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At least 55 records · Page 3Linked to original sources
PubMed2005

Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size.

RATIONALE: Aerosol particle size influences the extent, distribution, and site of inhaled drug deposition within the airways. OBJECTIVES: We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery. METHODS: In a randomized, double-blind, placebo-controlled study, 12 subjects with asthma (FEV1, 76.8 +/- 11.4% predicted) inhaled technetium-99m-labeled monodisperse albuterol aerosols (30-microg dose) of 1.5-, 3-, and 6-microm mass median aerodynamic diameter, at slow (30-60 L/min) and fast (> 60 L/min) inspiratory flows. Lung and extrathoracic radioaerosol deposition were quantified using planar gamma-scintigraphy. Pulmonary function and tolerability measurements were simultaneously assessed. Clinical efficacy was also compared with unlabeled monodisperse albuterol (15-microg dose) and 200 microg metered-dose inhaler (MDI) albuterol. RESULTS: Smaller particles achieved greater total lung deposition (1.5 microm [56%], 3 microm [50%], and 6 microm [46%]), farther distal airways penetration (0.79, 0.60, and 0.36, respective penetration index), and more peripheral lung deposition (25, 17, and 10%, respectively). However, larger particles (30-microg dose) were more efficacious and achieved greater bronchodilation than 200 microg MDI albuterol (deltaFEV1 [ml]: 6 microm [551], 3 microm [457], 1.5 microm [347], MDI [494]). Small particles were exhaled more (1.5 microm [22%], 3 microm [8%], 6 microm [2%]), whereas greater oropharyngeal deposition occurred with large particles (15, 31, and 43%, respectively). Faster inspiratory flows decreased total lung deposition and increased oropharyngeal deposition for the larger particles, with less bronchodilation. A shift in aerosol distribution to the proximal airways was observed for all particles. CONCLUSIONS: Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation. Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.

Administration, Inhalation↗
PubMed2005

Finite-size scaling and particle-size cutoff effects in phase-separating polydisperse fluids.

We study the liquid-vapor phase behavior of a polydisperse fluid using grand canonical simulations and moment free energy calculations. The strongly nonlinear variation of the fractional volume of liquid across the coexistence region prevents naive extrapolation from detecting the cloud point. We describe a finite-size scaling method which, nevertheless, permits accurate determination of cloud points from simulations of a single system size. By varying a particle-size cutoff, we find that the cloud point density is highly sensitive to the presence of rare large particles; this could affect the reproducibility of experimentally measured phase behavior in colloids and polymers.

Journal Article↗
PubMed1994

Airborne birch pollen antigens in different particle sizes.

Two particle samplers for ambient air, situated together: a static size-selective bio-aerosol sampler (SSBAS) and a Burkard pollen and spore trap were compared in sampling intact birch pollen grains through one flowering period of Betula (a total of 44 days). The SSBAS trapped pollen grains three times more efficiently than the Burkard trap, but the variations in pollen counts were significantly correlated. In contrast, birch pollen antigenic activity and the pollen count in the Burkard samples were not closely correlated. The antigenic concentration was occasionally high both before and after the pollination period. There was a high birch pollen antigenic activity in particle size classes where intact pollen grains were absent, even on days when the pollen count was very low. Correspondingly, on days with high birch pollen counts in the air, pollen antigenic activity was on several occasions low, indicating that pollen grains were empty of antigenic material. The small particle size classes are especially important to allergic patients because they are able to penetrate immediately into the alveoli and provoke asthmatic reactions. Therefore, aerobiological information systems based on pollen and spore counts should be supplemented with information concerning antigenic activities in the air.

Air Pollutants↗
PubMed1991

Effects of grass maturity and legume substitution on large particle size reduction and small particle flow from the rumen of cattle.

