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A new method for semi-automated quantitation of E-rosettes using a particle size analyser (Coulter Channelyzer).

Visual counts of the number of SRBC attached to individual lymphocytes in E-rosette preparations from 3 healthy young adults were made by 3 experienced observers: from these data the size distribution profile of particles in each E-rosette preparation was calculated. In parallel experiments the size distribution profile was measured directly with a particle size analyser (Coulter Counter and Channelyzer): in every case the observed profile lay within the 95% confidence band around the reconstructed profiles. It was concluded that the Coulter Channelyzer profile is an accurate measurement of the E-rosette size distribution and that particle sizing could provide a reasonable basis for semi-automated tests for E-rosettes. A mathematical model has been developed by which the percentage of lymphocytes forming E-rosettes, the distribution of number of attached SRBC and the average avidity of the lymphocyte receptor for SRBC could be deduced from the size-distribution profiles. The method has a high degree of precision, and a good correlation (P less than 0.01) was obtained when the percentage of E-rosettes (defined for this purpose as having three or more attached SRBC) obtained from the new method was compared with results from standard light microscopy.

Animals↗

NAD (P) H oxidase p22 phox C242T polymorphism affects LDL particle size and insulin resistance in Japanese subjects.

Elevated cardiovascular risk is associated with an increased number of small, dense low-density lipoprotein (LDL) particles, which exhibit increased susceptibility to lipid oxidation, however, the mechanism determining LDL particle size has never been fully elucidated. We have examined the association between the C242T polymorphism of the p22 phox gene, which is a small subunit of vascular NAD(P)H oxidase, and both LDL particle size and clinical characteristics in 260 healthy subjects. Peak LDL particle diameter (LDL-PPD) was measured by continuous disk polyacrylamide gel electrophoresis. Twenty-one of the 217 subjects with the CC genotype showed pattern B (median LDL-PPD under 25.5 nm), whereas, none of the 43 subjects with TC + TT genotypes showed pattern B. The pattern B fraction was significantly larger in the CC group than in the TC + TT group (p = 0.030). The subjects with the CC genotype also showed a significantly higher fasting glucose level, plasma insulin level, and insulin resistance index of homeostasis model assessment (HOMA-R) than those with the TC + TT genotype. Our data demonstrate that variation in the small NAD(P)H oxidase subunit p22 phox gene substantially influences LDL particle size and may also reflect differences in the insulin sensitivity of non-diabetic subjects.

Adult↗

Effects of fiber content and particle size of forage on the flow of microbial amino acids from continuous culture fermenters.

Eight dual-flow continuous culture fermenters (1320 mL) were used in two 10-d consecutive periods to study the effects of fiber content and particle size on rumen fermentation, nutrient flow, and the profile and flow of amino acids (AA) from microbial origin. Treatments were arranged in a 2 x 2 factorial; the main factors were fiber content (high fiber [HF] = 67% alfalfa hay, 33% concentrate; low fiber [LF] = 39% alfalfa hay, 61% concentrate) and forage stem particle size (ground not to pass a 3-mm sieve = large size [LS]; ground to pass a 1-mm sieve = small size [SS]). On the last day of the experiment, liquid- (LAB) and solid- (SAB) associated bacteria were isolated from each fermenter for chemical analysis. Microbial N and AA flows were estimated using LAB or SAB composition data. Total volatile fatty acid concentration was higher for LF (122 mM) than for HF (102 mM). The proportion of acetate was higher for HF (63.5%) than for LF (58.2%). When SS was fed instead of LS, there was a reduction in the acetate proportion (63.4% vs 58.3%, respectively) and in the acetate to propionate ratio (3.13 vs. 2.41, respectively). Bacterial N flow was higher, and dietary N flow was lower, in SS compared with LS when LAB were used for calculations. Efficiency of microbial protein synthesis (EMPS) was affected by particle size, when LAB were used for calculations, and by fiber content, when SAB were used for calculations. The AA profile of LAB differed from SAB in 4 of 16 AA. The fiber content and particle size had small effects on microbial AA profile. However, the bacterial AA flow was higher in 13 of 16 AA, when SAB instead of LAB were used for calculations. Estimates of bacterial N flow, EMPS, AA profile, and flows of microbial origin were dependent on the type of microbial population used for calculations. The representativeness of the microbial samples is essential for the accurate prediction of the AA flow from microbial origin.

