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PubMed2004

Effects of powder particle size and binder viscosity on intergranular and intragranular particle size heterogeneity during high shear granulation.

A study was performed in order to elucidate the effects of powder particle size and binder viscosity on intergranular and intragranular particle size heterogeneities. Granules were produced by melt granulation in a high shear mixer from each of four calcium carbonates having mean particle sizes in the range of 5.5-63.1 microm. Each of three polyethylene glycols (PEGs) having viscosities in the range of approximately 40-14,000 mPas were applied as meltable binders. The size distribution of the calcium carbonate particles in three granule size fractions (125-250, 355-500, and 800-1000 microm) was measured after disintegration of the granules. Intragranular particle size heterogeneities were evaluated qualitatively by means of scanning electron microscopy. A preferential growth of the smaller particles was found to give rise to a higher content of small particles in large granules when calcium carbonates with mean particle sizes of 11.7, 34.5, and 63.1 microm were granulated with a binder of low viscosity. The use of a binder of medium or high viscosity leads to a marked reduction of these heterogeneities. A preferential growth of larger particles was seen when calcium carbonates with mean particle sizes of 5.5 and 11.7 microm were granulated with a highly viscous binder. The use of a binder with low or medium viscosity resulted in an increased homogeneity. Intragranular particle size heterogeneities were primarily seen when 5.5 and 11.7 microm calcium carbonate particles were granulated with a highly viscous binder.

Excipients↗
PubMed1995

Influence of cohesive properties of micronized drug powders on particle size analysis.

Particle size analysis results with respect to micronized, mean particle size below 10 microns, furosemide, chloramphenicol palmitate and acetaminophen particles are dealt with in this paper. Special consideration was given to the effect of the agglomeration of particles on data generated by three size measurement techniques. The physicochemical basis for preparing sufficiently well dispersed and stable suspensions for analysis by employing mechanical methods of pretreatment are shown. Furthermore, methods to determine the state of dispersion and methods to assess the individual particle size before size analysis are described. An attempt was also made to establish the statistical confidence that can be assigned to a particular instrument and the confidence level that may be placed on comparative data obtained with the different particle size analysers. Results especially showed the impact of the agglomeration of very small furosemide particles, mean size 3 microns, on particle size analysis and the importance of controlling the cohesive properties of this drug. To overcome the problems associated with agglomeration more attention must be paid to the physical properties of the drug substance. Combining particle size analysis with bulk density, surface area and microscopical studies also helped to identify potential problems.

Acetaminophen↗
PubMed1998

Smaller sized particles are preferentially taken up by alveolar type II pneumocytes.

The uptake of both lung surfactant and other particles from the alveolar space plays an essential role in surfactant metabolism, host defense and may be of relevance for targeting drugs into alveolar cells. To better understand the effect of particle size on the uptake by type II pneumocytes, rat type II cells in primary culture were investigated. We observed that inert latex particles of 15 nm were taken up to a much greater extent than bigger particles. No strong size dependency was observed in the range from about 200 to 1000 nm. A similar observation was made with a natural lipid extracted lung surfactant which was taken up to a greater extent when prepared at particles of about 100 nm than a preparation with a particle size range from about 200-2000 nm. Alveolar type II cells take up smaller particles better than larger ones, but the size selectivity is rather limited. These type II cell properties may contribute to a preferential elimination of the smaller particle fractions from the alveolar space.

Animals↗
PubMed1994

Correlation between particle size, in vivo particle persistence, and lung injury.

Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles in the lung and may correlate with adverse pulmonary effects. We investigated such correlations using a model involving TiO2 particles of two particle sizes (20 nm diameter, ultrafine; 250 nm diameter, fine) of the same crystalline structure (anatase). A 12-week inhalation experiment in rats resulted in a similar mass deposition of the two particle types in the lower respiratory tract. The ultrafine particles elicited a persistently high inflammatory reaction in the lungs of the animals compared to the larger-sized particles. In the postexposure period (up to 1 year) retention in the alveolar space per se was not different between fine and ultrafine TiO2. However, the following differences between the particle types were noted: a significantly different total pulmonary retention, both quantitatively (significantly prolonged retention of the ultrafine TiO2) and qualitatively (increased translocation to the pulmonary interstitium and persistence there of the ultrafine TiO2); greater epithelial effects (Type II cell proliferation; occlusion of pores of Kohn) and the beginning of interstitial fibrotic foci with ultrafine TiO2; significant sustained impairment of alveolar macrophage function after ultrafine TiO2 exposure as measured by the clearance of test particles. A correlation between particle surface area and effects was observed. A comparison of the adverse reactions with dosimetric parameters of TiO2 in different lung compartments in the postexposure period showed a correlation of the persistence of effects in both the alveolar and interstitial space with the persistence of particles in the respective compartment.

