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Effect of drug particle size in ultrasound compacted tablets. Continuum percolation model approach.

The main objective of this work is to study the influence of the drug particle size on the pharmaceutical availability of ultrasound compacted tablets. Inert matrix systems containing different drug particle sizes were prepared using both, an ultrasound-assisted press and a traditional eccentric machine. Potassium chloride was used as drug model and Eudragit RS-PM as matrix forming excipient. The excipient particle size was kept constant. The cross-sectional microphotographs of ultrasound tablets show the existence of a quasi-continuum medium. Keeping constant the drug load, US-tablets showed very similar release rates, whereas for traditional tablets, an increase in the particle size resulted in a clear decrease in the release rate. In these tablets, the excipient forms an almost continuum medium. In an infinite theoretical system of these characteristics, the size of the drug particles will not modify the percolation threshold. The percolation of the excipient in this system can be assimilated to a continuum percolation model. In accordance with the proposed model, a lower influence of the drug particle size on the drug release rate was obtained for the US-tablets in comparison with traditional tablets. This fact can be indicative of the similarity of the drug percolation thresholds in these systems.

Acrylic Resins↗

Lipid emulsions of palmitoylrhizoxin: effects of particle size on blood dispositions of emulsion lipid and incorporated compound in rats.

Emulsion formulations of various particle sizes for the highly lipophilic antitumour agent, RS-1541 (13-O-palmitoylrhizoxin), were prepared using dioctanoyldecanoylglycerol (ODO) as lipids and polyoxyethylene-(60)-hydrogenated castor oil (HCO-60) as a surfactant. These emulsions were evaluated as injectable drug carriers and compared with a colloidal solution. Both in vitro and in vivo after i.v. administration, RS-1541 was distributed into lipoproteins from the colloidal solution. When applied as emulsions of various particle sizes (124-419 nm) in vitro, RS-1541 was retained and stabilized within the emulsions. In the in vivo study, however, retention of RS-1541 in the emulsions after i.v. injection depended on their size. The small-particle emulsions (94-112 nm) resulted in long retention, and the large-particle emulsions (415-474 nm) led to short retention. Lipolysis rates of emulsion particles by lipoprotein lipase also depended on their size, indicating rapid lipolysis for small-particle emulsions (133 nm). However, the lipolysis was not such an extensive one, showing 10-30% release of capric acid from ODO within 6 h. Blood dispositions of capric acids approximately paralleled those of RS-1541 after i.v. injection of various particle size emulsions (130-368 nm) to rats, although relatively rapid eliminations of capric acids compared with RS-1541 were observed for the small-particle size emulsions (130 nm). These results suggest that when injected as emulsion formulations, the highly lipophilic antitumour agent, RS-1541, has behaviour similar to that of the emulsion particles in the body, which is dependent on the size of the latter. Thus, by properly selecting the particle size, lipid emulsions consisting of ODO and HCO-60 are expected to be effective and useful DDS carriers for RS-1541.

Animals↗

Effect of source and particle size of supplemental phosphate on rumen function of steers fed high concentrate diets.

We examined effects of source and particle size of supplemental defluorinated rock phosphate, to meet phosphorus requirements, on rumen function of 195-kg Holstein steers fed high concentrate. Two sources and two particle sizes of each source were evaluated in a 5 X 5 Latin square with 14-day periods. There was no effect of source on ruminal mH [- log (mean (H+)]; however, ruminal mH was higher in animals fed supplements of larger particle size. This effect was also evident when rumen pH versus time curves were integrated below pH 6. Animals fed supplements of larger particle size had less area below pH 6 than those fed supplements of smaller size. Ruminal buffering capacity at pH 7 was affected by diet; however, orthogonal comparisons between treatment means were not significant. Neither source nor particle size of the supplement affected ruminal fluid osmolality, total volatile fatty acid concentration, or fecal starch. Water intake and ruminal dry matter on HyCal supplemented diets; however, there was also a trend toward increasing rumen fluid volume. The net effect was little change of dilution rate of ruminal fluid. This may explain why rumen fermentation was not affected greatly. Conventional phosphate supplements may have potential as rumen buffering agents, but higher levels of feeding should be studied.

Animals↗

Reducing particle size of corn in lactation diets from 1,200 to 400 micrometers improves sow and litter performance.