Amino Acids↗

Physical properties of organic particulate UV-absorbers used in sunscreens. I. Determination of particle size with fiber-optic quasi-elastic light scattering (FOQELS), disc centrifugation, and laser diffractometry.

In this study microparticles consisting of a benzotriazole derivative, which are used as absorbers for UV radiation in cosmetic sunscreens, were investigated. The particles were micronized in presence of a dispersing agent by means of a ball milling process. According to the energy input different particle sizes were produced in the range of 0.16 to 4 microm. The particle sizes obtained after different stages of the micronization process were measured using fiber-optic quasi-elastic light scattering (FOQELS), disc centrifugation, and laser diffractometry. All methods showed satisfactory agreement over the whole range of sizes. With the FOQELS technique the particle size distribution could be resolved to sizes well below 0.1 microm.

Centrifugation↗

Effect of particle size on the prolonged action of subcutaneous danazol in male and female rats.

OBJECTIVE: To investigate the effects of two different particle sizes of danazol in male and female rats. DESIGN: Prospective, vehicle-controlled study. SETTING: Undergraduate college research facility and medical research laboratory. ANIMALS: 18 castrated male rats and 18 cycling female rats. INTERVENTION(S): Preparations of danazol with particle sizes of 2.05 microm or 5.2 microm were administered as a single subcutaneous injection of 400 mg/kg to castrated male rats or estrus-cycling females. MAIN OUTCOME MEASURE(S): Serum LH level in males and estrous cycle length in females. RESULT(S): In males, both preparations significantly (P<. 001) suppressed serum LH by day 5 of treatment. Gonadotropin levels remained low throughout the 35-day study in rats that received the larger-particle danazol, whereas LH levels began to increase after 25 days in rats that received smaller-particle danazol. In females, the normal 4- to 5-day estrous cycle interval was prolonged to 38.7 days (P<.001) in those that received the larger-particle danazol and 25.5 days in those that received the smaller-particle danazol. CONCLUSION(S): The results demonstrate the prolonged effectiveness of a single subcutaneous dose of danazol and indicate that one might be able to predict the effective duration of activity by changing the particle size of the danazol administered.

Administration, Cutaneous↗

Disposition of disodium cromoglycate administered in three particle sizes.

1 Disodium cromoglycate (DSCG) was administered in three particle sizes to five human subjects. 2 Urinary excretion of DSCG, as a proportion of the dose, was highest following small particles; the lower values recorded following intermediate-sized and large particles were similar. 3 DSCG deposited in the mouth was highest following large particles; the lower values recorded following intermediate-sized and small particles were similar. 4 The data were examined in relation to the recent observation that the protective effect of small particles of DSCG is dramatically superior to that of large particles.

Adult↗

Effect of particle size, air flow and inhaler device on the aerosolisation of disodium cromoglycate powders.

Recently, the dispersion of mannitol powders has demonstrated the importance of particle size, air flow and inhaler device (Chew and Chan, 1999). The aim of the present study is to extend our investigation to a different compound, disodium cromoglycate (DSCG) powders. Solid state characteristics of the powders were assessed by particle sizing, scanning electron microscopy, X-ray powder diffraction, moisture content, particle density determination and freeze fracture. The aerosol behaviour of the powders was studied by dispersion using Rotahaler(R) and Dinkihaler(R), connected to a four-stage liquid impinger operating at 30-120 l/min. Three amorphous powders with a mass median diameter (MMD) of 2.3, 3.7, 5.2 microm and a similar polydispersity were prepared. The particles were nearly spherical with a particle density of 1.6 g/cm(3) and moisture content of 6.6 wt.%. Using Rotahaler(R), the maximum fine particle fraction (FPF(max)) for all three powders was only 15 wt.%, attained at the highest flow of 120 l/min. Using Dinkihaler(R), the FPF(max) was two to four times higher, being 36 and 29 wt.% for the 2.3 and 3.7 microm powder, respectively, at 60 l/min; and 18 wt.% for the 5.2 microm powder at 120 l/min. Hence, the study shows that the FPF in the DSCG powder aerosols was determined by the interaction of the particle size, air flow and inhaler design. The attribution of the amorphous nature and the different physico-chemical properties of the powder may explain the incomplete and low dispersibility of DSCG.