Five ruminally and abomasally cannulated heifers (average weight 365 kg) were fed 6 kg/d of early (EOG) or late (LOG) maturity orchardgrass (OG) hay with or without replacement of EOG or LOG by 1.5 kg/d red clover hay (RC) in a 5 x 5 Latin square design. A fifth treatment, of LOG supplemented with 100 g/d casein (LOG + C), was used to evaluate the effect of supplemental protein. In situ fiber digestion, in vivo nutrient digestion and rate of passage from the rumen of large (retained on a 1.68-mm screen; labeled with La) and small (passed a 1.68-mm screen; labeled with Sm) EOG and LOG particles were determined in heifers fed these diets. Early maturity OG hay had 20% and 62%, respectively, greater (P less than .05) rates, and 61% and 73%, respectively, greater (P less than .05) extents of in situ NDF and ADF disappearance than LOG. Red clover substitution for OG increased (P less than .05) in situ extent of NDF disappearance by 6%. Early maturity OG large and small particles had 40% and 36%, respectively, greater (P less than .05) rates of passage than LOG. Large and small particle ruminal pool sizes were increased (P less than .05) by 115% and 33%, respectively, with LOG. Red clover substitution for OG increased (P less than .10) large and small particle output (kg/d) from the rumen by 15% and large particle rate of passage by 20%. Grass maturity may be affecting intake through rate of large particle size reduction and passage and small particle passage, although legume supplementation of OG may influence intake by increasing rate of large particle size reduction and passage.

Animal Feed↗
PubMed1975

Biopharmaceutical factors influencing LD50. Part II: Particle size.

The effect of particle size on the time elapsing between administration and loss of righting reflex and % of deaths by determining the LD50 has been studied in mice. The drug used was pentobarbituric acid. In one preparation the particle size was less than 44 mum and in the other preparation it was greater than 297 mum and less than 420 mum. For both preparations a 1% sodium carboxymethylcellulose solution was used as suspending medium. It was found that both the curve for loss of righting reflex and the log dose-response curve, and hence the LD50, were significantly shifted to the right. There is a reflex LRR between the suspended pentobarbituric acid and the equivalent amount of sodium pentobarbital, both in 1% sodium carboxymethylcellulose solution. In reporting LD50 data it is essential not only to state the exact composition of the vehicle (viscosity factor) but also to state the exact particle size or particle size range, because by using increasing particle size the LD50 decreases.

Absorption↗
PubMed2002

The effect of particle size reduction by grinding on subsampling variance for explosives residues in soil.

Efforts to characterize the surface soil contamination on military training ranges have been compromised by the inability to obtain representative subsamples of soils submitted to analytical laboratories for determination of explosives residues. Two factors affecting subsampling error for explosives residues were examined using soils collected from hand grenade and anti-tank ranges. These factors were increased subsample size and particle size reduction prior to subsampling of soils. Increasing the subsample size from 2 to 50 g did not reduce the soil subsampling error because of the extreme heterogeneous distribution of the solid contaminants. Alternatively, particle size reduction by machine grinding on a ring mill reduced subsampling error to less than 10% relative standard deviation for replicate analyses using 10-g subsamples.

Environmental Monitoring↗
PubMed2005

High-pressure aerosol suspensions--a novel laser diffraction particle sizing system for hydrofluoroalkane pressurised metered dose inhalers.

In this study, a novel laser diffraction particle size analysis dispersion system, capable of sizing particles in situ within suspension hydrofluoroalkane (HFA) pressurised metered dose inhalers (pMDIs), was developed and tested. The technique was compared to four indirect particle sizing methods commonly used to determine the size of particles suspended in HFA pMDIs. The median volume diameter obtained using laser diffraction of both the salbutamol sulphate and fluticasone propionate suspended either in 2H, 3H-decafluoropentane or perfluoropentane (employed as surrogate propellants) was over one-order of magnitude larger than the particle sizes of the drugs suspended in HFA 134a. In contrast, the "in-flight" particle size using the Sympatec inhaler 2000 laser diffraction equipment undersized the particles, predicting higher delivery efficacy compared to the other sizing methods. However, the size of particles suspended in HFAs derived using the novel pressurised dispersion system, showed a linear correlation with the impaction results, r2=0.8894 (n=10). The novel pressure cell sizing technique proved to be simple to use, has the ability to be automated and was accurate, suggesting it could be an essential tool in the development of new suspension-based pMDI formulations.