One hundred primiparous sows were used to determine the effects of particle size of corn in lactation diets on sow and litter performance. The sows were fed a corn-soybean meal-based diet with the corn ground to 1,200, 900, 600, or 400 microns. Particle size of corn had no influence on sow BW or backfat loss (P > .30), subsequent weaning-to-estrus interval (P > .40), or percentage of sows returning to estrus (P > .09). However, ADFI was increased (linear effect, P < .04) as particle size was reduced from 1,200 to 400 microns. Pig survivability was not affected (P > .30) but litter BW gain was increased by 11% when sows were fed diets with 400 vs 1,200 microns corn (linear effect, P < .05). Apparent digestibilities of DM, N, and GE were increased by 5, 7, and 7%, respectively, as particle size was reduced from 1,200 to 400 microns (linear effects, P < .001). Intake of DE was increased 14% (13.7 to 15.6 Mcal/d) as corn particle size was reduced from 1,200 to 400 microns. Intakes of digestible DM and N also were increased (11 and 14%, respectively), whereas fecal excretions of DM and N were decreased by 21 and 31%, respectively (linear effects, P < .001). Reducing particle size increased severity of ulceration and keratinization (nonzero correlations of P < .04 and P < .004, respectively) in the esophageal region of the stomach, although the changes were not associated with reduced sow performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Influence of particle size, antigen load, dose and additional adjuvant on the immune response from antigen loaded PLA microparticles.

Polylactide (PLA) polymer particles entrapping tetanus toxoid (TT) were evaluated in terms of particle size, antigen load, dose and additional adjuvant for achieving high and sustained anti-TT antibody titer from single point intramuscular immunization. Admixture of polymer entrapped TT and alum improved the immune response in comparison to particle-based immunization. High and long lasting antibody titer was achieved upon immunization with 2-8 microm size particles. Microparticles within the size range 50-150 microm elicited very low serum antibody response. Immunization with very small particles (<2 microm) and with intermediate size range particles (10-70 microm) elicited comparable antibody response from single point immunization but lower in comparison to that achieved while immunizing with 2-8 microm size particles. Potentiation of antibody response on immunization of admixture of microparticles and alum was also dependent on particle size. These results indicate the need of optimal particle sizes in micron ranges for improved humoral response from single point immunization. Increasing antigen load on polymer particles was found to have positive influence on generation of antibody titers from particle based immunization. Maximum peak antibody titer of approximately 300 microg/mL was achieved on day 50 upon immunization with particles having highest load of antigen (94 microg/mg of polymer). Increase in dose of polymer entrapped antigen resulted in concomitant increase in peak antibody titers indicating the importance of antigen stability, particle size and load on generating reproducible immune response. Optimization of particle size, antigen load, dose and use of additional adjuvant resulted in high and sustained anti-TT antibody titers over a period of more than 250 days from single point immunization. Serum anti-TT antibody titers from single point immunization of admixrure of PLA particles and alum was comparable with immunization from two divided doses of alum adsorbed TT.

Adjuvants, Immunologic↗

In vivo limestone solubilization in commercial Leghorns: role of dietary calcium level, limestone particle size, in vitro limestone solubility rate, and the calcium status of the hen.

Three experiments were conducted to determine the possible interaction of particle size, in vitro limestone solubility rate, and the Ca status of the hen, respectively, with dietary Ca level and in vivo Ca solubilization in laying hens. The in vivo Ca solubilization in hens was determined by subtracting Ca recovered as limestone in the excreta (by repeated washing) from Ca fed as limestone. Limestones of two different particle sizes [.5 to .8 mm (small) versus 2 to 5 mm (large)] with the same in vitro solubility rates were used in Experiment 1. Limestones of two different in vitro solubility rates (4 versus 10%/15 min in .079 N HCl) with the same particle size in Experiment 2 were assessed for in vivo Ca solubilization. In both experiments, laying hens were fed diets containing graded levels of Ca: 1.5, 3.0, 4.5, and 6.0%. In Experiment 3, hens fed a Ca-deficient (1%) diet for 1 wk were compared with hens fed a diet containing 3.75% Ca to assess in vivo Ca solubilization as influenced by graded dietary Ca levels: 1.5, 3.0, and 4.5% Ca. In vivo Ca solubilization in hens was influenced (P less than .05) by dietary Ca level (inverse relationship), limestone particle size (large particle greater than small particle), and Ca status of hens (Ca-deficient hens greater than normal hens). In vivo Ca solubilization in laying hens, for the particle size tested, was not influenced by in vitro limestone solubility rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influences of preparation conditions on particle size and DNA-loading efficiency for poly(DL-lactic acid-polyethylene glycol) microspheres entrapping free DNA.

