejection forces than the control batch, demonstrating their lubrication effect. Furthermore, the disintegration time and dissolution rates of these tablets made of the formulations coprocessed with lubricants were enhanced, even for those coated with the hydrophobic material such as MgSt that has been previously reported to inhibit dissolution. However, the tablets made with silica-coated powders would not disintegrate. This study indicated the feasibility of a single-step dry coating process to produce powders with both flow-aid and lubrication effects, which are suitable for direct compression. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air-Liquid Interface Cultured Cell Layer.

    PubMed

    Asai, Ayumu; Okuda, Tomoyuki; Yamauchi, Tomoyo; Sugiura, Yuka; Okamoto, Hirokazu

    2016-01-01

    Most safety evaluations of dry powder inhalers (DPIs) using cultured cells have been performed with dry powder formulations dissolved in a medium. However, this method is not considered to be suitable to evaluate the safety of inhaled dry powder formulations correctly since it cannot reflect the actual phenomenon on the respiratory epithelial surface. In this study, we established a novel in-vitro safety evaluation system suitable for DPIs by combining an air-liquid interface cultured cell layer and a device for dispersing dry powders, and evaluated the safety of candidate excipients of dry powders for inhalation. The safety of excipients (sugars, amino acids, cyclodextrins, and positive controls) in solutions was compared using submerged cell culture systems with a conventional 96-well plate and Transwell(®). The sensitivity of the cells grown in Transwell(®) was lower than that of those grown in the 96-well plate. Dry powders were prepared by spray-drying and we evaluated their safety with a novel in-vitro safety evaluation system using an air-liquid interface cultured cell layer. Dry powders decreased the cell viability with doses more than solutions. On the other hand, dissolving the dry powders attenuated their cytotoxicity. This suggested that the novel in-vitro safety evaluation system would be suitable to evaluate the safety of DPIs with high sensitivity.

  9. Development of a rapid screening protocol for selection of strains resistant to spray drying and storage in dry powder.

    PubMed

    Reimann, S; Grattepanche, F; Baggenstos, C; Rezzonico, E; Berger, B; Arigoni, F; Lacroix, C

    2010-06-01

    An efficient screening method for selection of Bifidobacterium longum strains resistant to spray drying and storage was developed based on randomly amplified polymorphic DNA (RAPD) for identification of the best survivors in mixed strains bacterial preparations. Three different primers were used to generate RAPD profiles of 22 B. longum strains. All strains were distinguished according to their RAPD profiles except for the strain NCC2705 and its H(2)O(2) resistant derivative variant. The 22 strains were grouped in 3 batches of 7, 7 and 8 strains and subjected to spray drying and storage at 30 and 37 °C under anaerobic conditions. Batch survival rates after spray drying reached 17.1±4.4%. Strains showing the highest prevalence and/or resistance to storage at 37 °C were selected from individual batches for subsequent spray drying and storage testing. After 67 days of storage, NCC572 was identified as the dominant strain in powder. The stability of strain NCC572 was confirmed by performing single spray drying and storage tests. Out of 22 B. longum strains, a robust strain was identified by combining RAPD with a simultaneous screening test for survival under spray drying and storage. The method allowed a fast screening of B. longum strains in mixture for resistance to spray drying and storage compared to traditional screening procedures carried out with individual strains, in the same conditions. This approach could be applied to other stress conditions.

  10. Non-steroidal anti-inflammatory drug for pulmonary administration: design and investigation of ketoprofen lysinate fine dry powders.

    PubMed

    Stigliani, Mariateresa; Aquino, Rita P; Del Gaudio, Pasquale; Mencherini, Teresa; Sansone, Francesca; Russo, Paola

    2013-05-01

    Pulmonary inflammation is an important therapeutic target in cystic fibrosis (CF) patients, aiming to limit and delay the lung damage. The purpose of the present research was to produce respirable engineered particles of ketoprofen lysinate, a non-steroidal anti-inflammatory drug able to fight lung inflammatory status by direct administration to the site of action. Micronized drug powders containing leucine as dispersibility enhancer were prepared by co-spray drying the active compound and the excipient from water or hydro-alcoholic feeds. Microparticles were fully characterized in terms of process yield, particle size distribution, morphology and drug content. The ability of the drug to reach the deepest airways after aerosolization of spray-dried formulations was evaluated by Andersen cascade impactor, using the monodose DPI as device. In order to investigate the behaviour of the drug once in contact with lung fluid, an artificial CF mucus was prepared. Drug permeation properties were evaluated interposing the mucus layer between the drug and a synthetic membrane mounted in Franz-type diffusion cells. Finally, the effect of the engineered particles on vitality of human airway epithelial cells of patients homozygous for ΔF 508 CF (CuFi1) was studied and compared to that of raw active compound. Results indicated that powders engineering changed the diameter and shape of the particles, making them suitable for inhalation. The mucus layer in the donor compartment of vertical diffusion cells slowed down drug dissolution and permeation, leucine having no influence. Cell proliferation studies evidenced that the spray drying process together with the addition of leucine reduced the cytotoxic effect of ketoprofen lysine salt as raw material, making the ketoprofen lysinate DPI a very promising product for the inflammation control in CF patients.

  11. 30 CFR 75.1101-16 - Dry powder chemical systems; sensing and fire-suppression devices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... activate the fire-control system, sound an alarm and stop the conveyor drive motor in the event of a rise... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Dry powder chemical systems; sensing and fire..., DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Fire...

  12. Bronchodilator effect of disodium cromoglycate administered as a dry powder in exercise induced asthma.

    PubMed Central

    Horn, C R; Jones, R M; Lee, D; Brennan, S R

    1984-01-01

    A double-blind, placebo controlled study of the effects of disodium cromoglycate (DSCG), administered as a dry powder via the spinhaler, in established exercise-induced asthma, was carried out. DSCG resulted in an increase in the rate of recovery compared with placebo. The findings confirm that DSCG has bronchodilator properties. PMID:6439234

  13. A novel electrostatic dry powder coating process for pharmaceutical dosage forms: immediate release coatings for tablets.

    PubMed

    Qiao, Mingxi; Zhang, Liqiang; Ma, Yingliang; Zhu, Jesse; Chow, Kwok

    2010-10-01

    An electrostatic dry powder coating process for pharmaceutical solid dosage forms was developed for the first time by electrostatic dry powder coating in a pan coater system. Two immediate release coating compositions with Opadry® AMB and Eudragit® EPO were successfully applied using this process. A liquid plasticizer was sprayed onto the surface of the tablet cores to increase the conductivity of tablet cores to enhance particle deposition, electrical resistivity reduced from greater than 1×10(13)Ωm to less than 1×10(9)Ωm, and to lower the glass transition temperature (T(g)) of the coating polymer for film forming in the pan coater. The application of liquid plasticizer was followed by spraying charged coating particles using an electrostatic charging gun to enhance the uniform deposition on tablet surface. The coating particles were coalesced into a thin film by curing at an acceptable processing temperature as formation was confirmed by SEM micrographs. The results also show that the optimized dry powder coating process produces tablets with smooth surface, good coating uniformity and release profile that are comparable to that of the tablet cores. The data also suggest that this novel electrostatic dry powder coating technique is an alternative to aqueous- or solvent-based coating process for pharmaceutical products. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  14. Adenosine dry powder inhalation for bronchial challenge testing, part 2: proof of concept in asthmatic subjects.

    PubMed

    Lexmond, Anne J; van der Wiel, Erica; Hagedoorn, Paul; Bult, Wouter; Frijlink, Henderik W; ten Hacken, Nick H T; de Boer, Anne H

    2014-09-01

    Adenosine is an indirect stimulus to assess bronchial hyperresponsiveness (BHR(2)) in asthma. Bronchial challenge tests are usually performed with nebulised solutions of adenosine 5'-monophosphate (AMP(3)). The nebulised AMP test has several disadvantages, like long administration times and a restrictive maximum concentration that does not result in BHR in all patients. In this study, we investigated the applicability of dry powder adenosine for assessment of BHR in comparison to nebulised AMP. Dry powder adenosine was prepared in doubling doses (0.01-80 mg) derived from the nebulised AMP test with addition of two higher doses. Five asthmatic subjects performed two bronchial challenge tests, one with nebulised AMP following the 2-min tidal breathing method; the second with dry powder adenosine administered with an investigational inhaler and single slow inhalations (inspiratory flow rate 30-40 L/min). All subjects reached a 20% fall in FEV₁(4) with the new adenosine test (PD20(5)) compared to four subjects with the AMP test (PC₂₀(6)). Dry powder adenosine was well tolerated by all subjects and better appreciated than nebulised AMP. In conclusion, this new bronchial challenge test appears to be a safe and convenient alternative to the nebulised AMP test to assess BHR in asthmatic subjects.

  15. Systematic review of the dry powder inhalers colistimethate sodium and tobramycin in cystic fibrosis.

    PubMed

    Uttley, Lesley; Harnan, Sue; Cantrell, Anna; Taylor, Chris; Walshaw, Martin; Brownlee, Keith; Tappenden, Paul

    2013-12-01

    This systematic review evaluated evidence for two dry powder formulations, colistimethate sodium and tobramycin, for the treatment of chronic Pseudomonas aeruginosa in cystic fibrosis, as part of the UK national recommendation process for new technologies. Electronic bibliographic databases were searched in May 2012 (MEDLINE, MEDLINE in-Process, EMBASE, Cochrane Library databases, CINAHL, Web of Science, Conference Proceedings Citation Index and BIOSIS Previews). Relevant outcomes included rate and extent of microbial response (e.g. sputum density of P. aeruginosa), lung function (e.g. forced expiratory volume in 1 s (FEV1)), frequency, severity of acute exacerbations and adverse events. Three trials were included, and both dry powder formulations were reported to be non-inferior in the short term to nebulised tobramycin for FEV1. However, long-term follow-up data were missing and the effect on exacerbation rates was not always reported. Whilst short-term results showed that both dry powder drugs were non-inferior to nebulised tobramycin, there was no long-term follow-up and no phase 3 trials compared nebulised and dry powder colistimethate sodium. The use of FEV1 as the primary end-point may not accurately represent changes in lung health. This review illustrates the difficulty in assessing new technologies where the evidence base is poor.

  16. Optimised process and formulation conditions for extended release dry polymer powder-coated pellets.

    PubMed

    Terebesi, Ildikó; Bodmeier, Roland

    2010-05-01

    The objective of this study was to improve the film formation and permeability characteristics of extended release ethylcellulose coatings prepared by dry polymer powder coating for the release of drugs of varying solubility. Ethylcellulose (7 and 10 cp viscosity grades) and Eudragit(R) RS were used for dry powder coating of pellets in a fluidised bed ball coater. Pre-plasticised ethylcellulose powder was prepared by spray-drying aqueous ethylcellulose dispersions (Surelease(R) and Aquacoat(R)) or by hot melt extrusion/cryogenic grinding of plasticised ethylcellulose. Chlorpheniramine maleate and theophylline were used as model drugs of different solubilities. The film formation process, polymeric films and coated pellets were characterised by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), scanning electron microscopy (SEM) and dissolution testing. Film formation and extended drug release was achieved with ethylcellulose, a polymer with a high glass transition temperature (T(g)) without the use of water, which is usually required in dry powder coating. DMA-measurements revealed that plasticised ethylcellulose had a modulus of elasticity (E') similar to the low T(g) Eudragit(R) RS. With increasing plasticiser concentration, the T(g) of ethylcellulose was reduced and the mechanical properties improved, thus facilitating coalescence of the polymer particles. SEM-pictures revealed the formation of a dense, homogeneous film. The lower viscosity grade ethylcellulose (7 cp) resulted in better film formation than the higher viscosity grade (10 cp) and required less stringent curing conditions. Successful extended release ethylcellulose coatings were also obtained by coating with pre-plasticised spray-dried ethylcellulose powders as an alternative to the separate application of pure ethylcellulose powder and plasticiser. The permeability of the extended release coating could be controlled by using powder blends of ethylcellulose with the

  17. Promising ternary dry powder inhaler formulations of cromolyn sodium: formulation and in vitro-in vivo evaluation.

    PubMed

    Elbary, Ahmed Abd; El-laithy, Hanan M; Tadros, Mina I

    2007-06-01

    Glucose monohydrate and sorbitol were evaluated as alternative carriers to á-lactose monohydrate in dry powder inhalations. Cromolyn sodium (CS) - carrier binary formulae were prepared and tested in vitro by aerosolization via a twin stage impinger using three types of inhaler devices; Spinhaler, Aerolizer and Handihaler. Glucose monohydrate and sorbitol-containing formulae that were inhaled via a Handihaler showed significantly higher drug fine particle fractions (P<0.001) than that of the same formulae aerosolized via other devices. Upon storage of the prepared formulae under uncontrolled humidity, that may be encountered during storage and use, marked reductions in these fractions were observed. Incorporation of an optimum Aerosil 200 concentration, as a ternary component, minimized this effect. A urinary excretion pharmacokinetic method was used to evaluate the bioavailability of the selected ternary formulae, inhaled via a Handihaler, relative to the marketed Intal Spincaps, inhaled via a Spinhaler. It was found that the relative bioavailability percentages of the developed formulae were more than twice that of the marketed one suggesting possible future utilization of these more effective ternrry formulae using the more efficient Handihaler inhaler device.

  18. Particle aerosolisation and break-up in dry powder inhalers: evaluation and modelling of impaction effects for agglomerated systems.

    PubMed

    Wong, William; Fletcher, David F; Traini, Daniela; Chan, Hak-kim; Crapper, John; Young, Paul M

    2011-07-01

    This study utilised a combination of computational fluid dynamics (CFD) and standardised entrainment tubes to investigate the influence of impaction on the break-up and aerosol performance of a model inhalation formulation. A series of entrainment tubes, with different impaction plate angles were designed in silico and the flow characteristics, and particle tracks, were simulated using CFD. The apparatuses were constructed using three-dimensional printing. The deposition and aerosol performance of a model agglomerate system (496.3-789.2 μm agglomerates containing 3.91 μm median diameter mannitol particles) were evaluated by chemical analysis and laser diffraction, respectively. Analysis of the mannitol recovery from the assembly and CFD simulations indicated that mass deposition on the plate was dependent on the impactor angle (45°-90°) but independent of the airflow rate (60-140 L·min(-1)). In comparison, wall losses, perpendicular to the impactor plate were dependent on both the impactor angle and flow rate. Analysis of the particle size distribution exiting the impactor assembly suggested mannitol aerosolisation to be independent of impactor angle but dependent on the air velocity directly above the impactor plate. It is proposed that particle-wall impaction results in initial agglomerate fragmentation followed by reentrainment in the airstream above the impaction plate. Such observations have significant implications in the design of dry powder inhaler devices.

  19. Spray Dried Sodium Zirconate: A Rapid Absorption Powder for CO2 Capture with Superior Cyclic Stability.

    PubMed

    Bamiduro, Faith; Ji, Guozhao; Brown, Andy P; Valerie A Dupont, Valerie A; Zhao, Ming; Milne, Steve J

    2017-04-03

    Improved powders for capturing CO2 at high temperatures are required for H2 production using sorption enhanced steam reforming. This paper examines the relationship between particle structure and carbonation rate for two types of Na2ZrO3 powder. Hollow spray-dried micro-granules with a wall thickness of 100-300 nm corresponding to the dimensions of the primary acetate derived particles gave ~75 wt % theoretical CO2 conversion after a process-relevant 5 min exposure to 15 vol % CO2. A conventional powder prepared by solid state reaction carbonated more slowly, only achieving 50 % conversion due to a greater proportion of the reaction requiring bulk diffusion through the densely agglomerated particles. The hollow granular structure of the spray dried powder was retained post-carbonation but chemical segregation resulted in islands of an amorphous Na-rich phase (Na2CO3) within a crystalline ZrO2 particle matrix. Despite this phase separation, the reverse reaction to re-form Na2ZrO3 could be achieved by heating each powder to 900 °C in N2 (no dwell time). This resulted in a very stable multicycle performance in 40 cycle tests using TGA for both powders. Kinetic analysis of TGA data showed the carbonation process fits an Avrami-Erofeyev 2-D nucleation and nuclei growth model, consistent with microstructural evidence of a surface driven transformation. Thus, we demonstrate that spray-drying is a viable processing route to enhance the carbon capture performance of Na2ZrO3 powder.

  20. Comparison of different drying methods on the physical properties, bioactive compounds and antioxidant activity of raspberry powders.

    PubMed

    Si, Xu; Chen, Qinqin; Bi, Jinfeng; Wu, Xinye; Yi, Jianyong; Zhou, Linyan; Li, Zhaolu

    2016-04-01

    Dehydration has been considered as one of the traditional but most effective techniques for perishable fruits. Raspberry powders obtained after dehydration can be added as ingredients into food formulations such as bakery and dairy products. In this study, raspberry powders obtained by hot air drying (HAD), infrared radiation drying (IRD), hot air and explosion puffing drying (HA-EPD), infrared radiation and microwave vacuum drying (IR-MVD) and freeze drying (FD) were compared on physical properties, bioactive compounds and antioxidant activity. Drying techniques affected the physical properties, bioactive compounds and antioxidant activity of raspberry powders greatly. FD led to significantly higher (P < 0.05) values of water solubility (45.26%), soluble solid (63.46%), hygroscopicity (18.06%), color parameters and anthocyanin retention (60.70%) of raspberry powder compared with other drying methods. However, thermal drying techniques, especially combined drying methods, were superior to FD in final total polyphenol content, total flavonoid content and antioxidant activity. The combined drying methods, especially IR-MVD, showed the highest total polyphenol content (123.22 g GAE kg(-1) dw) and total flavonoid content (0.30 g CAE kg(-1) dw). Additionally, IR-MVD performed better in antioxidant activity retention. Overall, combined drying methods, especially IR-MVD, were found to result in better quality of raspberry powders among the thermal drying techniques. IR-MVD could be recommended for use in the drying industry because of its advantages in time saving and nutrient retention. © 2015 Society of Chemical Industry.

  1. Preparation and characterization of spray-dried tobramycin powders containing nanoparticles for pulmonary delivery.

    PubMed

    Pilcer, Gabrielle; Vanderbist, Francis; Amighi, Karim

    2009-01-05

    Using high-pressure homogenization and spray-drying techniques, novel formulations were developed for manufacturing dry powder for inhalation, composed of a mixture of micro- and nanoparticles in order to enhance lung deposition. Particle size analysis was performed by laser diffraction. Spray-drying was applied in order to retrieve nanoparticles in dried-powder state from tobramycin nanosuspensions. The aerolization properties of the different formulations were evaluated by a multi-stage liquid impinger. Suspensions of nanoparticles of tobramycin containing Na glycocholate at 2% (w/w) relative to tobramycin content and presenting a mean particle size about 200 nm were produced. The results from the spray-dried powders showed that the presence of nanoparticles in the formulations improved particle dispersion properties during inhalation. The fine particle fraction (percentage of particles below 5 microm) increased from 36% for the raw micronized tobramycin material to about 61% for the most effective formulation. These new nanoparticle-containing tobramycin DPI formulations, based on the use of very low level of excipient and presenting high lung deposition properties, offer very important perspectives for improving the delivery of drugs to the pulmonary tract.

  2. Effect of vegetable proteins on physical characteristics of spray-dried tomato powders.

    PubMed

    Tontul, Ismail; Topuz, Ayhan; Ozkan, Ceren; Karacan, Merve

    2016-09-01

    In the present study, the effectiveness of different vegetable proteins (pea protein isolate, soy protein isolate and zein from maize) at two different ratios (1% and 5%) on product yield and physical properties of spray-dried pulpy tomato juice was investigated. Additionally, these proteins were compared with whey protein concentrate which has a superior effect on spray dried products at the same concentrations. Additionally, plain tomato juice was also spray dried for comparison with vegetable proteins. The product yield of the tomato powders dried with the vegetable proteins was lower than with the whey protein concentrate. Among vegetable proteins, the highest product yield was produced with 1% soy protein isolate. In all products, there was a slight colour difference between the reconstituted tomato powders and the raw tomato juice, which indicated that pulpy tomato juice can be spray dried with minor colour change. All powders had unique free-flowing properties estimated as Carr index and Hausner ratio due to their large particles. © The Author(s) 2016.

  3. Effects of spray-drying conditions on the chemical, physical, and sensory properties of cheese powder.

    PubMed

    Koca, Nurcan; Erbay, Zafer; Kaymak-Ertekin, Figen

    2015-05-01

    Dairy powders are produced to increase the shelf life of fresh dairy products and for use as flavoring agents. In this study, 24 cheese powders produced under 7 different conditions were used to investigate the effects of spray-drying parameters (e.g., inlet air temperature, atomization pressure, and outlet air temperature) on the quality of white cheese powder. Composition, color, physical properties, reconstitution, and sensory characteristics of white cheese powders were determined. The results revealed that the white cheese powders produced in this study had low moisture content ratios and water activity values. High outlet air temperatures caused browning and enhanced Maillard reactions. Additionally, high outlet air temperatures increased wettability and dispersibility and decreased the solubility of white cheese powders. Free fat content was positively correlated with inlet air temperature and negatively correlated with outlet air temperature and atomization pressure. Sensory analyses revealed that white cheese powder samples had acceptable sensory characteristics with the exception of the sample produced at an outlet air temperature of 100°C, which had high scores for scorched flavor and color and low scores for cheese flavor.

  4. [Obtainment of pineapple juice powder by foam-mat drying].

    PubMed

    Beristain, C I; Cortés, R; Casillas, M A; Díaz, R

    1991-06-01

    The foam-mat production and stability using pineapple juice concentrate (25, 30 and 40 degrees Brix), adding a surfactants mixture and maltodextrin (DE 10) as co-adjuvant, stirred in a commercial mixer, was studied. Adequate foam formation conditions were as follows: concentrate of 25 degrees Brix using surface active agents (Sorbac 60-Polisorbac 80) 0.285% surface active agent/total solids, HLB = 6, and stirring time, 7 min. The foam was dehydrated in an oven dried with a horizontal air flow circulation set at 60, 70 and 80 degrees C using 3, 5 and 10 mm bed depths. The best conditions were obtained at 60 degrees C and 5 mm bed depth. The product had a particle size of sieve 40-80, and a moisture content of 3%. It was then packaged in multilayer plastic film and stored at environmental conditions. No brown color formation or mold growth was detected during storage. Pineapple juice and a refreshing drink were prepared. The general acceptability in a community indicated that 95% of the population involved accepted the product.

  5. Treatment of acute severe asthma with inhaled albuterol delivered via jet nebulizer, metered dose inhaler with spacer, or dry powder.

    PubMed

    Raimondi, A C; Schottlender, J; Lombardi, D; Molfino, N A

    1997-07-01

    Despite the increasing use of dry powder formulations in the ambulatory setting, there is a paucity of information on the efficacy of this therapeutic modality to treat acute severe asthma. In addition, studies that compared wet nebulization vs metered dose inhalers formulated with chlorofluorocarbon (CFCMDI) attached to holding chambers have yielded discrepant results. Thus, it is unclear which of the three delivery systems would elicit a superior bronchodilator response, particularly in patients with life-threatening asthma. In a prospective, randomized open design, we studied the response to inhaled albuterol (salbutamol) in 27 adult asthmatics presenting to the emergency department (ED) with an FEV1 <30% predicted. Subjects were treated with one of the following regimens (nine subjects in each group): group A, mean (SD) baseline FEV1 of 0.7 (0.2) L, received albuterol solution, 5 mg, via a nebulizer (Puritan-Bennett Raindrop; Lawrenceville, Ga) impelled with oxygen (O2) at 8 L/min; group B, baseline FEV1 of 0.6 (0.15) L, received albuterol, 400 microg, via a CFCMDI attached to a 145-mL valved aerosol holding chamber (Aerochamber; Trudell Medical; London, ON); and group C, baseline FEV1 of 0.6 (0.17) L, received albuterol powder, 400 microg, by another means (Rotahaler; Glaxo; Research Triangle Park, NC). All groups received the respective treatments on arrival in the ED, every 30 min during the first 2 h, and then hourly until the sixth hour. Clinical parameters and FEV1 were recorded on ED admission and 15 min after each dose of albuterol. At the time of ED admission, all patients also received continuous O2 and one dose of I.V. steroids (dexamethasone, 8 mg). The total dose of inhaled albuterol administered during the 6-h treatment was 45 mg of nebulized solution in group A and 3,600 microg of albuterol aerosol and dry powder in groups B and C, respectively. No significant differences were found in the population demographics, baseline FEV1, and arterial

  6. Kilogram-scale production of SnO(2) yolk-shell powders by a spray-drying process using dextrin as carbon source and drying additive.

    PubMed

    Choi, Seung Ho; Kang, Yun Chan

    2014-05-05

    A simple and general method for the large-scale production of yolk-shell powders with various compositions by a spray-drying process is reported. Metal salt/dextrin composite powders with a spherical and dense structure were obtained by spray drying and transformed into yolk-shell powders by simple combustion in air. Dextrin plays a key role in the preparation of precursor powders for fabricating yolk-shell powders by spray drying. Droplets containing metal salts and dextrin show good drying characteristics even in a severe environment of high humidity. Sucrose, glucose, and polyvinylpyrrolidone are widely used as carbon sources in the preparation of metal oxide/carbon composite powders; however, they are not appropriate for large-scale spray-drying processes because of their caramelization properties and adherence to the surface of the spray dryer. SnO2 yolk-shell powders were studied as the first target material in the spray-drying process. Combustion of tin oxalate/dextrin composite powders at 600 °C in air produced single-shelled SnO2 yolk-shell powders with the configuration SnO2 @void@SnO2 . The SnO2 yolk-shell powders prepared by the simple spray-drying process showed superior electrochemical properties, even at high current densities. The discharge capacities of the SnO2 yolk-shell powders at a current density of 2000 mA g(-1) were 645 and 570 mA h g(-1) for the second and 100th cycles, respectively; the corresponding capacity retention measured for the second cycle was 88 %. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Accessorized DPI: a Shortcut towards Flexibility and Patient Adaptability in Dry Powder Inhalation.

    PubMed

    Buttini, Francesca; Hannon, James; Saavedra, Kristi; Rossi, Irene; Balducci, Anna Giulia; Smyth, Hugh; Clark, Andy; Colombo, Paolo

    2016-12-01

    In this work, a novel powder dispersion add-on device, the AOS (Axial Oscillating Sphere), was studied in conjunction with commercially available DPI devices to improve the powder dispersion. An ordered mixture of formoterol fumarate and lactose was selected. We studied in two laboratories located at different altitudes the dispensing and dispersion of the drug at different flow rates, paying particular attention to a number of metrics of Fine Particle Dose (FPD). Two novel findings emerged from the data collected. First, the aerosol quality, measured as fine particle dose, can be increased by adding the accessory promoting the dispersion and de-aggregation of the formulation. The second finding was that, albeit the emitted dose was independent of altitude, the drug/lactose carrier DPI aerosolizing performance changed with the altitude of testing. In particular, fine particle dose depended on both altitude and device configuration. The RS01 inhaler without the AOS accessory used at higher altitude gave the lowest FPD values. By combining the AOS accessory with the DPI, however, the performance dependence on altitude/atmospheric pressure was essentially removed. Increasing inhaler performance can be achieved using an add-on accessory that enhances aerosol dispersion and minimizes flow rate dependency.

  8. Material accountancy measurement techniques in dry-powdered processing of nuclear spent fuels.

    SciTech Connect

    Wolf, S. F.

    1999-03-24

    The paper addresses the development of inductively coupled plasma-mass spectrometry (ICPMS), thermal ionization-mass spectrometry (TIMS), alpha-spectrometry, and gamma spectrometry techniques for in-line analysis of highly irradiated (18 to 64 GWD/T) PWR spent fuels in a dry-powdered processing cycle. The dry-powdered technique for direct elemental and isotopic accountancy assay measurements was implemented without the need for separation of the plutonium, uranium and fission product elements in the bulk powdered process. The analyses allow the determination of fuel burn-up based on the isotopic composition of neodymium and/or cesium. An objective of the program is to develop the ICPMS method for direct fissile nuclear materials accountancy in the dry-powdered processing of spent fuel. The ICPMS measurement system may be applied to the KAERI DUPIC (direct use of spent PWR fuel in CANDU reactors) experiment, and in a near-real-time mode for international safeguards verification and non-proliferation policy concerns.

  9. Subchronic Oral Dose Toxicity of Freeze-dried Powder of Allomyrina dichotoma Larvae.

    PubMed

    Noh, Jung-Ho; Yun, Eun-Young; Park, Heejin; Jung, Kyung-Jin; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2015-03-01

    The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatmentrelated changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material.

  10. Subchronic Oral Dose Toxicity of Freeze-dried Powder of Allomyrina dichotoma Larvae

    PubMed Central

    Noh, Jung-Ho; Yun, Eun-Young; Park, Heejin; Jung, Kyung-Jin; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2015-01-01

    The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatmentrelated changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material. PMID:25874035

  11. Formation of highly porous aerosol particles by atmospheric freeze-drying in ice clouds

    NASA Astrophysics Data System (ADS)

    Rudich, Yinon; Adler, Gabriela; Koop, Thomas; Taraniuk, Ilya; Moise, Tamar; Koren, Ilan; Heiblum, Reuven; Haspel, Carynelisa

    2014-05-01

    In cold high altitude cirrus clouds and anvils of high convective clouds in the tropics and mid-latitudes, ice partciles that are exposed to subsaturation conditions with respect to ice can sublimate, leaving behind residual modified aerosols. This freeze-drying process can occur in various types of clouds. In this talk we will describe experiements that simulate the atmospheric freeze-drying cycle of aerosols. We find that aerosols with high organic content can form highly porous particles (HPA) with a larger diameter and a lower density than the initial homogenous aerosol following ice subliation. We attribute this morphology change to phase separation upon freezing followed by a glass transition of the organic material that can preserve a porous structure follwoing ice sublimation. We find that the highly porous aerosol scatter solar light less efficiently than non-porous aerosol particles. A porous structure may explain the previously observed enhancement in ice nucleation efficiency of glassy organic particles. These observations may have implications for subsequent cloud formation cycles and aerosol albedo near cloud edges.

  12. The physical state of nafcillin sodium in frozen aqueous solutions and freeze-dried powders.

    PubMed

    Milton, N; Nail, S L

    1996-10-01

    The purpose of this study was to develop a better understanding of the physical chemistry of freeze drying of lyotropic liquid crystals using nafcillin sodium as a model solute. Solutions and freeze-dried powders of nafcillin sodium were studied by polarized light microscopy, differential scanning calorimetry, x-ray powder diffraction, and water vapor adsorption. Differential scanning calorimetry thermograms of nafcillin sodium solutions contain a melting endotherm at approximately -5.5 degrees C and, depending on the concentration and heating rate, a crystallization exotherm immediately after this endotherm followed by the melting endotherm of ice. When the sample is annealed at -4 degrees C, both the endotherm and exotherm are eliminated, and a new endotherm appears at approximately -1 degree C on the shoulder of the ice-melting endotherm. The data are interpreted as melting of a liquid crystalline phase, followed by crystallization. X-ray powder diffractograms of unannealed freeze-dried nafcillin sodium are consistent with a lamellar liquid crystal. Diffractograms of annealed freeze-dried nafcillin sodium indicate crystalline material which is a different crystal form than the monohydrate starting material. Moisture adsorption isotherms of the freeze-dried annealed (crystalline) and unannealed (liquid crystalline) nafcillin sodium show different affinities for moisture compared to the crystalline starting material. Solid-state stability data demonstrate that the freeze-dried liquid crystalline form of nafcillin sodium is much less stable than the freeze-dried crystal-line material. The literature recognizes two types of solute behavior on freezing, where the solute either crystallizes from the freeze concentrate or remains amorphous. Lyotropic liquid crystal formation during freezing represents a separate category of freezing behavior, the physical chemistry of which is worthy of further investigation.

  13. Culture and spray-drying of Tsukamurella paurometabola C-924: stability of formulated powders.

    PubMed

    Hernández, Armando; Weekers, Fréderic; Mena, Jesús; Pimentel, Eulogio; Zamora, Jesús; Borroto, Carlos; Thonart, Philippe

    2007-11-01

    The nematocidal agent, Tsukamurella paurometabola C-924, was cultured in a 300 l bioreactor. Spray-dried formulations of this microorganism were prepared using sucrose. At an outlet temperature 62 degrees C, survival rates between 12 and 85% were reached with sucrose up to 10% (w/w). The stability study of the powders showed that the best storage condition was at 4 degrees C under vacuum. A new method for the calculation of cell death order for bacteria stored at low temperatures was developed. Powders stored under vacuum showed an Arrhenius behavior in relation to cell death kinetics.

  14. Chargeability measurements of selected pharmaceutical dry powders to assess their electrostatic charge control capabilities.

