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PubMed2002

Solid state 'adsorption' of fine antibiotic powders onto sorbitol: effects of particle size, state of sorbed water and surface free energy characteristics.

A study has been made on the effects of the state of sorbed water, surface free energy characteristics and particle size on the 'adsorption' of fine antibiotic powders (ampicillin and amoxycillin trihydrates, cephalexin monohydrate and erythromycin ethylsuccinate) onto a special type of sorbitol (instant). 'Adsorption' was assessed by sieving before and after mixing, surface free energy characteristics were derived from contact angle measurements and state of sorbed water from sorption/desorption isotherms at different relative humidity, at 25 and 45 degrees C. It was found that sorbed water was externally located on sorbitol and erythromycin ethylsuccinate and internally on ampicillin, amoxycillin trihydrates and on cephalexin monohydrate, but in a different way of association as strongly bound hydrate and loosely bound hydrate water (reversible and exothermic for the latter). Erythromycin, with the highest interfacial energy value, resulted in greater extent of 'adsorption' than cephalexin of similar particle size, which had the lowest interfacial energy. The presence of sorbed water increased the 'adsorption' of ampicillin and amoxycillin trihydrates due to the contribution of capillary forces and due to their ability of hydrogen bonding at plactisized regions of sorbitol with higher moisture content and molecular mobility. The plactisizing effect of water sorbed on sorbitol is demonstrated by a logarithmic decrease of the yield pressure/elastic recovery ratio. The 'adsorption' of the low interfacial energy cephalexin monohydrate did not increase with the presence of water sorbed on sorbitol, presumably due to the lack of intermolecular hydrogen bonding ability, while 'adsorption' of erythromycin ethylsuccinate decreased, probably due to masking of the interparticle forces (van der Waal and electrostatic).

Adsorption↗

PubMed1993

Particle size effect of metastable calcium phosphates on crushing strength of self-setting bioactive calcium phosphate cement.

The resistance to crushing after a self-setting bioactive calcium phosphate cement, consisting of various particle sizes of tetracalcium phosphate (TECP), dicalcium phosphate dihydrate (DCPD) and hydroxyapatite (HAP), had hardened was tested after setting at 37 degrees C, 100% RH. X-ray diffraction suggested that the cement containing fine particles of DCPD and TECP was completely transformed to HAP, but that containing larger particles was not. Since particle size of both DCPD and TECP affected the dissolution rate, the crystal growth of HAP during cement formation depended on the specific surface area (Sw) of the raw materials. The crushing strength of the cement after hardening increased with an increase of its Sw.

Bone Cements↗

PubMed1996

Assessment of particle size distributions in workers' aerosol exposures.

A full description of the regional dosimetry of inhaled workplace aerosols requires information about the particle aerodynamic size distributions of inhaled aerosols for appropriate health-related species. Therefore, since the late 1970s, interest has risen in how to assess workers' aerosol exposures in terms of particle fractions which may be inhaled and penetrate down to different parts of the human respiratory tract. The personal inhalable dust spectrometer (PIDS) was proposed as a versatile sampling instrument for assessing workers' exposures along these lines. Raw data from this cascade impactor-based instrument are obtained initially in terms of discrete particulate masses collected on the individual impactor stages. Recovery of the desired particle size distribution is difficult because the mathematical inversion problem is 'ill-posed' (i.e., there are many possible solutions that would be consistent with the observed masses). However, a routine has been developed that involves considerations of the detailed deposition characteristics of the impactor stages, measurement errors and a priori assumptions about the shape of the expected particle size distribution (e.g., log-normal). These differ from other such routines in that account is taken not only of aerosol deposited at the impactor stages but also that collected inside the entry system. Hence the final result covers the whole inhalable range, for particles up to and exceeding 100 microns in aerodynamic diameter. The PIDS has recently been used in studies in several industries to examine inhalable particle size distributions for individual exposed workers. This paper considers the results of such studies, and discusses how they may be used to provide information not only about the inhalable, thoracic and respirable fractions identified in the latest particle size-selective sampling criteria (upon which it is expected that future aerosol standards will be based), but also other health-related fractions that may be defined numerically (including, for example, alveolar deposition fractions for workers with different breathing patterns relevant to the type of work undertaken).

Aerosols↗

PubMed2000

Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size.