Poly-DL-lactic acid-polyethylene glycol (PELA) with different contents and different molecular weight of polyethylene glycol (PEG) was used as a DNA delivery system. DNA-loaded PELA or poly(DL-lactic acid) (PLA) microspheres were prepared by the emulsion evaporation technique, which was based on the water-in-oil-in-water solvent evaporation method. The purpose of the present work was to investigate the factors influencing particle size and DNA loading efficiency for the PELA microspheres containing free DNA. During the preparation process, different conditions were used and the resulting microspheres were characterized by particle size and DNA loading efficiency. Microspheres prepared by PELA with a PEG (molecular weight: 6000 Da) content of 6-10% obtained the highest loading efficiency and smaller particle size among other PELA copolymer and PLA homopolymer. When the solvent of the oil phase was composed of methylene chloride and ethyl acetate (1:1, v/v), the highest loading efficiency and smaller particle size were also obtained for the PELA microspheres. The presence of the surfactant in oil phase influenced both the particle size and loading efficiency. Increasing the concentration of polymer in oil phase resulted in an increase of particle size and loading efficiency for DNA-loaded PELA microspheres. The addition of a hydrophilic polymer into the internal water phase ameliorated the DNA loading efficiency and reduced the particle size. Significant influences of DNA molecular weight and structure on the particle size and loading efficiency were observed. The volume and concentration of the external water phase also influenced the particle size and loading efficiency.

DNA↗

Size analysis of a pressurized metered dose inhaler-delivered suspension formulation by the API Aerosizer time-of-flight aerodynamic particle size analyzer.

Aerosizer time-of-flight (TOF) aerodynamic particle size analyzers (TSI-Amherst, Amherst, MA) are widely used for the rapid assessment of aerosols from a wide variety of drug delivery devices, including pressurized metered dose inhalers (pMDIs). This technique offers significant advantages in terms of rapid measurement times in comparison with the more time-consuming compendial methods such as the cascade impactor or multistage liquid impinger. Particle size analysis takes place by determining the TOF of individual particles following acceleration to supersonic velocity. No drug assay is performed; thus, the resulting size distribution also includes particles that do not contain any medication such as the excipients and surfactant that are present in most pMDI-based formulations. Illustrative data are presented for one particular formulation (Pulmicort: 200 micrograms of budesonide per dose; Astra Draco; Lund, Sweden) and demonstrate that bias from this source can significantly shift the reported particle distribution to finer sizes compared with impactor-based analysis in which direct assay for drug has taken place. In this case, the mass median aerodynamic diameter (MMAD) determined by an Aerosizer-LD was close to 2.4 microns, but was found to be approximately 4 microns using the cascade impactor-based procedure. Such a shift results in an overestimation of the fine particle fraction of the emitted dose, which may lead to misleading conclusions about the therapeutic benefit of a particular drug delivery system when making use of this formulation. TOF aerosol measurement techniques appear to be vulnerable to this type of bias for any suspension formulation in which the drug content is not homogeneously distributed within all particle sizes.

Bronchodilator Agents↗

Respiratory sensitization to diphenyl-methane-4,4'-diisocyanate (MDI) in guinea pigs: impact of particle size on induction and elicitation of response.