Administration, Inhalation↗
PubMed1999

Computerized measurement of LDL particle size in human serum. Reproducibility studies and evaluation of LDL particle size in relation to metabolic variables and the occurrence of atherosclerosis.

OBJECTIVES: The main aims of the present research project were to develop and evaluate a new software program for evaluation of LDL particle size applied to the gradient gel electrophoresis methodology without the use of previous ultracentrifugation, and to investigate the relationships among LDL particle size, metabolic variables and atherosclerosis, as measured by ultrasound, in subjects with different degrees of insulin resistance. METHODS: LDL particle size was determined by polyacrylamide gradient gel electrophoresis. RESULTS: Coefficient of variation for between-assay experiments was 0.3% (r = 0.99) for measurement of LDL peak particle size. LDL peak particle size was negatively correlated to serum triglycerides, apolipoprotein B, fasting insulin, BMI and diastolic blood pressure and positively correlated to HDL. Furthermore, subjects with moderate to large plaques in the carotid artery had smaller LDL particles compared to subjects without plaques. CONCLUSIONS: This project resulted in a highly reproducible, computerized method for the analysis of LDL particle size. The data suggest that it is possible to assess LDL particle size in serum without the use of previous ultra-centrifugation. LDL particle size was associated with metabolic variables and the occurrence of moderate to large plaques in the carotid artery.

Apolipoproteins B↗
PubMed1996

Gastrointestinal uptake of biodegradable microparticles: effect of particle size.

PURPOSE: To investigate the effect of microparticle size on gastrointestinal tissue uptake. METHODS: Biodegradable microparticles of various sizes using polylactic polyglycolic acid (50:50) co-polymer (100 nm, 500 nm, 1 micron, and 10 microns) and bovine serum albumin as a model protein were formulated by water-in-oil-in-water emulsion solvent evaporation technique. The uptake of microparticles was studied in rat in situ intestinal loop model and quantitatively analyzed for efficiency of uptake. RESULTS: In general, the efficiency of uptake of 100 nm size particles by the intestinal tissue was 15-250 fold higher compared to larger size microparticles. The efficiency of uptake was dependent on the type of tissue, such as Peyer's patch and non patch as well as on the location of the tissue collected i.e. duodenum or ileum. Depending on the size of microparticles, the Peyer's patch tissue had 2-200 fold higher uptake of particles than the non-patch tissue collected from the same region of the intestine. Histological evaluation of the tissue sections demonstrated that 100 nm particles were diffused throughout the submucosal layers while the larger size nano/microparticles were predominantly localized in the epithelial lining of the tissue. CONCLUSIONS: There is a microparticle size dependent exclusion phenomena in the gastrointestinal mucosal tissue with 100 nm size particles showing significantly greater tissue uptake. This has important implications in designing of nanoparticle-based oral drug delivery systems, such as an oral vaccine system.

Animals↗
PubMed1998

Particle size determination of a flocculated suspension using a light-scattering particle size analyzer.

Microscopy is a useful and direct method for measuring the particle size of a suspension because, in addition to the particle size and size distribution, it provides visual detection of the shape and state of aggregation of the particles in the suspension. However, this method suffers from the shortcomings of being tedious and time consuming. In this study, a light-scattering particle size analyzer was used to determine the particle size and size distribution of a flocculated suspension. The sonication of the sample prior to and during measurement was found to be critical in ensuring that data are representative of the size distribution of the primary particles of the suspension. The light-scattering results were further confirmed by data generated using a polarized light microscope equipped with an image analyzer.

Benzocaine↗
PubMed2000

Particle size determination of a three-component suspension using a laser-scattering particle size distribution analyzer.

In this study, a rapid and accurate particle size determination method using a light-scattering particle size analyzer was developed to measure the particle size and size distribution of a suspension containing three solid components: clotrimazole, triamcinolone, and sarafloxacin, which have different refractive indices. To ensure that data represent the size distribution of the primary particles of the suspension, the optimal sonication prior to and during measurement was determined. It was found that the results obtained using the average relative refractive index (RRI) of the three components agreed with the results obtained using three individual RRIs. In addition, the results from two analysts demonstrated good reproducibility of this method. The size distribution data of the suspension were also compared to those of the bulk drugs. The results showed that the median particle size of this three-component suspension is relatively close to that of clotrimazole, which accounts for 80% of solid particles in the suspension. Furthermore, the results obtained using the light-scattering technique were comparable to those obtained using a polarized light microscope equipped with an image analyzer, indicating acceptable accuracy of this technique.

Anti-Infective Agents↗
PubMed1997

The Surface Chemistry of Hybrid Nanometer-Sized Particles

Nanometer sized Au/TiO2 particles were synthesized by irradiation of a HAuCl4 solution containing colloidal TiO2 with light of wavelength (lambda) >330 nm. The absorption maximum attributed to the surface plasmon band of gold was observed at 530 nm, a red shift of about 10 nm from the position in aqueous solution. The particle size of Au/TiO2 determined by TEM was about 25 nm. The Au clusters are situated on the surface of TiO2 in terms of microcrystallite, which was confirmed by HRTEM, EDS, and XRD. A negative shift of binding energy in the Au 4f7/2 for gold cluster on the surface of TiO2 was found, and the electronic interaction between the metal and the support was discussed.