The efficacy of novel cancer therapeutics has been hampered by the ability to deliver these agents to the tumor at effective concentrations. Liposomes have been used as a method to overcome some delivery issues and, in combination with hyperthermia, have been shown to increase drug delivery to tumors. Particle size has been shown to affect the delivery of liposomes, but it is not known how hyperthermia affects size dependence. This study investigates the effect of hyperthermia (42 degrees C) on the extravasation of different sized nanoparticles (albumin; 100-, 200-, and 400-nm liposomes) from tumor microvasculature in a human tumor (SKOV-3 ovarian carcinoma) xenograft grown in mouse window chambers. In this model (at 34 degrees C), no liposomes were able to extravasate into the tumor interstitium. Hyperthermia enabled liposome extravasation of all sizes. The magnitude of hyperthermia-induced extravasation was inversely proportional to particle size. Thus, at normothermia (34 degrees C), the pore cutoff size for this model was between 7 and 100 nm (e.g., liposomes did not extravasate). At 42 degrees C, the pore cutoff size was increased to >400 nm, allowing all nanoparticles tested to be delivered to the tumor interstitium to some degree. With hyperthermia, the 100-nm liposome experienced the largest relative increase in extravasation from tumor vasculature. Hyperthermia did not enable extravasation of 100-nm liposomes from normal vasculature, potentially allowing for tumor-specific delivery. These experiments indicate that hyperthermia can enable and augment liposomal drug delivery to tumors and potentially help target liposomes specifically to tumors.

Albumins↗

PubMed2002

Dynamic behavior of suspended pollutants and particle size distribution in highway runoff.

Continuous runoff quality monitoring was conducted for one month at urban highway drainage with an area of 8.4 ha. Dynamic change of suspended solids and heavy metal concentrations were investigated during first flush periods, taking the particle size distribution into consideration. Except for Pb, the concentrations of TSS and heavy metals in runoff were within the range of the EMC reported in recent highway runoff research. Particle-bound heavy metals (Zn, Pb, and Cu) accounted for more significant pollutant loads than soluble fractions. Their content decreased with increasing total SS concentration in runoff samples. The results of particle size distribution (PSD) analysis of runoff samples indicate that high TSS concentration samples contained coarser particles. Based on the PSD results, a stepwise wash-off phenomenon of TSS under varying runoff rate conditions was explained by the different washoff behavior of fine (< 20 microm) and coarser particles.

Environmental Monitoring↗

PubMed1990

[Study of crystalline drugs by means of a polarizing microscope. XI. Analysis of the particle size distribution of a principle agent in a trituration of phenytoin].

By the immersion method with a polarizing microscope a principle agent phenytoin was identified from its 10 times trituration containing vehicles such as lactose and starch. A particle size distribution of phenytoin crystals in its trituration was determined by observing one of the habit parameters b from all the detectable particles of phenytoin under a microscope in a suspension of an immersion oil, nD: 1.555, in which phenytoin crystals having key refractive indexes, n1: 1.606, n2: 1.631, were clearly detectable from other vehicles. By the similarity of crystal habits in the same lot the particle size distribution of phenytoin crystals in its trituration was calculated from the values of observed parameter b and average values of habit coefficients, T(square root of ab/c): 2.004, L(b/a): 2.545, which were obtained from some previously identified phenytoin crystals.

Crystallization↗

PubMed1997

Fractional esterification rate of cholesterol in high density lipoprotein (HDL) can predict the particle size of low density lipoprotein and HDL in patients with coronary heart disease.

Fractional esterification rate of cholesterol in high density lipoprotein (HDL) (FER[HDL]) can predict the size distribution and physicochemical characteristics of HDL in plasma. In the present study, we investigated the correlation of FER(HDL) with the particle size of low density lipoprotein (LDL) (LDL-size) in 111 patients (81 males and 30 females) with coronary heart disease (CHD). The correlations of FER(HDL) and LDL-size with conventional lipid and lipoprotein parameters were also studied. FER(HDL) was closely associated with LDL-size (males: r = -0.618, females: r = -0.629, P < 0.001). Plasma levels of TG, HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C) and apo B were also associated with LDL-size in male CHD patients (r = -0.534, 0.314, 0.358, and -0.482, P < 0.01 or 0.001), while plasma levels of TG and apo B were associated with LDL-size in female patients (r = -0.350 and -0.348, P < 0.05). In a stepwise multiple regression analysis, FER(HDL) alone accounted for 38 and 40% of the variability in LDL-size in male and female CHD patients, respectively. Other parameters accounted for an additional 6-10%. With respect to the relation between FER(HDL) and HDL subfractions, FER(HDL) related only to HDL2-C (males: r = -0.640, females: r = -0.652, P < 0.001). This result suggests that FER(HDL) is better able to predict the presence (or absence) of large HDL, rather than that of small HDL. All these data taken together, suggest that FER(HDL) is a useful tool to predict the particle size of both LDL and HDL, even in CHD patients.