The impact of particle size of aerosolized polymeric diphenylmethane-4,4'-diisocyanate (MDI) for the induction and elicitation of respiratory sensitization was evaluated. Four groups of 16 female guinea pigs each received either the vehicle, repeated intradermal (id) injections (3 x 0.3% MDI), one high-level inhalation exposure of 15 min to 135 mg MDI/m(3) air using a small aerosol (MMAD approximately 1.7 microm) or large aerosol (MMAD approximately 3.8 microm). Three weeks later, animals were challenged subsequently with two ramped concentrations of MDI aerosol (average concentrations 16 and 49 mg/m(3) air, each for 15 min) and two different particle sizes, i.e., the MMAD was either approximately 1.6 microm or approximately 5.1 microm for the small- and large-size aerosol, respectively. Respiratory sensitization was assessed by two endpoints: the measurement of respiratory rate, and examination of influx of eosinophilic granulocytes into the mucosa and submucosa of the trachea, bronchi, and lung-associated lymph nodes (LALN). The recruitment of eosinophilic granulocytes into bronchial tissues was subdivided as follows: muscularis mucosae, submucosa, and perivascular. From measurements of respiratory rate, it would appear that guinea pigs sensitized by id injections or by inhalation exposure with the large aerosol tended to display a higher responsiveness than naive controls when challenged with the small aerosol. The recruitment of eosinophilic granulocytes in the bronchial tissue was greater in both inhalation induction groups as compared to the vehicle control. It appears that there was a somewhat greater response in animals sensitized by id injections or by inhalation exposure with the large aerosol and challenged with the small aerosol. Topographically, this difference was apparent only at the bronchial perivascular level and lung-associated lymph nodes (LALN), whereas at the submucosal and muscularis mucosae level the impact on particle size tended to be less pronounced. In summary, this study suggests that a brief, high-level inhalation exposure of MDI aerosol caused a sensitization of bronchial tissues in guinea pigs. The higher sensitization potency of the large aerosol may possibly be related to a dosimetric phenomenon because of the greater fraction of deposition of large particles within the upper respiratory tract. Overall, challenge exposures with this type of irritant aerosol appear to evoke more consistent effects when the MMAD is in the range of approximately 2 rather than approximately 5 microm.

Administration, Inhalation↗

Direct write-out of particle size distribution of inhaled aerosol deposition using a laser scattering method.

We developed a device to measure inhaled aerosol deposition in the lung from the difference in particle size distribution of the aerosol during inspiration and expiration. To measure quantity and size distribution of nebulized aerosol particles directly at the subject's mouth we used a He-Ne gas laser scattering technique. To test the reliability of the instrument, we measured particle size distributions of saline aerosols generated by four kinds of nebulizer and compared the results with those from a Malvern 2600D particle sizer as a standard of comparison. Measured mass median diameters (MMDs) were almost identical by both methods. Aerosol deposition in five normal subjects showed that the deposition fraction of the particles increased the larger the particle sizes inhaled. The data suggest that the newly developed aerosol spectrometer can directly analyze aerosol particle size distribution at the mouth during tidal breathing, and that the instrument is useful for quantitative analysis of aerosol inhaled and of inhaled aerosol deposition.

Aerosols↗

[Influence of wall polymer and preparation process on the particle size and encapsulation of hemoglobin microcapsules].

Methoxypoly (ethylene glycol)- block-poly (DL-lactide) (PELA) microcapsules containing bovine hemoglobin (BHb) were prepared by a W/O/W double emulsion-solvent diffusion process. The P50 and Hill coeffcient were 3466 Pa and 2.4 respectively, which were near to the natural bioactivity of bovine hemoglobin. The results suggested that polymer composition had significant influence on encapsulation efficiency and particle size of microcapsules. The encapsulation efficiency could reach 90% and the particle size 3 - 5 microm when the PELA copolymer containing MPEG 2000 block was used. The encapsulation efficiency and particle size increased with the concentration of PELA. Increasing the concentrations of NaCl in outer aqueous solution resulted in the increase of encapsulation efficiency and the decrease of particle size. As the concentration of stabilizer in outer aqueous solution increased in the range of 10 g/L to 20 g/L, the particle size reduced while encapsulation efficiency was increased, further increase of the stabilizer concentration would decrease encapsulation efficiency. Increasing of primary emulsion stirring rate was advantageous to the improvement of encapsulation efficiency though it had little influence on the particle size. The influence of re-emulsion stirring rate was complicated, which was not apparent in the case of large volume of re-emulsion solution. When the wall polymer and primary emulsion stirring rate were fixed, the encapsulation efficiency decreased as the particle size reduced.

Animals↗

The influence of drug and diluent particle size on the in vitro release of drug from hard gelatin capsules.

