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Effect of drug load and plate coating on the particle size distribution of a commercial albuterol metered dose inhaler (MDI) determined using the Andersen and Marple-Miller cascade impactors.

PURPOSE: The purpose of this study is to investigate the effect of drug load, the coating of impactor stages, and the design of cascade impactors on albuterol MDIs particle size distribution measurements. The results of the investigation will be used to explain the "loading effect" recently reported. METHODS: Particle size distribution parameters of a commercial albuterol MDI were measured using both Andersen (AI) and Marple-Miller (MMI) Cascade Impactors, where plates were either left uncoated or coated with silicone or glycerin. A previously validated HPLC-EC method was used for the assay of albuterol collected by the impactor and in single spray content determinations. RESULTS: Coating impactor collection plates had an impact on measured MMAD and GSD values for single puff measurements but very little or no effect for the multi puff measurements. Due to particle bounce, the percent of albuterol fine particles deposited in the filter and impactor finer stages (< 1.10 microns in AI and < 1.25 microns in MMI) in uncoated single puff experiments was much higher in comparison to either coated single puff or multi-puff (coated and uncoated) measurements. CONCLUSIONS: Evaluation of drug load and plate coating are necessary to determine whether observed particle size distributions are representative of the generated aerosol or are the result of particle bounce and reentrainment. In order to minimize particle bounce, especially for single puff determinations, it may be useful to apply a thin layer of a sticky coating agent to the surfaces of impactor plates.

Adrenergic beta-Agonists↗

Influence of relative humidity on particle size and UV sensitivity of Serratia marcescens and Mycobacterium bovis BCG aerosols.

SETTING: A study of Serratia marcescens and BCG aerosols. OBJECTIVE: To evaluate the effect of relative humidity (RH) on (1) the particle size and (2) sensitivity of 254nm germicidal ultraviolet (UV) irradiation. METHODS: We built a RH controlled experimental chamber into which bacteria were aerosolized, exposed to varying amounts of UV irradiance over measured time periods, and quantitatively evaluated for viability. Aerosolized Serratia marcescens and bacille Calmette-Guérin (BCG) were subject to UV doses ranging from 57-829 microW. sec/cm(2), and sampled with a six-stage Andersen culture plate impactor at RHs ranging from 25-95%. RESULTS: Percent survival for both organisms was inversely related to UV dose. Serratia marcescens was more susceptible to UV than BCG under all conditions. More than 95% of the bacterial aerosol particles were 1.1-4.7 microm in aerodynamic diameter, and particles sizes increased from low (25-36%) to high (85-95%) RH. The count median diameter ranged from 1.9-2.6 microm for Serratia marcescens and from 2.2-2.7 microm for BCG as RH increased. For both Serratia marcescens and BCG, resistance to UV increased as RH increased. The UV resistance of both Serratia marcescens and BCG aerosols dramatically increased at RH higher than 85%. CONCLUSIONS: Our results indicate that differences in UV dose, kinds of microorganisms, airborne particle size and RH affect UV susceptibility.

Aerosols↗

Measurement of the particle size of tablet excipients with the aid of video recording.

A method for the determination of the particle size of tablet excipients involving the use of video recording of microscopic examination of powders is described. The projected area of the particle profile was measured, and Feret's diameter and shape factors such as the elongation ratio, bulkiness factor, and surface factor were determined. Starch particles are the smallest among the excipients studied. Primojel particles are two to three times larger (Feret's diameter) and have up to 10 times greater projected areas. Particles of Avicel PH101, Ac-Di-Sol, Nymcel ZSD16 and ZSB10, and Polyplasdone XL have an irregular surface which results in large differences between the projected area diameter and the perimeter diameter. Particles of Nymcel and Ac-Di-Sol have the highest elongation ratio because of their cylindrical shape. Both Primojel and Starch have a low surface factor because of their spherical shape. This video-recording method is a simple system to observe, record, store, and retrieve particle-size data from microscopic examination of tablet excipients.

Excipients↗

The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)).