    PubMed

    Ramirez-Dorronsoro, Juan-Carlos; Jacko, Robert B; Kildsig, Dane O

    2006-01-01

    The purpose of this study was to develop an instrument (the Purdue instrument) and the corresponding methodologies to measure the electrostatic charge development (chargeability) of dry powders when they are in dynamic contact with stainless steel surfaces. The system used an inductive noncontact sensor located inside an aluminum Faraday cage and was optimized to measure the charging capabilities of a fixed volume of powder (0.5 cc). The chargeability of 5,5-diphenyl-hydantoin, calcium sulfate dihydrate, cimetidine, 3 grades of colloidal silicon dioxide, magnesium stearate, 4 grades of microcrystalline cellulose, salicylic acid, sodium carbonate, sodium salicylate, spray-dried lactose, and sulfinpyrazone were tested at 4 linear velocities, and the particle size distribution effect was assessed for 3 different grades of colloidal silicon dioxide and 4 different grades of microcrystalline cellulose. The chargeability values exhibited a linear relationship for the range of velocities studied, with colloidal silicon dioxide exhibiting the maximum negative chargeability and with spray-dried lactose being the only compound to exhibit positive chargeability. The instrument sensitivity was improved by a factor of 2 over the first generation version, and the electrostatic charge measurements were reproducible with relative standard deviations ranging from nondetectable to 33.7% (minimum of 3 replicates). These results demonstrate the feasibility of using the Purdue instrument to measure the electrostatic charge control capabilities of pharmaceutical dry powders with a reasonable level of precision.

  15. Combustion characteristics of dry coal-powder-fueled adiabatic diesel engine: Final report

    SciTech Connect

    Kakwani, R.M.; Kamo, R.

    1989-01-01

    This report describes the progress and findings of a research program aimed at investigating the combustion characteristics of dry coal powder fueled diesel engine. During this program, significant achievements were made in overcoming many problems facing the coal-powder-fueled engine. The Thermal Ignition Combustion System (TICS) concept was used to enhance the combustion of coal powder fuel. The major coal-fueled engine test results and accomplishments are as follows: design, fabrication and engine testing of improved coal feed system for fumigation of coal powder to the intake air; design, fabrication and engine testing of the TICS chamber made from a superalloy material (Hastelloy X); design, fabrication and engine testing of wear resistant chrome oxide ceramic coated piston rings and cylinder liner; lubrication system was improved to separate coal particles from the contaminated lubricating oil; control of the ignition timing of fumigated coal powder by utilizing exhaust gas recirculation (EGR) and variable TICS chamber temperature; coal-fueled engine testing was conducted in two configurations: dual fuel (with diesel pilot) and 100% coal-fueled engine without diesel pilot or heated intake air; cold starting of the 100% coal-powder-fueled engine with a glow plug; and coal-fueled-engine was operated from 800 to 1800 rpm speed and idle to full load engine conditions.

  16. Co-Spray Dried Mannitol/Poly(amidoamine)-Doxorubicin Dry-Powder Inhaler Formulations for Lung Adenocarcinoma: Morphology, In Vitro Evaluation, and Aerodynamic Performance.

    PubMed

    Zhong, Qian

    2017-08-23

    nhaled chemotherapeutics have emerged as a promising regimen to combat lung cancer as they maximize local drug concentration while significantly reduce systemic exposure. However, the poor lung/systemic safety profiles and lack of clinically efficient formulations restrict the applicability of inhaled chemotherapeutics. This work developed a dry-powder inhaler (DPI) formulation that dispersed a pH-responsive poly(amidoamine) dendrimer-doxorubicin conjugate (G4-12DOX) into mannitol microparticles. The dendrimer conjugate only releases cytotoxic agents in response to intracellular pH drop, leading to reduced systemic and local toxicity. This work investigated the effect of G4-12DOX content on the microparticle size and morphology, redispersibility, in vitro cytotoxicity, and aerosol properties of the formulations. The spray-dried G4-12DOX/mannitol microparticles showed smooth and spherical morphology with 1-4 μm in diameter. As the content of the G4-12DOX conjugate in the microparticles increased, the size, and degree of aggregation of microparticles increased dramatically. The G4-12DOX/mannitol microparticles were readily redispersed in the aqueous environment, reverting to nanoscale dendrimer conjugates to escape alveolar phagocytosis. All DPI formulations demonstrated the similar cytotoxicity as the original conjugate against a lung adenocarcinoma cell line. The emitted dose (ED) and fine particle fraction (FPF) of the DPI formulations decreased as the content of G4-12DOX increased, but EDs and FPFs of all formulations fell within the range of 85-60% and 60-40%, which were higher than those of commercial products (EDs = 40-60%; FPFs = 12-40%). Therefore, the spray-dried dendrimer/mannitol microparticle is an efficient and practical DPI formulation for direct delivery of large dose of chemotherapeutics to lung tumors.

  17. Fourier transform infared spectroscopy investigation of protein conformation in spray-dried protein/trehalose powders.

    PubMed

    French, Donna L; Arakawa, Tsutomu; Li, Tiansheng

    2004-03-01

    Spray drying is a way to generate protein solids (powders), which is also true for lyophilization. Sugars are used to protect proteins from conformational changes and chemical degradations arising from drying processes and storage conditions such as the humidity. The influence of trehalose and humidity on the conformation and hydration of spray-dried recombinant human granolucyte colony stimulating factor (rhG-CSF) and recombinant consensus interferon-alpha (rConIFN) was investigated using Fourier transform IR spectroscopy. The spectral analysis of spray-dried powders in the amide I region demonstrated that trehalose stabilized the alpha-helical conformation of both rhG-CSF and rConIFN proteins. Exposure of the pure protein powders to 33% relative humidity (RH) resulted in the formation of beta sheets and loss of turns but no change in alpha-helical structure. Trehalose reduced the magnitude of the changes in beta sheets and turns. Exposure of the pure protein powders to 75% RH resulted in the loss of alpha-helical conformation with a corresponding increase in beta structures (beta sheets and turns). Trehalose did not protect proteins from the loss of alpha-helical structures, but it reduced the formation of antiparallel beta sheets. Hydrogen-deuterium exchange (H-D exchange) was used to further characterize these hydration-induced conformational changes. At 33% RH the percent exchange of the protein decreased with increasing trehalose content, indicating a greater protection of the protein from H-D exchange by a higher concentration of trehalose. Such protection correlates with decreased conformational changes of the protein by trehalose at this humidity. At 75% RH the degree of H-D exchange of the protein was insensitive to the powder composition in all powders. Surprisingly, the H-D exchange of trehalose was low at about 20-25%, which was nearly independent of the protein/trehalose ratio and humidity, indicating that the exchangeable protons on trehalose

  18. Influence of granule characteristics on microstructure quality of compacts made from spray-dried powders

    NASA Astrophysics Data System (ADS)

    Balasubramanian, Sreeram

    Powder compaction is a widely used technique for the manufacture of high volume of ceramic components that have simple shapes and sizes. However, this technique is inherently prone to strength-limiting defects like large intergranular pores and remnants of the initial granule structure. These defects are a major obstacle that hinder the use of powder compaction to fabricate parts for applications where strength is an important criterion. The objective of this work is to understand the important factors that control the elimination of strength-limiting defects in compacts made from spray dried powders. The influence of granule density, internal lubricants, particle shape and external application of a plasticizer to already spray dried powders on compaction behavior was investigated. Emphasis was placed on role of these factors in the elimination of large intergranular pores and persistent granule interfaces. The powders were spray dried under varying conditions to tailor the granule characteristics, including granule density, granule size distribution, binder content and lubricant content. These powders were compacted at different pressures, and the microstructures of green and sintered compacts were then evaluated, and strength-limiting features were quantified. Comparisons were made on the basis of compaction curves, green strength, green density and microstructure quality at different pressures. Lowering the granule density reduced the number of granule relics and large intergranular pores. The presence of an internal lubricant improved particle packing and yielded compacts with higher green density and fewer large intergranular pores at comparable pressures. Spray dried powders with the externally applied plasticizer deformed at lower compaction pressures. This allowed easier knitting of particles across granule interfaces and elimination of large intergranular pores and persistent granule interfaces. Spherical (equiaxed) particles rearranged better at granule

  19. Burstable nanostructured micro-raspberries: Towards redispersible nanoparticles from dry powders.

    PubMed

    Stauch, Claudia; Ballweg, Thomas; Stracke, Werner; Luxenhofer, Robert; Mandel, Karl

    2017-03-15

    Despite immense progress in nanoscience and technology, one of the yet unsolved challenges is the redispersion of nanoparticles from dry powders back to the individual, primary particles. Herein, an easy to handle powder consisting of nanostructured micron sized raspberry-like particles is presented. These nanostructured micro-raspberries are composed of individual nanoparticles which are equipped with molecules that introduce a separating effect or "spring" functionality. Thereby, a powder system is obtained that allows for an easy and complete redispersibility of the agglomerates down to the level of individual nanoparticles in solvents and polymers. The mechanism of redispersibility involves mechanic stimuli/force as well as solvent like disintegration aspects ("like dissolves like" effect). Furthermore, by tailoring the degree of spacer-equipped particles, the bursting behavior can also be tuned, yielding different redispersion degrees. The redispersibility of the nanostructured micro-raspberries is demonstrated in solvents and silicone-based nanocomposites.

  20. Infrared Extinction Coefficients of Aerosolized Conductive Flake Powders and Flake Suspensions having a Zero-Truncated Poisson Size Distribution

    DTIC Science & Technology

    2012-11-01

    A twin-fluid atomizing nozzle was used to disseminate all materials into a stirred 190 m 3 cylindrical aerosol chamber. After dispersion by the... nozzle and thorough chamber mixing with a low speed fan, spectral aerosol transmittance and concentration were simultaneously measured to obtain spectral...varying concentrations were prepared by stirring and sonicating the powders in ethanol. A twin-fluid atomizing nozzle , consisting of a jet of the

  1. Purification and characterization of purple acid phosphatase PAP1 from dry powder of sweet potato.

    PubMed

    Kusudo, Tatsuya; Sakaki, Toshiyuki; Inouye, Kuniyo

    2003-07-01

    Purple acid phosphatase (PAP) was purified from sweet potato dry powder, which is used as a food additive. Spectrometric and enzymatic analyses, and analysis of the amino-terminal sequence indicated that the purified purple acid phosphatase was PAP1. High activity in neutral and acidic conditions, broad substrate specificity, and good thermal stability of PAP1 suggest the possibility of practical applications of PAP1.

  2. A New Quantitative Method for Evaluating Dry Powder Inhalation Efficiency in Asthma Patients.

    PubMed

    Liang, Yasha; Hu, Hefang; Tian, Cuijie; Lei, Yi; Liu, Chuntao; Luo, Fengming

    2016-10-01

    Many methods have been developed to evaluate dry powder inhalation techniques and their efficiency for disease control in asthma patients. However, it is difficult to apply these methods to clinical practice and research. In this study, we introduce a simple new method that can be applied to dry powder inhalation techniques to evaluate their efficiency in clinical practice. Twenty volunteers were recruited to evaluate the reliability of this new method. One hundred one asthma patients who met the inclusion criteria participated in this study. A dark cloth covered the outlet of the inhaler during dry powder inhalation. The image formed by the inhalation process was evaluated using analysis software and converted into integrated optical density (IOD). Inhalation techniques were scored before and after inhalation technique training, and asthma control was evaluated using the Asthma Control Questionnaire (ACQ) before inhalation technique training. The relative standard deviation of IOD ranged from 3.8% to 7.8%. In patients with or without inhaler prior use, both the IOD and inhalation technique scores improved significantly after inhalation technique training (p < 0.05). Inhalation technique scores were positively correlated with IOD before (r = 0.80, p < 0.001) and after inhalation technique training (r = 0.52, p < 0.001). In patients with prior inhaler experience, ACQ results were negatively correlated with inhalation technique scores (r = -0.44; p < 0.05) and IOD (r = -0.52; p < 0.05). The results from this study demonstrated that this quantitative method is equivalent to traditional methods for dry powder inhalation evaluation. This study also indicated that training significantly improved the inhalation technique and efficiency in asthma patients with or without prior inhaler use.

  3. Development of an Inhaled Sustained Release Dry Powder Formulation of Salbutamol Sulphate, an Antiasthmatic Drug

    PubMed Central

    Kumaresan, C.; Sathishkumar, K.

    2016-01-01

    The present research was aimed to develop and characterize a sustained release dry powder inhalable formulation of salbutamol sulphate. The salbutamol sulphate microparticles were prepared by solvent evaporation method using biodegradable polymer poly (D,L-lactic-co-glycolic acid) to produce salbutamol sulphate microparticle mixed with carrier respirable grade lactose for oral inhalation of dry powder. The drug content were estimated to produce 1 mg sustained release salbutamol sulphate per dose. Total four formulations K1, K2, K3 and K4 were prepared with 1:1, 1:2, 1:3, 1:4 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid). The developed formulations were studied for physicochemical properties, in vitro drug relase and Anderson cascade impaction studies. The prepared formulations effectively releases drug for 12 h in diffusion bag studies. Based on dissolution performance the 1:1 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid) produces in vitro release 92.57% at 12 h and having particle size of microparticles (D0.5μm) 5.02±0.6 and the pulmonary deposition of dry powder 34.5±3.21 (respiratory fraction in percentage). PMID:27168692

  4. Development of an Inhaled Sustained Release Dry Powder Formulation of Salbutamol Sulphate, an Antiasthmatic Drug.

    PubMed

    Kumaresan, C; Sathishkumar, K

    2016-01-01

    The present research was aimed to develop and characterize a sustained release dry powder inhalable formulation of salbutamol sulphate. The salbutamol sulphate microparticles were prepared by solvent evaporation method using biodegradable polymer poly (D,L-lactic-co-glycolic acid) to produce salbutamol sulphate microparticle mixed with carrier respirable grade lactose for oral inhalation of dry powder. The drug content were estimated to produce 1 mg sustained release salbutamol sulphate per dose. Total four formulations K1, K2, K3 and K4 were prepared with 1:1, 1:2, 1:3, 1:4 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid). The developed formulations were studied for physicochemical properties, in vitro drug relase and Anderson cascade impaction studies. The prepared formulations effectively releases drug for 12 h in diffusion bag studies. Based on dissolution performance the 1:1 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid) produces in vitro release 92.57% at 12 h and having particle size of microparticles (D0.5μm) 5.02±0.6 and the pulmonary deposition of dry powder 34.5±3.21 (respiratory fraction in percentage).

  5. Production of spray-dried honey jackfruit (Artocarpus heterophyllus) powder from enzymatic liquefied puree.

    PubMed

    Wong, Chen Wai; Tan, Hong Hock

    2017-02-01

    This paper presents the enzymatic liquefaction process for honey jackfruit optimized with Pectinex(®) Ultra SP-L and Celluclast(®) 1.5 L individually or in combinations at different concentrations (0-2.5% v/w) and incubation time (0-2.5 h). Treatment with combinations of enzymes showed a greater effect in the reduction of viscosity (83.9-98.8%) as compared to single enzyme treatment (64.8-87.3%). The best parameter for enzymatic liquefaction was obtained with 1.0% (v/w) Pectinex(®) Ultra SP-L and 0.5% (v/w) Celluclast(®) 1.5 L for 1.5 h. Spray drying process was carried out using different inlet temperatures (140-180 °C) and maltodextrin concentrations (10-30% w/w). Results indicated that the spray-dried honey jackfruit powder produced at 160 °C with 30% w/w maltodextrin gave the highest product yield (66.90%) with good powder qualities in terms of water activity, solubility, moisture content, hygroscopicity, color and bulk density. The spray-dried honey jackfruit powder could potentially be incorporated into various food products.

  6. Preparation of redispersible liposomal dry powder using an ultrasonic spray freeze-drying technique for transdermal delivery of human epithelial growth factor

    PubMed Central

    Yin, Fei; Guo, Shiyan; Gan, Yong; Zhang, Xinxin

    2014-01-01

    In this work, an ultrasonic spray freeze-drying (USFD) technique was used to prepare a stable liposomal dry powder for transdermal delivery of recombinant human epithelial growth factor (rhEGF). Morphology, particle size, entrapment efficiency, in vitro release, and skin permeability were systematically compared between rhEGF liposomal dry powder prepared using USFD and that prepared using a conventional lyophilization process. Porous and spherical particles with high specific area were produced under USFD conditions. USFD effectively avoided formation of ice crystals, disruption of the bilayer structure, and drug leakage during the liposome drying process, and maintained the stability of the rhEGF liposomal formulation during storage. The reconstituted rhEGF liposomes prepared from USFD powder did not show significant changes in morphology, particle size, entrapment efficiency, or in vitro release characteristics compared with those of rhEGF liposomes before drying. Moreover, the rhEGF liposomal powder prepared with USFD exhibited excellent enhanced penetration in ex vivo mouse skin compared with that for powder prepared via conventional lyophilization. The results suggest that ultrasonic USFD is a promising technique for the production of stable protein-loaded liposomal dry powder for application to the skin. PMID:24729702

  7. Preparation of redispersible liposomal dry powder using an ultrasonic spray freeze-drying technique for transdermal delivery of human epithelial growth factor.

    PubMed

    Yin, Fei; Guo, Shiyan; Gan, Yong; Zhang, Xinxin

    2014-01-01

    In this work, an ultrasonic spray freeze-drying (USFD) technique was used to prepare a stable liposomal dry powder for transdermal delivery of recombinant human epithelial growth factor (rhEGF). Morphology, particle size, entrapment efficiency, in vitro release, and skin permeability were systematically compared between rhEGF liposomal dry powder prepared using USFD and that prepared using a conventional lyophilization process. Porous and spherical particles with high specific area were produced under USFD conditions. USFD effectively avoided formation of ice crystals, disruption of the bilayer structure, and drug leakage during the liposome drying process, and maintained the stability of the rhEGF liposomal formulation during storage. The reconstituted rhEGF liposomes prepared from USFD powder did not show significant changes in morphology, particle size, entrapment efficiency, or in vitro release characteristics compared with those of rhEGF liposomes before drying. Moreover, the rhEGF liposomal powder prepared with USFD exhibited excellent enhanced penetration in ex vivo mouse skin compared with that for powder prepared via conventional lyophilization. The results suggest that ultrasonic USFD is a promising technique for the production of stable protein-loaded liposomal dry powder for application to the skin.

  8. Formulation development and rheological studies of palatable cefetamet pivoxil hydrochloride dry powder suspension

    PubMed Central

    Sateesha, SB.; Rajamma, AJ.; Shekar, HS.; Divakar, G.

    2011-01-01

    Background and the purpose of the study Because of its intense bitter taste and susceptibility to moisture Cefetamet Pivoxil (CPH) is presently available only in the form of tablet. The aim of this study was to develop taste masked CPH dry powder suspension. Methods Methods employed for formulations were: a) Film coating of CPH using Eudragit E100 and subsequent adsorption on different carriers such as spray-dried lactose, sodium starch glycolate and spray-dried mannitol and b) Complexation of CPH with three different ion exchange resins indion 234 amberlite IRP64 and amberlite IRP69. Results Taste viz evaluation as recognized by volunteers revealed that coating with Eudragit E100 and subsequent adsorption on different carriers do not mask the bitter taste of the drug. Suspensions prepared using amberlite IRP64 and amberlite IRP69 were extremely palatable with no bitter after taste. They showed pseudoplastic flow behavior and were too viscous even after shearing for sufficient duration of time and exhibited poor pourability. The suspension made with indion 234 was palatable with slight or no bitter after taste. It demonstrated plastic flow with negligible thixotropy. It had moderate viscosity at rest and could be poured after a reasonable amount of shaking. CPH dry powder suspensions were very unstable under different conditions except under refrigeration. A 5% degradation of drug was occurred in reconstituted suspension in 4 days period when stored at room temperature. Conclusion Dry powder suspension prepared with indion 234 having 5% overages was stable even after 4th day of reconstitution and palatable with slight or no bitter after taste. PMID:22615648

  9. Development of a Soluplus budesonide freeze-dried powder for nasal drug delivery.

    PubMed

    Pozzoli, Michele; Traini, Daniela; Young, Paul M; Sukkar, Maria B; Sonvico, Fabio

    2017-09-01

    The aim of this work was to develop an amorphous solid dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a novel polymer Soluplus(®) (BASF, Germany) using a freeze-drying technique, in order to improve dissolution and absorption through the nasal route. The small volume of fluid present in the nasal cavity limits the absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically insoluble and normally administered as a suspension-based nasal spray. The formulation was prepared through freeze-drying of polymer-drug solution. The formulation was assessed for its physicochemical (specific surface area, calorimetric analysis and X-ray powder diffraction), release properties and aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells, in order to elucidate the efficacy of the Soluplus-BUD formulation. The freeze-dried Soluplus-BUD formulation (LYO) showed a porous structure with a specific surface area of 1.4334 ± 0.0178 m(2)/g. The calorimetric analysis confirmed an interaction between BUD and Soluplus and X-ray powder diffraction the amorphous status of the drug. The freeze-dried formulation (LYO) showed faster release compared to both water-based suspension and dry powder commercial products. Furthermore, a LYO formulation, bulked with calcium carbonate (LYO-Ca), showed suitable aerodynamic characteristics for nasal drug delivery. The permeation across RPMI 2650 nasal cell model was higher compared to a commercial water-based BUD suspension. Soluplus has been shown to be a promising polymer for the formulation of BUD amorphous solid suspension/solution. This opens up opportunities to develop new formulations of poorly soluble drug for nasal delivery.

  10. Air classifier technology (ACT) in dry powder inhalation Part 3. Design and development of an air classifier family for the Novolizer multi-dose dry powder inhaler.

    PubMed

    de Boer, A H; Hagedoorn, P; Gjaltema, D; Goede, J; Frijlink, H W

    2006-03-09

    In this study, the design of a multifarious classifier family for different applications is described. The main design and development steps are presented as well as some special techniques that have been applied to achieve preset objectives. It is shown by increasing the number of air supply channels to the classifier chamber (from 2 to 8), that the fine particle losses from adhesion onto the classifier walls can be reduced from 75% to less than 5% of the real dose for soft (spherical) agglomerates. By applying a bypass flow that is arranged as a co-axial sheath of clean air around the aerosol cloud from the classifier, the airflow resistance of the classifier can be controlled over a relatively wide range of values (0.023-0.041 kPa(0.5) min l(-1)). This, without affecting the fine particle dose or increasing the fine particle losses in the inhaler. Moreover, the sheath flow can be modelled to reduce the depositions in the induction port to the cascade impactor or in the patient's mouth, which are the result of back flows in these regions. The principle of powder induced pressure drop reduction across a classifier enables assessment of the amount of powder in the classifier at any moment during inhalation, from which classifier loading (from the dose system) and discharge rates can be derived. This principle has been applied to study the residence time of a dose in the classifier as function of the carrier size fraction and the flow rate. It has been found that this residence time can be controlled in order to obtain an optimal balance between the generated fine particle fraction and the inhalation manoeuvre of the patient. A residence time between 0.5 and 2 s at 60 l/min is considered favourable, as this yields a high fine particle dose (depending on the type of formulation used) and leaves sufficient inhaled volume for particle transport into the deep lung.

  11. Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients.

    PubMed

    Akdag Cayli, Yagmur; Sahin, Selma; Buttini, Francesca; Balducci, Anna Giulia; Montanari, Serena; Vural, Imran; Oner, Levent

    2017-08-01

    This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis. Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to prepare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The particle size distribution, dissolution rate and permeability across Calu-3 cell monolayers were analyzed. The aerodynamic parameters of dry powders were determined using the Andersen cascade impactor (ACI). After the micronization process, the particle sizes of the raw materials significantly decreased. X-ray and DSC results indicated that although ciprofloxacin showed no changes in its crystal structure, the structure of levofloxacin became amorphous after the micronization process. FT-IR spectra exhibited the characteristic peaks for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of micro-homogenized and spray-dried ciprofloxacin were higher than that of untreated ciprofloxacin. ACI results showed that all formulations had a mass median aerodynamic diameter less than 5 μm; however, levofloxacin microparticles showed higher respirability than ciprofloxacin powders did. The permeability of levofloxacin was higher than those of the ciprofloxacin formulations. Together, our study showed that these methods could suitably characterize antibiotic and mucolytic-containing dry powder inhalers.

  12. Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus a prevailing dry powder inhaler and a metered-dose inhaler.

    PubMed

    Gillespie, Michael; Song, Sharon; Steinfeld, Jonathan

    2015-01-01

    A novel inhalation-driven multidose dry powder inhaler (MDPI) that eliminates the need for the patient to coordinate device actuation with inhalation has been developed for delivery of inhaled asthma medications. To characterize the pharmacokinetics of single-dose fluticasone propionate (Fp) MDPI compared with single doses of Fp dry powder inhaler (DPI) and a metered-dose inhaler (MDI) in healthy subjects. This was a single-center, open-label, randomized, three-period crossover, single-dose pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized to one of six treatment sequences that contained three treatment arms: Fp MDPI 400 μg/inhalation × two inhalations (800 μg total dose); Fp DPI 250 μg/inhalation × four (1000 μg total dose); and Fp MDI 220 μg/inhalation × four (880 μg total dose). Pharmacokinetics (area under concentration-versus-time curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life [t½]), safety, and tolerability were assessed for each treatment. Plasma Fp concentration-versus-time curves were comparable across treatments. Geometric mean AUC0-t and Cmax for Fp MDPI 800 μg were 19% and 18% higher, respectively, compared with Fp DPI 1000 μg, and 47% and 82% higher, respectively, compared with Fp MDI 880 μg. Median tmax (60.0-60.6 minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three treatments. Single-dose Fp was well tolerated, with no new safety issues noted. Single-dose administration of Fp MDPI 800 μg produced systemic exposure comparable with those for Fp DPI 1000 μg and Fp MDI 880 μg.

  13. Jet-vortex spray freeze drying for the production of inhalable lyophilisate powders.

    PubMed

    Wanning, Stefan; Süverkrüp, Richard; Lamprecht, Alf

    2017-01-01

    Spray-freeze-dried powders were suggested for nasal, epidermal (needle-free injection) or pulmonary application of proteins, peptides or nucleic acids. In spray-freeze-drying processes an aqueous solution is atomized into a refrigerant medium and subsequently dried by sublimation. Droplet-stream generators produce a fast stream of monodisperse droplets, where droplets are subject to collisions and therefore the initial monodispersity is lost and droplets increase in diameter, which reduces their suitability for pulmonary application. In jet-vortex-freezing, a droplet-stream is injected into a vortex of cold process gas to prevent droplet collisions. Both the injection position of the droplet-stream and the velocity of the cold gas vortex have an impact on the size distributions of the resulting powders. A model solution containing mannitol (1.5%m/V) and maltodextrin (1.5%m/V) was sprayed at 5 droplet-stream positions at distances between 1mm and 30mm from the gas jet nozzle and 5 gas velocities (0.8-6.8m/s) at a process temperature of -100°C. Mean geometric diameters of the highly porous particles (bulk density: 0.012±0.007g/cm3) ranged between 55±4 and 98±4μm. Evaluation of the aerodynamic properties by Next-Generation-Impactor (NGI) analysis showed that all powders had high emitted doses (98±1%) and fine-particle fractions ranged between 4±1% and 21±2%. It was shown that jet-vortex freezing is a suitable method for the reproducible production of lyophilized powders with excellent dispersibility in air, which has a high potential for nasal and pulmonary drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

    PubMed

    Kolanjiyil, Arun V; Kleinstreuer, Clement; Sadikot, Ruxana T

    2016-11-03

    Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of

  15. Hazardous Waste Water Remediation by Ecoresin-Dry Cow Dung Powder

    NASA Astrophysics Data System (ADS)

    Bagla, Hemlata; Barot, Nisha

    2013-04-01

    Water, the matter, matrix, medium and the mother of our life, is indeed one of the drivers of Nature. Through water cycle only the intra and inter equilibrium is maintained constantly between entire 'green' and 'blue'. Unfortunately, with each successive epoch of industrialization and urbanization, human societies have produced non-biodegradable waste hulk with far beyond handling capacities of mankind. At this juncture the very need is to appreciate and move towards the cost as well as time effective scientific alternatives for the removal of aqueous heavy metal pollutants. Green chemistry advocates the utilization of naturally available bio-resins which are environmentally benign alternative to current synthetic materials and technologies employed for waste water treatment. This explicit investigation aims to explore Dry Cow dung powder, DCP, a natural biosorbent as a green and clean alternative for the aqueous waste water treatment. It is naturally available bio-organic, complex, polymorphic humified fecal matter of cow and is enriched with minerals, carbohydrates, fats, proteins, bile pigments, aliphatic - aromatic species such as 'Humic acid'(HA). The HA has been successfully extracted by authors from DCP and this piece of work has been published in the International Journal [1]. We have developed simple, efficient and eco-friendly method for the removal of aqueous heavy metal pollutant such as Cr(VI) [2], Cd(II), Cr(III) [3] and Hg(II) as well radiotoxic 90Sr(II) [4], employing DCP. DCP is employed without any pre or post treatment. Being freely and easily available DCP has an edge over processed natural adsorbent considering their cost, time and energy efficiency. In nutshell we have to remember that prevention is better than the cure. If we fail to meet this, the situation will surely augment which will drain our water, our life, to slaughters knife..! Reference: 1. H.K.Bagla, N.S.Barot, Soil Amendement by Green Supplement: Dry Cowdung powder, EGUGA - 11

  16. Evaluation of a dry powder delivery system for laninamivir in a ferret model of influenza infection.

    PubMed

    Panozzo, Jacqueline; Oh, Ding Yuan; Margo, Kenneth; Morton, David A; Piedrafita, David; Mosse, Jennifer; Hurt, Aeron C

    2015-08-01

    Laninamivir is a long-acting antiviral requiring only a single dose for the treatment of influenza infection, making it an attractive alternative to existing neuraminidase inhibitors that require multiple doses over many days. Like zanamivir, laninamivir is administered to patients by inhalation of dry powder. To date, studies investigating the effectiveness of laninamivir or zanamivir in a ferret model of influenza infection have administered the drug in a solubilised form. To better mimic the delivery action of laninamivir in humans, we assessed the applicability of a Dry Powder Insufflator™ (DPI) as a delivery method for laninamivir octanoate (LO) in ferrets to determine the effectiveness of this drug in reducing influenza A and B virus infections. In vitro characterisation of the DPI showed that both the small particle sized LO (0.7-6.0μm diameter) and the large particle sized lactose carrier (20-100μm diameter) were effectively discharged. However, LO delivered to ferrets via the DPI prior to infection with either A(H1N1)pdm09 or B viruses had a limited effect on nasal inflammation, clinical symptoms and viral shedding compared to placebo. Our preliminary findings indicate the feasibility of administering powder drugs into ferrets, but a better understanding of the pharmacokinetics and pharmacodynamics of LO in ferrets following delivery by the DPI is warranted prior to further studies.

  17. Sodium cromoglycate: spincaps or metered dose aerosol.

    PubMed Central

    Robson, R A; Taylor, B J; Taylor, B

    1981-01-01

    1 Sodium cromoglycate administered as a dry powder inhalation (20 mg/dose) via the Spinhaler was compared with a metered dose aerosol (2 mg/dose) in an eight week double dummy double blind crossover trial in 29 asthmatic children. 2 The powder formulation was associated with significantly less symptoms (night wheeze, night cough, day wheeze, day cough, activity) and bronchodilator intake; and significantly greater weight gain than aerosol therapy. There were no significant differences in morning or evening peak flow measurements on the two treatments. 3 The powder may be more effectively inhaled than the aerosol or the dose of the aerosol may not be large enough. PMID:6789851

  18. The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder.

    PubMed

    Yang, Michael Y; Verschuer, Jordan; Shi, Yuyu; Song, Yang; Katsifis, Andrew; Eberl, Stefan; Wong, Keith; Brannan, John D; Cai, Weidong; Finlay, Warren H; Chan, Hak-Kim

    2016-11-20

    The present study investigates the effect of DPI resistance and inhalation flow rates on the lung deposition of orally inhaled mannitol dry powder. Mannitol powder radiolabeled with (99m)Tc-DTPA was inhaled from an Osmohaler™ by healthy human volunteers at 50-70L/min peak inhalation flow rate (PIFR) using both a low and high resistance Osmohaler™, and 110-130L/min PIFR using the low resistance Osmohaler™ (n=9). At 50-70L/min PIFR, the resistance of the Osmohaler™ did not significantly affect the total and peripheral lung deposition of inhaled mannitol [for low resistance Osmohaler™, 20% total lung deposition (TLD), 0.3 penetration index (PI); for high resistance Osmohaler™, 17% TLD, 0.23 PI]. Increasing the PIFR 50-70L/min to 110-130L/min (low resistance Osmohaler™) significantly reduced the total lung deposition (10% TLD) and the peripheral lung deposition (PI 0.21). The total lung deposition showed dependency on the in vitro FPF (R(2)=1.0). On the other hand, the PI had a stronger association with the MMAD (R(2)=1.0) than the FPF (R(2)=0.7). In conclusion the resistance of Osmohaler™ did not significantly affect the total and regional lung deposition at 50-70L/min PIFR. Instead, the total and regional lung depositions are dependent on the particle size of the aerosol and inhalation flow rate, the latter itself affecting the particle size distribution.

  19. Influence of primary crystallisation conditions on the mechanical and interfacial properties of micronised budesonide for dry powder inhalation.