The in vitro release of a drug from capsules containing different proportions of controlled particle size fractions of acetylsalicylic acid and lactose, has been assessed in terms of the time for 50% of the drug content of the capsule to be released into solution during a dissolution test (T50), and by a standard disintegration test. In general the two types of test gave closely related responses although some discrepancies existed with certain systems. For capsules containing only the drug, the value of T50 increased as the particle size of the drug decreased. The addition of lactose generally reduced the T50 value, the extent of the reduction showing greater dependence on the proportion of lactose added than its particle size. Capsule formulations containing 80% w/w of lactose had values of T50 which were independent of drug or diluent particle size. Capsule formulations containing lower proportions of lactose usually had an optimum combination of particle size fractions of drug and diluent for maximum drug release. The relationship between drug release and the porosity within the capsule was dependent on the particle size of the drug.

Aspirin↗

Cell tagging with clinically approved iron oxides: feasibility and effect of lipofection, particle size, and surface coating on labeling efficiency.

PURPOSE: To evaluate the effect of lipofection, particle size, and surface coating on labeling efficiency of mammalian cells with superparamagnetic iron oxides (SPIOs). MATERIALS AND METHODS: Institutional Review Board approval was not required. Different human cell lines (lung and breast cancer, fibrosarcoma, leukocytes) were tagged by using carboxydextran-coated SPIOs of various hydrodynamic diameters (17-65 nm) and a dextran-coated iron oxide (150 nm). Cells were incubated with increasing concentrations of iron (0.01-1.00 mg of iron [Fe] per milliliter), including or excluding a transfection medium (TM). Cellular iron uptake was analyzed qualitatively at light and electron microscopy and was quantified at atomic emission spectroscopy. Cell visibility was assessed with gradient- and spin-echo magnetic resonance (MR) imaging. Effects of iron concentration in the medium and of lipofection on cellular SPIO uptake were analyzed with analysis of variance and two-tailed Student t test, respectively. RESULTS: Iron oxide uptake increased in a dose-dependent manner with higher iron concentrations in the medium. The TM significantly increased the iron load of cells (up to 2.6-fold, P < .05). For carboxydextran-coated SPIOs, larger particle size resulted in improved cellular uptake (65 nm, 4.37 microg +/- 0.08 Fe per 100 000 cells; 17 nm, 2.14 microg +/- 0.06 Fe per 100 000 cells; P < .05). Despite larger particle size, dextran-coated iron oxides did not differ from large carboxydextran-coated particles (150 nm, 3.81 microg +/- 0.46 Fe per 100 000 cells; 65 nm, 4.37 microg +/- 0.08 Fe per 100 000 cells; P > .05). As few as 10 000 cells could be detected with clinically available MR techniques by using this approach. CONCLUSION: Lipofection-based cell tagging is a simple method for efficient cell labeling with clinically approved iron oxide-based contrast agents. Large particle size and carboxydextran coating are preferable for cell tagging with endocytosis- and lipofection-based methods.

Cells, Cultured↗

Lipoprotein subclasses and particle sizes and their relationship with coronary artery calcification in men and women with and without type 1 diabetes.

Type 1 diabetes is associated with increased coronary atherosclerosis, especially in women, even though such patients often have an apparently normal lipid profile. We examined whether lipoprotein particle sizes and subclasses differed between type 1 diabetic subjects (n = 194, age 30-55 years) and age- and sex-matched control subjects (n = 195). We examined whether any abnormalities were of similar magnitude in men and women. The relationship of particle size to electron beam computer tomography-defined coronary artery calcification, a measure of atherosclerosis, was also examined. Proton nuclear magnetic resonance (NMR) spectroscopy was used to quantify VLDL, LDL, and HDL subclass levels and average particle size on fasting samples. LDL size and subclass were similar in diabetic and nondiabetic men. In contrast, in women diabetes was associated with less large and more small LDL and a reduced LDL size (mean difference 0.2 nm; P = 0.0009). This greater effect of diabetes on LDL size in women compared with men was significant (P = 0.007). Diabetes was associated with more large and less small HDL and, to a similar degree in both sexes, a higher HDL size (difference of 0.4 nm in men and 0.3 nm in women; both P < 0.0001). There were no definitive abnormalities in VLDL size. In nondiabetic subjects, lower average HDL particle size, lower LDL size, and higher VLDL size were significantly associated with coronary calcification (P = 0.001, 0.02, and 0.04, respectively). Thus the HDL size differences with diabetes would be expected to be antiatherogenic and the LDL size differences pro-atherogenic. However, there was no clear relationship between particle size and calcification in diabetic subjects. We conclude that in the general population NMR spectroscopy-derived particle size reveals important information about the atherogenicity of lipoprotein profile. Type 1 diabetes is associated with differences in NMR-derived particle size, but their pathogenic significance is unclear.