Aerosol Propellants↗
PubMed2004

Influence of the size of micronized active pharmaceutical ingredient on the aerodynamic particle size and stability of a metered dose inhaler.

Pharmaceutical inhalers are often used to treat pulmonary diseases. Only active pharmaceutical ingredient (API) particles from these inhalers that are less than approximately 5 microm are likely to reach the lung and be efficacious. This study was designed to investigate the impact of micronized API particle size on the aerodynamic particle size distribution (PSD) profile and the particle size stability of a suspension metered dose inhaler (MDI) containing propellant HFA-227 (1,1,1,2,3,3,3 heptafluoropropane) and a corticosteroid. The median API particle size ranged from 1.1 microm to 1.8 microm (97% to 70% of particles <3 microm, respectively). This study showed that increasing the particle size of the API used to manufacture a suspension MDI product increased the aerodynamic PSD of the MDI product. Furthermore, upon storage of the MDI product under temperature cycling conditions, samples containing larger-size API particles were less stable with respect to their aerodynamic PSD than those with smaller-size API particles. It was found that size-dependent particle growth and/or aggregation of the suspended API may be occurring as a result of temperature cycling. In conclusion, this study has shown that the particle size of the raw API impacts the properties and stability of the emitted aerosol spray. Based on the findings from this study, it is recommended that the API particle size be carefully controlled in order to meet specifications set for the finished MDI product.

Metered Dose Inhalers↗
PubMed1984

Distribution of particle sizes in food comminuted by human mastication.

The masticatory performance of an individual may be quantified by describing the size distribution of particles of a comminuted test food as a function of the number of chewing strokes. A standardized sieving method and a standardized artificial test food (Optosil) were used to obtain reproducible results. Some measurements were performed using peanuts. The distribution of particle sizes of the comminuted food was adequately described by a Rosin-Rammler distribution function for the seven participating individuals which characterizes the size distribution by the median particle size (x50) and the broadness of the distribution (b). The broadness variable b hardly depends on the number of chewing strokes, and the differences in b between the individuals are small. Considerable differences in the median particle sizes at a given number of chewing strokes were observed between the subjects, reflecting differences in efficiency of comminution of a test food. For all subjects, the median particle size decreased as a function of the number of chewing strokes N according to the relation, x50 = c X N-d. Variables c and d characterized the efficiency of comminution by the subjects.

Arachis↗
PubMed1998

Optical Sizing of Ultrafine Metallic Particles: Retrieval of Particle Size Distribution from Spectral Extinction Measurements.

The inverse problem of optical sizing of ultrafine metallic particles from the spectral extinction measurements in the visible range is investigated. Solving the inverse problem becomes possible due to the strong size effect which in the framework of classical electrodynamics can be described by the dependence of complex refractive index on the particle size. It is shown that the size effect leads to the considerable increase of information content of spectral extinction data with respect to desired size composition of the particles. This makes it possible to retrieve the size distribution of ultrafine metallic particles with reasonably high accuracy, including the Rayleigh size region. The analysis is performed mainly within the framework of numerical tests by the typical example of ultrafine silver particles in a gelatin matrix. The results in retrieving of size distribution from experimentally measured extinction spectra are also presented. Calculations of spectral extinction coefficient are made by means of Mie theory. In so doing, the dielectric function of particles is modified by using the electron's mean free path limitation model. Copyright 1998 Academic Press.

Journal Article↗
PubMed2004

Relationship between encapsulated drug particle size and initial release of recombinant human growth hormone from biodegradable microspheres.

Protein microencapsulation in biodegradable polymers is a promising route to provide for sustained release. One important characteristic in this regard is the size of the particles encapsulated within the microspheres. In this investigation, we have employed spray-freeze drying to generate particles for encapsulation, and examined the effect of various atomization conditions. Conditions were identified resulting in minimization of the particle size for the therapeutic protein recombinant human growth hormone (rhGH). The polymer employed was poly(lactide-co-glycolide) (PLG). The greatest friability for the powder, and hence smallest particle size (e.g., sub-micron), was achieved as the mass flow ratio of atomization (air to liquid) was increased. Protein powders over a range of particle sizes were encapsulated in biodegradable microspheres using a cryogenic, non-aqueous process. The initial release (both in vitro and in vivo) from these batches was found to decrease with decreasing encapsulated protein particle size; these findings are consistent with the percolation theory. Hence, judicious selection of process variables to reduce the particle size of rhGH is one strategy that can be used to minimize initial release of the microencapsulated protein.