Journal Article↗
PubMed2001

Investigation of the influence of mean HPMC particle size and number of polymer particles on the release of aspirin from swellable hydrophilic matrix tablets.

The effects of hydroxypropyl methylcellulose (HPMC) of different particle size ranges, size distributions and concentrations on the release behaviour of aspirin from a swellable matrix tablet system were studied. A mean HPMC (Methocel K15M Premium) particle size of 113 microm was identified as a critical threshold in this study. Drug release rate increased markedly when polymer particle size was increased above 113 microm. Release rate was much less sensitive to changes in particle size below 113 microm. Aspirin release mechanism followed first order kinetics where mean HPMC particle size was below 113 microm. Release mechanism deviated from first order kinetics when the mean particle size was above 113 microm. Polymer fractions with similar mean particle size but differing size distribution were also observed to influence drug release rate but not release mechanism. First order release constant K(1) was found to be quantitatively related to the reciprocal of the cube root of both mean polymer particle size and number of polymer particles in the matrix.

Aspirin↗
PubMed1997

Self-selection of dietary protein and energy by broilers grown under a tropical climate: effect of feed particle size on the feed choice.

Broilers, 2 wk of age, that had been previously adapted to energy: protein choice feeding, were offered corn (either ground, cracked, or presented as whole grains) and a protein concentrate (43.7% CP) in mash or pellet form. When corn was fed as whole grains, protein concentrate in the selected diet was significantly higher (35.1%) than with cracked corn (29.3%) or ground corn (29.1%). Presenting the concentrate as pellets resulted in a significantly higher concentration in the diet (32.7%) than when mash concentrate was fed (29.6%). Live BW at 4 and 6 wk of age were not significantly affected by feed texture. However, offering corn as whole grains or concentrate as pellets induced a significant improvement in feed efficiency. Total time to eat larger size particles (whole grains, pelleted concentrate) was significantly less than total time to eat ground corn or mash concentrate. Furthermore, the mean duration of the feeding bouts was two times shorter for whole grains (48 s) than for ground corn (98 s) and for pelleted concentrate (56 s) than for mash concentrate (114 s). Chickens ate whole grains or pellets at a significantly slower rate (number of pecks per second feeding time) than when eating ground corn or mash concentrate. There was a rejection during the first 24 h when the form of the concentrate (mash to pellets) was changed. Full adaptation to the new size of the concentrate required about 3 d.

Analysis of Variance↗
PubMed2005

Surface modification of crosslinked poly(styrene-divinyl benzene) micrometer-sized particles of narrow size distribution by ozonolysis.

Micrometer-sized polystyrene template particles of narrow size distribution were prepared by dispersion polymerization of styrene in 2-methoxyethanol. Uniform micrometer-sized polystyrene/crosslinked poly(styrene-divinyl benzene) composite particles were formed by a single-step swelling process of the template particles with styrene, divinyl benzene and benzoyl peroxide, followed by polymerization at 70 degrees C. Uniform micrometer-sized crosslinked poly(styrene-divinyl benzene) particles of higher surface area were produced by dissolution of the template polystyrene part of the former composite particles with N,N-dimethylformamide. Hydroperoxide conjugated crosslinked poly(styrene-divinyl benzene) particles were produced by ozonolysis of these particles. The effect of ozonolysis conditions, such as exposure time and flow rate of the ozone, on the hydroperoxide conjugation to the crosslinked particles was also studied. Functionalization of the crosslinked poly(styrene-divinyl benzene) particles was performed by graft polymerization of vinylic monomers such as acrylonitrile and chloromethylstyrene on the hydroperoxide conjugated crosslinked particles. This was accomplished by raising the temperature (e.g., 70 degrees C) of deairated acetonitrile dispersions containing the hydroperoxide conjugated particles and the vinylic monomers. The influence of various polymerization parameters on the grafting yield, e.g., monomer concentration, conjugated hydroperoxide concentration, and temperature, was also elucidated.

Journal Article↗
PubMed2005

Trapping force on a finite-sized particle in a dielectrophoretic cage.

The point dipole (PD) model is routinely used for estimating the dielectrophoretic (DEP) force acting on a particle placed in the nonuniform electric fields of dielectrophoresis devices, such as square cages. We show that if the particle size is much smaller than the dielectrophoretic cage size, the PD model accurately approximates the actual DEP force, computed numerically using the Maxwell stress tensor method. However, when the two sizes are comparable, the actual DEP force differs significantly in both magnitude and direction from that given by the PD model.

Journal Article↗