Aged↗

PubMed2003

Biodistribution of 131I-BSA loaded gelatin microspheres after peroral application to BALB/c mice--particle size study.

Biodistribution studies of radiolabelled 131I-BSA loaded gelatin microspheres were carried out on BALB/c mice after peroral administration. To two groups, radiolabelled 131I-BSA gelatin microspheres of different particle size, 1.2 +/- 1.1 microm and 7.0 +/- 1.2 microm, were administered orally. To the control group, a solution of 131I-BSA was administered orally as well. Biodistribution was followed periodically within 15 days as the percent of total radioactivity present in the stomach and small intestine with Peyer's patches and mesentery, in colon with Peyer's patches, appendix and mesentery, in liver, spleen, blood, kidney, lungs and heart. Preliminary in vitro biodegradation and drug release studies confirmed the potential of gelatin microspheres to protect the antigen of interest from enzymatic degradation in the gut, and to release it in a controlled manner. The biodistribution data confirmed that particle uptake into Peyer's patches and passage to the liver and spleen via the mesentery lymph supply and nodes increased with decreasing particle size.

Administration, Oral↗

PubMed2004

Bidisperse electrorheological fluids using hydrolyzed styrene-acrylonitrile copolymer particles: synergistic effect of mixed particle size.

Monodisperse micron-sized styrene-acrylonitrile copolymer (SAN) particles with three different sizes (about 5, 10, and 15 microm) were prepared by a two-step seeded polymerization and used for a study of bidisperse electrorheological (ER) suspensions. The effect of the particle size and the size-mixing fraction on ER properties was studied with varying the size of these monodisperse copolymer particles. When the two particle sizes were mixed, the suspension generally showed a decrease in the shear yield stress, reaching a minimum value. However, a bidisperse ER suspension of large particles containing a small fraction of fine particles showed an interesting synergy effect of size mixing on ER response, giving enhanced yield stresses over the other size-mixing fractions. This synergistic ER suspension also showed a great increase in the viscoelastic property. The current density of suspensions was maximum at the synergistic bidisperse suspension. This synergy effect in a particular bidisperse suspension was investigated in view of the structure model consideration and was concluded to be due to a close packing and a peculiar structural ordering at an optimum size ratio and mixing fraction.

Journal Article↗

PubMed2003

Influence of the metering chamber volume and actuator design on the aerodynamic particle size of a metered dose inhaler.

Presented in this work are the results of a study designed to investigate the impact of the valve metering chamber volume and actuator design on the aerodynamic particle size distribution (PSD) of a suspension metered dose inhaler (MDI) containing propellant HFA-227. It was hypothesized that the valve metering volume and the actuator design in the MDI could influence the PSD of the emitted dose since it would affect the aerosol spray dynamics. The PSD results from this study, measured using cascade impaction, revealed that samples containing an actuator intended for oral delivery (rectangular mouthpiece and orifice diameter of approximately 0.5 mm) produced a higher fine particle dose (FPD) than those containing an actuator intended for nasal delivery (circular nosetip and orifice diameter of approximately 1 mm). In addition, the drug PSD profile was shown to be more sensitive to differences in the particle size of the suspended material when the oral actuator was used compared to when the nasal actuator was used. The valve metering chamber (25 vs. 63 microL volume) did not appear to have a major effect on the product aerodynamic PSD or the droplet size. These results demonstrate the importance of actuator design and orifice size in determining the aerodynamic PSD of an MDI.

Administration, Intranasal↗

PubMed1990

Pulmonary delivery of peptide drugs: effect of particle size on bioavailability of leuprolide acetate in healthy male volunteers.

Leuprolide acetate, a nonapeptide with potent luteinizing hormone releasing hormone (LHRH) agonist activity, has low oral bioavailability. Unique aerosols of leuprolide acetate were developed and particle size distribution studies were carried out. A light scattering method (Malvern Model 2600c) was compared to the impaction method (Andersen Sampler) for measuring size distribution. Results showed the Malvern method to be comparable to the impaction method with the Malvern being faster and easier to use. Absolute bioavailability of leuprolide acetate in healthy human male volunteers ranged from 4% to 18% and agreed well with particle size data. Bioavailability corrected for respirable fraction ranged from 35% to 55%, indicating that the pulmonary route may have high potential for systemic delivery of this peptide.

Adult↗

PubMed2005

Association of low-density lipoprotein particle size distribution and cardiovascular risk factors in children.