OBJECTIVES: To evaluate if logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol (Log[TG/HDL-C]) correlates with cholesterol esterification rates in apoB-lipoprotein-depleted plasma (FER(HDL)) and lipoprotein particle size. DESIGN AND METHODS: We analyzed previous data dealing with the parameters related to the FER(HDL) (an indirect measure of lipoprotein particle size). In a total of 1433 subjects from 35 cohorts with various risk of atherosclerosis (cord plasma, children, healthy men and women, pre- and postmenopausal women, patients with hypertension, type 2 diabetes, dyslipidemia and patients with positive or negative angiography findings) were studied. RESULTS: The analysis revealed a strong positive correlation (r = 0.803) between FER(HDL) and Log(TG/HDL-C). This parameter, which we propose to call "atherogenic index of plasma" (AIP) directly related to the risk of atherosclerosis in the above cohorts. We also confirmed in a cohort of 35 normal subjects a significant inverse correlation of LDL size with FER(HDL) (r = -0.818) and AIP (r = -0.776). CONCLUSION: Values of AIP correspond closely to those of FER(HDL) and to lipoprotein particle size and thus could be used as a marker of plasma atherogenicity.

Adult↗

Effect of bran particle size on stool weight.

The increase in stool weight after feeding 20 g (dry weight) of bran daily was measured when this was of large particle size and after milling to small particle size. Twenty-eight investigations were carried out in 21 normal subjects. With coarse bran, stool weight was significantly greater than with the fine bran (mean 219.4 g/d coarse bran, 199-0 g/d fine bran: difference 20.4 g SE +/-6.4, P less than 00.1). The coarse bran also had a greater water-holding capacity (7.3 g water/g coarse bran, 3.9 water/g fine bran). Coarse bran was 2 1/2 times the volume of fine gran for a given weight and more fine bran will, therefore, be taken when bran is prescribed by the spoonful.

Adult↗

Effect of particle size of forage and rumen cannulation upon chewing activity and laterality in dairy cows.

Three ruminally cannulated Holstein dairy cows housed in free stalls (with .7% slope) were fed three total mixed rations, differing in silage particle size, in a 3 x 3 Latin square design. Observations on cow behavior were made every 5 min during 24 h for each of three periods. Additional observations of six cows (three intact, three cannulated) housed under identical conditions yielded information concerning recumbent rumination activity and laterality. Results indicated that decreasing particle size of forage reduced time spent ruminating, whether standing or recumbent, and had no effect upon rumination rate or number of rumination bouts per 24-h period. Eating time was unaffected by treatment. Effect of forage particle size upon baseline rumination activity appeared to be most pronounced from 0800 to 2000 h, although maximum rumination activity occurred during nighttime hours. Ruminally cannulated cows demonstrated increased right-side laterality (70%) compared with intact cows (47%), but the cows tend to ruminate while lying on their left side. The percentage of time spent ruminating while recumbent on the left side was similar (55%) for intact and cannulated cows.

Animals↗

Dermally adhered soil: 1. Amount and particle-size distribution.

The risk associated with the dermal absorption of chemicals from contaminated soil is, in part, a function of particle size distribution, as determined by either dry or wet sieving techniques. For the soils tested, the adhered soil fractions were shown to be independent of organic matter content and soil origin. Soil moisture content becomes a factor only for very moist soils. Results show that the adhered fractions of dry or moderately moist soils with wide distributions of particle sizes generally consist of particles of diameters <63 microm. Consequently, dermal absorption experiments using larger size fractions may be of limited relevance to actual situations of soil exposure.

Adsorption↗

Effects of particle size and physical form of diets on mast cell numbers, histamine, and stem cell factor concentration in the small intestine of broiler chickens.

The aim of this study was to investigate the hypothesis that particle size and diet form may affect the growth of mast cells and histamine release from the small intestine of broiler chickens. A total of 288, day-old male broiler chicks were randomly allocated to 1 of 4 corn-soy diets in a 2 x 2 factorial design. The factors included particle size (coarse vs. fine) and physical form (mash vs. pellet). The birds were housed in 90 x 60 cm pens containing 12 birds, and each treatment contained 6 replicate pens of birds from d 1 to 22. On d 22, 6 broilers from each treatment were slaughtered. Tissues from the small intestine (duodenum, jejunum, and ileum) were obtained to quantify mast cells using the toluidine blue staining technique. The results showed that mast cells in the jejunum were concentrated in the upper part of the villus in birds fed the coarsely ground mash diet, whereas mast cells were evenly distributed throughout the intestine in birds fed the other 3 diets. The number of mast cells was significantly lower in the duodenum (P = 0.04), jejunum (P < 0.01), and ileum (P = 0.01) of birds fed coarsely ground diets compared with finely ground diets, and there was no difference in mast cell numbers between birds fed mashed or pelleted diets at any site in the intestine. The histamine content (P = 0.02) and stem cell factor concentration (P = 0.03) were markedly lower in the jejunum of birds that were fed coarsely ground diets compared with finely ground diets. The stem cell factor concentration in the duodenum (P < 0.01) and jejunum (P = 0.05) was higher in birds fed pelleted compared with mash diets. The overall results of this experiment suggest that particle size and diet form affect mast cell number and histamine content in the small intestine by regulation of stem cell factor concentration.