Aerosols↗

Effect of particle size on performance. 3. Grinding pelleting interactions.

Three experiments were conducted to study the effect of particle size obtained by grinding wheat and sorghum in a hammer mill (HM) or roller mill (RM) on broiler performance. Broilers were fed a mash diet or crumbles to 4 wk of age, then pellets to 7 wk of age. When fed as a mash, diets produced with RM-ground grain improved performance. The effect of grinding was additive to that of pelleting. The interactive effects observed between grinding method and the form of the feed on body weight and feed intake were explained by the higher response to pelleting when grains were ground in HM vs RM. The positive effect of grinding in RM on feed utilization was found to be additive to that of pelleting in all three experiments. The response of females to feed texture was less pronounced than that of males. In males, feeding pellets vs mash increased mortality due to ascites threefold, whereas grinding method had no effect. Females were less susceptible to ascites than males, and feed texture had no effect in this respect. The effects of grinding and pelleting on the gastrointestinal tract segments were additive. The main effects of feed texture were a significant increase in stomach weight and that of its contents following HM grinding and a decrease in these following pelleting, with no interactions between the two.

Adipose Tissue↗

Association of gestational diabetes mellitus and low-density lipoprotein (LDL) particle size.

A predominance of small, dense low-density lipoproteins (LDL) is characteristic of the dyslipidemic state seen in type 2 diabetes. However, no study has investigated the association in gestational diabetes mellitus (GDM), which is pathophysiologically similar to type 2 diabetes. We hypothesized that LDL particle size is reduced in GDM cases compared with controls. Gradient gel electrophoresis was used to characterize LDL subclass phenotypes in non-fasting intrapartum plasma from 105 GDM cases and 96 controls. All participants were free of pre-existing diabetes or hypertension. The authors used logistic regression to estimate odds ratios (OR) and 95 % confidence intervals (CI) adjusted for confounders. Women with this phenotype had a significant 4.9-fold (95 % CI: 1.1-23.2) increased risk of GDM compared with those with the large, buoyant phenotype. The magnitude of this association was attenuated when plasma triglyceride and other confounders were included in the model (OR=4.2, 95 % CI: 0.5-39.5). Mean LDL particle size in GDM cases was smaller compared with controls (270.1 vs. 272.7A, p=0.003). The OR of GDM risk was 1.8 (95 % CI: 0.9-3.3) for every 10-A reduction in LDL particle size. Large prospective studies are needed to evaluate the association between smaller LDL particle size in early pregnancy with subsequent GDM risk.

Adult↗

Particle size analysis in pharmaceutics: principles, methods and applications.

Physicochemical and biopharmaceutical properties of drug substances and dosage forms can be highly affected by the particle size, a critical process parameter in pharmaceutical production. The fundamental issue with particle size analysis is the variety of equivalent particle diameters generated by different methods, which is largely ascribable to the particle shape and particle dispersion mechanism involved. Thus, to enable selection of the most appropriate or optimal sizing technique, cross-correlation between different techniques may be required. This review offers an in-depth discussion on particle size analysis pertaining to specific pharmaceutical applications and regulatory aspects, fundamental principles and terminology, instrumentation types, data presentation and interpretation, in-line and process analytical technology. For illustration purposes, special consideration is given to the analysis of aerosols using time-of-flight and cascade impactor measurements, which is supported by a computational analysis conducted for this review.

Aerosols↗

Filler particle size and composite resin classification systems.

The currently used composite resin classification systems need review if they are to continue to serve as descriptives and quantitative parameters denoting the filler particle content of these materials. Examination of the particles in 12 composite resins using a technique of washing the filler particles from the matrix of the composite resin was presented as yet another method of grouping composites according to filler particle content. Light microscopic examination of the filler particles that remained provided a separation of the 12 materials into four easily distinguished groups based on filler particle sizes. The wear of the 12 composite resins determined in a previous study was examined in relation to the classification of the materials by the currently available systems. The wear values were also examined using the groupings of the materials according to their filler particle sizes as determined by separating the particles from the matrix by the washing technique. Grouping composites on the basis of the filler particle sizes found after washing was easily correlated with wear and supported the suggestion that composites with smaller filler particles wear less.