AIM: The objective of this study was to investigate whether the presence of small, dense lipoproteins, which are thought to be related to the metabolic syndrome caused by insulin resistance, can be predicted by routine serum lipid profiling. METHODS: The relationship between low-density lipoprotein (LDL) particle size and serum lipid levels was analysed in 284 school children (148 boys and 136 girls), aged 7 to 13 y old. LDL particle size was determined by gradient gel electrophoresis. RESULTS: The LDL particle diameter was significantly correlated with the serum levels of high-density lipoprotein cholesterol (HDL-C) (r = - 0.437, p < 0.001) and triglycerides (TG) (r = -0.432, p < 0.001), and with the atherogenic index (AI) [total cholesterol/ HDL-C] (r = -0.450, p < 0.001), while only weak correlations were observed with the serum levels of total cholesterol, apolipoprotein Al and apolipoprotein B. No significant relationship was observed between LDL particle diameter and the serum LDL-C level. CONCLUSION: The presence of small, dense LDL as a metabolic marker of lifestyle-related diseases in children seems to be reflected by a serum lipid profile characterized by an elevation in TG, a reduction in HDL-C, and a raised AI.

Adolescent↗

PubMed2003

Influence of the storage orientation on the aerodynamic particle size of a suspension metered dose inhaler containing propellant HFA-227.

Presented in this work are the results of a study designed to investigate the impact of the storage position on the particle size distribution (PSD) of a steroid suspension metered dose inhaler (MDI) containing propellant HFA-227. It was hypothesized that the orientation of MDI samples upon storage could influence the PSD of the emitted dose, since it determines the amount of contact the liquid formulation has with the valve and therefore the quantity of nonvolatile leachable materials from the valve components that may enter the product and potentially impact the aerosol spray dynamics. Samples stored in the valve down orientation (i.e., complete contact of the liquid formulation with the valve) showed a higher level of leachables compared to those samples stored valve up (i.e., minimal contact of the formulation with the valve). The valve down samples were found to produce larger particles in the emitted aerosol spray using both cascade impaction, the preferred method of regulatory submission, as well as laser diffraction. It was postulated that the larger particle size of the inverted samples was attributed to its higher levels of leachables. Based on our findings, it is recommended that in order to set appropriate controls on the product PSD, the storage orientation of the product will need to be considered.

Adsorption↗

PubMed1984

Concentration and particle size distribution in smoke from marijuana cigarettes with different delta 9-tetrahydrocannabinol content.

Particle size and mass concentration are important determinants of site and quantity of respiratory tract deposition of aerosols. Particle concentrations and size distributions of smoke from marijuana cigarettes with different concentrations (as measured in the marijuana leaf) of delta 9-tetrahydrocannabinol (delta 9-THC) were measured using a single particle aerodynamic relaxation time (SPART) analyzer. The SPART analyzer measures aerodynamic diameter of single suspended particles at a rate of 3000/min. Cigarettes were smoked using a 35-cc, 2-sec puffing device attached to a diluter; dilution and analysis were completed within 4 sec of puff generation. The size distribution of smoke from all marijuana cigarettes was similar to that for tobacco cigarettes, ranging from 0.35 to 0.43 micron (count median aerodynamic diameter). The particle number and mass concentration increased as delta 9-THC concentration increased, being, respectively, 2.2- and 3.8-fold higher in the marijuana cigarette leaf with highest delta 9-THC concentration compared to the placebo marijuana cigarette. These data indicate the need for quantitative comparisons of other potentially toxic constituents in marijuana cigarettes of different delta 9-THC concentrations.

Cannabis↗

PubMed2000

Lipoprotein correlates of LDL particle size.

Correlations of low-density lipoprotein (LDL) predominant particle diameters (PPD) were investigated in samples taken from the San Antonio Family Heart Study. A frequency histogram showed LDL PPD occurs in at least two distinct modes, at about 25.5 and 26.9 nm, with the nadir at about 26.2 nm. Triglyceride (TG) concentrations were strongly correlated with LDL PPD, accounting for nearly 50% of the variation. However, examination of the relationship between TG concentrations and LDL PPD showed considerable overlap of the two LDL size categories for samples having intermediate levels of TG (1-3 mmol/l). In order to examine the factors associated with particle size variation within this region of overlap, 163 pairs of samples, which contrasted peak particle diameters, were matched for TG concentrations and for sex and age. In this matched set, LDL-related measures (i.e. LDL-C, apoB, apoE, and TG concentrations) did not differ. However, several high-density lipoprotein (HDL) measures were significantly related to the LDL particle size category. This category predicted a substantial proportion of variation in HDL-C (9.7%) and apoAI (7.5%) concentrations, and in HDL size distributions of cholesterol (13.6%) and apoAI (10.3%). Other traits related to insulin resistance syndrome (IRS) (glucose and insulin concentrations, blood pressure, and adiposity measures) were tested for association with the LDL size category. None of these traits were related to LDL size after adjusting for TG, except fasting and postchallenge glucose concentrations which showed modest correlations (P-values were 0.02 and 0.05, respectively). The data suggest that in addition to the strong effects of TG, there is also an aspect of LDL particle size variation that is strongly associated with variation in HDL concentration and particle size distribution, perhaps reflecting common metabolic determinants of lipoprotein size.