Animal Feed↗

Influence of particle size on the effectiveness of beet pulp fiber.

Sixteen Holstein cows in midlactation were used in a design based on a replicated 4 x 4 Latin square with the last period removed to determine the influence of particle size of beet pulp neutral detergent fiber (NDF) on its effectiveness as a replacement for alfalfa NDF. Diets were a low forage, low fiber diet [12.1 g of alfalfa NDF/100 g of dry matter (DM)], a normal forage diet (low forage plus 7.8 g of additional alfalfa NDF/100 g of DM), and two low forage diets with 5.3 g of NDF/100 g of DM from either whole or finely ground dried sugar beet pulp. Replacement of alfalfa fiber with beet pulp fiber increased milk protein yield because of the tendencies toward increased milk yield and protein concentration. However, milk fat concentration and yield were unaffected. The addition of beet pulp fiber, either whole or ground, to the basal low forage, low fiber diet did not affect yields of milk, protein, or fat, but milk protein concentration tended to be lower for cows fed the beet pulp diets than for cows fed the basal diet. Reducing the particle size of beet pulp increased DM intake but did not affect any of the milk yield measurements. Particle size reduction of beet pulp did not reduce its effectiveness as a fiber source as measured by changes in milk fat content.

Animal Nutritional Physiological Phenomena↗

Chemical composition associated with different particle size fractions in municipal, industrial, and agricultural wastewaters.

A more detailed characterization of particulate organic matter in wastewater streams is needed to improve solid-liquid separation and biological processes for wastewater treatment. The objective of this paper was to evaluate particle size distributions and the associated chemical composition for municipal, industrial, and agricultural waste streams. Most of the organic matter in these wastewaters was larger than a molecular weight of 10(3) amu and therefore would require extracellular hydrolysis before any bacterial metabolism. Particle size distributions were significantly different for the studied waste streams. In municipal wastewater, the organic matter was evenly distributed in all eight size fractions ranging from 10(3) amu up to 63 microm. The industrial and agricultural wastewaters, however, contained mainly soluble organic matter (<10(3) amu) and larger particles (>1.2 microm for the industrial and >10 microm for the agricultural waste) leaving a gap in the size range of large macromolecules and colloids. The relative protein and carbohydrate concentrations varied for the different size fractions compared to the measured chemical oxygen demand (COD) in the corresponding size fraction. Thus, the design of the solid-liquid separation at a treatment plant could be used to purposefully modify the overall chemical composition of the organic matter before further biological treatment. Particle size distributions will influence design and operation of biological nutrient removal processes such as denitrification or biological phosphorus removal that may be carbon limited if a large fraction of the organic matter is composed of large particles with slow hydrolysis rates. Measured particle size distributions for the different waste streams in this study (municipal, industrial, agricultural) were significantly different requiring specific approaches for treatment plant design.

Filtration↗

Particle size and density in spray drying-effects of carbohydrate properties.

The purpose of this study was to examine some fundamental aspects of the particle formation during spray drying, related to particle size and density. Particles were prepared in a laboratory spray dryer from carbohydrates with different solubility and crystallization propensity, such as lactose, mannitol, and sucrose/dextran 4:1. The feed concentrations ranged from 1% w/w to saturated and the size of droplets and particles were measured by laser diffraction. Particles were also characterized by various microscopy techniques (i.e., scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and light microscopy), differential scanning calorimetry (DSC), gas adsorption, and gas pycnometry. As demonstrated larger particles could be obtained by either increasing the droplet size during atomization; increasing the concentration of the feed solution; or decreasing the solubility of the solute. The apparent particle density, measured by gas pycnometry, was found negatively correlated to the feed concentration. Due to the nonlinear relationship between the feed concentration and the particle size, it was concluded that higher solids load would cause an increase in the effective particle density and that the reduction in the apparent particle density was a result of a gradually less permeable particle surface. Further, the crystallization propensity of the carbohydrate influenced the particle formation and resulted in either hollow or porous particles.