Adult↗

A method for the preparation of polylactic acid microcapsules of controlled particle size and drug loading.

A solvent partition technique for the microencapsulation of hydrocortisone-polylactic acid has been developed for the preparation of microcapsules of controlled particle size distribution and drug loading. The method involves continuous injection of a drug-polymer solution with a syringe infusion pump into flowing mineral oil where microcapsules are formed as the solvent of the drug-polymer is partitioned into the mineral oil. Using preselected syringe needle size and mechanical control of the mineral oil flow rate at the needle tip, microcapsules of consistent particle sizes and desired drug loadings were prepared. Microcapsules of different internal structures were also prepared by varying the solvent system for the drug-polymer preparation. Dissolution studies showed that at the same drug loading, the rate of the percentage drug release increased with decreasing particle size, and that at similar particle size distributions, the rate increased with increasing drug loading. These results indicate that both the particle size distribution, and the drug loading must be controlled in a microencapsulation process to produce microcapsules of controlled drug release rate.

Capsules↗

Effect of particle size and food on gastric residence time of non-disintegrating solids in beagle dogs.

The gastric residence times of various sizes of radio-opaque particles and tablets were measured in beagle dogs by X-ray, both in the fasted state and after a single meal. During the course of the studies, changes in intragastric pH were also monitored with a radiotelemetric pH sensor, the Heidelberg capsule. The gastric residence time increased with increasing particle size and with particles greater than or equal to 5 mm in diameter approached a plateau value both in the fasted state and after feeding. This value was about 7.5 h after feeding and about 1.5 h in the fasted state, and probably corresponded to the occurrence of the interdigestive migratory myoelectric complex (IMMC wave). The pH in the stomach was variable in the fasted state, but an abrupt pH increase (up to pH 6-7) was observed during the emptying of larger tablets. In some instances this high pH in the stomach was maintained until the next IMMC wave occurred. The gastric emptying of larger tablets administered with food was also associated with an abrupt pH increase.

Animals↗

Effect of particle size on the tissue distribution of iodized emulsified fat following intravenous administration.

Three iodinated fat emulsions were tested by intravenous injection to rats: coarse with a mean size of particles of 7 micrometers, fine with a mean size of 1.3 micrometers, and ultrafine with a mean size of 0.7 micrometers. Iodine content analysis and scintigraphy of radioactive iodinated emulsions show important differences. Coarse emulsion is almost entirely fixed in the liver and the lungs; fine emulsion has a higher relative liver fixation; and ultrafine emulsion has a hepatosplenic fixation of short duration. Degradation of contrast medium is slow with coarse emulsion and very fast with ultrafine emulsion which is responsible for the rising iodine concentration in blood. Fine emulsion is a good compromise between excessive pulmonary fixation of coarse emulsion and high iodine peak in the blood after injections of ultrafine emulsion. The dose of 0.2 ml/kg of fine emulsion gives persistent enhancement of hepatic parenchyma without significant toxicity.

Animals↗

Particle size effects in bioleaching of pyrite by acidophilic thermophile Sulfolobus metallicus (BC).

The effect of mineral particle size on the bioleaching of pyrite by the acidophilic thermophile Sulfolobus metallicus was investigated in a batch bioreactor. Decreasing the particle size from a mean diameter of 202 micron (size fraction: 150-180 micron) to a mean diameter of 42.5 micron (size fraction: 25-45 micron) enhanced the bioleaching rate from 0.05 kg m(-3) h(-1) to 0.098 kg m(-3) h(-1). The particle size distribution of the mineral in this range did not influence the morphology and growth kinetics of the cells. The values of specific growth rate (mu) and yield factor (Y) were 0.018-0.025 h(-1) and 0.67x10(11)-1.45x10(11) cells (g iron)(-1), respectively. Decreasing the particle size of the mineral to a mean diameter of 6.40 micron (size fraction <25 micron) adversely influenced the activity of the cells. The presence of fine particles apparently damaged the structure of the cells, resulting in their inability to oxidise pyrite.

Bioreactors↗