    PubMed

    Kubavat, Harshal A; Shur, Jagdeep; Ruecroft, Graham; Hipkiss, David; Price, Robert

    2012-07-01

    Investigate the influence of primary crystallisation conditions on the mechanical properties and secondary processing behaviour of budesonide for dry powder inhaler (DPI) formulations. Young's modulus of two batches of budesonide crystals (samples A and B) produced using different anti-solvents was determined using nanoindentation. Physicochemical and surface interfacial properties via the cohesive-adhesive balance (CAB) approach to colloid probe atomic force microscopy (AFM) of air-jet micronised budesonide crystals were also investigated. These data were correlated to in vitro aerosolization performance of carrier-based DPI formulations containing either budesonide samples A or B and lactose monohydrate. Young's modulus of budesonide samples A and B crystals was 0.95 and 4.04 GPa, respectively. Sample A crystals with low Young's modulus exhibited poorer micronisation efficiency than sample B. CAB analysis of micronised budesonide samples A and B, suggest that sample B budesonide had a greater adhesion to lactose than sample A. These data correlated with in vitro aerosolisation studies, which showed that the fine particle delivery of budesonide sample A was higher than that of sample B. In conclusion, crystallisation conditions may affect the mechanical properties of budesonide, and therefore secondary processing of the material and their interfacial properties and product performance in carrier based DPI formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Quality assurance test of delivered dose uniformity of multiple-dose inhaler and dry powder inhaler drug products.

    PubMed

    Tsong, Yi; Dong, Xiaoyu; Shen, Meiyu; Lostritto, Richard T

    2015-01-01

    The delivered dose uniformity is one of the most critical requirements for dry powder inhaler (DPI) and metered dose inhaler products. In 1999, the Food and Drug Administration (FDA) issued a Draft Guidance entitled Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products-Chemistry, Manufacturing and Controls Documentation and recommended a two-tier acceptance sampling plan that is a modification of the United States Pharmacopeia (USP) sampling plan of dose content uniformity (USP34<601>). This sampling acceptance plan is also applied to metered dose inhaler (MDI) and DPI drug products in general. The FDA Draft Guidance method is shown to have a near-zero probability of acceptance at the second tier. In 2000, under the request of The International Pharmaceutical Aerosol Consortium, the FDA developed a two-tier sampling acceptance plan based on two one-sided tolerance intervals (TOSTIs) for a small sample. The procedure was presented in the 2005 Advisory Committee Meeting of Pharmaceutical Science and later published in the Journal of Biopharmaceutical Statistics (Tsong et al., 2008). This proposed procedure controls the probability of the product delivering below a pre-specified effective dose and the probability of the product delivering over a pre-specified safety dose. In this article, we further propose an extension of the TOSTI procedure to single-tier procedure with any number of canisters.

  1. Effects of Whey Powder Supplementation on Dry-Aged Meat Quality

    PubMed Central

    2016-01-01

    The objective of this study was to determine the effect of dietary supplementation with whey powder (WP, 1g/kg feed) from weaning to slaughter (150 d) on dry-aged loin quality of pigs. Fifty-eight pigs were randomly divided into two dietary treatment groups (seven replications of four pigs per treatments). Basal diet with 0.1% whey powder was supplied to the WP group. Basal diet was used for the control group (CON). Diet whey protein did not appear to influence the moisture or protein contents. However, ash and fat contents were significantly (p<0.05) decreased in the WP group compared to the control group. Drip loss was significantly (p<0.05) lower in the WP group than that of the control group. Increasing redness with decreasing lightness was found in the inner loin of the WP group. Calcium and iron contents in the WP group were significantly higher than those in the control group. Protein degradation was higher in the WP group than that in the control group (p<0.05), whereas shear force was lower in the WP group than that in the control group (p<0.05). In conclusion, the basal diet supplemented with 0.1% whey powder influence negatively the lipid oxidation of meat whereas the texture property and mineral composition of meat from whey powder fed pigs are developed. PMID:27433111

  2. The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze-Drying for Production

    PubMed Central

    Kanojia, Gaurav; Have, Rimko ten; Bakker, Arjen; Wagner, Koen; Frijlink, Henderik W.; Kersten, Gideon F. A.; Amorij, Jean-Pierre

    2016-01-01

    In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn’s disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.e. both the physical integrity and biological activity (TNF binding) were retained. Accelerated stability studies (1 month at 60°C) showed that the TNF binding ability of Infliximab was conserved in the freeze-dried formulations, whereas the liquid counterpart lost all TNF binding. After thermal treatment, the dried formulations showed some chemical modification of the IgG in the dextran-sucrose formulation, probably due to Maillard reaction products. This study indicates that, with the appropriate formulation, both spray-drying and freeze-drying may be useful for (bulk) powder production of Infliximab. PMID:27706175

  3. Identification of Polymorphic Forms of Active Pharmaceutical Ingredient in Low-Concentration Dry Powder Formulations by Synchrotron X-Ray Powder Diffraction.

    PubMed

    Egusa, Kenji; Okazaki, Fumiaki; Schiewe, Joerg; Werthmann, Ulrike; Wolkenhauer, Markus

    2017-09-13

    The identification of different (pseudo) polymorphs of an active pharmaceutical ingredient in dry powder formulations is of importance during development and entire product lifecycle, e.g., quality control. Whereas determination of polymorphic differences of pure substances is rather easy, in dry powder formulations, it is generally difficult and the difficulties increase particularly, if the substance of interest is present only in low concentrations in the formulation. Such a formulation is Spiriva(®) inhalation powder (Boehringer Ingelheim), which contains only 0.4 w/w% of the active pharmaceutical ingredient tiotropium bromide monohydrate in a matrix of α-lactose monohydrate as excipient. In this study, identification of 0.4 w/w% tiotropium bromide in the dry powder formulation was examined by X-ray powder diffraction (XRPD) using a synchrotron radiation source and the results were compared with the conventional laboratory XRPD measurements. The detection limit of tiotropium bromide by the laboratory XRPD was around 2-5 w/w%, and hence, detection of 0.4 w/w% tiotropium bromide was impossible. The synchrotron XRPD was capable to detect significantly lower level of tiotropium bromide by at least an order of magnitude. Four different polymorphic forms of tiotropium bromide present at 0.4 w/w% concentration in lactose powder blends were unambiguously identified by the synchrotron XRPD method.

  4. Improved respirable fraction of budesonide powder for dry powder inhaler formulations produced by advanced supercritical CO2 processing and use of a novel additive.

    PubMed

    Miyazaki, Yuta; Aruga, Naoki; Kadota, Kazunori; Tozuka, Yuichi; Takeuchi, Hirofumi

    2017-08-07

    A budesonide (BDS) suspension was obtained via advanced supercritical carbon dioxide (scCO2) processing. Thereafter, the suspension was freeze-dried (FD) to produce BDS particles for dry powder inhaler formulations (scCO2/FD processing). The scCO2/FD processed BDS powder showed low crystallinity by powder X-ray diffraction and a rough surface by scanning electron microscopy. The respirable fraction of BDS was assessed using a twin impinger and revealed that the amount of the scCO2/FD processed sample that reached stage 2 was 4-fold higher than that of the supplied powder. To extend the utility of scCO2 processing, BDS particles for dry powder inhalers were fabricated by combining the scCO2 system with various additives. When BDS was processed via scCO2/FD in the presence of the novel additive, namely, monoglyceride stearate (MGS), the residual BDS/MGS particles remaining in the capsule and devices decreased, followed by an increase in the respirable fraction of BDS 6-fold higher than with the supplied powder. The scCO2/FD processed BDS/MGS particles had a smooth surface, in contrast to the scCO2/FD processed BDS particles. A combination of BDS and an appropriate additive in scCO2 treatment may induce changes in particle surface morphology, leading to an improvement in the inhalation properties of BDS. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Evaluation of the Aromatase Inhibition Potential of Freeze-Dried Grape Powder

    PubMed Central

    Allen, Summer V.; Pruthi, Sandhya; Suman, Vera J.; Hoskin, Tanya L.; Vachon, Celine M.; Ingle, James N.; Olson, Janet E.

    2016-01-01

    Objective To determine the role of freeze-dried grapes as a potential aromatase inhibitor by testing of plasma hormone levels. Methods A six-week study was conducted involving postmenopausal women during which 94 g of freeze-dried grape powder was consumed in addition to their usual diet. Plasma hormones were measured before and after the treatment. Results Of the 18 women involved in the study, average age and body mass index were 61.4 years and 24.4 respectively. For the hormone levels studied, the following median (interquartile range) percentage changes from baseline to six-week values were found: estradiol +11.8% (−34.4%, +44.2%), p = .42; estrone +3.4% (−15.7%, +12.9%), p = .64; estrone sulfate +5.3% (−19.9%, +56.3%), p = .35; testosterone −1.5% (−14.7%, +10.7%), p = .97; and androstenedione +12.6% (−17.1%, +49.1%), p = .15. The hormone levels did not significantly change between baseline and six weeks. Further, the changes that were observed did not tend to go in the hypothesized direction (estrogens and conjugates increased slightly, and testosterone decreased slightly). Only androstenedione showed a trend toward change in the hypothesized direction. Conclusions In this study, there was no evidence that plasma hormone levels are altered by six weeks of daily consumption of 94 g of freeze-dried grape powder. PMID:25167077

  6. Development of controlled-release cisplatin dry powders for inhalation against lung cancers.

    PubMed

    Levet, Vincent; Rosière, Rémi; Merlos, Romain; Fusaro, Luca; Berger, Gilles; Amighi, Karim; Wauthoz, Nathalie

    2016-12-30

    The present study focuses on the development of dry powders for inhalation as adjuvant chemotherapy in lung cancer treatment. Cisplatin was chosen as a potential candidate for a local treatment as it remains the main platinum component used in conventional chemotherapies, despite its high and cumulative systemic toxicities. Bulk cisplatin was reduced to submicron sizes using high-pressure homogenization, mixed with a solubilized lipid and/or PEGylated component and then spray-dried to produce controlled-release dry powder formulations. The obtained formulations were characterized for their physicochemical properties (particle size and morphology), aerodynamic performance and release profiles. Cisplatin content and integrity were assessed by electrothermal atomic absorption spectrometry and (195)Pt nuclear magnetic resonance spectroscopy. DPI formulations with cisplatin contents ranging from 48.5 to 101.0% w/w exhibited high fine particle fractions ranging from 37.3% to 51.5% of the nominal dose. Formulations containing cisplatin microcrystals dispersed in solid lipid microparticles based on acceptable triglycerides for inhalation and PEGylated excipients showed a controlled-release for more than 24h and a limited burst effect. These new formulations could provide an interesting approach to increasing and prolonging drug exposure in the lung while minimizing systemic toxicities.

  7. Dry powder inhalers (DPIs)--a review of device reliability and innovation.

    PubMed

    Islam, Nazrul; Gladki, Ellen

    2008-08-06

    A wide range of dry powder inhaler (DPI) devices are currently available on the market to deliver drugs into lungs with a view to maximise drug delivery with low variability. DPIs also face numerous clinical challenges, particularly related to variable patient factors such as age, clinical condition and inspiratory flow. Due to the drug formulation and the design of devices, different DPIs do not show the same performance and manufacturers are taking a variety of device design approaches. The characteristics of an ideal DPI, recent innovations in powder formulation and device design are not universally reliable in terms of dose variability, clinical efficacy, user friendliness and economy. This mini review examines whether device reliability is more important than innovation. This study enables a comparison of the relative merits of optimising existing DPIs or seeking to develop novel devices.

  8. Optimisation of spray-drying process variables for dry powder inhalation (DPI) formulations of corticosteroid/cyclodextrin inclusion complexes.

    PubMed

    Cabral-Marques, Helena; Almeida, Rita

    2009-09-01

    This study aims to develop and characterise a beclomethasone diproprionate:gamma-cyclodextrin (BDP:gamma-CYD) complex and to optimise the variables on the spray-drying process, in order to obtain a powder with the most suitable characteristics for lung delivery. The spray-dried powder--in a mass ratio of 2:5 (BDP:gamma-CYD)--was physically mixed with three carriers of different particle sizes and in different ratios. Particle-size distribution, shape and morphology, moisture content, and uniformity in BDP content of formulations were studied. In vitro aerolisation behaviour of the formulations was evaluated using the Rotahaler, and the performance was characterised based on the uniformity of emitted dose and aerodynamic particle-size distribution (respirable fraction (RF), as a percentage of nominal dose (RFN) and emitted dose (RFE)). The most suitable conditions for the preparation of BDP:gamma-CYD complexes were obtained with the solution flow of 5 ml/min, T(in) of 70 degrees C and T(out) of 50 degrees C. Statistically significant differences in the aerodynamic performances were obtained for formulations containing BDP:gamma-CYD complexes prepared using different solution flows and different T(in) (p<0.05). RFN and RFE vary in direct proportion with T(in), while an inverse relationship was observed for the solution flow. A direct correlation between the RFE and the T(out) was identified. Performance of the formulations was compared with an established commercial product (Beclotaide Rotacaps 100 microg) with improved performance of RF: formulations with respitose carrier attained RFN and RFE twofold greater, and formulations based on 63-90 microm fraction lactose and trehalose achieved a threefold improvement; also, all formulations showed that the percentage of dose of BDP deposited in the "oropharynx" compartment was reduced to half.

  9. Physicochemical characterization and water vapor sorption of organic solution advanced spray-dried inhalable trehalose microparticles and nanoparticles for targeted dry powder pulmonary inhalation delivery.

    PubMed

    Li, Xiaojian; Mansour, Heidi M

    2011-12-01

    Novel advanced spray-dried inhalable trehalose microparticulate/nanoparticulate powders with low water content were successfully produced by organic solution advanced spray drying from dilute solution under various spray-drying conditions. Laser diffraction was used to determine the volumetric particle size and size distribution. Particle morphology and surface morphology was imaged and examined by scanning electron microscopy. Hot-stage microscopy was used to visualize the presence/absence of birefringency before and following particle engineering design pharmaceutical processing, as well as phase transition behavior upon heating. Water content in the solid state was quantified by Karl Fisher (KF) coulometric titration. Solid-state phase transitions and degree of molecular order were examined by differential scanning calorimetry (DSC) and powder X-ray diffraction, respectively. Scanning electron microscopy showed a correlation between particle morphology, surface morphology, and spray drying pump rate. All advanced spray-dried microparticulate/nanoparticulate trehalose powders were in the respirable size range and exhibited a unimodal distribution. All spray-dried powders had very low water content, as quantified by KF. The absence of crystallinity in spray-dried particles was reflected in the powder X-ray diffractograms and confirmed by thermal analysis. DSC thermal analysis indicated that the novel advanced spray-dried inhalable trehalose microparticles and nanoparticles exhibited a clear glass transition (T(g)). This is consistent with the formation of the amorphous glassy state. Spray-dried amorphous glassy trehalose inhalable microparticles and nanoparticles exhibited vapor-induced (lyotropic) phase transitions with varying levels of relative humidity as measured by gravimetric vapor sorption at 25°C and 37°C.

  10. Effect of carrier type and spray drying on the physicochemical properties of powdered and reconstituted pomegranate juice (Punica Granatum L.).

    PubMed

    Yousefi, Shima; Emam-Djomeh, Zahra; Mousavi, S M

    2011-12-01

    Pomegranate juice was diluted to 12° Brix and carriers (maltodextrin, gum Arabic, waxy starch) were added with varying concentrations of cellulose before being reduced to powder by spray drying. All carrier concentrations improved dryer yield, with gum Arabic being the most effective. The bulk density of the powder decreased when higher carrier concentrations were used. As cellulose concentration increased in solution, the solubility of the final product decreased. The optical properties of the powder were affected by the type and concentration of the carrier; powders produced with gum Arabic showed the greatest color change. Adding a carrier increased the Tg of the powder and its storage stability. Variation in the anthocyanin may be related to the type of carrier agent and its behavior during spray drying.

  11. [Effect of air humidity on traditional Chinese medicine extract of spray drying process and prediction of its powder stability].

    PubMed

    He, Yan; Xie, Yin; Zheng, Long-jin; Liu, Wei; Rao, Xiao-yong; Luo, Xiao-jian

    2015-02-01

    In order to solve the adhesion and the softening problems of traditional Chinese medicine extract during spray drying, a new method of adding dehumidified air into spray drying process was proposed, and the storage stability conditions of extract powder could be predicted. Kouyanqing extract was taken as model drug to investigate on the wet air (RH = 70%) and dry air conditions of spray drying. Under the dry air condition, the influence of the spray drying result with different air compression ratio and the spray-dried powder properties (extract powder recovery rate, adhesion percentage, water content, angle of repose, compression ratio, particle size and distribution) with 100, 110, 120, 130, 140 °C inlet temperature were studied. The hygroscopic investigation and Tg value with different moisture content of ideal powder were determined. The water activity-equilibrium moisture content (aw-EMC) and the equilibrium moisture content-Tg (EMC-Tg) relationships were fitted by GAB equation and Gordon-Taylor model respectively, and the state diagram of kouyanqing powder was obtained to guide the rational storage conditions. The study found that in the condition of dry air, the extract powder water content decreased with the increase of air compression ratio and the spray drying effect with air compression ratio of 100% was the best performance; in the condition of wet air, the extract powder with high water content and low yield, and the value were 4.26% and 16.73 °C, while, in the dry air condition the values were 2.43% and 24.86 °C with the same other instru- ment parameters. From the analysis of kouyanqing powder state diagram, in order to keep the stability, the critical water content of 3.42% and the critical water content of 0.188. As the water decreased Tg value of extract powder is the major problem of causing adhesion and softening during spray drying, it is meaningful to aid dehumidified air during the process.

  12. Use of a cognitive ergonomics approach to compare usability of a multidose dry powder inhaler and a capsule dry powder inhaler: an open-label, randomized, controlled study.

    PubMed

    Franks, Mark; Briggs, Pamela

    2004-11-01

    Usability (ease of use) is an important feature of inhalers to ensure optimal dose delivery The aim of this study was to compare the usability of a multidose dry powder inhaler (mDPI) and a capsule dry powder inhaler (cDPI) in older individuals, using a range of qualitative and quantitative techniques from the field of cognitive ergonomics. Participants aged >50 years were enrolled in this 2-visit, open-label, randomized, controlled, parallel-group study conducted at Northumbria University, Newcastle upon Tyne, United Kingdom. Participants who had used an inhaler or were inhaler naive were randomized to use the mDPI or cDPI. At visit 1, the inhaler procedure was demonstrated twice by the investigator. Participants then repeated the procedure (although they were not expected to inhale because no drug was to be administered) until they made 3 consecutive correct attempts. They also undertook a range of tests to assess their confidence in using the device, manual dexterity, and self-efficacy At visit 2 (2 days later), participants made a single inhaler attempt before receiving any demonstrations from the investigator; this was intended to simulate clinical practice, in which the patient may not use an inhaler for a few days after it is prescribed. Participants then completed the inhaler procedure 10 times while undertaking a concurrent distracter task. The number of critical errors (ie, those having a high impact on dose delivery) was recorded for all attempts. To facilitate subsequent correlation analyses, an overall performance measure was derived from a combination of the results of the single inhaler trial and the 10 trials with a distracter. Eighty individuals (51 women, 29 men; mean [SD] age, 74.1 [7.5] years) participated in the study(40 participants per device). Forty of the participants (50%) had used an inhaler previously; 40 (50%) were inhaler naive. Based on the overall performance measure, participants testing the mDPI made significantly fewer critical

  13. Size-dependent chemical ageing of oleic acid aerosol under dry and humidified conditions

    NASA Astrophysics Data System (ADS)

    Al-Kindi, Suad S.; Pope, Francis D.; Beddows, David C.; Bloss, William J.; Harrison, Roy M.

    2016-12-01

    A chemical reaction chamber system has been developed for the processing of oleic acid aerosol particles with ozone under two relative humidity conditions: dry and humidified to 65 %. The apparatus consists of an aerosol flow tube, in which the ozonolysis occurs, coupled to a scanning mobility particle sizer (SMPS) and an aerosol time-of-flight mass spectrometer (ATOFMS) which measure the evolving particle size and composition. Under both relative humidity conditions, ozonolysis results in a significant decrease in particle size and mass which is consistent with the formation of volatile products that partition from the particle to the gas phase. Mass spectra derived from the ATOFMS reveal the presence of the typically observed reaction products: azelaic acid, nonanal, oxononanoic acid and nonanoic acid, as well as a range of higher molecular weight products deriving from the reactions of reaction intermediates with oleic acid and its oxidation products. These include octanoic acid and 9- and 10-oxooctadecanoic acid, as well as products of considerably higher molecular weight. Quantitative evaluation of product yields with the ATOFMS shows a marked dependence upon both particle size association (from 0.3 to 2.1 µm diameter) and relative humidity. Under both relative humidity conditions, the percentage residual of oleic acid increases with increasing particle size and the main lower molecular weight products are nonanal and oxononanoic acid. Under dry conditions, the percentage of higher molecular weight products increases with increasing particle size due to the poorer internal mixing of the larger particles. Under humidified conditions, the percentage of unreacted oleic acid is greater, except in the smallest particle fraction, with little formation of high molecular weight products relative to the dry particles. It is postulated that water reacts with reactive intermediates, competing with the processes which produce high molecular weight products. Whilst the

  14. Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality by design approach for product construction.

    PubMed

    Belotti, Silvia; Rossi, Alessandra; Colombo, Paolo; Bettini, Ruggero; Rekkas, Dimitrios; Politis, Stavros; Colombo, Gaia; Balducci, Anna Giulia; Buttini, Francesca

    2014-08-25

    An amikacin product for convenient and compliant inhalation in cystic fibrosis patients was constructed by spray-drying in order to produce powders of pure drug having high respirability and flowability. An experimental design was applied as a statistical tool for the characterization of amikacin spray drying process, through the establishment of mathematical relationships between six Critical Quality Attributes (CQAs) of the finished product and five Critical Process Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for particle engineering, in general did not benefit the CQAs of the spray dried powders for inhalation. The spray drying feed solution required the inclusion of 10% (v/v) ethanol in order to reach the desired aerodynamic performance of powders. All desirable function solutions indicated that the favourable concentration of amikacin in the feed solution had to be kept at 1% w/v level. It was found that when the feed rate of the sprayed solution was raised, an increase in the drying temperature to the maximum value (160 °C) was required to maintain good powder respirability. Finally, the increase in drying temperature always led to an evident increase in emitted dose (ED) without affecting the desirable fine particle dose (FPD) values. The application of the experimental design enabled us to obtain amikacin powders with both ED and FPD, well above the regulatory and scientific references. The finished product contained only the active ingredient, which keeps low the mass to inhale for dose requirement.

  15. Formulation Screening and Freeze-Drying Process Optimization of Ginkgolide B Lyophilized Powder for Injection.

    PubMed

    Liu, Daichun; Galvanin, Federico; Yu, Ying

    2017-08-28

    The purpose of this study was to prepare ginkgolide B (GB) lyophilized powder for injection with excellent appearance and stable quality through a formulation screening and by optimizing the freeze-drying process. Cremophor EL as a solubilizer, PEG 400 as a latent solvent, and mannitol as an excipient were mixed to increase the solubility of GB in water to more than 18 times (about from 2.5 × 10(-4) mol/L (0.106 mg/mL) to 1.914 mg/mL). Formulation screening was conducted by orthogonal design where the content of GB in the solution before lyophilization (using external standard method of HPLC) and reconstitution time after lyophilization were the two evaluation indexes. The optimized formulations were GB in an amount of 2 mg/mL, Cremophor EL in an amount of 16% (v/v), PEG 400 in an amount of 9% (v/v), mannitol in an amount of 8% (w/v), and the solution pH of 6.5. Through four single-factor experiments (GB adding order, preparation temperature of GB solution, adding amount, and adsorption time of activated carbon), the preparation process of GB solution was confirmed. The glass transition temperature of maximally GB freeze-concentrated solution was - 17.6°C through the electric resistance method. GB lyophilized powder began to collapse at - 14.0°C, and the fully collapsed temperature was - 13.0°C, which were determined by freeze-drying microscope. When the collapse temperature was determined, the primary drying temperature was obtained. Thereby, the freeze-drying curve of GB lyophilized powder was initially identified. The freeze-drying process was optimized by orthogonal design, the qualified product appearance and residual moisture content were the two evaluation indexes. The optimized process parameters and process were (1) shelf temperature, decreased from room temperature to - 45.0°C, at 0.5°C/min in 2 h; (2) shelf temperature increased from - 45.0 to - 25.0°C, at 0.1°C/min, maintained for 3 h, and the chamber pressure was held at 10

  16. A Preference Study of Two Placebo Dry Powder Inhalers in Adults with COPD: ELLIPTA® Dry Powder Inhaler (DPI) versus DISKUS® DPI.

    PubMed

    Yun Kirby, Suyong; Zhu, Chang-Qing; Kerwin, Edward M; Stanford, Richard H; Georges, George

    2016-01-01

    Patients' preference is an important factor in selecting an inhaler treatment for COPD. The DISKUS® dry powder inhaler (DPI), which has been available to deliver several COPD medications for a decade, and the ELLIPTA® DPI, developed for the delivery of newer once-daily medications for patients with COPD, were studied in terms of patient preference and inhaler-specific attributes. We conducted a randomized, open-label, crossover study in patients with COPD. Patients used placebo ELLIPTA DPI once daily and placebo DISKUS DPI twice daily, for ∼1 week each, while continuing their COPD medications. Endpoints were: inhaler preference based on size of the numbers on the dose-counter (primary); the number of steps needed and inhaler size (secondary); and based on comfort of the mouthpiece, ease of opening, overall preference, and dosing regimen preference ('other'). Safety assessments included adverse events (AEs). A total of 287 patients were randomized. A significantly (p < 0.001) larger proportion of patients preferred the ELLIPTA DPI over DISKUS DPI for each of the tested attributes and overall, and preferred once-daily over twice-daily dosing. AEs were reported for 36 patients (13%); one (dry mouth) was considered to be related to the placebo-containing DISKUS DPI. Three patients had five non-fatal serious AEs, none were deemed inhaler-related. This study demonstrated that more patients with COPD preferred five specific inhaler attributes of the ELLIPTA DPI over DISKUS DPI and overall, and preferred once-daily versus twice-daily dosing. Safety profiles were consistent with those expected for COPD.

  17. Dry powder inhalers and the right things to remember: a concept review.

    PubMed

    Dal Negro, Roberto W

    2015-01-01

    Dry powder inhalers (DPIs) are widely and increasingly used in clinical practice because they represent a substantial advancement in inhalation technology. The effectiveness of a powdered drug to inhale depends on the inspiratory flow rate generated by the patient and on the turbulence produced by the intrinsic resistance of the DPI. While the inspiratory flow is variable with the patient's ability and conditions, the turbulence is differently sized within each device because depending of its technical design. There are higher - medium-, and low-resistance devices. With low-resistance DPIs, the disaggregation and the microdispersion of the drug highly depend on the patient's inhalation airflow rate, because the role of the resistance-induced turbulence is obviously negligible in these cases. This flow-rate dependency is minimized in the presence of a sufficient regimen of turbulence as in the case of medium-resistance DPIs. Both the disaggregation and the micro-dispersion of the powdered drug are optimized in these circumstances even in the absence of a maximal inspiratory flow rate. The low resistance DPIs should not be regarded as the best performer DPIs because their intrinsic low-resistance regimen requires a higher inspiratory airflow rate and effort, which frequently cannot be achieved by subjects suffering from a disease-induced airflow limitation. Only when the ratio between the inhalation flow rate and the DPI intrinsic resistance is balanced, the speed of the particulate, the distribution of the drug within the lung, and the variability of the effective inhaled dose are optimized.

  18. Tetrachloroethene recovery and hazard reduction of spent powders from dry cleaning process.

    PubMed

    Petrucci, Elisabetta; Scarsella, Marco; De Filippis, Paolo; Di Palma, Luca

    2015-04-01

    Dry cleaning facilities using perchloroethylene produce a solid waste consisting of spent filtering powders with a high content of residual perchloroethylene, together with dyes and non-volatile residues. Untreated spent powders, classified as hazardous waste, cannot be disposed in landfill and incineration represents the only viable alternative. In this study, together with a full characterisation of the waste, the removal and recovery of the residual perchloroethylene by means of different heat treatments was investigated. In particular, tests of distillation and stripping with air and steam were carried out, evaluating the effectiveness of the treatments by quantifying the residual perchloroethylene in the samples treated. The results obtained show that the spent filtering powders contained about 25% wt. of perchloroethylene and that the maximum perchloroethylene recovery was obtained by steam stripping; approximately 98% after only 50 minutes. However, this treatment accounted for the production of a liquid mixture containing perchloroethylene and of a solid waste that required a further washing with boiling water to decrease the residual organic content below the eligibility criteria for landfill disposal. © The Author(s) 2015.

  19. Chemical composition and antioxidant activity of dried powder formulations of Agaricus blazei and Lentinus edodes.

    PubMed

    Carneiro, Andreia A J; Ferreira, Isabel C F R; Dueñas, Montserrat; Barros, Lillian; da Silva, Roberto; Gomes, Eleni; Santos-Buelga, Celestino

    2013-06-15

    Several mushroom species have been pointed out as sources of antioxidant compounds, in addition to their important nutritional value. Agaricus blazei and Lentinus edodes are among the most studied species all over the world, but those studies focused on their fruiting bodies instead of other presentations, such as powdered preparations, used as supplements. In the present work the chemical composition (nutrients and bioactive compounds) and antioxidant activity (free radical scavenging activity, reducing power and lipid peroxidation inhibition) of dried powder formulations of the mentioned mushroom species (APF and LPF, respectively) were evaluated. Powder formulations of both species revealed the presence of essential nutrients, such as proteins, carbohydrates and unsaturated fatty acids. Furthermore, they present a low fat content (<2g/100g) and can be used in low-calorie diets, just like the mushrooms fruiting bodies. APF showed higher antioxidant activity and higher content of tocopherols and phenolic compounds (124 and 770 μg/100g, respectively) than LPF (32 and 690 μg/100g). Both formulations could be used as antioxidant sources to prevent diseases related to oxidative stress.

  20. Evolution of the internal dynamics of two globular proteins from dry powder to solution.

    PubMed Central

    Pérez, J; Zanotti, J M; Durand, D

    1999-01-01

    Myoglobin and lysozyme picosecond internal dynamics in solution is compared to that in hydrated powders by quasielastic incoherent neutron scattering. This technique is sensitive to the motions of the nonexchangeable hydrogen atoms in a sample. Because these are homogeneously distributed throughout the protein structure, the average dynamics of the protein is described. We first propose an original data treatment to deal with the protein global motions in the case of solution samples. The validity of this treatment is checked by comparison with classical measurements of the diffusion constants. The evolution with the scattering vector of the width and relative contribution of the quasielastic component was then used to derive information on the amount of local diffusive motions and their characteristic average relaxation time. From dry powder to coverage by one water layer, the surface side chains progressively acquire the possibility to diffuse locally. On subsequent hydration, the main effect of water is to improve the rate of these diffusive motions. Motions with higher average amplitude occur in solution, about three times more than for a hydrated powder at complete coverage, with a shorter average relaxation time, approximately 4.5 ps compared to 9.4 ps for one water monolayer. PMID:10388771

  1. Development of a Freeze-Dried Fungal Wettable Powder Preparation Able to Biodegrade Chlorpyrifos on Vegetables

    PubMed Central

    Chen, Shaohua; Xiao, Ying; Hu, Meiying; Zhong, Guohua

    2014-01-01

    Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711), a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM). The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues. PMID:25061758

  2. Development of a freeze-dried fungal wettable powder preparation able to biodegrade chlorpyrifos on vegetables.

    PubMed

    Liu, Jie; He, Yue; Chen, Shaohua; Xiao, Ying; Hu, Meiying; Zhong, Guohua

    2014-01-01

    Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711), a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM). The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues.

  3. Structural, physicochemical and biological properties of spray-dried wine powders.

    PubMed

    Wilkowska, Agnieszka; Czyżowska, Agata; Ambroziak, Wojciech; Adamiec, Janusz

    2017-08-01

    Different fruit wines, chokeberry, blackcurrant and blueberry, were spray-dried using hydroxypropyl-β-cyclodextrin (HP-β-CD) and inulin (IN). The structural, physicochemical, and biological properties of the spray-dried wine powders were studied over 12months of storage in darkness at 8°C. Identification and quantification of single phenolic compounds before and after storage revealed that HP-β-CD had a positive effect on anthocyanin retention during storage for all microcapsules tested. Similar decreases in anthocyanin were found for blackcurrant and chokeberry powders, ranging from 7.3 to 8.9% with HP-β-CD and 12.3 to 12.5% with IN. Levels of anthocyanin losses in blueberry wine microcapsules were much greater: 19.9% (HP-β-CD) and 22.7% (IN). The high antiradical activities of blackcurrant and chokeberry wine microcapsules were stable and remained unchanged during storage. All wine microcapsules revealed significant activity against medically important bacterial strains. The HP-β-CD samples showed generally higher activity against the test microorganisms compared to IN microcapsules, especially at concentrations of 100mg/mL. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Evolution of antioxidants in dietary fiber powder produced from white cabbage outer leaves: effects of blanching and drying methods.