Adult↗

PubMed2004

Particle size distribution of food boluses after mastication of six natural foods.

There is a large variability between and among individuals in the physiology of mastication, but it is not known whether this produces a similar variability in the particle sizes of food boluses at the end of the chewing process. Food boluses obtained just before swallowing were analyzed in ten subjects (aged 36.7 +/- 9.5 yrs) with normal dentition. Food samples of 3 nuts (peanut, almond, pistachio) and 3 vegetables (cauliflower, radish, and carrot) were chewed and expectorated after self-estimated complete mastication. Measurements with sieving and laser diffraction methods indicated that particles were much larger in vegetables than in nuts. Particle size distributions were similar among nuts and among vegetables. Surprisingly, no inter-individual variability was observed in the particle distributions for the 6 foods, although several sequence variables differed markedly. A need for a bolus to be prepared with a precisely determined texture before it can be swallowed may explain the inter-subject variability of the masticatory function.

Deglutition↗

PubMed2001

Effects of corn particle size and source on performance of lactating cows fed direct-cut grass-legume forage.

We conducted two experiments to evaluate the effects of corn supplementation, source of corn, and corn particle size on performance and nutrient utilization of lactating dairy cows. In experiment 1, treatments were 1) direct-cut grass-legume forage without supplement, 2) direct-cut forage plus 10 kg DM of ground dry shelled corn-based concentrate, and 3) direct-cut forage plus 10 kg DM of coarsely ground high moisture ear corn-based concentrate. In experiment 2, treatments were 1) direct-cut grass-legume forage plus 10 kg DM of ground dry shelled corn-based concentrate, 2) direct-cut forage plus 10 kg DM of coarsely ground high moisture ear corn-based concentrate, and 3) direct-cut forage plus 10 kg of DM finely ground high moisture ear corn-based concentrate. Both experiments were designed as 3 x 3 Latin squares replicated three times. In experiment 1, yields of milk and milk protein increased with concentrate supplementation, but were not affected by source of corn. Solids-corrected milk yield tended to increase with grain supplementation. Dry matter intake increased with concentrate supplementation, but was not affected by source of corn or corn particle size. Corn supplements decreased ruminal pH and acetate to propionate ratio and increased ruminal propionate concentration. Grain supplements reduced ruminal ammonia concentration, increased concentration of urine allantoin, and increased the urinary allantoin to creatinine ratio. In the second study, fine grinding of high moisture corn reduced fecal starch plus free glucose levels and tended to increase its apparent digestibility. In both experiments, starch plus free glucose intake was higher on the diets with dry corn, but its utilization was not affected by source of corn.

Animal Feed↗

PubMed2000

In-line moisture measurement during granulation with a four-wavelength near infrared sensor: an evaluation of particle size and binder effects.

Factors affecting in-line near infrared (NIR) moisture measurement with a four-wavelength sensor were evaluated (choice of binder used in granulation liquid and the increase in particle size). An entire NIR spectrum is not necessary for the measurement of water, and often the use of only a few NIR wavelengths around the water band enables reliable and high-speed detection of moisture. Glass ballotini and microcrystalline cellulose (MCC) were used as model test materials. The binders studied were poly[1-(2-oxo-1-pyrrolidinyl)ethylene] (PVP) and gelatin. Full off-line NIR spectra of test materials at different levels of binder solutions were measured. The major spectral features for both the binders were bands around 1700 nm (first overtones CH related stretches) and 2200 nm (combination bands). Gelatin also had an NH band around 1500 nm (first overtones of NH stretches) and combination bands at about 2050 nm. Particle size effects were observed as an increase in spectra baseline. All these factors should be considered when choosing NIR wavelengths used for detection of water with a fixed wavelength set-up. A robust calibration model enables the development of in-process control of wet granulation processes.

Calibration↗