Acrylic Resins↗

Differences in aerodynamic particle size distributions of innovator and generic beclomethasone dipropionate aerosols used with and without a large volume spacer.

BACKGROUND: The equivalence of generic beclomethasone dipropionate (BDP) formulations with their innovator counterpart must be demonstrated if generic formulations are to be used. This study has examined the aerodynamic particle size distributions of both innovator and generic formulations of BDP and the effect of a large volume spacer (Volumatic) on these distributions. METHODS: Aerosol clouds of three formulations of BDP delivering 250 micrograms per metered dose were characterised using a high precision multistage liquid impinger, and the amount of drug in different particle size bands was determined by spectrophotometric assay. RESULTS: The mean (SD) respirable fractions of Becloforte, Beclazone, and Filair without the spacer (n = 10) were 24.1 (2.1)%, 23.1 (2.7)%, and 23.0 (2.1)% respectively; however, the ratio of deposition on stage 4 of the impinger to that on stage 3 was lower for Beclazone and for Filair than for Becloforte, implying a smaller proportion of fine particles for the generic products. When the three products delivered via the Volumatic spacer device were compared, the respirable fraction for Becloforte (n = 10) was 25.0 (4.0)%, but those of Beclazone (n = 10) and Filair (n = 11) were 16.0 (1.9)% and 14.6 (3.4)%. Repeat testing (n = 5) at a later date showed higher mean respirable fractions for all three products, but a trend towards the highest respirable fraction for Becloforte, and the same rank order for the other two products. CONCLUSIONS: These in vitro findings suggest that the particle size distributions of the two generic formulations of BDP are not equivalent to that of the innovator product. Some differences in particle size distributions might not have been detected by a twin impinger. Clinical testing would be required to assess the therapeutic equivalence of innovator and generic corticosteroid products used with or without spacer devices.

Aerosols↗

The effect of dose on the characterization of aerodynamic particle-size distributions of beclomethasone dipropionate metered-dose inhalers.

The aerodynamic particle-size distribution for two doses of a Becloforte metered-dose inhaler (MDI) was measured by use of a twin-stage impinger (TSI), the new multi-stage (five-stage) liquid impinger (MSLI) and the Andersen cascade impactor (ACI) (n = 5 for each apparatus). The mean (s.d.) fine-particle doses measured by the three techniques for the Becloforte MDI were 40.3 (1.2), 45.7 (0.5) and 41.8 (0.4)% w/w, respectively; the median mass aerodynamic diameters (MMAD) measured using the MSLI and the ACI were 3.50 and 3.73 microns, respectively. The MSLI fine particle (< 6.8 microns) doses for 2, 5, 10, 20, 30 and 40 doses from Becloforte MDIs (n = 5 for each dose) were 49.7 (0.7), 52.9 (1.2), 45.3 (0.6), 45.5 (0.71), 45.9 (0.7) and 46.4 (0.7)% w/w, respectively. Values obtained using the ACI (< 5.8 microns) were 40.8 (1.0), 41.0 (0.8), 44.4 (0.5), 43.1 (0.4), 42.8 (0.5) and 40.4 (0.4)% w/w (n = 4). MMAD values measured with the MSLI were 3.39, 3.46, 3.75, 3.91, 4.15 and 4.45 microns, respectively; using the ACI they were 3.46, 3.54, 3.61, 3.66, 3.73 and 3.85 microns. The results indicate that the measured aerodynamic particle-size distributions of beclomethasone dipropionate MDIs are affected by the dose dispensed and by the apparatus used for measurement.

Administration, Inhalation↗

Influence of particle size on diffusion-limited aggregation.