    PubMed

    Tanongkankit, Yardfon; Chiewchan, Naphaporn; Devahastin, Sakamon

    2015-04-01

    White cabbage outer leaves, which are usually discarded both during industrial processing and selling in a consumer market, have proven to be a good source of dietary fiber (DF) as well as antioxidants and can be effectively transformed into functional DF powder. In the past, however, only hot air drying was used to prepare DF powder from cabbage outer leaves although it is well recognized that this drying technique could lead to much quality degradation of a dried product. This work was therefore aimed at studying the evolution of selected important antioxidants, e.g., phenolic compounds and vitamin C, in white cabbage outer leaves during vacuum drying at 60, 70 and 80 °C. The effect of pretreatment viz. steam blanching was also evaluated. The results showed that there were losses of antioxidants during steam blanching; vacuum dried blanched leaves nevertheless contained higher antioxidant contents and activity than dried unblanched leaves. Losses of antioxidants during vacuum drying were also noted to be less than those during hot air drying. Overall, the results showed that there were no differences in the antioxidants retention among all the tested conditions performed in this study. Therefore, the most suitable condition for the production of antioxidant DF powder from cabbage outer leaves is vacuum drying at 80 °C as this condition requires the minimum specific energy consumption.

  5. Relationship between surface concentration of L-leucine and bulk powder properties in spray dried formulations.

    PubMed

    Mangal, Sharad; Meiser, Felix; Tan, Geoffrey; Gengenbach, Thomas; Denman, John; Rowles, Matthew R; Larson, Ian; Morton, David A V

    2015-08-01

    The amino acid L-leucine has been demonstrated to act as a lubricant and improve the dispersibility of otherwise cohesive fine particles. It was hypothesized that optimum surface L-leucine concentration is necessary to achieve optimal surface and bulk powder properties. Polyvinylpyrrolidone was spray dried with different concentration of L-leucine and the change in surface composition of the formulations was determined using X-ray photoelectron spectroscopy (XPS) and time of flight-secondary ion mass spectrometry (ToF-SIMS). The formulations were also subjected to powder X-ray diffraction analysis in order to understand the relationship between surface concentration and solid-state properties of L-leucine. In addition, the morphology, surface energy and bulk cohesion of spray dried formulations were also assessed to understand the relation between surface L-leucine concentration and surface and bulk properties. The surface concentration of L-leucine increased with higher feed concentrations and plateaued at about 10% L-leucine. Higher surface L-leucine concentration also resulted in the formation of larger L-leucine crystals and not much change in crystal size was noted above 10% L-leucine. A change in surface morphology of particles from spherical to increasingly corrugated was also observed with increasing surface l-leucine concentration. Specific collapsed/folded over particles were only seen in formulations with 10% or higher l-leucine feed concentration suggesting a change in particle surface formation process. In addition, bulk cohesion also reduced and approached a minimum with 10% L-leucine concentration. Thus, the surface concentration of L-leucine governs particle formation and optimum surface L-leucine concentration results in optimum surface and bulk powder properties.

  6. Formulation of pH responsive peptides as inhalable dry powders for pulmonary delivery of nucleic acids

    PubMed Central

    Liang, Wanling; Kwok, Philip C.L.; Chow, Michael Y.T.; Tang, Patricia; Mason, A. James; Chan, Hak-Kim; Lam, Jenny. K.W.

    2013-01-01

    Nucleic acids have the potential to be used as therapies or vaccines for many different types of disease but delivery remains the most significant challenge to their clinical adoption. pH responsive peptides containing either histidine or derivatives of 2,3-diaminopropionic acid (Dap) can mediate effective DNA transfection in lung epithelial cells with the latter remaining effective even in the presence of lung surfactant containing bronchoalveolar fluid (BALF), making this class of peptides attractive candidates for delivering nucleic acids to lung tissues. To further assess the suitability of pH responsive peptides for pulmonary delivery by inhalation, dry powder formulations of pH responsive peptides and plasmid DNA, with mannitol as carrier, were produced by either spray drying (SD) or spray freeze drying (SFD). The properties of the two types of powders were characterised and compared using scanning electron microscopy (SEM), next generation impaction (NGI), gel retardation and in vitro transfection via a twin-stage impinger (TSI) following aerosolisation by a dry powder inhaler (Osmohaler™). Although the aerodynamic performance and transfection efficacy of both powders were good, the overall performance revealed SD powders to have a number of advantages over SFD powders and are the more effective formulation with potential for efficient nucleic acid delivery through inhalation. PMID:23702276

  7. Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

    PubMed

    Wu, Na; Zhang, Xinxin; Li, Feifei; Zhang, Tao; Gan, Yong; Li, Juan

    2015-01-01

    Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5-15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery.

  8. Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure

    PubMed Central

    Wu, Na; Zhang, Xinxin; Li, Feifei; Zhang, Tao; Gan, Yong; Li, Juan

    2015-01-01

    Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5–15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery. PMID:26347257

  9. Aerosol dry deposition on vegetative canopies. Part II: A new modelling approach and applications

    NASA Astrophysics Data System (ADS)

    Petroff, Alexandre; Mailliat, Alain; Amielh, Muriel; Anselmet, Fabien

    2008-05-01

    This paper presents a new approach for the modelling of aerosol dry deposition on vegetation. It follows a companion article, in which a review of the current knowledge highlights the need for a better description of the aerosol behaviour within the canopy [Petroff, A., Mailliat, A., Amielh, M., Anselmet, F., 2008. Aerosol dry deposition on vegetative canopies. Part I: Review of present knowledge. Atmospheric Environment, in press, doi:10.1016/j.atmosenv.2007.09.043]. Concepts from multi-phase flow studies are used for describing the canopy medium and deriving a time and space-averaged aerosol balance equation and the associated deposition terms. The closure of the deposition terms follows an up-scaling procedure based on the statistical distribution of the collecting elements. This aerosol transport model is then applied in a stationary and mono-dimensional configuration and takes into account the properties of the vegetation, the aerosol and the turbulent flow. Deposition mechanisms are Brownian diffusion, interception, inertial and turbulent impactions, and gravitational settling. For each of them, a parameterisation of the particle collection is derived and the quality of their predictions is assessed by comparison with wind-tunnel deposition measurements on coniferous twigs [Belot, Y., Gauthier, D., 1975. Transport of micronic particles from atmosphere to foliar surfaces. In: De Vries, D.A., Afgan, N.H. (Eds.), Heat and Mass Transfer in the Biosphere. Scripta Book, Washington, DC, pp. 583-591; Belot, Y., 1977. Etude de la captation des polluants atmosphériques par les végétaux. CEA, R-4786, Fontenay-aux-Roses; Belot, Y., Camus, H., Gauthier, D., Caput, C., 1994. Uptake of small particles by canopies. The Science of the Total Environment 157, 1-6]. Under a real canopy configuration, the predictions of the aerosol transport model compare reasonably well with detailed on-site deposition measurements of Aitken mode particles [Buzorius, G., Rannik, Ü., M

  10. New dry powders for inhalation containing temozolomide-based nanomicelles for improved lung cancer therapy.

    PubMed

    Rosière, Rémi; Gelbcke, Michel; Mathieu, Véronique; Van Antwerpen, Pierre; Amighi, Karim; Wauthoz, Nathalie

    2015-09-01

    Besides the numerous advantages of a chemotherapy administered by the inhalation route for lung cancer therapy, dry powder for inhalation (DPI) offers many advantages compared to other techniques and seems to be a technique that is well-adapted to an anticancer treatment. DPI formulations were developed using the cytotoxic drug temozolomide and a new folate-grafted self-assembling copolymer, a conjugate of three components, folate-polyethylene glycol-hydrophobically-modified dextran (F-PEG-HMD). F-PEG-HMD was synthesized using carbodiimide-mediated coupling chemistry in three main steps. F-PEG-HMD was characterized by 1H-NMR, mass spectrometry and thermal analysis. F-PEG-HMD presented a critical micellar concentration in water of 4x10-7 M. F-PEG-HMD nanomicelles were characterized by a trimodal particle size distribution with Z-average diameter of 83±1 nm in water. Temozolomide-loaded nanomicelles were prepared by solubilization of F-PEG-HMD in the presence of temozolomide. Temozolomide solubility in water was increased in the presence of F-PEG-HMD (2-fold increase in molar solubility) which could potentially lead to increased local concentrations in the tumor site. The temozolomide-loaded F-PEG-HMD nanomicelles were characterized by a Z-average diameter of ~50 to ~60 nm, depending on the F-PEG-HMD concentration used. The nanomicelles were then spray-dried to produce dry powders. Temozolomide remained stable during all the formulation steps, confirmed by similar in vitro anticancer properties for the DPI formulations and a raw temozolomide solution. Two of the developed DPI formulations were characterized by good aerodynamic properties (with a fine particle fraction of up to 50%) and were able to release the F-PEG-HMD nanomicelles quickly in aqueous media. Moreover, in vitro, the two DPI formulations showed wide pulmonary deposition in the lower respiratory tract where adenocarcinomas are more often found. The present study, therefore, shows that F

  11. Intranasal delivery of Norwalk virus-like particles formulated in an in-situ gelling, dry powder vaccine

    PubMed Central

    Velasquez, Lissette S.; Shira, Samantha; Berta, Alice N.; Kilbourne, Jacquelyn; Medi, Babu M.; Tizard, Ian; Ni, Yawei; Arntzen, Charles J.; Herbst-Kralovetz, Melissa M.

    2011-01-01

    The development of a vaccine to prevent norovirus infections has been focused on immunization at a mucosal surface, but has been limited by the low immunogenicity of self-assembling Norwalk virus-like particles (NV VLPs) delivered enterically or at nasal surfaces. Nasal immunization, which offers the advantage of ease of immunization, faces obstacles imposed by the normal process of mucociliary clearance, which limits residence time of applied antigens. Herein, we describe the use of a dry powder formulation (GelVac) of an inert in-situ gelling polysaccharide (GelSite) extracted from Aloe vera for nasal delivery of NV VLP antigen. Powder formulations, with or without NV VLP antigen, were similar in structure in dry form or when rehydrated in simulated nasal fluids. Immunogenicity of the dry powder VLP formulation was compared to equivalent antigen/adjuvant liquid formulations in animals. For the GelVac powder, we observed superior NV-specific serum and mucosal (aerodigestive and reproductive tracts) antibody responses relative to liquid formulations. Incorporation of TLR7 agonist gardiquimod in dry powder formulations did not enhance antibody responses, although its inclusion in liquid formulations did enhance VLP immunogenicity irrespective of the presence or absence of GelSite. We interpret these data as showing that GelSite-based dry powder formulations 1.) stabilize the immunogenic structural properties of VLPs and 2.) induce systemic and mucosal antibody titers which are equal or greater than those achieved by VLPs plus adjuvant in a liquid formulation. We conclude that in-situ gelation of the GelVac dry powder formulation at nasal mucosal surfaces delays mucociliary clearance and thereby prolongs VLP antigen exposure to immune effector sites. PMID:21640778

  12. Investigation of the potential for direct compaction of a fine ibuprofen powder dry-coated with magnesium stearate.

    PubMed

    Qu, Li; Zhou, Qi Tony; Gengenbach, Thomas; Denman, John A; Stewart, Peter J; Hapgood, Karen P; Gamlen, Michael; Morton, David A V

    2015-05-01

    Intensive dry powder coating (mechanofusion) with tablet lubricants has previously been shown to give substantial powder flow improvement. This study explores whether the mechanofusion of magnesium stearate (MgSt), on a fine drug powder can substantially improve flow, without preventing the powder from being directly compacted into tablets. A fine ibuprofen powder, which is both cohesive and possesses a low-melting point, was dry coated via mechanofusion with between 0.1% and 5% (w/w) MgSt. Traditional low-shear blending was also employed as a comparison. No significant difference in particle size or shape was measured following mechanofusion. For the low-shear blended powders, only marginal improvement in flowability was obtained. However, after mechanofusion, substantial improvements in the flow properties were demonstrated. Both XPS and ToF-SIMS demonstrated high degrees of a nano-scale coating coverage of MgSt on the particle surfaces from optimized mechanofusion. The study showed that robust tablets were produced from the selected mechanofused powders, at high-dose concentration and tablet tensile strength was further optimized via addition of a Polyvinylpyrrolidone (PVP) binder (10% w/w). The tablets with the mechanofused powder (with or without PVP) also exhibited significantly lower ejection stress than those made of the raw powder, demonstrating good lubrication. Surprisingly, the release rate of drug from the tablets made with the mechanofused powder was not retarded. This is the first study to demonstrate such a single-step dry coating of model drug with MgSt, with promising flow improvement, flow-aid and lubrication effects, tabletability and also non-inhibited dissolution rate.

  13. Nano-liposomal dry powder inhaler of tacrolimus: Preparation, characterization, and pulmonary pharmacokinetics

    PubMed Central

    Chougule, Mahavir; Padhi, Bijay; Misra, Ambikanandan

    2007-01-01

    The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal dispersion was passed through high pressure homogenizer. Tacrolimus nano-liposomes (NLs) were separated by centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different additives like lactose, sucrose, and trehalose, and L-leucine as antiadherent. The dispersion was spray dried and spray dried powders were characterized. In vitro and in vivo pulmonary deposition was performed using Andersen Cascade Impactor and intratracheal instillation in rats respectively. NLs were found to have average size of 140 nm, 96% ± 1.5% drug entrapment, and zeta potential of 1.107 mV. Trehalose based formulation was found to have low density, good flowability, particle size of 9.46 ± 0.8 μm, maximum fine particle fraction (FPF) of 71.1 ± 2.5%, mean mass aerodynamic diameter (MMAD) 2.2 ± 0.1 μm, and geometric standard deviation (GSD) 1.7 ± 0.2. Developed formulations were found to have in vitro prolonged drug release up to 18 hours, following Higuchi’s Controlled Release model. In vivo studies revealed maximal residence of tacrolimus within lungs of 24 hours, suggesting slow clearance from the lungs. The investigation provides a practical approach for direct delivery of tacrolimus encapsulated in NLs for controlled and prolonged retention at the site of action. It may play a promising role as rescue therapy in reducing the risk of acute rejection and chronic rejection. PMID:18203434

  14. Effects of drying methods on the physicochemical and compressional characteristics of Okra powder and the release properties of its metronidazole tablet formulation.

    PubMed

    Bakre, L G; Jaiyeoba, K T

    2009-02-01

    A study has been made of the effects of sun and oven drying methods on the physicochemical characteristics and compressibility of Okra powder and the release properties of its metronidazole tablet formulation. Corn starch was used as the reference standard. The mechanical properties of the tablets were evaluated using crushing strength and friability, while the release properties were determined using the disintegration times and dissolution rates. The results obtained showed that sun-dried Okra powder had smaller particle size, exhibited good flow and possessed higher hydration and swelling capacities compared to the oven dried samples. The compressibility of Okra powders assessed by the indices of plasticity from Heckel (Py) and Kawakita plots (Pk) showed that sun dried Okra powders had higher Py but lower Pk values than the oven-dried Okra powder. Metronidazole tablets formulated with oven dried Okra powder formed stronger tablets than tablets containing sun dried Okra powder. Generally, tablets containing sun dried Okra powders had faster disintegration and dissolution than tablets formulated with oven-dried powder. The results suggest that the choice of drying method during the processing of pharmaceutical raw materials is critical to its physicochemical properties and the release properties of its tablet formulations.

  15. Effects of Drying Temperature on Antioxidant Activities of Tomato Powder and Storage Stability of Pork Patties

    PubMed Central

    2016-01-01

    This study was performed to evaluate the antioxidant activity of oven-dried tomato powder (OTP) as affected by drying temperature and the effect of OTP on the product quality of pork patties. Three OTP products were obtained by drying of fresh tomato at 60, 80 and 100℃ oven until constant weight was obtained. Total phenolic content of three kinds of OTPs ranged from 1.95 to 5.94 g/100 g. The highest amount of total phenolic compound was observed in OTP dried at 100℃. Antioxidant activity of three kinds of OTPs was measured by 1,1-diphenyl-2-pycrylhydrazyl (DPPH)-radical scavenging activity, iron chelating ability, reducing power and measurement of lipid peroxide in linoleic acid emulsion system. In all parameters, OTP at 100℃ showed the higher antioxidant activity than other temperatures (p<0.05). Based on the model study, the physicochemical properties, and antioxidant and antimicrobial activities of pork patties containing 1% OTP were measured. Redness of pork patties were increased with the addition of OTPs (p<0.05). Thiobarbituric acid reactive substances (TBARS) values of raw pork patties containing OTPs were lower than those of control (CTL) until 7 d of storage, regardless of drying temperatures (p<0.05). Peroxide values of pork patties made with OTP (1%) were lower than those of CTL until the end of storage time (p<0.05). However, no antimicrobial activities were observed among the treatments (p>0.05). Therefore, OTPs could be used as a natural antioxidant in meat products. PMID:27499664

  16. The ELLIPTA® Dry Powder Inhaler: Design, Functionality, In Vitro Dosing Performance and Critical Task Compliance by Patients and Caregivers.

    PubMed

    Grant, Andrew C; Walker, Richard; Hamilton, Melanie; Garrill, Karl

    2015-12-01

    Dry powder inhalers (DPIs) are commonly used for the delivery of inhaled medications, and should provide consistent, efficient dosing, be easy to use correctly, and be liked by patients; these attributes can all affect patient compliance and therefore treatment efficacy. The ELLIPTA(®) DPI was developed for the delivery of once-daily therapies for the treatment of asthma and chronic obstructive pulmonary disease. It has moderate resistance to airflow and can hold one or two blister strips, with each blister containing a sealed single dose of medication. Monotherapies can be delivered by the single-strip configuration and, in the two-strip configuration, one dose from each strip can be aerosolized simultaneously to allow combination therapies to be delivered, which enables the formulations for each product to be developed individually, since they are stored separately until the point of administration. There are three principal operating steps to administer a dose: open, inhale, close. This article summarizes the design, functionality, and in vitro dose-delivery characteristics of the ELLIPTA inhaler, and describes the results of human factors validation tests, designed to assess the performance of critical tasks required to use the inhaler. Results from the in vitro studies indicate that the ELLIPTA inhaler performs consistently with respect to in vitro dose delivery characteristics at a range of flow rates that can be achieved by the target population (≥30 L/min) and over its 30-day in-use life. Data from the human factors validation tests demonstrated that almost all participants (≥97%) were able to complete each of the steps required to prepare a dose for inhalation without error. Overall, the ELLIPTA inhaler has a versatile single- or two-strip design that allows it to be used for the delivery of a range of treatment options. It also improves patient ease-of-use when compared with the DISKUS(®) DPI.

  17. The ELLIPTA® Dry Powder Inhaler: Design, Functionality, In Vitro Dosing Performance and Critical Task Compliance by Patients and Caregivers

    PubMed Central

    Grant, Andrew C.; Hamilton, Melanie; Garrill, Karl

    2015-01-01

    Abstract Dry powder inhalers (DPIs) are commonly used for the delivery of inhaled medications, and should provide consistent, efficient dosing, be easy to use correctly, and be liked by patients; these attributes can all affect patient compliance and therefore treatment efficacy. The ELLIPTA® DPI was developed for the delivery of once-daily therapies for the treatment of asthma and chronic obstructive pulmonary disease. It has moderate resistance to airflow and can hold one or two blister strips, with each blister containing a sealed single dose of medication. Monotherapies can be delivered by the single-strip configuration and, in the two-strip configuration, one dose from each strip can be aerosolized simultaneously to allow combination therapies to be delivered, which enables the formulations for each product to be developed individually, since they are stored separately until the point of administration. There are three principal operating steps to administer a dose: open, inhale, close. This article summarizes the design, functionality, and in vitro dose-delivery characteristics of the ELLIPTA inhaler, and describes the results of human factors validation tests, designed to assess the performance of critical tasks required to use the inhaler. Results from the in vitro studies indicate that the ELLIPTA inhaler performs consistently with respect to in vitro dose delivery characteristics at a range of flow rates that can be achieved by the target population (≥30 L/min) and over its 30-day in-use life. Data from the human factors validation tests demonstrated that almost all participants (≥97%) were able to complete each of the steps required to prepare a dose for inhalation without error. Overall, the ELLIPTA inhaler has a versatile single- or two-strip design that allows it to be used for the delivery of a range of treatment options. It also improves patient ease-of-use when compared with the DISKUS® DPI. PMID:26372466

  18. Physicochemical and thermal properties of taro (Colocasia esculenta sp) powders as affected by state of maturity and drying method.

    PubMed

    Himeda, M; Njintang, Y N; Gaiani, C; Nguimbou, R M; Scher, J; Facho, B; Mbofung, C M F

    2014-09-01

    The study was aimed at determining the effect of harvesting time and drying method on the thermal and physicochemical properties of taro powder, Sosso ecotype. A 5 × 2 factorial experiment with 5 harvesting times (6, 7, 8, 9 and 10 months after planting) and 2 drying methods (sun and electric oven drying) was used for this purpose. The variance component analysis revealed harvesting time as the most important factor affecting all the variables measured. In particular the proteins and available sugar contents of the powders increased significantly with increase in harvesting time. The same was true of the gelling property and water absorption capacity of the powders. It was equally observed that the temperatures (start, peak and end) and enthalpy of gelatinization of the powders increased with harvesting time. It is concluded that harvesting sosso-taro at full maturity (10 months after planting) and sun-drying produces food powders with excellent gelling properties among others.

  19. Insights into the roles of carrier microstructure in adhesive/carrier-based dry powder inhalation mixtures: Carrier porosity and fine particle content.

    PubMed

    Shalash, Ahmed O; Molokhia, Abdulla M; Elsayed, Mustafa M A

    2015-10-01

    To gain insights into complex interactions in carrier-based dry powder inhalation mixtures, we studied the relationships between the carrier microstructural characteristics and performance. We used mercury intrusion porosimetry to measure the microstructural characteristics and to also derive the air permeability of eight carriers. We evaluated the performances of inhalation mixtures of each of these carriers and fluticasone propionate after aerosolization from an Aerolizer®. We did not observe a simple relationship between the carrier total porosity and the performance. Classification of the porosity according to pore size, however, provided interesting insights. The carrier nanoporosity, which refers to pores smaller than micronized drug particles, has a positive influence on the performance. Nanopores reduce the carrier effective contact area and the magnitude of interparticulate adhesion forces in inhalation mixtures. The carrier microporosity, which refers to pores similar in size to drug particles, also has a positive influence on the performance. During mixing, micropores increase the effectiveness of frictional and press-on forces, which are responsible for breaking up of cohesive drug agglomerates and for distribution of drug particles over the carrier surface. On the other hand, the carrier macroporosity, which refers to pores larger than drug particles, apparently has a negative influence on the performance. This influence is likely mediated via the effects of macropores on the powder bed tensile strength and fluidization behavior. The air permeability better represents these effects. The inhalation mixture performance improved as the carrier air permeability decreased. Interestingly, as the carrier fine particle content increased, the carrier microporosity increased and the carrier air permeability decreased. This proposes a new mechanism for the positive effect of fine excipient materials on the performance of carrier-based inhalation mixtures. Fine

  20. Odour quality of spray-dried hens' egg powders: the influence of composition, processing and storage conditions.

    PubMed

    Rannou, Cécile; Texier, Florence; Moreau, Michelle; Courcoux, Philippe; Meynier, Anne; Prost, Carole

    2013-06-01

    This study aimed to determine whether compositional or processing parameters have an influence on the odour quality of egg powders. The parameters tested were: whole egg vs. egg yolk, polyunsaturated fatty acid (PUFA) enrichment, spray-drying temperature (160°C vs. 180°C), production scale (industrial vs. pilot plant), storage temperature (15°C vs. 30°C) and time (1, 2, 4 and 8 months). The quality of egg powders was evaluated by sensory analysis using free sorting, and by gas chromatography coupled to mass spectrometry and olfactometry. PUFA enrichment and spray-drying temperature do not affect the odour of egg yolk powders. There are significant differences between the odour of whole-egg and egg-yolk powders as well as between powders produced on an industrial scale or in a pilot plant. An increase in the odour intensity of egg powders was observed during storage, while unpleasant odours were perceived when the egg powders were stored at 30°C. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. A uHPLC-MS mathematical modeling approach to dry powder inhaler single agglomerate analysis.

    PubMed

    Pennington, Justin; Lena, John; Medendorp, Joseph; Ewing, Gary

    2011-10-01

    Demonstration of content uniformity (CU) is critical toward the successful development of dry powder inhalers (DPIs). Methods for unit dose CU determination for DPI products are well-established within the field of respiratory science. Recent advances in the area include a uHPLC-MS method for high-throughput uniformity analysis, which allows for a greater understanding of blending operations as the industry transitions to a quality-by-design approach to development. Further enhancements to this uHPLC-MS method now enable it to determine CU and sample weight at the single agglomerate level, which is roughly 50× smaller than a unit dose. When coupled with optical microscopy-based agglomerate sizing, the enhanced uHPLC-MS method can also predict the density and porosity of individual agglomerates. Expanding analytical capabilities to the single agglomerate level provides greater insights and confidence in the DPI manufacturing process.

  2. Effects of Aggregate Gradation on Drying Micro-Surfacing added by Waste Rubber Powders

    NASA Astrophysics Data System (ADS)

    Ye, Yali; Guo, Jinke; Hou, Fengjian

    2017-06-01

    In order to research the effects of aggregate gradation on micro-surfacing, the control variable method was used, the effects of different aggregate gradation on drying micro-surfacing added by waste rubber powders were studied, through a series of laboratory testing, indexes such as mixing time, cohesion torque, wet track abrasion value, load wheel value were studied. The results showed that intermediate gradation with 10% and 11% of the bitumen-aggregate ratio had the optimal performance. The mixing time and cohesion torque could all meet specification requirements; its anti-wear value and the adhering sand amount were smaller than conventional. So the micro-surfacing layer should form the internal compact, but also the formation of rough surface.

  3. A proposed definition of the 'activity' of surface sites on lactose carriers for dry powder inhalation.

    PubMed

    Grasmeijer, Floris; Frijlink, Henderik W; de Boer, Anne H

    2014-06-02

    A new definition of the activity of surface sites on lactose carriers for dry powder inhalation is proposed which relates to drug detachment during dispersion. The new definition is expected to improve the understanding of 'carrier surface site activity', which stimulates the unambiguous communication about this subject and may aid in the rational design and interpretation of future formulation studies. In contrast to the currently prevailing view on carrier surface site activity, it follows from the newly proposed definition that carrier surface site activity depends on more variables than just the physicochemical properties of the carrier surface. Because the term 'active sites' is ambiguous, it is recommended to use the term 'highly active sites' instead to denote carrier surface sites with a relatively high activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Soluble Nutrient and Trace Metal Fluxes from Aerosol Dry Deposition to Elkhorn Slough, CA

    NASA Astrophysics Data System (ADS)

    Gray, E. T.; Paytan, A.; Haskins, J.

    2009-12-01

    Atmospheric deposition has been widely recognized as a source of pollutants and nutrients to coastal ecosystems. Specifically, deposition includes nitrogen compounds, sulfur compounds, mercury, pesticides, phosphate, trace metals and other toxic compounds that can travel great distances in aerosols. These components can come from both natural (volcanoes, mineral dust, forest fires) and anthropogenic (fossil fuels, chemical byproducts, incineration of waste) sources. These pollutants may affect ecosystem health and water quality with environmental impacts such as eutrophication, contaminated fish and harmful algal blooms. In this study we focus on dry deposition to Elkhorn Slough, California. Size fractionated aerosol samples (PM 2.5 and PM 10) collected continuously over a seven day period using a cascade impactor are used along with a deposition model to determine the soluble nutrient and trace metal fluxes on the Elkhorn Slough ecosystem. Atmospheric deposition inputs will be compared to other sources and their potential impact evaluated.

  5. Dry powder inhalers: which factors determine the frequency of handling errors?

    PubMed

    Wieshammer, Siegfried; Dreyhaupt, Jens

    2008-01-01

    Dry powder inhalers are often used ineffectively, resulting in a poor level of disease control. To determine how often essential mistakes are made in the use of Aerolizer, Discus, HandiHaler and Turbuhaler and to study the effects of age, severity of airflow obstruction and previous training in inhalational technique by medical personnel on the error rate. Two hundred and twenty-four newly referred outpatients (age 55.1 +/- 20 years) were asked how they had been acquainted with the inhaler and to demonstrate their inhalational technique. The inhaler-specific error rates were as follows: Aerolizer 9.1%, Discus 26.7%, HandiHaler 53.1% and Turbuhaler 34.9%. Compared to Aerolizer, the odds ratio of an ineffective inhalation was higher for HandiHaler (9.82, p < 0.01) and Turbuhaler (4.84, p < 0.05). The error rate increased with age and with the severity of airway obstruction (p < 0.01). When training had been given as opposed to no training, the odds ratio of ineffective inhalation was 0.22 (p < 0.01). If Turbuhaler is used, the estimated risks range from 9.8% in an 18-year-old patient with normal lung function and previous training to 83.2% in an 80-year-old patient with moderate or severe obstruction who had not received any training. Dry powder inhalers are useful in the management of younger patients with normal lung function or mild airway obstruction. In older patients with advanced chronic obstructive pulmonary disease, the risk of ineffective inhalation remains high despite training in inhalational technique. A metered-dose inhaler with a spacer might be a valuable treatment alternative in a substantial proportion of these patients. (c) 2007 S. Karger AG, Basel.

  6. Nanosized rods agglomerates as a new approach for formulation of a dry powder inhaler

    PubMed Central

    Salem, HF; Abdelrahim, ME; Eid, K Abo; Sharaf, MA

    2011-01-01

    Background: Nanosized dry powder inhalers provide higher stability for poorly water-soluble drugs as compared with liquid formulations. However, the respirable particles must have a diameter of 1–5 μm in order to deposit in the lungs. Controlled agglomeration of the nanoparticles increases their geometric particle size so they can deposit easily in the lungs. In the lungs, they fall apart to reform nanoparticles, thus enhancing the dissolution rate of the drugs. Theophylline is a bronchodilator with poor solubility in water. Methods: Nanosized theophylline colloids were formed using an amphiphilic surfactant and destabilized using dilute sodium chloride solutions to form the agglomerates. Results: The theophylline nanoparticles thus obtained had an average particle size of 290 nm and a zeta potential of −39.5 mV, whereas the agglomerates were 2.47 μm in size with a zeta potential of −28.9 mV. The release profile was found to follow first-order kinetics (r2 > 0.96). The aerodynamic characteristics of the agglomerated nanoparticles were determined using a cascade impactor. The behavior of the agglomerate was significantly better than unprocessed raw theophylline powder. In addition, the nanoparticles and agglomerates resulted in a significant improvement in the dissolution of theophylline. Conclusion: The results obtained lend support to the hypothesis that controlled agglomeration strategies provide an efficient approach for the delivery of poorly water-soluble drugs into the lungs. PMID:21383856

  7. Aerosol flow reactor production of fine Y1Ba2Cu3O7 powder: Fabrication of superconducting ceramics

    NASA Astrophysics Data System (ADS)

    Kodas, T. T.; Engler, E. M.; Lee, V. Y.; Jacowitz, R.; Baum, T. H.; Roche, K.; Parkin, S. S. P.; Young, W. S.; Hughes, S.; Kleder, J.; Auser, W.

    1988-05-01

    An aerosol flow reactor operating at 900-1000 °C is used to prepare high-purity Y1Ba2Cu3O7 powders with a uniform chemical composition and a submicron to micron average particle size by thermally decomposing aerosol droplets of a solution consisting of the nitrate salts of Y, Ba, and Cu in a 1:2:3 ratio. The powders were at least 99% reacted based on thermogravimetric analysis, and the x-ray diffraction pattern is essentially that of Y1Ba2Cu3O7. Magnetic susceptibility measurements showed the powders to be superconducting with a transition at 90 K even for average reactor residence times as short as 20 s. Sintering cold-pressed pellets between 900 and 1000 °C provides dense, fine grained (average size on the order of 1 μm) superconducting ceramics with sharp 90 K transitions. The grain size and shape of a final sintered part could be varied depending on powder production, processing, and sintering conditions.

  8. Development of the aerosol generation system for simulating the dry deposition behavior of radioaerosol emitted by the accident of FDNPP

    NASA Astrophysics Data System (ADS)

    Zhang, Z.

    2015-12-01

    A large amount of radioactivity was discharged by the accident of FDNPP. The long half-life radionuclide, 137Cs was transported through the atmosphere mainly as the aerosol form and deposited to the forests in Fukushima prefecture. After the dry deposition of the 137Cs, the foliar uptake process would occur. To evaluate environmental transfer of radionuclides, the dry deposition and following foliar uptake is very important. There are some pioneering studies for radionuclide foliar uptake with attaching the solution containing stable target element on the leaf, however, cesium oxide aerosols were used for these deposition study [1]. In the FDNPP case, 137Cs was transported in sulfate aerosol form [2], so the oxide aerosol behaviors could not represent the actual deposition behavior in this accident. For evaluation of whole behavior of 137Cs in vegetation system, fundamental data for deposition and uptake process of sulfate aerosol was desired. In this study, we developed aerosol generation system for simulating the dry deposition and the foliar uptake behaviors of aerosol in the different chemical constitutions. In this system, the method of aerosol generation based on the spray drying. Solution contained 137Cs was send to a nozzle by a syringe pump and spraying with a high speed air flow. The sprayed mist was generated in a chamber in the relatively high temperature. The solution in the mist was dried quickly, and micro size solid aerosols consisting 137Cs were generated. The aerosols were suctioned by an ejector and transported inside a tube by the dry air flow, then were directly blown onto the leaves. The experimental condition, such as the size of chamber, chamber temperature, solution flow rate, air flow rate and so on, were optimized. In the deposition experiment, the aerosols on leaves were observed by a SEM/EDX system and the deposition amount was evaluated by measuring the stable Cs remaining on leaf. In the presentation, we will discuss the detail

  9. Limited influence of dry deposition of semivolatile organic vapors on secondary organic aerosol formation in the urban plume

    NASA Astrophysics Data System (ADS)

    Hodzic, A.; Madronich, S.; Aumont, B.; Lee-Taylor, J.; Karl, T.; Camredon, M.; Mouchel-Vallon, C.