Animals↗
PubMed2006

Identification of critical process variables affecting particle size following precipitation using a supercritical fluid.

The critical processing parameters affecting average particle size, particle size distribution, yield, and level of residual carrier solvent using the supercritical anti-solvent method (SAS) were identified. Carbon dioxide was used as the supercritical fluid. Methylprednisolone acetate was used as the model solute in tetrahydrofuran. Parameters examined included pressure of the supercritical fluid, agitation rate, feed solution flow rate, impeller diameter, and nozzle design. Pressure was identified as the most important process parameter affecting average particle size, either through the effect of pressure on dispersion of the feed solution into the precipitation vessel or through the effect of pressure on solubility of drug in the CO2/organic solvent mixture. Agitation rate, impeller diameter, feed solution flow rate, and nozzle design had significant effects on particle size, which suggests that dispersion of the feed solution is important. Crimped HPLC tubing was the most effective method of introducing feed solution into the precipitation vessel, largely because it resulted in the least amount of clogging during the precipitation. Yields of 82% or greater were consistently produced and were not affected by the processing variables. Similarly, the level of residual solvent was independent of the processing variables and was present at 0.0002% wt/wt THF or less.

Carbon Dioxide↗
PubMed1993

Relationship between apolipoprotein E and low density lipoprotein particle size.

The relationships between the particle size of low density lipoproteins (LDL) and various lipid parameters, including apolipoprotein (apo) E concentration and apo E phenotype, were analyzed in plasma samples obtained from 196 apparently healthy 35-year-old males. The LDL particle size was determined by gradient gel electrophoresis. Using stepwise multiple regression analysis it was found that LDL particle size correlated negatively to the plasma concentrations of triglyceride (r = -0.497, P < 0.001), apo E (r = -0.415, P < 0.001), apo B (r = 0.395, P < 0.001) and cholesterol (r = -0.235, P < 0.001) and correlated positively to the plasma concentrations of apo A-I (r = 0.297, P < 0.001) and apo A-II (r = 0.145, P < 0.05). However, the LDL particle size did not differ significantly among the different apo E phenotypes. Indeed, when entered as a variable in the multiple regression analysis, the apo E phenotype was not correlated to the LDL particle size. It is concluded that the LDL particle size is related to the plasma concentrations of triglyceride, apo E, apo B, apo A-I, apo A-II and cholesterol and is not affected by the apo E phenotype in healthy 35-year-old males.

Adult↗
PubMed2004

Association between LDL particle size and postprandial increase of remnant-like particles in Japanese type 2 diabetic patients.

Small, dense LDL, as well as chylomicron- and VLDL-remnant lipoproteins, are known to be important risk factors for coronary heart disease in patients with type 2 diabetes mellitus. The aim of this study was to clarify the relationship between LDL particle size and postprandial remnant lipoprotein levels in Japanese type 2 diabetic patients. Forty-six patients with type 2 diabetes mellitus were divided into tertiles according to LDL particle size. The peak LDL particle diameter was <26.30 nm in tertile 1, 26.30-26.85 nm in tertile 2, and >26.85 nm in tertile 3. After a test meal, tertile 1 had a significantly greater increment of triglycerides (TG), remnant-like particle (RLP)-TG, and RLP-cholesterol (RLP-C) than tertiles 2 and 3. There was a negative correlation between LDL particle size and the postprandial increases of TG, RLP-TG, and RLP-C. These results indicate that smaller sized LDL particles may be a marker of fasting state for an exaggerated postprandial increase of remnant lipoproteins as well as an increase of TG-rich lipoproteins.

Adolescent↗