The influence of particle size on diffusion-limited aggregation (DLA) has been investigated by computer simulations. For DLA clusters consisting of two kinds of particles with different sizes, when large particles are in the minority, the patterns of clusters appear asymmetrical and nonuniform, and their fractal dimensions D(f) increase compared with one-component DLA. With increasing size of large particles, D(f) increases. This increase can be attributed to two reasons: one is that large particles become new growth centers; the other is the big masses of large particles. As the concentration ratio x(n) of large particles increases, D(f) will reach a maximum value D(f(m)) and then decrease. When x(n) exceeds a certain value, the morphology and D(f) of the two-component DLA clusters are similar to those of one-component DLA clusters.

Journal Article↗

Compaction simulator studies of a new drug substance: effect of particle size and shape, and its binary mixtures with microcrystalline cellulose.

The compaction characteristics of a new drug substance with two crystal habits and particle size fractions as well as its binary mixtures with microcrystalline cellulose were studied using an integrated compaction research system under 300 and 450 MPa pressures. The results indicate that the drug substance has poor intrinsic compaction properties. The three-dimensional hexagonal crystal habit or smaller particle size consistently produced a slightly higher total work of compaction as compared with the cubic brick habit or larger particle size, respectively. However, neither crystal habit produced a coherent compact. The compactability of the drug substance was improved by the inclusion of microcrystalline cellulose, and the crushing strength of the compacts increased as the amount of microcrystalline cellulose in the binary mixture was increased. Such correlation was not observed when the compaction data were evaluated using either the Heckel equation or the percentage porosity change as a function of applied pressure.

Cellulose↗

Adhesion as an interplay between particle size and surface roughness.

Surface roughness plays an important role in the adhesion of small particles. In this paper we have investigated adhesion as a geometrical effect taking into account both the particle size and the size of the surface features. Adhesion is studied using blunt model particles on surfaces up to 10 nm root-mean-square (RMS) roughness. Measurements with particles both smaller and larger than surface features are presented. Results indicate different behavior in these areas. Adhesion of particles smaller than or similar in size to the asperities depend mainly on the size and shape of the asperities and only weakly on the size of the particle. For large particles also the particle size has a significant effect on the adhesion. A new model, which takes the relative size of particles and asperities into account, is also derived and compared to the experimental data. The proposed model predicts adhesion well over a wide range of particle/asperity length scales.

Journal Article↗

Effect of feeding whole cereals on performance, starch digestibility and duodenal particle size distribution in broiler chickens.

1. An experiment was conducted to study the effects of whole wheat, oats and barley at different inclusion levels on performance, starch digestibility, duodenal particle size distribution, gizzard weight and pH of gizzard contents for broiler chickens. 2. Feed consumption and weight gain were significantly reduced when ground cereals were replaced by whole cereals (P < 0.05). However, feed conversion efficiency was not affected by inclusion of up to 440 g/kg of whole wheat, and up to 300 g/kg of whole oats and barley. 3. Duodenal particle size was measured by laser diffraction to below 1 micron in size. A remarkably large proportion of particles were below 100 microns, with as much as 50% of the particles in the duodenum being below 40 microns in size. Inclusion of moderate amounts of whole cereals reduced the duodenal mean particle size. Large inclusions of whole cereals decreased (P < 0.05) the proportion of particles up to 40 microns in size, and increased (P < 0.05) the proportion with size between 100 and 300 microns. 4. Starch digestibility was improved (P < 0.05) by replacing ground wheat or barley with whole wheat or barley. 5. There was no consistent effect of cereal species or feed form on the pH value of the gizzard contents.

Animals↗

Measurement of the percentage volume particle size distribution of powdered microcrystalline cellulose using reflectance near-infrared spectroscopy.

This is the first reported method for determining the percentage volume particle size distribution of a powder (microcrystalline cellulose) by near-infrared (NIR) reflectance spectroscopy. A total of 113 samples of powdered microcrystalline cellulose were used from six different commercially available grades, with different moisture contents (range: 0.9-4.8% m/m). NIR reflectance measurements of these samples were made in narrow soda glass vials. Reference particle size data for the samples were acquired by laser diffraction. The NIR data were then calibrated to measure particle size by partial least squares regression. The effects of a range of different NIR data pre-treatments on calibration and prediction precision were investigated. Overall, simple absorbance data were found to produce regression models with the best predictive ability (root mean square error of prediction = 0.90%). The method was also found to be insensitive to moisture content.

Cellulose↗