    2013-06-01

    The dry deposition of volatile organic compounds (VOCs) and its impact on secondary organic aerosols (SOA) are investigated in the Mexico City plume. Gas-phase chemistry and gas-particle partitioning of oxygenated VOCs are modeled with the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) from C3 to C25 alkanes, alkenes, and light aromatics. Results show that dry deposition of oxidized gases is not an efficient sink for SOA, as it removes <5% of SOA within the city's boundary layer and ~15% downwind. Dry deposition competes with the gas-particle uptake, and only gases with fewer than ~12 carbons dry deposit while longer species partition to SOA. Because dry deposition of submicron aerosols is slow, condensation onto particles protects organic gases from deposition, thus increasing their atmospheric burden and lifetime. In the absence of this condensation, ~50% of the regionally produced mass would have been dry deposited.

  10. Electrochemical properties of MnS-C and MnO-C composite powders prepared via spray drying process

    NASA Astrophysics Data System (ADS)

    Jeon, Kyung Min; Cho, Jung Sang; Kang, Yun Chan

    2015-11-01

    Spherical micron-sized MnS-C and MnO-C composite powders are successfully prepared by post-treating the spray-dried precursor powders. Dextrin, which is used as the carbon source material, plays a key role in the preparation of the composite powders with regular morphologies; the bare MnS and MnO powders prepared from the spray solution without dextrin have irregular morphologies. The MnS-C composite powders prepared from the spray solution containing 17 g L-1 of dextrin have mixed crystal structures of α- and γ-MnS phases. These powders exhibit superior electrochemical properties compared with those of their MnS and MnO-C counterparts. For example, at a current density of 0.5 A g-1, the MnO-C powders have a 100th-cycle discharge capacity of 321 mA h g-1; the corresponding discharge capacities of the MnS powders prepared from spray solutions containing 0, 17, and 50 g L-1 of dextrin are 501, 786, and 636 mA h g-1, respectively.

  11. Aerosolizable gold nano-in-micro dry powder formulations for theragnosis and lung delivery.

    PubMed

    Silva, A Sofia; Sousa, Ana M; Cabral, Renato P; Silva, Marta C; Costa, Clarinda; Miguel, Sónia P; Bonifácio, Vasco D B; Casimiro, Teresa; Correia, Ilídio J; Aguiar-Ricardo, Ana

    2017-03-15

    Functionalized gold nanoparticles (AuNPs) have been widely investigated as promising multifunctional nanosystems for the theragnosis of lung cancer, the most common and prominent cause of cancer death worldwide. Nevertheless, nanoparticles are not in appropriate sizes for an accurate deep lung delivery and the lack of locally and effective delivery of therapeutic biomolecules to the deep lungs is, in fact, the major cause of low therapeutic outcome. Herein we incorporate, for the first time, AuNPs into respirable microparticles. AuNPs were functionalized with biocompatible oligo(2-oxazoline)-based optically stable fluorescent coatings, and conjugated with a laminin peptide (YIGSR) for targeted lung cancer delivery. These POxylated AuNPs were then incorporated into a chitosan matrix by a clean process, supercritical CO2-assisted spray drying (SASD), yielding nano-in-micro clean ultrafine dry powder formulations. The engineered formulations present the adequate morphology and flowability to reach the deep lung, with aerodynamic sizes ranging 3.2-3.8μm, and excellent fine particle fraction (FPF) (FPF of 47% for CHT-bearing targeted AuNPs). The optimal biodegradation and release profiles enabled a sustained and controlled release of the embedded nanoparticles, with enhanced cellular uptake, opening new prospects for future lung theragnosis.

  12. Dispersibility of lactose fines as compared to API in dry powders for inhalation.

    PubMed

    Thalberg, Kyrre; Åslund, Simon; Skogevall, Marcus; Andersson, Patrik

    2016-05-17

    This work investigates the dispersion performance of fine lactose particles as function of processing time, and compares it to the API, using Beclomethasone Dipropionate (BDP) as model API. The total load of fine particles is kept constant in the formulations while the proportions of API and lactose fines are varied. Fine particle assessment demonstrates that the lactose fines have higher dispersibility than the API. For standard formulations, processing time has a limited effect on the Fine Particle Fraction (FPF). For formulations containing magnesium stearate (MgSt), FPF of BDP is heavily influenced by processing time, with an initial increase, followed by a decrease at longer mixing times. An equation modeling the observed behavior is presented. Surprisingly, the dispersibility of the lactose fines present in the same formulation remains unaffected by mixing time. Magnesium analysis demonstrates that MgSt is transferred to the fine particles during the mixing process, thus lubrication both BDP and lactose fines, which leads to an increased FPF. Dry particle sizing of the formulations reveals a loss of fine particles at longer mixing times. Incorporation of fine particles into the carrier surfaces is believed to be behind this, and is hence a mechanism of importance as regards the dispersion performance of dry powders for inhalation.

  13. Spray dried inhalable ciprofloxacin powder with improved aerosolisation and antimicrobial activity.

    PubMed

    Osman, Rihab; Kan, Pei Lee; Awad, Gehanne; Mortada, Nahed; El-Shamy, Abd-Elhameed; Alpar, Oya

    2013-06-05

    In this study, the spray drying technique was used to prepare ciprofloxacin microparticles (CFX-MPs) for pulmonary administration. By virtue of its amphoteric properties, CFX was dissolved in either a slightly alkaline or acidic solution depending on the used polymer. Dextran and chitosan were used to prepare the MPs and modify the release characteristics of the drug. Particle surface modification was done with either DPPC or PEG. The effects of the manufacturing and formulation parameters on the drug-polymer interactions were investigated by thermal analysis and infrared spectroscopy. CFX-MPs showed improved aerosolisation properties and the encapsulated drug possessed high antimicrobial activity against two of the common and resistant respiratory pathogens: Pseudomonas aeruginosa and Staphylococus aureus. MPs were safe on the lung epithelial cells. Modulation of particle characteristics and drug release was possible by altering not only the polymer but also the type of the acid from which the powders were spray dried. MPs prepared with glutamic and aspartic acids showed better characteristics than those prepared with acetic and hydrochloric acids. Dextran modified particles showed improved aerosolisation properties and safety on lung epithelial cells.

  14. New aspects of developing a dry powder inhalation formulation applying the quality-by-design approach.

    PubMed

    Pallagi, Edina; Karimi, Keyhaneh; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

    2016-09-10

    The current work outlines the application of an up-to-date and regulatory-based pharmaceutical quality management method, applied as a new development concept in the process of formulating dry powder inhalation systems (DPIs). According to the Quality by Design (QbD) methodology and Risk Assessment (RA) thinking, a mannitol based co-spray dried formula was produced as a model dosage form with meloxicam as the model active agent. The concept and the elements of the QbD approach (regarding its systemic, scientific, risk-based, holistic, and proactive nature with defined steps for pharmaceutical development), as well as the experimental drug formulation (including the technological parameters assessed and the methods and processes applied) are described in the current paper. Findings of the QbD based theoretical prediction and the results of the experimental development are compared and presented. Characteristics of the developed end-product were in correlation with the predictions, and all data were confirmed by the relevant results of the in vitro investigations. These results support the importance of using the QbD approach in new drug formulation, and prove its good usability in the early development process of DPIs. This innovative formulation technology and product appear to have a great potential in pulmonary drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. The cohesive-adhesive balances in dry powder inhaler formulations I: Direct quantification by atomic force microscopy.

    PubMed

    Begat, Philippe; Morton, David A V; Staniforth, John N; Price, Robert

    2004-09-01

    To obtain a quantitative assessment of the cohesive and adhesive force balance within dry powder inhaler formulations. The atomic force microscope (AFM) colloid probe technique was used to measure the adhesive and cohesive force characteristics of dry powder systems containing an active component (budesonide, salbutamol sulphate) and alpha-lactose monohydrate. To minimize the variations in contact area between colloid probe and substrates, nanometer smooth crystal surfaces of the drugs and the excipient were prepared. The uniformity in contact area allowed accurate and reproducible force measurements. Cohesive-adhesive balance (CAB) graphs were developed to allow direct comparison of the interaction forces occurring in model carrier-based formulations. A salbutamol sulphate-lactose system revealed a significant tendency for the two materials to adhere, suggesting a propensity for the powder to form a homogenous blend. In contrast, the budesonide-lactose system exhibited strong cohesive properties suggesting that the formulation may exhibit poor blend homogeneity and potential for segregation upon processing and handling. The novel approach provides a fundamental insight into the cohesive-adhesive balances in dry powder formulations and further understanding of powder behavior.

  16. Application of spray granulation for conversion of a nanosuspension into a dry powder form.

    PubMed

    Bose, Sonali; Schenck, Daniel; Ghosh, Indrajit; Hollywood, Al; Maulit, Ester; Ruegger, Colleen

    2012-08-30

    The in vivo effect of particle agglomeration after drying of nanoparticles has not been extensively studied till date based on current literature review. The purpose of this research was to evaluate the feasibility of spray granulation as a processing method to convert a nanosuspension of a poorly water soluble drug into a solid dosage form and to evaluate the effect of the transformation into a solid powder on the in vivo exposure in beagle dogs. Formulation variables like the level of stabilizer in the nanosuspension formulation, granulation substrate and drug loading in the granulation were evaluated. The granules were characterized for moisture content, drug content, particle size, crystallinity and in vitro dissolution rate. Granulations with 10% drug loading showed dissolution profiles comparable to the nanosuspension, slightly slower dissolution profiles were observed at 20% drug loading. This can be attributed to an increase in the surface hydrophobicity at a higher drug loading and the formation of agglomerates that were harder to disintegrate, thereby compromising the dissolution rate. An in vivo PK study in beagle dogs showed an 8-fold increase and a 6-fold increase in the AUC(0-48) from the nanosuspension and dried nanosuspension formulations respectively compared to the coarse suspension. Also, the nanosuspension and dried nanosuspension formulations showed a 12-fold and 8-fold increase in the C(max) respectively compared to the coarse suspension. This shows the feasibility of using spray granulation as a processing method to convert a nanosuspension into a solid dosage form with improved in vivo exposure compared to the coarse suspension formulation.

  17. Brewer's Yeast, Saccharomyces cerevisiae, Enhances Attraction of Two Invasive Yellowjackets (Hymenoptera: Vespidae) to Dried Fruit and Fruit Powder.

    PubMed

    Babcock, Tamara; Gries, Regine; Borden, John; Palmero, Luis; Mattiacci, Analía; Masciocchi, Maité; Corley, Juan; Gries, Gerhard

    2017-09-01

    The German yellowjacket, Vespula germanica F., and common yellowjacket, Vespula vulgaris L. (Hymenoptera: Vespidae), are pests of significant economic, environmental, and medical importance in many countries. There is a need for the development and improvement of attractive baits that can be deployed in traps to capture and kill these wasps in areas where they are a problem. Yellowjackets are known to feed on fermenting fruit, but this resource is seldom considered as a bait due to its ephemeral nature and its potential attractiveness to nontarget species. We analyzed the headspace volatiles of dried fruit and fruit powder baits with and without Brewer's yeast, Saccharomyces cerevisiae, using gas chromatography-mass spectrometry, and we field tested these baits for their attractiveness to yellowjackets in Argentina. The addition of yeast to dried fruit and fruit powder changed the volatile compositions, increasing the number of alcohols and acids and decreasing the number of aldehydes. Dried fruit and fruit powder baits on their own were hardly attractive to yellowjackets, but the addition of yeast improved their attractiveness by 9- to 50-fold and surpassed the attractiveness of a commercial heptyl butyrate-based wasp lure. We suggest that further research be done to test additional varieties and species of yeasts. A dried fruit or fruit powder bait in combination with yeast could become a useful tool in the management of yellowjackets. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  18. Physical and Nutritional Properties of Catfish Roe Spray Dried Protein Powder and its Application in an Emulsion System

    USDA-ARS?s Scientific Manuscript database

    Soluble spray dried protein powder (CRP) was made from catfish roe and its physical and nutritional properties evaluated. An emulsion system (CRPE) was developed using CRP and rheological properties compared with two commercial mayonnaises (RME and RVE). CRP contained 67 % protein, 4.5% moisture, ...

  19. Effect of pre-treatments and drying methods on quality attributes of sweet bell-pepper (Capsicum annum) powder.

    PubMed

    Sharma, Rakesh; Joshi, V K; Kaushal, M

    2015-06-01

    Pre-treatments and methods of drying for producing good quality dried bell pepper powder for use in the ready-to-eat (RTE) food products were optimized. Out of various pre-treatments used (blanching in boiling water, KMS, CA and combination of KMS + CA at different concentrations), soaking of bell pepper shreds in KMS@ 0.20 % + CA@ 0.50 % after blanching fasten the drying process (19.75 h) compared to control (22.60 h), when dried in mechanical dehydrator at 58 ± 2 °C. Blanching prior to drying improved the rate of drying and produced product with lower acidity (1.25 %). The samples (T7) treated with KMS@ 0.20 % + CA@ 0.50 % significantly (p < 0.05) retained the ascorbic acid content (47.75 mg/100 g) and also attained highest score for colour (8.0), texture (7.5) and overall acceptability (7.5) compared to rest of the treatments. Among different methods of drying, pre-treated bell peppers dried in solar poly tunnel drier produced bright red coloured powder with relatively higher amounts of sugars and ascorbic acid content, hence was optimized. Visual lump formation was observed at 19.75 % and 18.50 % critical moisture contents, which equilibrated at 42 % and 45 % RH for bell pepper powders dried in a mechanical dehydrator and solar poly tunnel drier, respectively.

  20. Aerosol profiling with lidar in the Amazon Basin during the wet and dry season

    NASA Astrophysics Data System (ADS)

    Baars, H.; Ansmann, A.; Althausen, D.; Engelmann, R.; Heese, B.; Müller, D.; Artaxo, P.; Paixao, M.; Pauliquevis, T.; Souza, R.

    2012-11-01

    For the first time, multiwavelength polarization Raman lidar observations of optical and microphysical particle properties over the Amazon Basin are presented. The fully automated advanced Raman lidar was deployed 60 km north of Manaus, Brazil (2.5°S, 60°W) in the Amazon rain forest from January to November 2008. The measurements thus cover both the wet season (Dec-June) and the dry or burning season (July-Nov). Two cases studies of young and aged smoke plumes are discussed in terms of spectrally resolved optical properties (355, 532, and 1064 nm) and further lidar products such as particle effective radius and single-scattering albedo. These measurement examples confirm that biomass burning aerosols show a broad spectrum of optical, microphysical, and chemical properties. The statistical analysis of the entire measurement period revealed strong differences between the pristine wet and the polluted dry season. African smoke and dust advection frequently interrupt the pristine phases during the wet season. Compared to pristine wet season conditions, the particle scattering coefficients in the lowermost 2 km of the atmosphere were found to be enhanced, on average, by a factor of 4 during periods of African aerosol intrusion and by a factor of 6 during the dry (burning) season. Under pristine conditions, the particle extinction coefficients and optical depth for 532 nm wavelength were frequently as low as 10-30 Mm-1 and <0.05, respectively. During the dry season, biomass burning smoke plumes reached to 3-5 km height and caused a mean optical depth at 532 nm of 0.26. On average during that season, particle extinction coefficients (532 nm) were of the order of 100 Mm-1 in the main pollution layer (up to 2 km height). Ångström exponents were mainly between 1.0 and 1.5, and the majority of the observed lidar ratios were between 50-80 sr.

  1. Airborne Measurements of Carbonaceous Aerosols in Southern Africa during the Dry Biomass Burning Season

    NASA Technical Reports Server (NTRS)

    Kirchstetter, Thomas W.; Novakov, T.; Hobbs, Peter V.; Magi, Brian

    2003-01-01

    Particulate matter collected aboard the University of Washington's (UW) Convair-580 research aircrafi over southem Afiica during the dry biomass burning season was analyzed for total carbon (TC), organic carbon (OC), and black carbon (BC) contents using thermal and optical methods. Samples were collected in smoke plumes of burning savanna and in regional haze. A known artifact, produced by the adsorption of organic gases on the quartz filter substrates used to collect the particulate matter samples, comprised a significant portion of the TC collected. Consequently, conclusions derived from the data are greatly dependent on whether or not OC concentrations are corrected for this artifact. For example, the estimated aerosol coalbedo (1 - single scattering albedo (SSA)), which is a measure of aerosol absorption, of the biomass smoke samples is 60% larger using corrected OC concentrations. Thus, the corrected data imply that the biomass smoke is 60% more absorbing than do the uncorrected data. The BC to (corrected) OC mass ratio (BC/OC) of smoke plume samples (0.18 plus or minus 0.06) is lower than that of samples collected in the regional haze (0.25 plus or minus 0.08). The difference may be due to mixing of biomass smoke with background air characterized by a higher BC/OC ratio. A simple source apportionment indicates that biomass smoke contributes about three quarters of the aerosol burden in the regional haze, while other souxes (e.g., fossil fuel burning) contribute the remainder.

  2. Airborne measurements of carbonaceous aerosols in southern Africa during the dry, biomass burning season

    SciTech Connect

    Kirchstetter, Thomas W.; Novakov, T.; Hobbs, Peter V.; Magi, Brian

    2002-06-17

    Particulate matter collected aboard the University of Washington's Convair-580 research aircraft over southern Africa during the dry, biomass burning season was analyzed for total carbon, organic carbon, and black carbon contents using thermal and optical methods. Samples were collected in smoke plumes of burning savanna and in regional haze. A known artifact, produced by the adsorption of organic gases on the quartz filter substrates used to collect the particulate matter samples, comprised a significant portion of the total carbon collected. Consequently, conclusions derived from the data are greatly dependent on whether or not organic carbon concentrations are corrected for this artifact. For example, the estimated aerosol co-albedo (1 - single scattering albedo), which is a measure of aerosol absorption, of the biomass smoke samples is 60 percent larger using corrected organic carbon concentrations. Thus, the corrected data imply that the biomass smoke is 60 percent more absorbing than do the uncorrected data. The black carbon to (corrected) organic carbon mass ratio (BC/OC) of smoke plume samples (0.18/2610.06) is lower than that of samples collected in the regional haze (0.25/2610.08). The difference may be due to mixing of biomass smoke with background air characterized by a higher BC/OC ratio. A simple source apportionment indicates that biomass smoke contributes about three-quarters of the aerosol burden in the regional haze, while other sources (e.g., fossil fuel burning) contribute the remainder.

  3. Spray‐Dried Sodium Zirconate: A Rapid Absorption Powder for CO2 Capture with Enhanced Cyclic Stability

    PubMed Central

    Bamiduro, Faith; Ji, Guozhao; Brown, Andy P.; Dupont, Valerie A.

    2017-01-01

    Abstract Improved powders for capturing CO2 at high temperatures are required for H2 production using sorption‐enhanced steam reforming. Here, we examine the relationship between particle structure and carbonation rate for two types of Na2ZrO3 powders. Hollow spray‐dried microgranules with a wall thickness of 100–300 nm corresponding to the dimensions of the primary acetate‐derived particles gave about 75 wt % theoretical CO2 conversion after a process‐relevant 5 min exposure to 15 vol % CO2. A conventional powder prepared by solid‐state reaction carbonated more slowly, achieving only 50 % conversion owing to a greater proportion of the reaction requiring bulk diffusion through the densely agglomerated particles. The hollow granular structure of the spray‐dried powder was retained postcarbonation but chemical segregation resulted in islands of an amorphous Na‐rich phase (Na2CO3) within a crystalline ZrO2 particle matrix. Despite this phase separation, the reverse reaction to re‐form Na2ZrO3 could be achieved by heating each powder to 900 °C in N2 (no dwell time). This resulted in a very stable multicycle performance in 40 cycle tests using thermogravimetric analysis for both powders. Kinetic analysis of thermogravimetric data showed the carbonation process fits an Avrami–Erofeyev 2 D nucleation and nuclei growth model, consistent with microstructural evidence of a surface‐driven transformation. Thus, we demonstrate that spray drying is a viable processing route to enhance the carbon capture performance of Na2ZrO3 powder. PMID:28371521

  4. Formation of anisotropic Tl-1212, Tl-2212, Tl-1223 and Tl-2223 particles using aerosol flow reacted powders

    SciTech Connect

    Paranthaman, M.; Goyal, A.; Heatherly, D.E.; Kroeger, D.M.

    1994-12-31

    Highly anisotropic particles of Tl-1212, Tl-2212, Tl-1223 and Tl-2223 superconductors were grown. The Tl-free precursor powders with the compositions Ba{sub 1}Ca{sub 2}Cu{sub 3}Ag{sub 0.37}O{sub 6} and Ba{sub 2}Ca{sub 2}Cu{sub 3}Ag{sub 0.37}O{sub 7} were prepared using an aerosol flow reactor. These precursor powders were then post-annealed in 0.1 atm oxygen at 700 C for 4h to reduce the carbon present and mixed with Tl{sub 2}O{sub 3} (typical composition of Tl{sub x}; x = 0.6--1.0). The Tl-containing powders were heated in sealed gold tubes between 650--890 C for various times. X-ray diffraction showed that the Tl-2212 and Tl-2223 phases were stable over a wide range of temperatures. Scanning electron microscopy showed evidence for the presence of high aspect-ratio particles. These highly anisotropic particles may be of interest for the preparation of powder-in-tube and other powder deposited conductors, for current leads, and for grain alignment studies.

  5. A GCM investigation of impact of aerosols on the precipitation in Amazon during the dry to wet transition

    NASA Astrophysics Data System (ADS)

    Gu, Yu; Liou, K. N.; Jiang, J. H.; Fu, R.; Lu, Sarah; Xue, Y.

    2016-06-01

    The climatic effects of aerosols on the precipitation over the Amazon during the dry to wet transition period have been investigated using an atmospheric general circulation model, NCEP/AGCM, and the aerosol climatology data. We found increased instability during the dry season and delayed wet season onset with aerosols included in the model simulation, leading to the delay of the maximum precipitation over the Amazon by about half a month. In particular, our GCM simulations show that surface solar flux is reduced in the Amazon due to the absorption and scattering of the solar radiation by aerosols, leading to decreased surface temperature. Reduced surface solar flux is balanced by decreases in both surface sensible heat and latent heat fluxes. During the wet season, the subtropical system over the Amazon has a shallower convection. With the inclusion of aerosols in the simulation, precipitation in the rainy season over the Amazon decreases in the major rainfall band, which partially corrects the overestimate of the simulated precipitation in that region. The reduced surface temperature by aerosols is also coupled with a warming in the middle troposphere, leading to increased atmosphere stability and moisture divergence over the Amazon. However, during the dry season when the convective system is stronger over the Amazon, rainfall increases in that region due to the warming of the air over the upper troposphere produced by biomass burning aerosols, which produces an anomalous upward motion and a convergence of moisture flux over the Amazon and draws the moisture and precipitation further inland. Therefore, aerosol effects on precipitation depend on the large-scale atmospheric stability, resulting in their different roles over the Amazon during the dry and wet seasons.

  6. Dry Lung as a Physical Model in Studies of Aerosol Deposition.

    PubMed

    Morozov, Victor N; Kanev, Igor L

    2015-10-01

    A new physical model was developed to evaluate the deposition of micro- and nanoaerosol particles (NAPs) into the lungs as a function of size and charges. The model was manufactured of a dry, inflated swine lung produced by Nasco company (Fort Atkinson, WI). The dry lung was cut into two lobes and a conductive tube was glued into the bronchial tube. The upper 1-2-mm-thick layer of the lung lobe was removed with a razor blade to expose the alveoli. The lobe was further enclosed into a plastic bag and placed within a metalized plastic box. The probability of aerosol deposition was calculated by comparing the size distribution of NAPs passed through the lung with that of control, where aerosol passed through a box bypassing the lung. Using this new lung model, it was demonstrated that charged NAPs are deposited inside the lung substantially more efficiently than neutral ones. It was also demonstrated that deposition of neutral NAPs well fits prediction of the Multiple-Path Particle Dosimetry (MPPD) model developed by the Applied Research Associates, Inc. (ARA).

  7. Preclinical Dose Ranging Studies of a Novel Dry Powder Norovirus Vaccine Formulation

    PubMed Central

    Springer, Michael J.; Ni, Yawei; Finger-Baker, Isaac; Ball, Jordan P.; Hahn, Jessica; DiMarco, Ashley V.; Kobs, Dean; Horne, Bobbi; Talton, James D.; Cobb, Ronald R.

    2016-01-01

    Norovirus is the primary cause of viral gastroenteritis in humans with multiple genotypes currently circulating worldwide. The development of a successful norovirus vaccine is contingent on its ability to induce both systemic and mucosal antibody responses against a wide range of norovirus genotypes. Norovirus virus like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered intranasally. Incorporation of these VLPs into an intranasal powder vaccine offers the advantage of simplicity and induction of neutralizing systemic and mucosal antibodies. Nasal immunization, which provides the advantage of ease of administration and a mucosal delivery mechanism, faces the real issue of limited nasal residence time due to mucociliary clearance. Herein, we describe a novel dry powder (GelVac™) formulation of GI or GII.4 norovirus VLPs, two dominant circulating genotypes, to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs. Systemic and mucosal immunogenicity of each of the VLPs was observed in a dose dependant manner. In addition, a boosting effect was observed after the second dosing of each VLP antigen. With the GelVac™ formulation, a total antigen dose of ≥15 µg was determined to be the maximally immunogenic dose for both GI and GII.4 norovirus VLP based on evaluation for 56 days. Taken together, these results indicate that norovirus VLPs could be used as potential vaccine candidates without using an immunostimilatory adjuvant and provides a basis for the development of a GelVac™ bivalent GI/GII.4 norovirus VLP vaccine. PMID:26873053

  8. Coordinated Airborne, Spaceborne, and Ground-Based Measurements of Massive, Thick Aerosol Layers During the Dry Season in Southern Africa

    NASA Technical Reports Server (NTRS)

    Schmid, B.; Redemann, J.; Russell, P. B.; Hobbs, P. V.; Hlavka, D. L.; McGill, M. J.; Holben, B. N.; Welton, E. J.; Campbell, J.; Torres, O.; Hipskind, R. Stephen (Technical Monitor)

    2002-01-01

    During the dry-season airborne campaign of the Southern African Regional Science Initiative (SAFARI 2000), unique coordinated observations were made of massive, thick aerosol layers. These layers were often dominated by aerosols from biomass burning. We report on airborne Sunphotometer measurements of aerosol optical depth (lambda=354-1558 nm), columnar water vapor, and vertical profiles of aerosol extinction and water vapor density that were obtained aboard the University of Washington's Convair-580 research aircraft. We compare these with ground-based AERONET Sun/sky radiometer results, with ground based lidar data MPL-Net), and with measurements from a downward-pointing lidar aboard the high-flying NASA ER-2 aircraft. Finally, we show comparisons between aerosol optical depths from the Sunphotometer and those retrieved over land and over water using four spaceborne sensors (TOMS (Total Ozone Mapping Spectrometer), MODIS (Moderate Resolution Imaging Spectrometer), MISR (Multiangle Imaging Spectroradiometer) and ATSR-2 (Along Track Scanning Radiometer)).

  9. Coordinated Airborne, Spaceborne and Ground-based Measurements of Massive Thick Aerosol Layers during the Dry Season in Southern Africa

    NASA Technical Reports Server (NTRS)

    Schmid, B.; Redemann, J.; Russell, P. B.; Hobbs, P. V.; Hlavka, D. L.; McGill, M. J.; Holben, B. N.; Welton, E. J.; Campbell, J. R.; Torres, O.

    2003-01-01

    During the dry season airborne campaign of the Southern African Regional Science Initiative (SAFARI 2000), coordinated observations were made of massive thick aerosol layers. These layers were often dominated by aerosols from biomass burning. We report on airborne Sun photometer measurements of aerosol optical depth (lambda = 0.354- 1.557 microns), columnar water vapor, and vertical profiles of aerosol extinction and water vapor density that were obtained aboard the University of Washington's Convair-580 research aircraft. We compare these with ground-based AERONET Sun/sky radiometer results, with ground based lidar data (MPL-Net), and with measurements from a downward pointing lidar aboard the high-flying NASA ER-2 aircraft. Finally, we show comparisons between aerosol optical depths fiom the Sun photometer and those retrieved over land and over water using four spaceborne sensors (TOMS, MODIS, MISR, and ATSR-2).

  10. Comparison of aerosol and cloud condensation nuclei between wet and dry seasons in Guangzhou, southern China.

    PubMed

    Duan, Junyan; Tao, Jun; Wu, Yunfei; Cheng, Tiantao; Zhang, Renjian; Wang, Yanyu; Zhu, Hailin; Xie, Xin; Liu, Yuehui; Li, Xiang; Kong, Lingdong; Li, Mei; He, Qianshan

    2017-12-31

    Cloud condensation nuclei (CCN), condensation nuclei (CN) and aerosol chemical composition were measured simultaneously at an urban site of Guangzhou from July to August 2015 and in January 2016, and the seasonal variations of aerosol activated fractions (NCCN/NCN) as well as their relevant influence factors were further studied accordingly. NCN is generally higher in winter (dry season), whereas NCCN and NCCN/NCN are mostly higher in summer (wet season) instead. In particular, NCCN and NCCN/NCN are much lower at smaller supersaturation levels (SS<0.2) in winter. In spite of similar diurnal variations for NCCN and NCN, NCCN/NCN indicates an opposite tendency, relatively lower at midday, dusk and before midnight. Other than the size of particles as well as their chemical composition, some other factors, such as mass, gas precursors, pollutant transportation, meteorological conditions, etc., also contribute to the variations of NCCN and NCCN/NCN. Particles from the local source or local-oceanic combination source cast influence on CN and CCN significantly, while the pollutants originating from and crossing over distant polluted areas contribute largely to CCN/CN. NCN and NCCN are relatively higher under pollution-free conditions in summertime and polluted conditions in wintertime, but NCCN/NCN is just the opposite. On various polluted conditions, aerosol CCN activities are greatly discrepant between summer and winter, especially during mist or heavy haze periods. The results imply that anthropogenic pollutants exert critical impacts on aerosol CCN activation. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. SECONDARY ORGANIC AEROSOL FORMATION FROM THE OXIDATION OF AROMATIC HYDROCARBONS IN THE PRESENCE OF DRY SUBMICRON AMMONIUM SULFATE AEROSOL

    EPA Science Inventory

    A laboratory study was conducted to examine formation of secondary organic aerosols. A smog chamber system was developed for studying gas-aerosol interactions in a dynamic flow reactor. These experiments were conducted to investigate the fate of gas and aerosol phase compounds ...

  12. SECONDARY ORGANIC AEROSOL FORMATION FROM THE OXIDATION OF AROMATIC HYDROCARBONS IN THE PRESENCE OF DRY SUBMICRON AMMONIUM SULFATE AEROSOL

    EPA Science Inventory

    A laboratory study was conducted to examine formation of secondary organic aerosols. A smog chamber system was developed for studying gas-aerosol interactions in a dynamic flow reactor. These experiments were conducted to investigate the fate of gas and aerosol phase compounds ...

  13. Green ambrosia for Soil- Dry Cow Dung Powder: Rhexistasy to Biostasy

    NASA Astrophysics Data System (ADS)

    Bagla, Hemlata; Barot, Nisha

    2013-04-01

    "Greener ambrosia for Soil - Dry cow dung powder: Rhexistasy to Biostasy" Pedosphere, the soil with its biotic and abiotic component, is produced by lithosphere`s interactions with atmosphere, hydrosphere and biosphere. The theory of Biorhexistasy proposed by pedologist H. Erhart [1], describes two crucial climatic phases of soil i.e. Biostasy, period of soil formation and Rhexistasy, periods of soil erosion. Humus, the organic matter in soil, permits better aeration, enhances the absorption and releases nutrients, and makes the soil less susceptible to leaching and erosion [2], thus the agent of soil`s vitality. Mismanagement of soil, leads to the degradation of millions of acres of land through erosion, compaction, salinization and acidification. Among these threats salinity is a major abiotic stress reducing the yield of wide variety of crops all over the world [3]. It is been proved that Humic Acid (HA) treatment can ameliorate the deleterious effects of salt stress by increasing root growth, altering mineral uptake, and decreasing membrane damage, thus inducing salt tolerance in plants [4]. HA can be inexpensively incorporated into soils via different biowastes. Dry cow dung powder (DCP), is naturally available bio-organic, complex, polymorphic humified fecal matter, enriched with minerals, carbohydrates, fats, proteins, bile pigments, aliphatic - aromatic species such as HA, Fulvic Acid (FA) etc [5]. The microbial consortium enables DCP with considerable potentials for biodegradation and biotransformation of even saline soil and further contributes to many biogeochemical processes, boosting humus content of soil. Due to unambiguous biological, microbiological as well as chemical inert properties of DCP, it has been successfully utilized as a fertilizer and soil conditioner since ages in India, one of the leading agrarian countries of the world. Thus we summarize that DCP is one of the best contenders for the biostasy and desaliner of soil, aptly, soil

  14. Structural, functional and in vitro digestion characteristics of spray dried fish roe powder stabilised with gum arabic.