Aerosols↗

Influence of particle size of hydroxyapatite as a capping agent on cell proliferation of cultured fibroblasts.

The influence of particle size of biomaterials on cell reaction and cell proliferation was studied by means of coculturing fibroblasts with calcium phosphate ceramics. Both dense and porous hydroxyapatite ceramics obtained under different sintering conditions were selected, and two particle sizes of 300 and 40 micrometers were used to examine cell reaction. The four materials were each cocultured with dental pulp-derived fibroblasts for 7 days. Cell reaction was observed by phase-contrast microscopy and scanning electron microscopy. Cell proliferation was measured by counting the number of trypsinized cells in 7-day-old culture. On the seventh day, the dense 300-micrometer particles of hydroxyapatite were completely covered by cultured cells that had proliferated on the dish surface. On the other hand, the porous and dense 40-micrometer particles were captured or gathered by the cultured cells, which seemed not to proliferate. The porous 300-micrometer particles were accompanied by numerous small broken pieces on the dish surface, and the cells proliferated only around the large particles. From these results, the dense 300-micrometer particles of hydroxyapatite can be considered the most appropriate biomaterial.

Biocompatible Materials↗

Acute changes in lipid, lipoprotein, apolipoprotein, and low-density lipoprotein particle size after an endurance triathlon.

The effect of an endurance triathlon (2.4-mile swim, 112-mile bicycle ride, 26.2-mile run, in succession) on plasma total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I and B levels, and LDL particle size was determined in 34 male and six female participants 6 to 12 hours before and immediately after the completion of the triathlon. Plasma TG decreased significantly (70% decrease) in both men and women. In men the change in plasma TG was inversely associated with baseline TG values (P less than .0001). Plasma TC and LDL cholesterol did not change significantly in male athletes but decreased significantly in women. A significant increase in HDL cholesterol was observed in both men (18% increase, P less than .0001) and women (5% increase, P less than .01). In men the increase in HDL cholesterol was inversely correlated with the decrease in triglycerides (P less than .0002). Plasma apo A-I levels increased significantly only in the male group (P less than .005), whereas plasma apo B levels decreased significantly in both men and women (P less than .0005). LDL particle size increased in seven males, whereas in the remaining males and all females no change in LDL size was observed. The increase in LDL particle size in these seven subjects was associated with a greater decline in plasma TG compared with the remaining men (P less than .005) and women (P less than .03). These results indicate that prolonged strenuous physical exercise can induce acute modifications of plasma lipoproteins, which may in part be related to enhanced lipolysis.

Apolipoprotein A-I↗

Development of a laser diffraction method for the determination of the particle size of aerosolised powder formulations.

Impactor data are an essential component of marketing authorisation for new dry powder aerosol formulations. However such data are time-consuming to obtain and therefore impede the rapid screening of pilot formulations. In this phase of development it would be of considerable benefit to employ a technique where data acquisition was more rapid, such as laser diffraction, to predict the fine particle fraction. It was the aim of this study to investigate whether this is a feasible premise. Five different formulations were prepared, each containing 1.5% (w/w) micronised salbutamol base (volume median diameter: 2.42 microm) blended with the sieved fraction (63-90 microm) of one of the following sugars: regular crystalline lactose, spray dried lactose "Zeparox", sorbitol, maltose and dextrose monohydrate. A Perspex box was constructed to contain particles released from a glass inhaler and allow the particles to be measured by laser diffraction at different flow rates. After being validated using monodisperse aerosols, this assembly was then employed to measure the particle size distributions of each powder formulation and its respective sugar carrier at flow rates ranging from 28.3 to 100 l min(-1). Aerodynamic particle size distribution of salbutamol base from each formulation was also measured after aerosolisation at 28.3 l min(-1) from the glass inhaler into an Andersen cascade impactor. The flight of monodisperse particles with diameters (2-6 microm) in the desired size range of dry powders for inhalation could be contained and the size distribution determined by laser diffraction using the assembly at all flow rates investigated. Treatment of the particle size distributions measured by laser diffraction, i.e. examining only the aerosol particles with diameter <60 microm, highlighted the fine fraction (<5 microm) and enabled the aerosolisation of different blends to be feasibly compared at a range of different flow rates. The blends containing the following excipients could be placed in the following order of increasing fine fraction: spray-dried lactose<dextrose<<maltose<lactose<sorbitol. At 28.3 l min(-1) a significant linear correlation was found between the fine fractions measured by laser diffraction and the salbutamol fine fractions determined by inertial impaction (R(2)=87.4%, p=0.02, ANOVA). Therefore, the laser diffraction technique could prove to be an important tool for particle size characterisation of dry powder aerosol formulations.