    PubMed

    Binsi, P K; Natasha, Nayak; Sarkar, P C; Muhamed Ashraf, P; George, Ninan; Ravishankar, C N

    2017-04-15

    Fish roes are considered as nutritionally valuable for their high content of essential fatty acids and amino acids. However, roe lipids undergo considerable extent of oxidation during processing and storage, imparting objectionable bitter taste and rancid flavour to roe products. Hence, the objective of the study was to reconstitute the roe mass and microencapsulate lipid fraction, so that small oil droplets are entrapped within a dry matrix of roe proteins during spray drying. Prior to spray drying, the emulsion was stabilised with gum arabic as it also act as a co-wall polymer. The microscopic images indicated presence of larger aggregates in unstabilised powder (RC) compared to well-separated particles in stabilised powder (RG). Incorporation of gum arabic retarded rancidity development during storage. In vitro digestive pattern of roe powder indicated higher amount of oil release in RG. These observations highlight the potential of converting the soft textured carp roe mass into stable fish roe powder with superior storage stability and functionality. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Physicochemical and in vitro deposition properties of salbutamol sulphate/ipratropium bromide and salbutamol sulphate/excipient spray dried mixtures for use in dry powder inhalers.

    PubMed

    Corrigan, Deirdre O; Corrigan, Owen I; Healy, Anne Marie

    2006-09-28

    The physicochemical and aerodynamic properties of spray dried powders of the drug/drug mixture salbutamol sulphate/ipratropium bromide were investigated. The in vitro deposition properties of spray dried salbutamol sulphate and the spray dried drug/excipient mixtures salbutamol sulphate/lactose and salbutamol sulphate/PEG were also determined. Spray drying ipratropium bromide monohydrate resulted in a crystalline material from both aqueous and ethanolic solution. The product spray dried from aqueous solution consisted mainly of ipratropium bromide anhydrous. There was evidence of the presence of another polymorphic form of ipratropium bromide. When spray dried from ethanolic solution the physicochemical characterisation suggested the presence of an ipratropium bromide solvate with some anhydrous ipratropium bromide. Co-spray drying salbutamol sulphate with ipratropium bromide resulted in amorphous composites, regardless of solvent used. Particles were spherical and of a size suitable for inhalation. Twin impinger studies showed an increase in the fine particle fraction (FPF) of spray dried salbutamol sulphate compared to micronised salbutamol sulphate. Co-spray dried salbutamol sulphate:ipratropium bromide 10:1 and 5:1 systems also showed an increase in FPF compared to micronised salbutamol sulphate. Most co-spray dried salbutamol sulphate/excipient systems investigated demonstrated FPFs greater than that of micronised drug alone. The exceptions to this were systems containing PEG 4000 20% or PEG 20,000 40% both of which had FPFs not significantly different from micronised salbutamol sulphate. These two systems were crystalline unlike most of the other spray dried composites examined which were amorphous in nature.

  16. Preparation and characterization of physically modified glass beads used as model carriers in dry powder inhalers.

    PubMed

    Zellnitz, Sarah; Redlinger-Pohn, Jakob Dominik; Kappl, Michael; Schroettner, Hartmuth; Urbanetz, Nora Anne

    2013-04-15

    The aim of this work is the physical modification and characterization of the surface topography of glass beads used as model carriers in dry powder inhalers (DPIs). By surface modification the contact area between drug and carrier and thereby interparticle forces may be modified. Thus the performance of DPIs that relies on interparticle interactions may be improved. Glass beads were chosen as model carriers because various prospects of physical surface modification may be applied without affecting other factors also impacting interparticle interactions like particle size and shape. To generate rough surfaces glass beads were processed mechanically by friction and impaction in a ball mill with different grinding materials that were smaller and harder with respect to the glass beads. By varying the grinding time (4 h, 8 h) and by using different grinding media (tungsten carbide, quartz) surfaces with different shades of roughness were generated. Depending on the hardness of the grinding material and the grinding time the surface roughness was more or less pronounced. Surface roughness parameters and specific surface area were determined via several complementary techniques in order to get an enhanced understanding of the impact of the modifying procedure on the surface properties of the glass beads.

  17. The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder.

    PubMed

    Ishizaka, Toshihiko; Okada, Sachie; Takemoto, Eri; Tokuyama, Emi; Tsuji, Eriko; Mukai, Junji; Uchida, Takahiro

    2007-10-01

    The aim of the present study was to identify a medicine which strongly enhanced the bitterness of clarithromycin dry syrup (CAMD) when administered concomitantly and to develop a method to suppress this enhanced bitterness. The bitterness enhancement was evaluated not only by gustatory sensation tests but also using pH and taste sensor measurements of the mixed sample. A remarkable bitterness enhancement was found when CAMD was mixed with the acidic powder L-carbocysteine. The acidic pH (pH 3.40) of the suspension made from these two preparations, seemed to be due to enhanced release of clarithromycin caused by the dissolution of the alkaline polymer film-coating. Several methods for preventing this bitterness enhancement were investigated. Neither increasing the volume of water taken with the mixture, nor changing the ratio of CAMD:L-carbocysteine in the mixture, were effective in reducing the bitterness intensity of the CAMD/L-carbocysteine mixture. The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, which has a neutral pH, followed by the L-carbocysteine suspension. Similar results were obtained for the bitterness suppression of azithromycin fine granules with L-carbocysteine. The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, when they need to be administered together with acidic drug formulations.

  18. Pulmonary selectivity and local pharmacokinetics of ambroxol hydrochloride dry powder inhalation in rat.

    PubMed

    Ren, Y C; Wang, L; He, H B; Tang, X

    2009-05-01

    The aim of this study was to investigate the local pharmacokinetics and site-specific target efficiency of ambroxol hydrochloride (AH) dry powder inhalation (DPI) by comparing lung epithelial lining fluid (ELF) and plasma AH levels after tracheal administration (TA) with those after intravenous administration. Twelve rats were divided into two groups, one of which was given AH DPI (20 mg/kg) via the trachea and the other was given the same dose AH by intravenous injection (i.v.). Afterwards, each group was subdivided into two groups. The concentration of AH in the ELF was determined by microdialysis in one group while the concentration of AH in plasma was determined in the other group. After AH DPI (20 mg/kg) was given via the trachea, AH achieved a high local concentration in ELF and reached a C(max) at 1.5 h in plasma. After the same dose AH was given by i.v., AH reached a C(max) in ELF at 1.25 h. The (AUC(0-t))(ELF)/(AUC(0-t))(plasma) ratio (1.05-2.25) after TA differed significantly from the ratio (0.029-0.039) observed after intravenous administration (p < 0.05). All these results indicate that AH DPI can be delivered to a specific targeted site and achieve high target efficiency in ELF. DPI could be a useful drug delivery system for AH therapy of pulmonary diseases.

  19. Simple and inexpensive method for cryopreservation of fish sperm combining straw and powdered dry ice.

    PubMed

    Yasui, George Shigueki; Arias-Rodriguez, Lenin; Fujimoto, Takafumi; Arai, Katsutoshi

    2008-01-01

    Here, we propose a simple and inexpensive method for fish sperm cryopreservation. Sperm samples of the loach Misgurnus anguillicaudatus (Teleostei: Cobitidae) were diluted 7-fold by an extender containing 63.5 mM NaCl, 114 mM KCl, 20 mM Tris and 10% methanol. The cryogenic straws were placed in three kinds of self-made tubes which diameter was changed by commercially available materials and then immersed into powdered dry ice for 2 min and plunged into liquid nitrogen. This procedure resulted in a cooling rate at -421.4 +/- 119.84 (control), -55.8 +/- 4.32 (tube 1), -40.2 +/- 3.43 (tube 2) and -33.3 +/- 2.09 C/min (tube 3). In the slowest cooling rate by the tube 3, total motility (72 +/- 3 %), duration (146 +/- 12 s) and hatching rates (29 +/- 04 %) were higher than those by other rates. Progressive motility (83 +/- 5 %) did not differ significantly from fresh samples.

  20. Evaluation of in vitro in vivo correlations for dry powder inhaler delivery using artificial neural networks.

    PubMed

    de Matas, Marcel; Shao, Qun; Richardson, Catherine H; Chrystyn, Henry

    2008-01-01

    The aim of these experiments was to investigate the use of artificial neural networks (ANNs) for generating models able to predict the relative lung bioavailability and clinical effect of salbutamol when delivered to healthy volunteers and asthmatic patients from dry powder inhalers (DPIs). ANN software was used to model in vitro, demographic and in vivo data from human subjects for four different DPI formulations containing salbutamol sulfate. In 12 volunteers, a model linking the in vitro aerodynamic characteristics of the emitted dose and volunteer body surface area with the urinary excretion of drug and its metabolite in the 24h period after inhalation was established. In 11 mild asthmatics, a predictive model correlating in vitro data, baseline lung function, body surface area and age with post-treatment improvements in forced expiratory volume in 1s (FEV1) was also generated. Models validated using unseen data from individual subjects receiving the different DPI formulations were shown to give predictions of in vivo performance. The squared correlation coefficients (R2) for plots comparing predicted and observed in vivo outcomes were 0.83 and 0.84 for urinary excretion and lung function data, respectively. It can therefore be concluded that ANN models have the potential to predict the in vivo performance of DPIs in individual subjects.

  1. Liposomal amphotericin B dry powder inhaler: effect of fines on in vitro performance.

    PubMed

    Shah, S P; Misra, A

    2004-10-01

    The aim of the present investigation was to improve in vitro pulmonary deposition of amphotericin B (AMB) liposomal dry powder inhaler (LDPI) formulations. Liposomes with negative (AMB1) and positive (AMB2) charge were prepared by the reverse phase evaporation (REV) technique, extruded to reduce size, separated from unentrapped drug and lyophilized using an optimized cryoprotectant to achieve maximum drug retention. Lactose carrier (Sorbolac 400) in varying mass ratio with or without addition of fines (500# sieved Pharmatose 325M) in different mixing sequence were used to formulate AMB LDPI formulations. In vitro evaluation was done with twin stage impinger (TSI) for fine particle fraction. The lactose carrier containing 10% fines was found to be optimum blend at 1:6 mass ratio of liposome: lactose. The addition of fines and order of mixing fines were found to influence the fine particle fraction (FPF) significantly. FPF of LDPI formulations using a Rotahaler (Cipla, India) as delivery device at 30, 60 and 90 L/min were found to be 23.1 +/- 1.5 percent and 17.3 +/- 2.2 percent; 25.3 +/- 1.8 percent and 19.6 +/- 1.5 percent and 28.4 +/- 2.1 percent and 22.9 +/- 1.9 percent for AMB1 and AMB2 respectively.

  2. Deposition and fine particle production during dynamic flow in a dry powder inhaler: a CFD approach.

    PubMed

    Milenkovic, J; Alexopoulos, A H; Kiparissides, C

    2014-01-30

    In this work the dynamic flow as well as the particle motion and deposition in a commercial dry powder inhaler, DPI (i.e., Turbuhaler) is described using computational fluid dynamics, CFD. The dynamic flow model presented here is an extension of a steady flow model previously described in Milenkovic et al. (2013). The model integrates CFD simulations for dynamic flow, an Eulerian-fluid/Lagrangian-particle description of particle motion as well as a particle/wall interaction model providing the sticking efficiency of particles colliding with the DPI walls. The dynamic flow is imposed by a time varying outlet pressure and the particle injections into the DPI are assumed to occur instantaneously and follow a prescribed particle size distribution, PSD. The total particle deposition and the production of fine particles in the DPI are determined for different peak inspiratory flow rates, PIFR, flow increase rates, FIR, and particle injection times. The simulation results for particle deposition are found to agree well with available experimental data for different values of PIFR and FIR. The predicted values of fine particle fraction are in agreement with available experimental results when the mean size of the injected PSD is taken to depend on the PIFR. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Edetate calcium disodium nanoparticle dry powder inhalation: a novel approach against heavy metal decorporation.

    PubMed

    Kumar, Neeraj; Soni, Sandeep; Jaimini, Abhinav; Ahmad, Farhan Jalees; Bhatnagar, Aseem; Mittal, Gaurav

    2011-09-15

    Objective was to develop and characterize nano-edetate calcium disodium (Ca-Na(2)EDTA) dry powder inhaler (DPI), and assess its in vitro and in vivo deposition using pharmacoscintigraphy techniques. Factors influencing nanoparticle formation including concentration of drug, polymer solution and stirring rate were determined. Optimized formulation was characterized with the help of SEM, TEM and Malvern Zetasizer studies. Any change in physical characteristics after nanosizing was determined by FT-IR, XRD and DSC studies. Anderson cascade impaction showed that nano Ca-Na(2)EDTA exhibited significantly higher respirable fraction of 67.35±2.27% and 66.40±2.87% by scintigraphic and spectroscopic analysis respectively, as compared to 10.08±1.17% and 9.36±1.02% respectively for micronized form. Ventilation lung scintigraphy done in 12 volunteers showed significant increase in drug delivery till alveolar region with nano Ca-Na(2)EDTA. The developed formulation may have a role in neutralizing heavy metal toxicity through inhalation route, including radio-metal contamination. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Predicting Pulmonary Pharmacokinetics from In Vitro Properties of Dry Powder Inhalers.

    PubMed

    Bhagwat, Sharvari; Schilling, Uta; Chen, Mong-Jen; Wei, Xiangyin; Delvadia, Renishkumar; Absar, Mohammad; Saluja, Bhawana; Hochhaus, Günther

    2017-08-10

    The ability of two semi-mechanistic simulation approaches to predict the systemic pharmacokinetics (PK) of inhaled corticosteroids (ICSs) delivered via dry powder inhalers (DPIs) was assessed for mometasone furoate, budesonide and fluticasone propionate. Both approaches derived the total lung doses and the central to peripheral lung deposition ratios from clinically relevant cascade impactor studies, but differed in the way the pulmonary absorption rate was derived. In approach 1, the rate of in vivo drug dissolution/absorption was predicted for the included ICSs from in vitro aerodynamic particle size distribution and in vitro drug solubility estimates measured in an in vivo predictive dissolution medium. Approach 2 derived a first order absorption rate from the mean dissolution time (MDT), determined for the test formulations in an in vitro Transwell(®) based dissolution system. Approach 1 suggested PK profiles which agreed well with the published pharmacokinetic profiles. Similarly, within approach 2, input parameters for the pulmonary absorption rate constant derived from dissolution rate experiments were able to reasonably predict the pharmacokinetic profiles published in literature. Approach 1 utilizes more complex strategies for predicting the dissolution/absorption process without providing a significant advantage over approach 2 with regard to accuracy of in vivo predictions.

  5. Dermal exposure to dry powder spray paints using PXRF and the method of Dirichlet tesselations.

    PubMed

    Roff, Martin; Bagon, David A; Chambers, Helen; Dilworth, E Martin; Warren, Nicholas

    2004-04-01

    This paper describes workplace dermal exposure measurements that were carried out by the Health and Safety Laboratory as part of the EU RISKOFDERM project to measure dust contamination. Exposure to dry powder spray paints was measured at five sites on 12 subjects. Twenty-two samples were obtained, of which eight contained triglycidyl isocyanurate (TGIC) and 14 did not. All subjects wore Tyvek whole body oversuits and some wore sampling gloves. These were either analysed in their entirety to extract the TGIC or surface scanned over representative areas using a portable X-ray fluorescence spectrometer (PXRF) to detect barium or titanium in the fillers of the paints. The method of Dirichlet tessellation was used to map the scans and the technique was developed further for these studies to extend measurements to gloves and to take limits of detection into consideration. The PXRF allowed dusts to be measured in situ that would otherwise be difficult to extract from the material and analyse by other means. The geometric mean surface loading rate of the 22 oversuits was 43 micro g/cm/(2)/h (GSD = 6.0) and of the 23 pairs of sampling gloves was 970 micro g/cm(2)/h (GSD = 8.6). Exposure patterns could be attributed to the arrangements of the subjects, spray booths and the workpieces. Similar exposures were found for TGIC and titanium fillers in factories with similar methods of ventilation.

  6. Moisture Sorption and Thermodynamic Properties of Vacuum-Dried Capsosiphon fulvescens Powder

    PubMed Central

    Zuo, Li; Rhim, Jong-Whan; Lee, Jun Ho

    2015-01-01

    The moisture sorption isotherms of vacuum-dried edible green alga (Capsosiphon fulvescens) powders were determined at 25, 35, and 45°C and water activity (aw) in the range of 0.11~0.94. An inversion effect of temperature was found at high water activity (>0.75). Various mathematical models were fitted to the experimental data, and Brunauer, Emmett, and Teller model was found to be the most suitable model describing the relationship between equilibrium moisture content and water activity (<0.45). Henderson model could also provide excellent agreement between the experimental and predicted values despite of the intersection point. Net isosteric heat of adsorption decreased from 15.77 to 9.08 kJ/mol with an increase in equilibrium moisture content from 0.055 to 0.090 kg H2O/kg solids. The isokinetic temperature (Tβ) was 434.79 K, at which all the adsorption reactions took place at the same rate. The enthalpy-entropy compensation suggested that the mechanism of the adsorption process was shown to be enthalpy-driven. PMID:26451360

  7. Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler.

    PubMed

    Newman, S; Malik, S; Hirst, R; Pitcairn, G; Heide, A; Pabst, J; Dinkelaker, A; Fleischer, W

    2002-12-01

    The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed. Ten healthy non-smoking subjects completed a two-way cross-over study assessing the pulmonary deposition of salbutamol (200 microg) from the MAGhaler at high (60 l/min) and low (30 l/min) peak inhaled flow rates (PIFRs), representing maximal and sub-maximal inspiratory efforts. The formulation was radiolabelled with 99mTc, and lung and oropharyngeal depositions were quantified by gamma scintigraphyThe mean (SD)% ofthe delivered dose deposited in the lungs was 26.4 (4.3)% at 60 l/min and 21.1 (5.1)% at 30 l/min (P < 0.05), corresponding to mean lung depositions of 52.8 and 42.2 microg salbutamol, respectively. The distribution of drug within different lung regions did not vary significantly with inhaled flow rate. The data provided proof of concept for the novel inhaler device and the innovative drug formulation. In comparison with previous deposition data obtained with other DPIs, the lung deposition was relatively high, relatively reproducible (coefficient of variation 16% at 60 l/min) and relatively insensitive to the change in peak inhaled flow rate.

  8. The effect of engineered mannitol-lactose mixture on dry powder inhaler performance.

    PubMed

    Kaialy, Waseem; Larhrib, Hassan; Martin, Gary P; Nokhodchi, Ali

    2012-08-01

    To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures. Mannitol and lactose individually and the two sugars with three different ratios were crystallised/co-crystallised using anti-solvent precipitation technique. Obtained crystals were sieved to separate 63-90 μm size fractions and then characterised by size, shape, density and in vitro aerosolisation performance. Solid state of crystallized samples was studied using FT-IR, XRPD and DSC. At unequal ratios of mannitol to lactose, the elongated shape dominated in the crystallisation process. However, lactose exerted an opposite effect to that of mannitol by reducing elongation ratio and increasing the crystals' width and thickness. Crystallised β-lactose showed different anomers compared to commercial lactose (α-lactose monohydrate). Crystallised α-mannitol showed different polymorphic form compared to commercial mannitol (β-mannitol). Crystallised mannitol:lactose showed up to 5 transitions corresponding to α-mannitol, α-lactose monohydrate, β-lactose, 5α-/3β-lactose and 4α-/1β-lactose. In vitro deposition assessments showed that crystallised carriers produced more efficient delivery of salbutamol sulphate compared to formulations containing commercial grade carriers. The simultaneous crystallization of lactose-mannitol can be used as a new approach to improve the performance of DPI formulations.

  9. Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance.

    PubMed

    Suwandecha, Tan; Wongpoowarak, Wibul; Srichana, Teerapol

    2016-01-01

    Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60 L/min. The mass median aerodynamic diameter was around 2.8-4 μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5-7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.

  10. Using acoustics to estimate inspiratory flow rate and drug removed from a dry powder inhaler.

    PubMed

    Holmes, Martin S; Seheult, Jansen; Geraghty, Colm; D'Arcy, Shona; Costello, Richard W; Reilly, Richard B

    2013-01-01

    Morbidity and mortality rates of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are rising. There is a strong requirement for more effective management of these chronic diseases. Dry powder inhalers (DPIs) are one kind of devices currently employed to deliver medication aimed at controlling asthma and COPD symptoms. Despite their proven effectiveness when used correctly, some patients are unable to reach the inspiratory flow rate required to remove medication from the breath actuated devices and as a result, the medication does not reach the airways. This study employs an acoustic recording device, attached to a common DPI to record the audio signals of simulated inhalations. A rotameter was used to measure the flow rate through the inhaler while a milligram weighing scale was used to measure the amount of drug removed from each simulated inhalation. It was found that a strong correlation existed (R(2)>0.96) when average power, median amplitude, root mean square and mean absolute deviation were used to predict peak inspiratory flow rate. At a flow of 30 L/Min (mean absolute deviation=0.0049), it was found that 77% of the total emitted dose was removed from the inhaler. Results indicate that acoustic measurements may be used in the prediction of inspiratory flow rate and quantity of medication removed from an inhaler.

  11. Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.

    PubMed

    Huang, Joanne; D'Souza, Ajit J; Alarcon, Jason B; Mikszta, John A; Ford, Brandi M; Ferriter, Matthew S; Evans, Michelle; Stewart, Todd; Amemiya, Kei; Ulrich, Robert G; Sullivan, Vincent J

    2009-05-01

    The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V fusion protein of Y. pestis for vaccination against plaque in a mouse model. Mice were immunized with reconstituted spray-freeze-dried F1-V powder via intramuscular injection, microneedle-based intradermal delivery, or noninvasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against lethal subcutaneous challenge with 1,000 50% lethal doses of Y. pestis at levels equivalent to those elicited by unprocessed liquid formulations (70 to 90% protection). The feasibility of intradermal and intranasal delivery of reconstituted powder F1-V vaccine was also demonstrated. Overall, microneedle-based intradermal delivery was shown to be similar in efficacy to intramuscular injection, while intranasal administration required an extra dose of vaccine to achieve similar protection. In addition, the results suggest that seroconversion against F1 may be a better predictor of protection against Y. pestis challenge than seroconversion against either F1-V or V. In summary, we demonstrate the preclinical feasibility of using a reconstituted powder F1-V formulation and microneedle-based intradermal delivery to provide protective immunity against plague in a mouse model. Intranasal delivery, while feasible, was less effective than injection in this study. The potential use of these alternative delivery methods and a powder vaccine formulation may result in substantial health and economic benefits.

  12. Spinning-disk generation and drying of monodisperse solid aerosols with output concentrations sufficient for single-breath inhalation studies.

    PubMed

    Byron, P R; Hickey, A J

    1987-01-01

    The air-driven spinning-disk aerosol generator was modified to allow the production of monodisperse dry spherical aerosols of disodium fluorescein (as model solute) in high output concentrations. Output concentrations were determined by filtration. Optical and aerodynamic size distributions were determined microscopically (after electrostatic precipitation) and by cascade impaction. The generator housing allowed the entrainment of 25-microns primary aqueous solution droplets in a 10-L X min-1 downward flow of dry, filtered air. Internal equipment surfaces were machined flush and polished to minimize aerosol losses. Primary droplets were dried within a stainless steel pipe encased in a tube furnace. Water vapor was removed by diffusion drying. Disk-driven air, satellite droplets, and additional dilution air were vented to waste without using a vacuum. Generator yields were increased by reducing the size of the satellite droplet extraction gap. Aerosols were generated reproducibly by delivering aqueous solutions at a rate of 0.2 mL X min-1 to the center of the disk and spinning at 1000 rps. Dry aerosols, with mass median aerodynamic diameters of 2, 4.9, and 9 microns, were produced in concentrations of 0.89, 5.48, and 54.6 micrograms X L-1 from aqueous solutions containing 0.0374, 0.584, and 3.4% solute by weight. Geometric standard deviations were less than 1.2 in all cases. Concentrations are several times higher than others in the literature and are suitable for single-breath inhalation studies of therapeutic aerosol deposition and effect.

  13. Superiority of wet-milled over dry-milled superfine powdered activated carbon for adsorptive 2-methylisoborneol removal.

    PubMed

    Pan, Long; Matsui, Yoshihiko; Matsushita, Taku; Shirasaki, Nobutaka

    2016-10-01

    Superfine powdered activated carbon (SPAC), which is produced from conventionally sized powdered activated carbon (PAC) by wet milling in a bead mill, has attracted attention for its high adsorptive removal ability in both research and practice. In this study, the performance of dry-milled SPAC was investigated. 2-Methylisoborneol (MIB), an earthy-musty compound commonly targeted by water treatment systems, was used as the target adsorbate. Dry-milled SPAC exhibited lower adsorptive removal of MIB than wet-milled SPAC, even when both SPACs were produced from the same PAC and were composed of particles of the same size. One reason for the lower removal of MIB by the dry-milled SPAC was a higher degree of aggregation in the dry-milled SPAC after production; as a result the apparent particle size of dry-milled SPAC was larger than that of wet-milled SPAC. The dry-milled SPAC was also more negatively charged than the wet-milled SPAC, and, owing to its higher repulsion, it was more amenable to dispersion by ultrasonication. However, even after the dry-milled SPAC was ultrasonicated so that its apparent particle size was similar to or less than that of the wet-milled SPAC, the dry-milled SPAC was still inferior in adsorptive removal to the wet-milled SPAC. Therefore, another reason for the lower adsorptive removal of dry-milled SPAC was its lower equilibrium adsorption capacity due to the oxidation during the milling. The adsorption kinetics by SPACs with different degrees of particle aggregation were successfully simulated by a pore diffusion model and a fractal aggregation model.

  14. A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration.

    PubMed

    Argenti, D; Shah, B; Heald, D

    2000-05-01

    The impending phaseout of chlorofluorocarbons as propellants in pressurized metered-dose inhalers used in the treatment of asthma has resulted in the development of alternative devices to deliver drug to the pulmonary airways. These alternative devices include metered-dose inhalers using environmentally friendly hydroflurocarbon propellants and breath-actuated dry-powder inhalers. The purpose of this study was to compare the single- and multiple-dose pharmacokinetics, pharmacodynamics, and tolerability of a newly developed hydroflurocarbon formulation of triamcinolone acetonide (Azmacort HFA 225 mcg Inhalation Aerosol) to that of the dry-powder formulation of budesonide (Pulmicort Turbuhaler 200 mcg). This three-way crossover study used 18 normal healthy subjects each receiving a 675 mcg dose of triamcinolone acetonide, 600 mcg dose of budesonide, or placebo twice a day for 5 days. Serial plasma samples were collected after the first and last dose of test medication for pharmacokinetic analysis. Pharmacodynamics were assessed by changes in hypothalamic-pituitary-adrenal axis function as measured by 8 a.m. serum cortisol, 24-hour overnight serum cortisol AUC(0-24), and 24-hour urinary-free cortisol after the last evening dose of test drug. Tolerability was assessed through physical examinations, vital signs, 12-lead ECG, routine clinical labs, and adverse events recording. Both compounds were systemically absorbed. However, no significant drug accumulation was noted with chronic dosing. Chronic dosing did result in a statistically significant 20% reduction in basal 24-hour serum cortisol AUC(0-24) for both compounds. There were no clinically significant abnormalities in physical examination, vital signs, 12-lead ECG, or routine clinical labs noted during the study. Overall, the study drugs were well tolerated, with adverse events characterized as mild to moderate in severity.

  15. Metered dose inhaler with spacer versus dry powder inhaler for delivery of salbutamol in acute exacerbations of asthma: a randomized controlled trial.

    PubMed

    Lodha, Rakesh; Gupta, Gaurav; Baruah, Bedanta Prakash; Nagpal, Rajiv; Kabra, S K

    2004-01-01

    Delivery of various drugs by aerosol inhalation is the mainstay of treatment of asthma. Many delivery systems have been developed for children, each having its own advantages and disadvantages. Studies comparing the clinical efficacy of metered dose inhalers (MDI) and dry powder inhalers (DPI) in the treatment of acute exacerbations of asthma in children are limited. We conducted a study to compare the response to salbutamol inhalation delivered by metered dose inhaler with a spacer versus rotahaler (DPI) in children presenting with mild or moderate acute exacerbations of asthma. Children in the age group of 5-15 years who presented with a mild or moderate acute exacerbation of asthma were randomized to receive 400 micrograms salbutamol by either a MDI with spacer or a DPI. The changes in the wheezing and accessory muscle scores, SaO2, and PEFR were recorded and subjected to statistical tests for significance. One hundred and fifty three children were studied; 78 were assigned to the MDI-spacer group and 75 to rotahaler (DPI) group. After receiving treatment, the PEFR improved by about 11% in both the groups. The oxygen saturation increased by 2% in both the groups. Within each group, the improvement in PEFR, SaO2, wheeze and accessory muscle score after the treatment was statistically significant. In both the groups the children co-operated equally well. Metered dose inhaler with spacer and dry powder inhaler have equal efficacy in delivering salbutamol in therapy of mild to moderate acute exacerbations of bronchial asthma in children between 5-15 years of age.

  16. Application of Freeze-Dried Powders of Genetically Engineered Microbial Strains as Adsorbents for Rare Earth Metal Ions.

    PubMed

    Moriwaki, Hiroshi; Masuda, Reiko; Yamazaki, Yuki; Horiuchi, Kaoru; Miyashita, Mari; Kasahara, Jun; Tanaka, Tatsuhito; Yamamoto, Hiroki

    2016-10-12

    The adsorption behaviors of the rare earth metal ions onto freeze-dried powders of genetically engineered microbial strains were compared. Cell powders obtained from four kinds of strains, Bacillus subtilis 168 wild type (WT), lipoteichoic acid-defective (ΔLTA), wall teichoic acid-defective (ΔWTA), and cell wall hydrolases-defective (EFKYOJLp) strains, were used as an adsorbent of the rare earth metal ions at pH 3. The adsorption ability of the rare earth metal ions was in the order of EFKYOJLp > WT > ΔLTA > ΔWTA. The order was the same as the order of the phosphorus quantity of the strains. This result indicates that the main adsorption sites for the ions are the phosphate groups and the teichoic acids, LTA and WTA, that contribute to the adsorption of the rare earth metal ions onto the cell walls. The contribution of WTA was clearly greater than that of LTA. Each microbial powder was added to a solution containing 16 kinds of rare earth metal ions, and the removals (%) of each rare earth metal ion were obtained. The scandium ion showed the highest removal (%), while that of the lanthanum ion was the lowest for all the microbial powders. Differences in the distribution coefficients between the kinds of lanthanide ions by the EFKYOJLp and ΔWTA powders were greater than those of the other strains. Therefore, the EFKYOJLp and ΔWTA powders could be applicable for the selective extraction of the lanthanide ions. The ΔLTA powder coagulated by mixing with a rare earth metal ion, although no sedimentation of the WT or ΔWTA powder with a rare earth metal ion was observed under the same conditions. The EFKYOJLp powder was also coagulated, but its flocculating activity was lower than that of ΔLTA. The ΔLTA and EFKYOJLp powders have a long shape compared to those of the WT or ΔWTA strain. The shapes of the cells will play an important role in the sedimentation of the microbial powders with rare earth metal ions. As the results, three kinds of the genetically

  17. Modelling size and structure of nanoparticles formed from drying of submicron solution aerosols

    NASA Astrophysics Data System (ADS)

    Bandyopadhyay, Arpan A.; Pawar, Amol A.; Venkataraman, Chandra; Mehra, Anurag

    2015-01-01

    Drying of submicron solution aerosols, under controlled conditions, has been explored to prepare nanoparticles for drug delivery applications. A computational model of solution drop evaporation is developed to study the evolution of solute gradients inside the drop and predict the size and shell thickness of precipitating nanoparticles. The model considers evaporation as a two-stage process involving droplet shrinkage and shell growth. It was corroborated that droplet evaporation rate controls the solute distribution within a droplet and the resulting particle structure (solid or shell type). At higher gas temperatures, rapid build-up of solute near drop surface from high evaporation rates results in early attainment of critical supersaturation solubility and a steeper solute gradient, which favours formation of larger, shell-type particles. At lower gas temperatures, formation of smaller, solid nanoparticles is indicated. The computed size and shell thickness are in good agreement with experimentally prepared lipid nanoparticles. This study indicates that solid or shell structure of precipitated nanoparticles is strongly affected by evaporation rate, while initial solute concentration in the precursor solution and atomized droplet size affect shell thickness. For the gas temperatures considered, evaporative cooling leads to droplet temperature below the melting point of the lipid solute. Thus, we conclude that control over nanoparticle size and structure, of thermolabile precursor materials suitable for drug delivery, can be achieved by controlling evaporation rates, through selection of aerosol processing conditions.

  18. Concurrent use of metered dose inhalers without spacer and dry powder inhalers by asthmatic children adversely affect proper inhalation technique

    PubMed Central

    Alotaibi, Saad; Hassan, Walid M; Alhashimi, Hashim

    2011-01-01

    Asthma is a common chronic disease of children. A good control of symptoms will improve quality of patient life. Inhalation technique is an important aspect in the management of asthma. The better the inhalation technique the better the lung deposition of asthma therapy especially inhaled corticosteroids. This will lead to better control of symptoms and improve adherence to treatment. In the following study the inhalation technique of asthma devices were compared using inhalation technique score system. The asthma devices studied were metered dose inhalers (pressurized MDI) without spacers and dry powder inhalers (DPI). The hypothesis studied was that the inhalation technique score of dry powder inhalers will be adversely affected with concurrent use of metered dose inhalers without spacers. PMID:21760757

  19. Concurrent use of metered dose inhalers without spacer and dry powder inhalers by asthmatic children adversely affect proper inhalation technique.

    PubMed

    Alotaibi, Saad; Hassan, Walid M; Alhashimi, Hashim

    2011-06-14

    Asthma is a common chronic disease of children. A good control of symptoms will improve quality of patient life. Inhalation technique is an important aspect in the management of asthma. The better the inhalation technique the better the lung deposition of asthma therapy especially inhaled corticosteroids. This will lead to better control of symptoms and improve adherence to treatment. In the following study the inhalation technique of asthma devices were compared using inhalation technique score system. The asthma devices studied were metered dose inhalers (pressurized MDI) without spacers and dry powder inhalers (DPI). The hypothesis studied was that the inhalation technique score of dry powder inhalers will be adversely affected with concurrent use of metered dose inhalers without spacers.

  20. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

    PubMed

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-06-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

  1. Sustained release coating of tablets with Eudragit(®) RS/RL using a novel electrostatic dry powder coating process.

    PubMed

    Qiao, Mingxi; Luo, Yanfeng; Zhang, Liqiang; Ma, Yingliang; Stephenson, Tyler Shawn; Zhu, Jesse

    2010-10-31

    The objectives of this study were to develop an electrostatic dry powder coating process for sustained coating tablets with Eudragit(®) RS/RL and to investigate the effects of various factors and operating conditions on the coating process and drug release profile. A liquid plasticizer (triethyl citrate) was sprayed onto the surface of the tablets followed by spraying coating powder by an electrostatic spray gun. The powder coated tablets were cured at elevated temperature for a film formation. Liquid plasticizer played important roles in lowering down the glass transition temperature (T(g)) of the coating polymer and increasing the surface electrical conduction of tablet cores. Electrostatic assisted coating deposition was confirmed by the fact that higher coating level was obtained with electrical charging than the ones without it. The micrographs of scanning electron microscopy (SEM) of coated tablets showed that the film formation mainly occurred during the curing step. Higher curing temperature and longer curing time help enhance the film formation. The in vitro drug release profiles indicated that curing time, temperature, coating level and ratio of Eudragit(®) RS/RL were the main factors affecting the sustained release profile. The electrostatic dry powder coating process has been demonstrated to be an alternative for tablet sustained release coating with Eudragit(®) RS and RL.

  2. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

    PubMed Central

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

    2014-01-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

  3. Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers.

    PubMed

    Tawfeek, Hesham M; Evans, Andrew R; Iftikhar, Abid; Mohammed, Afzal R; Shabir, Anjum; Somavarapu, Satyanarayana; Hutcheon, Gillian A; Saleem, Imran Y

    2013-01-30

    This study investigated optimizing the formulation parameters for encapsulation of a model mucinolytic enzyme, α-chymotrypsin (α-CH), within a novel polymer; poly(ethylene glycol)-co-poly(glycerol adipate-co-ω-pentadecalactone), PEG-co-(PGA-co-PDL) which were then applied to the formulation of DNase I. α-CH or DNase I loaded microparticles were prepared via spray drying from double emulsion (w(1)/o/w(2)) utilizing chloroform (CHF) as the organic solvent, L-leucine as a dispersibility enhancer and an internal aqueous phase (w(1)) containing PEG4500 or Pluronic(®) F-68 (PLF68). α-CH released from microparticles was investigated for bioactivity using the azocasein assay and the mucinolytic activity was assessed utilizing the degradation of mucin suspension assay. The chemical structure of PEG-co-(PGA-co-PDL) was characterized by (1)H NMR and FT-IR with both analyses confirming PEG incorporated into the polymer backbone, and any unreacted units removed. Optimum formulation α-CH-CHF/PLF68, 1% produced the highest bioactivity, enzyme encapsulation (20.08±3.91%), loading (22.31±4.34 μg/mg), FPF (fine particle fraction) (37.63±0.97%); FPD (fine particle dose) (179.88±9.43 μg), MMAD (mass median aerodynamic diameter) (2.95±1.61 μm), and the mucinolytic activity was equal to the native non-encapsulated enzyme up to 5h. DNase I-CHF/PLF68, 1% resulted in enzyme encapsulation (17.44±3.11%), loading (19.31±3.27 μg/mg) and activity (81.9±2.7%). The results indicate PEG-co-(PGA-co-PDL) can be considered as a potential biodegradable polymer carrier for dry powder inhalation of macromolecules for treatment of local pulmonary diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Consumption of Dried Apple Peel Powder Increases Joint Function and Range of Motion

    PubMed Central

    Attridge, Victoria L.; Benson, Kathleen F.; Beaman, Joni L.; Carter, Steve G.; Ager, David

    2014-01-01

    Abstract The goal for this study was to evaluate the effects of consumption of dried apple peel powder (DAPP) on joint function and range of motion (ROM). Additional in vitro and clinical testing was performed to suggest specific mechanisms of action. An open-label clinical pilot study involved 12 healthy people with moderate loss of joint ROM and associated chronic pain. The subjects consumed 4.25 g DAPP daily for 12 weeks, with evaluations at baseline, 2, 4, 8, and 12 weeks. ROM was evaluated at each visit using dual digital inclinometry. Pain scores were collected using Visual Analogue Scales. Blood draws enabled testing of serum antioxidant protective capacity using the cellular antioxidant protection (CAP-e) bioassay. Additional in vitro testing involved testing of cyclooxygenase-2 (COX-2) and lipoxygenase inhibition, cellular antioxidant protection by the CAP-e bioassay, and formation of reactive oxygen species (ROS) by polymorphonuclear (PMN) cells by flow cytometry. Twelve weeks of consumption of DAPP was associated with improved ROM. DAPP provided antioxidants that were available to enter into and protect cells from oxidative damage in vitro, and consumption of DAPP for 12 weeks was associated with a statistically significant improvement in serum antioxidant protective status. DAPP inhibited both COX-2 and lipoxygenase enzymes, and pretreatment of inflammatory PMN cells with DAPP before inflammatory stimulus resulted in reduced ROS formation. This suggests multifaceted anti-inflammatory properties of DAPP. Consumption of DAPP was associated with improved joint function and improved serum antioxidant protection status. The observed pain reduction may be associated with the improved antioxidant status and linked to the apple polyphenols' anti-inflammatory effects. PMID:25271471

  5. Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma

    PubMed Central

    Raphael, Gordon; Taveras, Herminia; Iverson, Harald; O’Brien, Christopher; Miller, David

    2016-01-01

    Abstract Objective: Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma. Methods: We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged ≥12 years with persistent asthma received placebo MDPI or albuterol MDPI 180 µg (2 inhalations × 90 µg/inhalation) 4 times/day for 12 weeks. In the 40-week open-label phase of the 52-week safety study, patients received albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) as needed (PRN). Results: During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n = 333) than albuterol MDPI (40%; n = 321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of β2-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (≤1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis. Conclusions: The safety profile of albuterol MDPI 180 μg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma. PMID:26369589

  6. Investigation of Appropriate Inhalation Technique for Mometasone Furoate Dry Powder Inhaler.

    PubMed

    Yokoyama, Haruko; Ito, Kanako; Mihashi, Hirokazu; Shiraishi, Yasuyuki; Takayanagi, Risa; Yamada, Yasuhiko

    2016-01-01

    The aim of this study was to establish an appropriate inhalation method with a mometasone furoate dry powder inhaler (MF-DPI). Utilizing a tone-based inhalation training device, we investigated the maximum peak inspiratory flow rate time (Tmax PIFR) and peak inspiratory flow rate (PIFR) to determine whether either had an influence on lung deposition with use of an MF-DPI. A low tone indicated a PIFR of 28 L/min and a high tone that of 40 L/min, while 60 L/min was considered to be the standard. We established an inhalation profile in consideration of a human inhalation pattern, in which Tmax PIFR was set at 0.5 s (Tmax PIFR 0.5 s) and 2.5 s (Tmax PIFR 2.5 s). The reference cut-off value derived with a cascade impactor test was used for evaluation of the rate of delivered dose in the lung, which was the amount of drug from stage 3 to 7 at all PIFRs. We then investigated the relationship of the fine particle fraction (FPF) with the claimed dose at Tmax PIFR of 0.5 s and PIFR. There were no differences among the Tmax PIFR values for the doses emitted from the device or for the rate of delivered doses in stages 3-7. However, FPF for the claimed dose at 40 L/min was significantly lower than that at 60 L/min, which was dependent on PIFR. Our results showed that PIFR but not Tmax PIFR has an effect on lung deposition after inhalation with an MF-DPI.

  7. Consumption of dried apple peel powder increases joint function and range of motion.

    PubMed

    Jensen, Gitte S; Attridge, Victoria L; Benson, Kathleen F; Beaman, Joni L; Carter, Steve G; Ager, David

    2014-11-01

    The goal for this study was to evaluate the effects of consumption of dried apple peel powder (DAPP) on joint function and range of motion (ROM). Additional in vitro and clinical testing was performed to suggest specific mechanisms of action. An open-label clinical pilot study involved 12 healthy people with moderate loss of joint ROM and associated chronic pain. The subjects consumed 4.25 g DAPP daily for 12 weeks, with evaluations at baseline, 2, 4, 8, and 12 weeks. ROM was evaluated at each visit using dual digital inclinometry. Pain scores were collected using Visual Analogue Scales. Blood draws enabled testing of serum antioxidant protective capacity using the cellular antioxidant protection (CAP-e) bioassay. Additional in vitro testing involved testing of cyclooxygenase-2 (COX-2) and lipoxygenase inhibition, cellular antioxidant protection by the CAP-e bioassay, and formation of reactive oxygen species (ROS) by polymorphonuclear (PMN) cells by flow cytometry. Twelve weeks of consumption of DAPP was associated with improved ROM. DAPP provided antioxidants that were available to enter into and protect cells from oxidative damage in vitro, and consumption of DAPP for 12 weeks was associated with a statistically significant improvement in serum antioxidant protective status. DAPP inhibited both COX-2 and lipoxygenase enzymes, and pretreatment of inflammatory PMN cells with DAPP before inflammatory stimulus resulted in reduced ROS formation. This suggests multifaceted anti-inflammatory properties of DAPP. Consumption of DAPP was associated with improved joint function and improved serum antioxidant protection status. The observed pain reduction may be associated with the improved antioxidant status and linked to the apple polyphenols' anti-inflammatory effects.

  8. Effect of inhaler design variables on paediatric use of dry powder inhalers.

    PubMed

    Lexmond, Anne J; Kruizinga, Tonnis J; Hagedoorn, Paul; Rottier, Bart L; Frijlink, Henderik W; de Boer, Anne H

    2014-01-01

    Age appropriateness is a major concern of pulmonary delivery devices, in particular of dry powder inhalers (DPIs), since their performance strongly depends on the inspiratory flow manoeuvre of the patient. Previous research on the use of DPIs by children focused mostly on specific DPIs or single inspiratory parameters. In this study, we investigated the requirements for a paediatric DPI more broadly using an instrumented test inhaler. Our primary aim was to assess the impact of airflow resistance on children's inspiratory flow profiles. Additionally, we investigated children's preferences for airflow resistance and mouthpiece design and how these relate to what may be most suitable for them. We tested 98 children (aged 4.7-12.6 years), of whom 91 were able to perform one or more correct inhalations through the test inhaler. We recorded flow profiles at five airflow resistances ranging from 0.025 to 0.055 kPa0.5.min.L-1 and computed various inspiratory flow parameters from these recordings. A sinuscope was used to observe any obstructions in the oral cavity during inhalation. 256 flow profiles were included for analysis. We found that both airflow resistance and the children's characteristics affect the inspiratory parameters. Our data suggest that a medium-high resistance is both suitable for and well appreciated by children aged 5-12 years. High incidences (up to 90%) of obstructions were found, which may restrict the use of DPIs by children. However, an oblong mouthpiece that was preferred the most appeared to positively affect the passageway through the oral cavity. To accommodate children from the age of 5 years onwards, a DPI should deliver a sufficiently high fine particle dose within an inhaled volume of 0.5 L and at a peak inspiratory flow rate of 25-40 L.min-1. We recommend taking these requirements into account for future paediatric inhaler development.

  9. Influence of an ultrasonic nozzle in spray-drying and storage on the properties of blueberry powder and microcapsules.

    PubMed

    Tatar Turan, Feyza; Cengiz, Alime; Sandıkçı, Dilara; Dervisoglu, Muhammet; Kahyaoglu, Talip

    2016-09-01

    Recently, ultrasonic nozzle technology has been applied in spray-drying because of its numerous advantages, including providing more uniform droplets and reducing damage observed in bioactive compounds. In this study, the production of blueberry powders and microcapsules by using an ultrasonic spray nozzle was investigated. Firstly, the important ultrasonic nozzle parameters were optimised by using response surface methodology and compared with a conventional nozzle (control). Secondly, powder and microcapsules obtained at the optimum point were stored at 22 °C and 35 °C at 0.32 water activity (aw ). The optimum conditions were estimated as 125 °C inlet air temperature, 9 W ultrasonic power and 8% feed pump rate. There was significantly difference (P < 0.05) in the total phenolic content and antioxidant power of microcapsules produced by an ultrasonic nozzle and a conventional nozzle. Because the temperature affected the stability of powders negatively, the blueberry powder showed higher losses than microcapsules in the content of bioactive compounds. In addition, the ultrasonic nozzle showed a significantly greater protective effect on physico-chemical properties than did the conventional nozzle. Results of the study point that the production of ultrasonic nozzle powders and microcapsules is feasible to use as a functional ingredient in food industry. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  10. Spray-dried powders containing tretinoin-loaded engineered lipid-core nanocapsules: development and photostability study.

    PubMed

    Marchiori, M C L; Ourique, A F; da Silva, C de B; Raffin, R P; Pohlmann, A R; Guterres, S S; Beck, R C R

    2012-03-01

    The influence of the spray-drying process on the ability of engineered lipid-core nanocapsules to protect tretinoin against UV degradation was evaluated. This approach represents a technological alternative to improve the microbiological stability, storage and transport properties of such formulations. Tretinoin-loaded lipid-core nanocapsules or tretinoin-loaded nanoemulsion were dispersed in lactose (10% w/v) and fed in the spray-drier to obtain a solid product (spray-dried powder containing tretinoin-loaded nanocapsules or nanoemulsion--SD-TTN-NCL or SD-TTN-NE, respectively). SD-TTN-NE showed a lower (p < or = 0.05) percentage of encapsulation (89 +/- 1%) compared to SD-TTN-NCL (94 +/- 2%). Redispersed SD-TTN-NCL and SD-TTN-NE showed z-average sizes of 204 +/- 2 nm and 251 +/- 9 nm, which were close to those of the original suspensions (220 +/- 3 nm and 239 +/- 14 nm, respectively). Similar percentage of photodegradation were determined for tretinoin loaded in nanocapsules (26.15 +/- 4.34%) or in the respective redispersed spray-dried powder (28.73 +/- 6.19 min) after 60 min of UVA radiation exposure (p > 0.05). Our experimental design showed for the first time that spray-dried lipid-core nanocapsules are able to protect tretinoin against UVA radiation, suggesting that the drying process did not alter the supramolecular structure of the lipid-core nanocapsules. Such powders are potential intermediate products for the development of nanomedicines containing tretinoin.

  11. Enhancing the Thermotolerance of Entomopathogenic Isaria fumosorosea SFP-198 Conidial Powder by Controlling the Moisture Content Using Drying and Adjuvants.

    PubMed

    Kim, Jae Su; Lee, Se Jin; Lee, Hyang Burm

    2014-03-01

    Entomopathogenic fungi are promising pest-control agents but their industrial applicability is limited by their thermosusceptibility. With an aim to increase the thermotolerance of Isaria fumosorosea SFP-198, moisture absorbents were added to dried conidial powder, and the relationship between its water potential and thermotolerance was investigated. Mycotized rice grains were dried at 10℃, 20℃, 30℃, and 40℃ and the drying effect of each temperature for 24, 48, 96, and 140 hr was determined. Drying for 48 hr at 10℃ and 20℃ reduced the moisture content to < 5% without any significant loss of conidial thermotolerance, but drying at 30℃ and 40℃ reduced both moisture content and conidial thermotolerance. To maintain thermotolerance during storage, moisture absorbents, such as calcium chloride, silica gel, magnesium sulfate, white carbon, and sodium sulfate were individually added to previously dried-conidial powder at 10% (w/w). These mixtures was then stored at room temperature for 30 days and subjected to 50℃ for 2 hr. The white carbon mixture had the highest conidial thermotolerance, followed by silica gel, magnesium sulfate, and then the other absorbents. A significant correlation between the water potential and conidial thermotolerance was observed in all conidia-absorbent mixtures tested in this study (r = -0.945). Conidial thermotolerance in wet conditions was evaluated by adding moisturized white carbon (0~20% H2O) to conidia to mimic wet conditions. Notably, the conidia still maintained their thermotolerance under these conditions. Thus, it is evident that conidial thermotolerance can be maintained by drying mycotized rice grains at low temperatures and adding a moisture absorbent, such as white carbon.

  12. Enhancing the Thermotolerance of Entomopathogenic Isaria fumosorosea SFP-198 Conidial Powder by Controlling the Moisture Content Using Drying and Adjuvants

    PubMed Central

    Lee, Se Jin; Lee, Hyang Burm

    2014-01-01

    Entomopathogenic fungi are promising pest-control agents but their industrial applicability is limited by their thermosusceptibility. With an aim to increase the thermotolerance of Isaria fumosorosea SFP-198, moisture absorbents were added to dried conidial powder, and the relationship between its water potential and thermotolerance was investigated. Mycotized rice grains were dried at 10℃, 20℃, 30℃, and 40℃ and the drying effect of each temperature for 24, 48, 96, and 140 hr was determined. Drying for 48 hr at 10℃ and 20℃ reduced the moisture content to < 5% without any significant loss of conidial thermotolerance, but drying at 30℃ and 40℃ reduced both moisture content and conidial thermotolerance. To maintain thermotolerance during storage, moisture absorbents, such as calcium chloride, silica gel, magnesium sulfate, white carbon, and sodium sulfate were individually added to previously dried-conidial powder at 10% (w/w). These mixtures was then stored at room temperature for 30 days and subjected to 50℃ for 2 hr. The white carbon mixture had the highest conidial thermotolerance, followed by silica gel, magnesium sulfate, and then the other absorbents. A significant correlation between the water potential and conidial thermotolerance was observed in all conidia-absorbent mixtures tested in this study (r = -0.945). Conidial thermotolerance in wet conditions was evaluated by adding moisturized white carbon (0~20% H2O) to conidia to mimic wet conditions. Notably, the conidia still maintained their thermotolerance under these conditions. Thus, it is evident that conidial thermotolerance can be maintained by drying mycotized rice grains at low temperatures and adding a moisture absorbent, such as white carbon. PMID:24808736

  13. Assessment of dry and wet atmospheric deposits of radioactive aerosols: application to Fukushima radiocaesium fallout.

    PubMed

    Gonze, Marc-André; Renaud, Philippe; Korsakissok, Irène; Kato, Hiroaki; Hinton, Thomas G; Mourlon, Christophe; Simon-Cornu, Marie

    2014-10-07

    The Fukushima Dai-ichi nuclear accident led to massive atmospheric deposition of radioactive substances onto the land surfaces. The spatial distribution of deposits has been estimated by Japanese authorities for gamma-emitting radionuclides through either airborne monitoring surveys (since April 2011) or in situ gamma-ray spectrometry of bare soil areas (since summer 2011). We demonstrate that significant differences exist between the two surveys for radiocaesium isotopes and that these differences can be related to dry deposits through the use of physically based relationships involving aerosol deposition velocities. The methodology, which has been applied to cesium-134 and cesium-137 deposits within 80-km of the nuclear site, provides reasonable spatial estimations of dry and wet deposits that are discussed and compared to atmospheric numerical simulations from the Japanese Atomic Energy Agency and the French Institute of Radioprotection and Nuclear Safety. As a complementary approach to numerical simulations, this field-based analysis has the possibility to contribute information that can be applied to the understanding and assessment of dose impacts to human populations and the environment around Fukushima.

  14. Preparation of ultra-fine powders from polysaccharide-coated solid lipid nanoparticles and nanostructured lipid carriers by innovative nano spray drying technology.

    PubMed

    Wang, Taoran; Hu, Qiaobin; Zhou, Mingyong; Xue, Jingyi; Luo, Yangchao

    2016-09-10

    In this study, five polysaccharides were applied as natural polymeric coating materials to prepare solid lipid nanoparticles (SLN) and nanostructure lipid carriers (NLC), and then the obtained lipid colloidal particles were transformed to solid powders by the innovative nano spray drying technology. The feasibility and suitability of this new technology to generate ultra-fine lipid powder particles were evaluated and the formulation was optimized. The spray dried SLN powder exhibited the aggregated and irregular shape and dimension, but small, uniform, well-separated spherical powder particles of was obtained from NLC. The optimal formulation of NLC was prepared by a 20-30% oleic acid content with carrageenan or pectin as coating material. Therefore, nano spray drying technology has a potential application to produce uniform, spherical, and sub-microscale lipid powder particles when the formulation of lipid delivery system is appropriately designed. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. A novel approach to the pulmonary delivery of liposomes in dry powder form to eliminate the deleterious effects of milling.

    PubMed

    Desai, Tejas R; Wong, Jonathan P; Hancock, Robert E W; Finlay, Warren H

    2002-02-01

    The effect of lyophilization and jet-milling on liposome integrity was investigated as a function of their ability to retain the encapsulated model drug on reconstitution of the dry products. The encapsulation efficiencies of the lyophilized and jet-milled formulations were determined at various concentrations of lactose. Lyophilization resulted in considerable leakage of the model drug at lower concentrations of lactose, and jet-milling further augmented the leakage for all the lyophilized formulations, with optimum retention obtained for formulations containing at least 10:1 molar ratio of lactose/lipid. In an attempt to overcome the deleterious effects of lyophilization and jet-milling, the feasibility of formulating phospholipid-based powders that result in spontaneous formation of liposomes in an aqueous environment has been investigated. Partitioning of three model drugs (viz., ciprofloxacin, CM3 peptide, and salbutamol sulfate) between the aqueous phase and spontaneously formed liposomes was determined in terms of encapsulation efficiency. The effects of several parameters, including lactose concentration, lipid composition, and lipid concentration on the encapsulation efficiency of these model drugs were investigated. The spontaneous formation of liposomes on dispersion of phospholipid-based powder formulations was further evidenced by freeze-fracture scanning electron microscopy. This novel approach for the delivery of liposomes in dry powder form appears promising because lyophilization is not involved and jet-milling of these powder formulations did not impact encapsulation efficiency. Jet-milled phospholipid-based powder formulations showed high encapsulation efficiencies of 96.2 +/- 1.4% for ciprofloxacin, 100% for CM3 peptide, and 45.3 +/- 3.1% for salbutamol sulfate compared with a high amount of leakage (> 50%) observed due to jet-milling of lyophilized liposome formulations encapsulating ciprofloxacin.

  16. Hollow crystalline straws of diclofenac for high-dose and carrier-free dry powder inhaler formulations.

    PubMed

    Yazdi, Ashkan K; Smyth, Hugh D C

    2016-04-11

    To crystallize diclofenac (DF) from diclofenac sodium (DFNa), to micronize DF and DFNa, and to evaluate in vitro aerodynamic performance of the jet-milled formulations From the acidic titration of aqueous DFNa, DF crystals were formed and were identified using thermal analysis, spectroscopy, and X-ray powder diffraction. Following the micronization of the DF and DFNa powders, the recovered samples were imaged, and their particle size distributions were evaluated. Samples before and after jet millings were characterized, and in vitro aerodynamic performance testing was performed on the DF sample before jet milling and the DF and DFNa samples following jet milling. Hollow needles of DF were precipitated. With similar particle size distributions, the jet-milled DFNa sample from the collection bag, and the DF sample from the cyclone were used for further characterization. Despite different deposition patterns in the Next Generation Impactor, the DF hollow needles had a comparable respirable fraction percentage to the jet-milled DF and DFNa particles. However, the jet-milled DF formulation had the best in vitro aerodynamic performance. Hollow, crystalline needles of DF were formed and possessed promising aerosol performance in comparison with the jet-milled powders. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Lidar Observations of Tropospheric Aerosols Over Northeastern South Africa During the ARREX and SAFARI-2000 Dry Season Experiments

    NASA Technical Reports Server (NTRS)

    Campbell, James R.; Welton, Ellsworth J.; Spinhirne, James D.; Ji, Qiang; Tsay, Si-Chee; Piketh, Stuart J.; Barenbrug, Marguerite; Holben, Brent; Starr, David OC. (Technical Monitor)

    2002-01-01

    During the ARREX-1999 and SAFARI-2000 Dry Season experiments a micropulse lidar (523 nm) instrument was operated at the Skukuza Airport in northeastern South Africa. The Mar was collocated with a diverse array of passive radiometric equipment. For SAFARI-2000 the processed Mar data yields a daytime time-series of layer mean/derived aerosol optical properties, including extinction-to-backscatter ratios and vertical extinction cross-section profile. Combined with 523 run aerosol optical depth and spectral Angstrom exponent calculations from available CIMEL sun-photometer data and normalized broadband flux measurements the temporal evolution of the near surface aerosol layer optical properties is analyzed for climatological trends. For the densest smoke/haze events the extinction-to-backscatter ratio is found to be between 60-80/sr, and corresponding Angstrom exponent calculations near and above 1.75. The optical characteristics of an evolving smoke event from SAFARI-2000 are extensively detailed. The advecting smoke was embedded within two distinct stratified thermodynamic layers, causing the particulate mass to advect over the instrument array in an incoherent manner on the afternoon of its occurrence. Surface broadband flux forcing due to the smoke is calculated, as is the evolution in the vertical aerosol extinction profile as measured by the Han Finally, observations of persistent elevated aerosol during ARREX-1999 are presented and discussed. The lack of corroborating observations the following year makes these observation; both unique and noteworthy in the scope of regional aerosol transport over southern Africa.

  18. Pulmonary Delivery of an Ultra-Fine Oxytocin Dry Powder Formulation: Potential for Treatment of Postpartum Haemorrhage in Developing Countries

    PubMed Central

    Ibrahim, Jibriil P.; Bischof, Robert J.; Nassta, Gemma C.; Olerile, Livesey D.; Russell, Adrian S.; Meiser, Felix; Parkington, Helena C.; Coleman, Harold A.; Morton, David A. V.; McIntosh, Michelle P.

    2013-01-01

    Oxytocin is recommended by the World Health Organisation as the most effective uterotonic for the prevention and treatment of postpartum haemorrhage. The requirement for parenteral administration by trained healthcare providers and the need for the drug solution to be maintained under cold-chain storage limit the use of oxytocin in the developing world. In this study, a spray-dried ultrafine formulation of oxytocin was developed with an optimal particle size diameter (1-5 µm) to facilitate aerosolised delivery via the lungs. A powder formulation of oxytocin, using mannitol, glycine and leucine as carriers, was prepared with a volume-based median particle diameter of 1.9 µm. Oxytocin content in the formulation was assayed using high-performance liquid chromatography-mass spectroscopy and was found to be unchanged after spray-drying. Ex vivo contractility studies utilising human and ovine uterine tissue indicated no difference in the bioactivity of oxytocin before and after spray-drying. Uterine electromyographic (EMG) activity in postpartum ewes following pulmonary (in vivo) administration of oxytocin closely mimicked that observed immediately postpartum (0-12 h following normal vaginal delivery of the lamb). In comparison to the intramuscular injection, pulmonary administration of an oxytocin dry powder formulation to postpartum ewes resulted in generally similar EMG responses, however a more rapid onset of uterine EMG activity was observed following pulmonary administration (129 ± 18 s) than intramuscular injection (275 ± 22 s). This is the first study to demonstrate the potential for oxytocin to elicit uterine activity after systemic absorption as an aerosolised powder from the lungs. Aerosolised oxytocin has the potential to provide a stable and easy to administer delivery system for effective prevention and treatment of postpartum haemorrhage in resource-poor settings in the developing world. PMID:24376618

  19. Pulmonary delivery of an ultra-fine oxytocin dry powder formulation: potential for treatment of postpartum haemorrhage in developing countries.

    PubMed

    Prankerd, Richard J; Nguyen, Tri-Hung; Ibrahim, Jibriil P; Bischof, Robert J; Nassta, Gemma C; Olerile, Livesey D; Russell, Adrian S; Meiser, Felix; Parkington, Helena C; Coleman, Harold A; Morton, David A V; McIntosh, Michelle P

    2013-01-01

    Oxytocin is recommended by the World Health Organisation as the most effective uterotonic for the prevention and treatment of postpartum haemorrhage. The requirement for parenteral administration by trained healthcare providers and the need for the drug solution to be maintained under cold-chain storage limit the use of oxytocin in the developing world. In this study, a spray-dried ultrafine formulation of oxytocin was developed with an optimal particle size diameter (1-5 µm) to facilitate aerosolised delivery via the lungs. A powder formulation of oxytocin, using mannitol, glycine and leucine as carriers, was prepared with a volume-based median particle diameter of 1.9 µm. Oxytocin content in the formulation was assayed using high-performance liquid chromatography-mass spectroscopy and was found to be unchanged after spray-drying. Ex vivo contractility studies utilising human and ovine uterine tissue indicated no difference in the bioactivity of oxytocin before and after spray-drying. Uterine electromyographic (EMG) activity in postpartum ewes following pulmonary (in vivo) administration of oxytocin closely mimicked that observed immediately postpartum (0-12 h following normal vaginal delivery of the lamb). In comparison to the intramuscular injection, pulmonary administration of an oxytocin dry powder formulation to postpartum ewes resulted in generally similar EMG responses, however a more rapid onset of uterine EMG activity was observed following pulmonary administration (129 ± 18 s) than intramuscular injection (275 ± 22 s). This is the first study to demonstrate the potential for oxytocin to elicit uterine activity after systemic absorption as an aerosolised powder from the lungs. Aerosolised oxytocin has the potential to provide a stable and easy to administer delivery system for effective prevention and treatment of postpartum haemorrhage in resource-poor settings in the developing world.

  20. Improvement of asthma therapy by a novel formoterol multidose dry powder inhaler.

    PubMed

    Moeller, Manfred; Grimmbacher, Stefanie; Munzel, Ullrich

    2008-01-01

    The objective of this post-marketing surveillance (PMS) was the evaluation of efficacy, tolerability, and acceptance of the advanced formoterol (CAS 73573-87-2) multidose dry powder inhaler (MDPI) Formatris 6 microg/12 microg Novolizer (FN) in asthmatic patients (n = 5219) in a real-life setting. A total of 2727 patients (52%) received concomitant anti-inflammatory treatment exclusively via a budesonide Novolizer (BN). Efficacy of the FN was assessed by measurement of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) before and after 4 weeks of therapy. The severity of cough, wheezing, diurnal dyspnea, nocturnal dyspnea and dyspnea on physical effort were assessed on a four-point scale, and a severity sum score was calculated. The patients' satisfaction with the multiple feedback mechanisms, handling and safety of the FN was also assessed. The physicians judged the patient compliance and any improved inhalation reassurance due to FN control mechanisms in comparison with other inhalation systems. FN use (n = 2727) was associated with improved lung function. After 4 weeks, PEF increased by 26% (from 270 L/min to 340 L/min) and the median FEV1 increased by 24% (from 2.1 L to 2.6 L). The median severity sum score decreased from 8.0 before therapy to 3.0 after therapy. Most patients assessed the control mechanisms and safety functions of the FN as 'very good' or 'good'. 96% of patients were satisfied with the optical control mechanism, 92% with the acoustic mechanism, 70% with the taste feedback, 89% with the dose counter and 76% with the overdose prevention. The majority of patients (95%) confirmed that the multiple feedback mechanisms reassured correct drug intake, with 83% rating the FN as 'much better' or 'better' than previously used inhalers. The physicians confirmed that in contrast to previously used inhalers the FN ensured correct inhalation in 87% of all patients. The physicians were satisfied with the patients' compliance in 95% of

  1. Efficacy of fluticasone metered-dose inhaler and dry powder inhaler for pediatric asthma.

    PubMed

    Miyahara, Hiroaki; Korematsu, Seigo; Nagakura, Tomokazu; Izumi, Tatsuro

    2008-02-01

    For the treatment of bronchial asthma, two types of fluticasone inhaler devices are available, namely, metered-dose inhaler with spacer (MDI-S) and the dry powder inhaler (DPI). The former is recommended for young children with a low peak inspiratory flow (PIF) and the latter for adolescents and adults. But the difference in the therapeutic efficacy between them has been studied only rarely in adolescent patients. In the present study, 21 post-elementary school-age patients with moderate persistent bronchial asthma (age 8-15 years, 10.3 +/- 2.1 years), who all had a sufficient PIF of 114 +/- 29 L/min, were examined in order to compare the two types of fluticasone inhalers. Eleven of 21 patients inhaled 200 microg/day Flutide using the MDI-S twice daily for 1 month in the first month, and the same dose using the DPI for the next month. The other 10 patients inhaled the opposite regimens. At the end of the each treatment, spirometry was examined. Measurements done before therapy and then at the end of MDI-S and DPI therapy, respectively, were as follows: forced expiratory volume in 1 s (FEV(1.0)), 72.4 +/- 18.2%, 91.5 +/- 18.2% and 84.1 +/- 16.3% (MDI-S vs DPI, P > 0.040); maximal mid-expiratory flow (MMEF), 62.0 +/- 23.6%, 88.7 +/- 26.5%, 79.3 +/- 33.4% (P > 0.044) and the peak expiratory flow (PEF) was 73.9 +/- 25.0%, 95.6 +/- 32.8%, and 90.5 +/- 29.5%, respectively (n.s.). MDI-S was thus found to be more effective in terms of %FEV(1.0) and in %MMEF. High therapeutic efficacy was obtained with the use of the MDI-S in fluticasone inhalation for post-elementary school-age patients with sufficient inspiration ability.