Aerosols↗

The effect of particle size distribution on an experimental glass-ionomer cement.

OBJECTIVES: The role of particle size and size distribution of glass powders in glass-ionomer cements (GICs) has been largely overlooked, being limited to demonstrations of the classical inverse size-strength relationship. This study investigated variation in properties of an experimental glass-ionomer cement when a combination of large ('Powder A') and small ('Powder B') particles was used. METHODS: Large- (mean size 9.60mum) and small-particle (3.34mum) glass powders were blended in various proportions and mixed with powdered polyacrylic acid to make a range of glass-ionomer powders. These powders were mixed with a glass-ionomer liquid (SDI Ltd, Australia) at powder to liquid ratios of 2:1, 2.5:1, and 3:1, and the resultant cements evaluated for working time, setting time, clinical handling, and compressive strength. Results were analysed by ANOVA. RESULTS: An increased proportion of smaller particles corresponded to higher strengths, and an increased proportion of larger particles with a decrease in viscosity of the unset cement. When 20-30% by weight of small particles was used, the paste demonstrated a peak in cohesion and working time, with a viscosity similar to commercial restorative GICs. SIGNIFICANCE: Optimisation of particle sizing and distribution may thus lead to glass-ionomer cements with improved clinical handling characteristics and greater strength, which may increase the longevity of the restoration.

Analysis of Variance↗

Collagen-induced platelet aggregation as studies by electronic particle size analysis.

The collagen-induced response of free platelets during aggregation was measured with an electronic particle size analyzer. Aggregation was induced in platelet-rich plasma by 0.05 mg/mL collagen. The reaction was followed turbidimetrically and samples for electronic particle size analysis were obtained during aggregation. Free platelet number decreased rapidly after the addition of collagen. This decrease preceded detectable changes in transmittance and a significant reduction in free platelet number was measured during the classical lag phase. In addition, the size distribution of free platelets at various times after the addition of collagen was not significantly altered indicating that large platelets are not preferentially involved in collagen-induced aggregation.

Collagen↗

Effect of particle size on the adsorption of theophylline onto activated charcoal, in vitro study.

The effective use of activated charcoal as oral adsorbent in the primary treatment of acute theophylline poisoning was studied in vitro. Adsorption capacities for theophylline onto activated charcoal of varying particle size were investigated. No difference in the equilibrium amount of theophylline adsorbed onto activated charcoal was recognized. This result could be explained by the physical properties of activated charcoal. The amount of theophylline adsorbed from physiological saline solution was greater than that from water. The smaller the particle size of activated charcoal, the faster theophylline was adsorbed. It was assumed that the increase of contact area by grounding activated charcoal of large particle size accelerated the adsorption of theophylline onto activated charcoal.

Adsorption↗

Particle size distribution analysis for the rapid detection of microbial infection of urine.

The accuracy and practicality of particle size distribution analysis for rapid screening of urine specimens are assessed. Six hundred urines were subjected simultaneously to routine bacteriological examinations and particle size distribution analysis using a Coulter Counter (ZBI) linked to a C1000 Channelyzer. There was complete agreement in the results of 593 (98.8%) specimens. Characteristic profiles of various bacterial species in infected specimens were consistently obtained. This system can easily be linked to any existing computer reporting in a district hospital laboratory, and the results of negative specimens (70--80%) can be obtained within 5--10 minutes.

Bacteriological Techniques↗