  2. [Preparation of freeze-dried powder of recombinate hirudin-2 nanoparticle for nasal delivery and permeability through nasal membrane in vitro].

    PubMed

    Chen, Ming-Xia; Zhang, Jian-Bao; Yu, Ji-Ping; Ye, Jing; Wei, Bao-Hong; Zhang, Yu-Jie

    2013-06-01

    To optimize the freeze-dried powder preparation technology of recombinate hirudin-2 (rHV2) nanoparticle which has bio-adhesive characteristic for nasal delivery, also to investigate its stability and permeability through nasal membrane in vitro. Taking the appearance, rediffusion of nanoparticle and rHV2 encapsulation efficiency as the evaluation indexes. Cryoprotector, the preparative technique and the effect of illumination and high temperature factors on its stability for rHV2 freeze-dried powder were investigated. Using Fraze diffusion cell technique, the permeability of rHV2 across rabbit nasal mucous membrane in chitosan solution, chitosan nanoparticle, and nanoparticle frozen-dried powder were compared with that in normal saline solution. The optimized preparation of rHV2 nanoparticle freeze-dried powder was as follows: 5% trehalose and glucose (1:1) was used as cryoprotector, nanoparticle solution was freezed for 24 h in vacuum frozen-dryer after being pre-freezed for 24 h. The content of rHV2 in the freeze-dried powder was 1.1 ug/mg. Illumination had little effect on the appearance, rediffusion and encapsulation efficiency of the rHV2 freeze-dried powder. High temperature could obviously influence the appearance of nanoparticle freeze-dried powder. The permeability coefficient (P) of nanoparticle was 5 times more than that in chictonson solution. It was indicated that chitosan nanoparticle has effect on increasing the permeability of rHV2. The freeze-dried powder of chitosan nanoparticle can be a good nasal preparation of rHV2.

  3. Secondary Organic Aerosol formation from isoprene photooxidation under dry conditions (CUMULUS project)

    NASA Astrophysics Data System (ADS)

    Brégonzio-Rozier, Lola; Siekmann, Frank; Giorio, Chiara; Temime-Roussel, Brice; Pangui, Edouard; Morales, Sébastien; Gratien, Aline; Ravier, Sylvain; Monod, Anne; Doussin, Jean-Francois

    2014-05-01

    Isoprene (2-methyl-1,3-butadiene, C5H8) is one of the most abundant non-methane hydrocarbons emitted into the troposphere. Its annual global emission has recently been estimated in the range of 440 to 660 TgC (Guenther et al., 2006). Because of its large concentrations and high reactivity with the hydroxyl radical (OH), isoprene can have a strong influence on tropospheric photochemistry. It has been determined recently that isoprene also plays a role in secondary organic aerosol (SOA) formation in the ambient atmosphere even if isoprene leads to low SOA yields. The aim of the present work was to study isoprene photo-oxidation with OH radical in order to investigate its oxidation products and resulting aerosol production. A special care was taken to the realism of the experiment: light source, NOx and OH levels and aging time (around 10 hours). Experiments were performed in the CESAM chamber (Wang et al., 2011) which was designed to investigate multiphase processes under realistic actinic flux, and accurate control of temperature. In each experiment, around 800 ppb of isoprene was injected in the chamber together with the OH source under dry conditions (<5 %RH) before irradiation. Gas-phase composition was analyzed in-situ by a Fourier Transform Infrared Spectrometer (FTIR), a Proton Transfer Reaction Mass Spectrometer (PTR-TOF-MS) and NOx and ozone analyzers. A Scanning Mobility Particle Sizer (SMPS) and an Aerodyne High Resolution Time-Of-Flight Aerosol Mass Spectrometer (HR-TOF-AMS) were also used to investigate SOA formation and composition. In all experiments, we noted a SOA production at the end of isoprene oxidation i.e. exhibiting a clear secondary products type growth. Several results (including SOA densities and yields, and O/C ratios) were obtained using SMPS and AMS data allowing us to characterize SOA formation and composition during the experiments. The characterization of the gaseous and particulate phases will be presented. While the SOA yields in

  4. Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer™ disposable high-dose dry powder inhaler.

    PubMed

    de Boer, Anne H; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

    2012-09-01

    To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer™ dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Comparison of predicted flow and particle behaviour from CFD computations with experimental data obtained with cascade impactor and laser diffraction analysis. Inhaler resistance, flow split, particle trajectories and particle residence times can well be predicted with CFD for a multiple classifier based inhaler like the Twincer™. CFD computations showed that the flow split of the Twincer™ is independent of the pressure drop across the inhaler and that the total flow rate can be decreased without affecting the dispersion efficacy or retention behaviour. They also showed that classifier symmetry can be improved by reducing the resistance of one of the classifier bypass channels, which for the current concept does not contribute to the swirl in the classifier chamber. CFD is a highly valuable tool for development and optimisation of dry powder inhalers. CFD can assist adapting the inhaler design to specific physico-chemical properties of the drug formulation with respect to dispersion and retention behaviour. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  5. DissolvIt: An In Vitro Method for Simulating the Dissolution and Absorption of Inhaled Dry Powder Drugs in the Lungs.

    PubMed

    Gerde, Per; Malmlöf, Maria; Havsborn, Lina; Sjöberg, Carl-Olof; Ewing, Pär; Eirefelt, Stefan; Ekelund, Katarina

    The main purpose of this work was to develop an in vitro method for simulating the dissolution and absorption of inhaled dry powder drugs that also mimics systemic pharmacokinetic data. A second purpose was to evaluate this method. DissolvIt(®) was developed as a simulation of the air-blood barrier of the upper airways, constituting: "airborne" particles deposited on a glass cover slip, a mucus simulant, a polycarbonate (basal) membrane, and a pumped albumin buffer simulating the pulmonary blood flow. The PreciseInhale(®) exposure system was used to aerosolize and deposit test formulations onto cover slips. The particle dissolution was observed by optical microscopy as particle disappearance, and it was started directly when the particles came into contact with the mucus simulant. Solute from the dissolving particles diffused through the barrier and was absorbed into the perfusate. The drug concentration in the perfusate over time and the remaining drug in the barrier at the end of the experiment were quantitated by using liquid chromatography-tandem mass spectrometry. Budesonide and fluticasone propionate generated different pharmacokinetic dissolution/absorption profiles in DissolvIt. This study indicates that DissolvIt simulates dissolution and absorption of drugs in the lung, and that DissolvIt also mimics pharmacokinetic profiles and parameters.

  6. Preferential decorporation of americium by pulmonary administration of DTPA dry powder after inhalation of aged PuO(2) containing americium in rats.

    PubMed

    Grémy, Olivier; Tsapis, Nicolas; Chau, Quang; Renault, Daniel; Abram, Marie-Claire; Van der Meeren, Anne

    2010-11-01

    After inhalation of plutonium oxides containing various percentages of americium in rats, we identified an acellular transient pulmonary compartment, the epithelial lining fluid (ELF), in which a fraction of actinide oxides dissolve prior to absorption and subsequent extrapulmonary deposit. Chelation therapy is usually considered to be poorly efficient after inhalation of actinide oxides. However, in the present study, prompt pulmonary administration of diethylenetraminepentaacetic acid (DTPA) as a dry powder led to a decrease in actinide content in ELF together with a limitation of bone and liver deposits. Because americium is more soluble than plutonium, higher amounts of americium were found in ELF, extrapulmonary tissues and urine. Our results also demonstrated that the higher efficacy of DTPA on americium compared to plutonium in ELF induced a preferential inhibition of extrapulmonary deposit and a greater urinary excretion of americium compared to plutonium. All together, our data justify the use of an early and local DTPA treatment after inhalation of plutonium oxide aerosols in which americium can be in high proportion such as in aged compounds.

  7. Investigation into the influence of primary crystallization conditions on the mechanical properties and secondary processing behaviour of fluticasone propionate for carrier based dry powder inhaler formulations.

    PubMed

    Kubavat, Harshal A; Shur, Jagdeep; Ruecroft, Graham; Hipkiss, David; Price, Robert

    2012-04-01

    To investigate the influence of primary crystallization conditions on the mechanical properties and secondary processing behaviour of fluticasone propionate (FP) for carrier based dry powder inhaler (DPI) formulations. Young's modulus of FP crystals produced using different anti-solvents was determined using nanoindentation. Physicochemical and surface interfacial properties via the cohesive-adhesive balance (CAB) approach to colloid probe atomic force microscopy (AFM) of air-jet micronised FP crystals were investigated. These data were correlated to in vitro aerosolization performance of binary and combination DPI formulations containing salmeterol xinafoate (SX). Young's modulus of FP crystals produced using different anti-solvents ranged from 0.6-12.4 GPa. Crystals with low Young's modulus required multiple passes in the microniser to reduce the particle size to less than 5 μm, whilst those with the highest Young's modulus required a single pass. CAB of micronized FP samples was similar with respect to lactose, however, their adhesive affinity to SX varied. Samples of FP with greatest adhesion to SX produced greater fine particle delivery of SX in combination DPI formulations. Crystallisation conditions may affect the mechanical properties of FP, and therefore secondary processing of the material and their interfacial properties and product performance in carrier based DPI formulations.

  8. Characterisation of Sol-Gel Synthesis of Phase Pure CaTiO3 Nano Powders after Drying

    NASA Astrophysics Data System (ADS)

    Mallik, P. K.; Biswal, G.; Patnaik, S. C.; Senapati, S. K.

    2015-02-01

    According to a few recent studies, calcium titanate (CT) is a material that is similar to hydroxyapatite in biological properties. However, calcium titanate is not currently being used in the biomedical applications as to hydroxyapatite. The objective is to prepare nano calcium titanate powders from the equimolar solution of calcium oxide, ethanol and Titanium (IV) isopropoxide via sol-gel synthesis. The phase analysis and morphology of powder particles were studied by X-ray diffraction (XRD), while the composition and size of powder particles were determined by Transmission electron microscope (TEM) attached with energy dispersive x-ray spectrometer (EDS). As results, XRD confirm the presence of phase pure crystalline CaTiO3 after drying at 100°C for 24 hours, while TEM analysis confirms about 13 nm sizes of CaTiO3 particles and some agglomerated particle of 20-30 nm. Moreover, EDS analysis indicates that the approximately stoichiometric Ca/Ti ratio 1:1 was obtained in the CaTiO3 powders. Finally, it can be concluded that described sol-gel synthesis could be novel method for the production of nano CaTiO3 particles at lower temperature compared to any other methods of production.

  9. Comparative Evaluation of Commercially Available Freeze Dried Powdered Probiotics on Mutans Streptococci Count: A Randomized, Double Blind, Clinical Study

    PubMed Central

    Nagaraj, Anup; Ganta, Shravani; Sidiq, Mohsin; Pareek, Sonia; Vishnani, Preeti; Acharya, Siddharth; Singh, Kushpal

    2015-01-01

    Objectives: Probiotic approaches are being considered to eliminate pathogenic microorganisms and are an alternative and promising way to combat infections by using harmless bacteria to displace pathogenic microorganisms. The aim of this study was to evaluate the effectiveness of commercially available freeze dried powdered probiotics on mutans streptococci count among 12–15 year-old Indian schoolchildren. Materials and Methods: The study was conducted in two phases of in-vitro (phase I) and in-vivo (phase II) study, which was a double blind, randomized and placebo controlled clinical trial. A total of 33 schoolchildren between 12–15 years were included in the study. They were randomly allocated to three groups. Group A included 11 children using freeze dried Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum and Bifidobacterium lactis. Group B included 11 children using freeze dried lactic acid bacillus only. Group C included 11 children using placebo powder. The study was conducted over a period of three weeks and examination and sampling of the subjects were done on days 0 (baseline), seven, 14 and 21. Results: For both the intervention groups A and B, statistically significant reduction (P<0.05) in salivary mutans streptococci counts was recorded up to the second week. Conclusion: Oral administration of probiotics showed a short-term effect on reduction of mutans streptococci count and showed a preventive role in caries development. PMID:27252756

  10. The effect of relative humidity on electrostatic charge decay of drugs and excipient used in dry powder inhaler formulation.

    PubMed

    Elajnaf, Abdulmajid; Carter, Paul; Rowley, Geoff

    2007-09-01

    Electrostatic forces arising from charge accumulation on drug and excipient powders cause agglomeration and adhesion of particles to solid surfaces and problems during the manufacture and use of many pharmaceutical dosage forms, including dry powder inhalers (DPIs). The ability of materials to dissipate the acquired charge is therefore important and the aim of this work was to investigate the charge decay of salbutamol sulfate, ipratropium bromide monohydrate and alpha-lactose monohydrate. Differences in tri-phasic charge decay rates of the three materials in the order ipratropium bromide > lactose > salbutamol sulfate were demonstrated after corona charging and all materials showed an increased decay rate as the relative humidity was increased up to 86%. Preformulation knowledge of charge accumulation and decay in such materials will contribute to formulation, manufacture and performance of pharmaceutical dosage forms in general, and in particular DPIs.

  11. Production and characterization of spray-dried theophylline powders prepared from fresh milk for potential use in paediatrics.

    PubMed

    Aguiar, João P; Fernandes, Tânia A P; Nese, Carlotta; Fernandes, Ana I; Pinto, João F

    2017-05-01

    This work evaluates the potential of using fresh milk to deliver theophylline to children. Theophylline-fresh milk systems were prepared using different solids ratios (0 : 1-1 : 0) and three fat contents in commercial milks (low, medium and high), which were spray-dried at different inlet air temperatures (Tinlet - 105, 130 and 150 °C). The process was evaluated for yield and the resulting powders for moisture content (MC), particle size and shape, density and wettability. Theophylline-milk potential interactions (differential scanning calorimetry (DSC) and FT-IR) and chemical (theophylline content) and microbiological stability of powders (shelf and in-use) were also evaluated. The production yield (13.6-76.0%), MC (0.0-10.3%) and contact angles in water (77.29-93.51°) were significantly (P < 0.05) affected by Tinlet , but no differences were found concerning the mean particle size (3.0-4.3 μm) of the different powders. The milk fat content significantly (P < 0.05) impacted on the density (1.244-1.552 g/cm(3) ). Theophylline content remained stable after 6 months of storage, before extemporaneous reconstitution. After reconstitution in water, low-fat milk samples (stored at 4 °C) met the microbial pharmacopoeia criteria for up to 7 days. No theophylline-milk components interaction was observed. Spray-dried milk-composed powders may be used as vehicles for theophylline delivery in paediatrics following further characterization and in-vivo evaluation. © 2016 Royal Pharmaceutical Society.

  12. In vitro evaluation of novel inhalable dry powders consisting of thioridazine and rifapentine for rapid tuberculosis treatment.

    PubMed

    Parumasivam, T; Chan, J G Y; Pang, A; Quan, D H; Triccas, J A; Britton, W J; Chan, H K

    2016-10-01

    Thioridazine is an orally administered antipsychotic drug with potential for treatment of drug-resistant tuberculosis (TB). However, drug-induced adverse cardiac effects have been reported when thioridazine was used at an efficacious oral dose of 200mg/day to treat TB. Pulmonary delivery of thioridazine could be a rational approach to reduce dose-related side effects while enabling high drug concentrations at the primary site of infection. The present study compares in vitro aerosol performance, storage stability, and in vitro antimicrobial activity and cytotoxicity of two inhalable powders composed of thioridazine and a first-line anti-TB drug, rifapentine. Formulation 1 is a combination of amorphous thioridazine and crystalline rifapentine, while Formulation 2 consisted of both drugs as amorphous forms. Both thioridazine-rifapentine formulations were found suitable for inhalation with a total fine particle fraction (<5μm) of 68-76%. The two powders had similar MIC90 to rifapentine alone, being 0.000625μg/mL and 0.005μg/ml against Mycobacterium tuberculosis H37Ra and M. tuberculosis H37Rv, respectively. In contrast, thioridazine alone had a MIC90 of 12.5μg/mL and 500μg/mL, against M. tuberculosis H37Ra and M. tuberculosis H37Rv, respectively, demonstrating no synergistic anti-TB activity. However, thioridazine and rifapentine in a ratio of 1:3 enhanced the killing of M. tuberculosis H37Ra within the human monocyte-derived macrophages (THP-1) compared to the single drug treatments. Both powders showed an acceptable half maximal inhibitory concentration (IC50) of 31.25μg/mL on both THP-1 and human lung epithelial (A549) cells. However, Formulation 1 showed greater chemical stability than Formulation 2 after three months of storage under low humidity (vacuum) at 20±3°C. In conclusion, we have demonstrated a novel inhalable powder consisted of amorphous thioridazine and crystalline rifapentine (Formulation 1) with a good aerosol performance, potent anti

  13. Laser-ablated nanofunctional polymers for the formulation of slow-release powders for dry powder inhalers: physicochemical characterization and slow-release characteristics.

    PubMed

    Coowanitwong, Intira; Arya, Vikram; Patel, Gina; Kim, Won-Seok; Craciun, Valentin; Rocca, James R; Singh, Rajiv; Hochhaus, Günther

    2007-11-01

    Recently, dry powder inhalation (DPI) powders coated with nanometre-thin layers of biodegradable polymers, prepared using pulse laser deposition (PLD), have been evaluated as a slow-release formulation for DPI use, with the goal of improving pulmonary selectivity. This paper describes evaluation of the chemical stability of one potential polymer, poly lactic acid (PLA), during the ablation process, the resulting respirable properties and potential cytotoxicity of coated glucocorticoid powders, and the resulting sustained-release characteristics of PLA-coated glucocorticoids creating using PLD. Triamcinolone acetonide (TA) and budesonide (BUD) were used as two model glucocorticoids to determine pulmonary targeting (PT) in-vivo. The chemical stability of PLA was determined at various laser energy densities. The respirable fraction and the cytotoxicity of the micronized particles of TA and BUD, coated using optimum laser energy density, were determined. In-vitro dissolution profiles were generated for the coated/uncoated formulations and an ex-vivo receptor binding assay was used to determine PT in rats. Increasing laser energy density led to decreases in molecular weight and film density, and increases in degradation products, roughness and thickness of the film. The mean dissolution time of coated formulations of BUD was longer (4 h) than with the less lipophilic TA (2 h). This correlated well with a more pronounced pulmonary selectivity observed for coated BUD ex-vivo. Stability and the physical properties of the film correlated with the laser energy density. We observed a direct relationship between the dissolution rate of the uncoated and coated formulation and the degree of PT; however, physiochemical properties of the drug (e.g. lipophilicity) may also contribute to the improved PT.

  14. Nanocrystals embedded in chitosan-based respirable swellable microparticles as dry powder for sustained pulmonary drug delivery.

    PubMed

    Ni, Rui; Zhao, Jing; Liu, Qiaoyu; Liang, Zhenglin; Muenster, Uwe; Mao, Shirui

    2017-03-01

    In this study, nanocrystals embedded in microparticles were designed to achieve sustained pulmonary drug delivery of hydrophobic drugs. Chitosan based microparticles were engineered to allow sustained drug release via swelling and mucoadhesive properties of the polymer. Taking cinaciguat as a hydrophobic model drug, drug nanocrystals were prepared by high pressure homogenization and then encapsulated in chitosan microparticles via spray drying. Through various in vitro characterizations, it was shown that drug loaded microparticles had a high drug loading with promising aerosolization characteristics (mean volume diameter (Dv50) 3-4μm, experimental mass mean aerodynamic diameter (MMADe) 4-4.5μm, fine particle fraction (FPF%) 40-45%, emitted dose (ED%) 94-95%). The microparticles showed high swelling capacity within 5min, with various sustained drug release rates depending on chitosan concentration and molecular weight. Furthermore, aerosolization performances under various inhalation conditions were investigated. It was found that both inspiratory flow rate and volume had an influence on the aerosolization of developed microparticles, indicating actual inhalation efficiency might be compromised under disease conditions. Taken together, in vitro data indicate that chitosan based swellable microparticles could potentially be useful as nanocrystal carrier to achieve sustained pulmonary delivery. To complete the feasibility assessment of this formulation principle, future in vivo safety and efficacy studies are needed.

  15. [Study on Xinyueshu spray drying assisted with copovidone and its effect on powder property].

    PubMed

    Jiang, Yan-Rong; Zhang, Zhen-Hai; Ding, Dong-Mei; Yan, Hong-Mei; Hu, Shao-Ying; Jia, Xiao-Bin

    2013-12-01

    To study the application characteristics of copovidone (PVP-S630) in Xinyueshu extracts during the spray drying process, and its effect on such pharmaceutical properties as micromeritics and drug release behavior. PVP-S630 was added into Xinyueshu extracts to study on the spray drying, the effect of different dosages of PVP-S630 against the wall sticking effect of the spray drying, as well as the power property of Xinyueshu spray drying power and the dissolution in vitro behavior of the effective component of hyperoside. The results showed that PVP-S630 revealed a significant anti-wall sticking effect, with no notable change in the grain size of the spray drying power, increase in the fluidity, improvement in the moisture absorption and remarkable rise in the dissolution in vitro behavior of hyperoside. It was worth further studying the application of PVP-S630 in spray drying power of traditional Chinese medicine.

  16. Platinum pharmacokinetics in mice following inhalation of cisplatin dry powders with different release and lung retention properties.

    PubMed

    Levet, Vincent; Merlos, Romain; Rosière, Rémi; Amighi, Karim; Wauthoz, Nathalie

    2017-01-30

    Pharmacokinetics of cisplatin administered by the pulmonary route were established in mice using dry powders inhaler (DPI) formulations showing immediate (F1) and controlled release (CR, solid lipid microparticles) in vitro, without (F2) or with PEGylated excipients (F3, F4). Formulation administration was realized using dry powder blends (correspondingly named thereafter F1B to F4B) able to reproducibly deliver particles in vivo using a DP-4M Dry Powder Insufflator™. Their platinum pharmacokinetics were established over 48h in lungs, total blood and non-target organs vs. IV and endotracheal nebulization (EN). EN and F1B were rapidly distributed from the lungs (t1/2(i) 2.6 and 5.0min). F2B was eliminated in ∼1h (t1/2(i) 9.0min). F3B lung retention was sustained for ∼7h (t1/2(i) 59.9min), increasing lung AUC 11-, 4- and 3-fold vs. IV, F1B and F2B. Total blood tmax were higher and AUC and Cmax lower using the pulmonary route vs. IV. Kidney Cmax was reduced 6-, 2- and 3-fold for F1B, F2B and F3B. AUC in kidneys were 2- to 3-fold lower for F1B and F2Bvs. IV but comparable for IV vs. F3B, probably because of kidney saturation. PEGylated solid lipid microparticles provided cisplatin particles with interesting lung retention and CR properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers.

    PubMed

    Ungaro, Francesca; d'Angelo, Ivana; Coletta, Ciro; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Perfetto, Brunella; Tufano, Maria Antonietta; Miro, Agnese; La Rotonda, Maria Immacolata; Quaglia, Fabiana

    2012-01-10

    Although few experimental studies have been handled so far to exploit the potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in the production of dry powders for antibiotic inhalation, there has been no comprehensive study on the role played by NP composition. In this work, we try to shed light on this aspect by designing and developing a pulmonary delivery system for antibiotics, such as tobramycin (Tb), based on PLGA NPs embedded in an inert microcarrier made of lactose, referred to as nano-embedded micro-particles (NEM). At nanosize level, helper hydrophilic polymers were used to impart the desired surface, bulk and release properties to PLGA NPs prepared by a modified emulsion-solvent diffusion technique. Results showed that poly(vinyl alcohol) (PVA) and chitosan (CS) are essential to optimise the size and modulate the surface properties of Tb-loaded PLGA NPs, whereas the use of alginate (Alg) allows efficient Tb entrapment within NPs and its release up to one month. Optimized formulations display good in vitro antimicrobial activity against P. aeruginosa planktonic cells. Furthermore, spray-drying of the NPs with lactose yielded NEM with peculiar but promising flow and aerosolization properties, while preserving the peculiar NP features. Nonetheless, in vivo biodistribution studies showed that PVA-modified Alg/PLGA NPs reached the deep lung, while CS-modified NPs were found in great amounts in the upper airways, lining lung epithelial surfaces. In conclusion, PLGA NP composition appears to play a crucial role in determining not only the technological features of NPs but, once processed in the form of NEM, also their in vitro/in vivo deposition pattern.

  18. Dry sliding wear behavior of ceramic-metal composite coatings prepared by plasma spraying of self-reacting powders

    NASA Astrophysics Data System (ADS)

    Dong, Yanchun; Yan, Dianran; He, Jining; Li, Xiangzhi; Zhang, Jianxin

    2006-09-01

    Ceramic-metal composite (CMC) coatings were deposited on the surface of Fe-0.14 0.22 wt.% C steel by plasma spraying of self-reacting Fe2O3-Al composite powders. The dry sliding friction and wear character of the CMC coatings are investigated in this paper. The wear resistance of the CMC coatings was significantly better than that of Al2O3 coatings under the same sliding wear conditions. The tough metal, which is dispersed in the ceramic matrix, obviously improved the toughness of the CMC coatings. Wear mechanisms of the CMC coatings were identified as a combination of abrasive and adhesive wear.

  19. Compaction of spray-dried ceramic powders: An experimental study of the factors that control green density

    SciTech Connect

    Readey, M.J.; Mahoney, F.M.

    1995-11-01

    The pressure-compaction response of a spray-dried, 94% alumina powder containing several percent of a polymeric binder was investigated as a function of die diameter and compact aspect ratio. The results show that the die fill density decreases markedly with decreasing die diameter and aspect ratio, while the final green density (at 120 MPa) decreases only slightly under the same conditions. These results suggest that the ratio of the initial compact dimensions to the size of the granules may be much more important than previously considered.

  20. Study on the preparation of Mn-Zn soft magnetic ferrite powders from waste Zn-Mn dry batteries.

    PubMed

    Peng, Chang-hong; Bai, Ben-shuai; Chen, Yi-feng

    2008-01-01

    Using waste Zn-Mn dry batteries, waste scrap iron and pyrolusite as raw materials, Mn-Zn soft magnetic ferrite powders were prepared through the process of simultaneous leaching, purification and co-precipitation. The experimental results indicated that the leached yields of Fe, Mn and Zn were 92.02%, 96.14% and 98.34%, respectively. The leached liquor was purified through these processes of sulfuration precipitation, fluorination precipitation and double salt precipitation deep purification process. Therefore, high removal yields of impurities could be achieved. Removal yields were as follows: Ca 99.7%, Mg 92.33%, Al 96.48%, Si 63.64%, Cu 99.86%, Pb 98.51%, Cd 53.0% and Ni 78.72%. Among these co-precipitation powders, the average mass content of the main components were Fe 41.41%, Mn 13.92% and Zn 4.49%, and the mass ratio of Fe:Zn:Mn was 69.2:23.3:7.5. Compared with the theoretical prescription (Fe:Mn:Zn=67.3:24.4:8.3), the absolute errors of main components were Fe +1.9%, Mn -1.1% and Zn -0.8%. Because of content impurities in co-precipitation powders (Ca<0.0028%, Mg<0.0053%, Al<0.0084%, SiO(2)<0.0023%, Pb<0.0031% and Cu<0.0010%), the qualities of these gained co-precipitation powders could compete with the demand for the preparation of soft magnetic ferrite. The magnetic properties also demonstrated that the soft magnetic ferrite samples, which were made from the co-precipitation powders prepared by used batteries, had the same qualities as PC30 made by the TDK Company.

  1. Preparation of simulated inert matrix fuel with different powders by dry milling method

    NASA Astrophysics Data System (ADS)

    Lee, Y.-W.; Kim, H. S.; Kim, S. H.; Joung, C. Y.; Na, S. H.; Ledergerber, G.; Heimgartner, P.; Pouchon, M.; Burghartz, M.

    1999-08-01

    Simulated zirconium oxide-based inert matrix fuel (IMF) has been prepared using cerium oxide replacing plutonium oxide, following the conventional pelletising route, in which an improved two-stage attrition mill was employed. Different methods have been applied for the powder preparation. In addition to powder mixing, nitrate solutions have been co-precipitated to bulk gel and to microspheres by the internal gelation process. The calcined porous microspheres were crushed in the attrition mill with a few passes. This co-precipitated powder was compared with three different mixtures of the four commercially available powders (ZrO 2, Y 2O 3, Er 2O 3 and CeO 2). Pellets of a standard size with relative densities higher than 90% TD and comparable grain and pore structures have been obtained. Based on these simulation tests both processes are found suitable for fabricating IMF pellets, which fulfil requirements of a commercial plutonium and uranium mixed oxide (MOX), where applicable. No intensive milling is required to form a solid solution in the sintering step for a (Zr,Y,Er,Ce)O 2- x pellet. For the fabrication of plutonium-containing IMF, a similar behaviour can be expected.

  2. Powder treatment process

    DOEpatents

    Weyand, John D.

    1988-01-01

    (1) A process comprising spray drying a powder-containing slurry, the slurry containing a powder constituent susceptible of oxidizing under the temperature conditions of the spray drying, while reducing the tendency for oxidation of the constituent by including as a liquid constituent of the slurry an organic liquid; (2) a process comprising spray drying a powder-containing slurry, the powder having been pretreated to reduce content of a powder constituent susceptible of oxidizing under the temperature conditions of the spray drying, the pretreating comprising heating the powder to react the constituent; and (3) a process comprising reacting ceramic powder, grinding the reacted powder, slurrying the ground powder, spray drying the slurried powder, and blending the dried powder with metal powder.

  3. Powder treatment process

    DOEpatents

    Weyand, J.D.

    1988-02-09

    Disclosed are: (1) a process comprising spray drying a powder-containing slurry, the slurry containing a powder constituent susceptible of oxidizing under the temperature conditions of the spray drying, while reducing the tendency for oxidation of the constituent by including as a liquid constituent of the slurry an organic liquid; (2) a process comprising spray drying a powder-containing slurry, the powder having been pretreated to reduce content of a powder constituent susceptible of oxidizing under the temperature conditions of the spray drying, the pretreating comprising heating the powder to react the constituent; and (3) a process comprising reacting ceramic powder, grinding the reacted powder, slurrying the ground powder, spray drying the slurried powder, and blending the dried powder with metal powder. 2 figs.

  4. Microencapsulation of anthocyanin-rich black soybean coat extract by spray drying using maltodextrin, gum Arabic and skimmed milk powder.

    PubMed

    Kalušević, Ana; Lević, Steva; Čalija, Bojan; Pantić, Milena; Belović, Miona; Pavlović, Vladimir; Bugarski, Branko; Milić, Jela; Žilić, Slađana; Nedović, Viktor

    2017-08-01

    Black soybean coat is insufficiently valorised food production waste rich in anthocyanins. The goal of the study was to examine physicochemical properties of spray dried extract of black soybean coat in regard to carrier materials: maltodextrin, gum Arabic, and skimmed milk powder. Maltodextrin and gum Arabic-based microparticles were spherical and non-porous while skimmed milk powder-based were irregularly shaped. Low water activity of microparticles (0.31-0.33), good powders characteristics, high solubility (80.3-94.3%) and encapsulation yields (63.7-77.0%) were determined. All microparticles exhibited significant antioxidant capacity (243-386 μmolTE/g), good colour stability after three months of storage and antimicrobial activity. High content of total anthocyanins, with cyanidin-3-glucoside as predominant, were achieved. In vitro release of anthocyanins from microparticles was sustained, particularly from gum Arabic-based. These findings suggest that proposed simple eco-friendly extraction and microencapsulation procedures could serve as valuable tools for valorisation and conversion of black soybean coat into highly functional and stable food colourant.

  5. Evaluation of folic acid release from spray dried powder particles of pectin-whey protein nano-capsules.

    PubMed

    Assadpour, Elham; Jafari, Seid-Mahdi; Maghsoudlou, Yahya

    2017-02-01

    Our main goal was to evaluate release kinetics of nano-encapsulated folic acid within a double W1/O/W2 emulsion. First, W1/O nano-emulsions loaded with folic acid were prepared and re-emulsified into an aqueous phase (W2) containing single whey protein concentrate (WPC) layer or double layer complex of WPC-pectin to form W1/O/W2 emulsions. Final double emulsions were spray dr