Modeling weight variability in a pan coating process using Monte Carlo simulations

The primary objective of the current study was to investigate process variables affecting weight gain mass coating variability (CV _m) in pan coating devices using novel video-imaging techniques and Monte Carlo simulations. Experimental information such as the tablet location, circulation time distribution, velocity distribution, projected surface area, and spray dynamics was the main input to the simulations. The data on the dynamics of tablet movement were obtained using novel video-imaging methods. The effects of pan speed, pan loading, tablet size, coating time, spray flux distribution, and spray area and shape were investigated. CV _m was found to be inversely proportional to the square root of coating time. The spray shape was not found to affect the CV _m of the process significantly, but an increase in the spray area led to lower CV _ms. Coating experiments were conducted to verify the predictions from the Monte Carlo simulations, and the trends predicted from the model were in good agreement. It was observed that the Monte Carlo simulations underpredicted CV _ms in comparison to the experiments. The model developed can provide a basis for adjustments in process parameters required during scale-up operations and can be useful in predicting the process changes that are needed to achieve the same CV _m when a variable is altered.     

The entrainment of sediments by the turbulent flow of water

This paper attempts to clarify the role of fluid turbulence in the entrainment process of particles from the flat bed of an alluvial channel. A 6 mm diameter sphere, placed in an array of similar particles on the bed of a laboratory flume, was connected to a 3-component force transducer. Dynamic measurements of longitudinal, lift and lateral force components were made with the particle at a number of positions above the bed. Detailed measurements of velocity and turbulence were also made. The velocity and force spectral measurements showed similarities in the longitudinal (streamwise) direction but the lift force component spectra were significantly different.An analytical model of the entrainment process is proposed, in which the impulse required to lift a sediment particle from the channel bed may be calculated. The experimental data has been used to evaluate the constants in the analytical expressions, and a relationship between the forces and turbulence intensity established. The analysis shows that the impulse required to entrain a particle may be expressed as a function of a dimensionless entrainment parameter, the turbulence intensity, and the initial angle of repose of the particle.     

Angular Circulation Speed of Tablets in a Vibratory Tablet Coating Pan

In this work, a single tablet model and a discrete element method (DEM) computer simulation are developed to obtain the angular circulation speed of tablets in a vibratory tablet coating pan for range of vibration frequencies and amplitudes. The models identify three important dimensionless parameters that influence the speed of the tablets: the dimensionless amplitude ratio (a/R), the Froude number (aω ²/g), and the tablet–wall friction coefficient, where a is the peak vibration amplitude at the drum center, ω is the vibration angular frequency, R is the drum radius, and g is the acceleration due to gravity. The models predict that the angular circulation speed of tablets increases with an increase in each of these parameters. The rate of increase in the angular circulation speed is observed to decrease for larger values of a/R. The angular circulation speed reaches an asymptote beyond a tablet–wall friction coefficient value of about 0.4. Furthermore, it is found that the Froude number should be greater than one for the tablets to start circulating. The angular circulation speed increases as Froude number increases but then does not change significantly at larger values of the Froude number. Period doubling, where the motion of the bed is repeated every two cycles, occurs at a Froude number larger than five. The single tablet model, although much simpler than the DEM model, is able to predict the maximum circulation speed (the limiting case for a large value of tablet–wall friction coefficient) as well as the transition to period doubling.     

Movement of surface markers along the pinocytotic pseudopodia ofAmoeba proteus

Summary The movement of latex beads over pinocytotic pseudopodia produced byAmoeba proteus was recorded in the presence of 117.65 mM EGTA as an inducer of pinocytosis. The results show that all particles flow in the direction of pseudopodial growth, with a slightly higher velocity than the advancing frontal edge. This means that markers are removed from the base of a pinocytotic pseudopodium and gradually approach the pseudopodium tip. Two particles on the surface of the same pseudopodium can move at the same rate or differ slightly in the velocity of their forward flow. A bead can move even if another blocks the channel orifice. Retrograde particle movement has never been observed. Whether all latex spheres bound to pinocytotic pseudopodia flow with the laterally mobile plasma membrane fraction, which slides over submembranous contractile layer, or whether the whole cortical complex, the actin network and the plasma membrane, move together towards the invagination site is discussed.     

Ultrasound Transmission Technique as a Potential Tool for Physical Evaluation of Monolithic Matrix Tablets

The aim of this study was to investigate the effects of tablet porosity and particle size fraction of compacted Starch acetate powders, with and without model drug caffeine, on acoustic properties of tablets. The ultrasound velocity was determined from the transmission measurements. Tablets of starch acetate (SA DS 2.7) powder with two particle size fractions of 0–53 and 0–710 μm were compressed with a compaction simulator. Porosities of tablets varied in the range from 12% to 43% for both particle size fractions. Strong associations were found between the ultrasound velocity and physical properties of the tablets such as porosity and particle size fraction. Interestingly, ultrasound velocity was practically insensitive to inclusion of the model drug caffeine with the concentrations used. Based on this study ultrasound transmission method is a potential non-destructive tool for studying structural changes of tablets and other solid dosage forms.     

Electrical Sizing of Particles in Suspensions: I. Theory

The processes involved during the passage of a suspended particle through a small cylindrical orifice across which exists an electric field are considered in detail. Expressions are derived for the resulting change in current in terms of the ratios of particle to orifice volume and particle to suspending fluid resistivity, and particle shape. Graphs are presented of the electric field and of the fluid velocity as functions of position within the orifice, and of the shape factor of spheroids as a function of their axial ratio and orientation in the electric field. The effects of the electric and hydrodynamic fields on the orientation of nonspherical particles and on the deformation of nonrigid spheres is treated, and the migration of particles towards the orifice axis is discussed. Oscillograms of current pulses produced by rigid, nonconducting spheres in various orifices are shown and compared with the theoretical predictions.     

Size and shape determination of fixed chylomicrons and emulsions with fluid or solid surfaces by three-dimensional analysis of shadows

Chylomicrons and chylomicron-sized emulsions are spherical particles in suspension but their shape and apparent size may be distorted by electron microscopy processing. To assess adsorption to grids, flattening, and shrinkage, chylomicrons and emulsions were fixed with osmium tetroxide and together with polystyrene beads were shadowed with platinum. Vertical profiles projected from particle shadows indicated that the chylomicrons and emulsions were slightly shrunken, slightly truncated, oblate spheroids while the polystyrene beads were spheres. Particle diameters were corrected by assuming that volumes of oblate spheroids on the grid surface were equal to volumes of spheres in the original lipid suspension. Because of the compensating effects of shrinkage (decreases diameter) and flattening (increases diameter) the differences between the means of measured diameters and corrected diameters were less than or equal to 5%.     

Local and average gloss from flat-faced sodium chloride tablets

The purpose of this study was to detect local gloss and surface structure changes of sodium chloride tablets. The changes in surface structure were reflected by gloss variation, which was measured using a diffractive optical element-based gloss-meter (DOG). By scanning a surface area, we constructed a 2-dimensional gloss map that characterized the tablet’s surface structure. The gloss variation results were compared with scanning electron microscopy (SEM) images and average surface roughness values that were measured by conventional diamond stylus profilometry. The profilometry data showed a decrease in tablet surface roughness as a function of compression force. In general, a smoother surface contributes to higher average gloss values. The average gloss values for this material, in contrast, showed a decrease as a function of the compression force. The sequence of particle fragmentation and deformation together with crack formation in sodium chloride particles resulted in a loss of gloss for single sodium chloride particles at the tablet surfaces, which could be detected by the DOG. These results were supported by the SEM images. The results show that detailed information regarding tablets’ surface structure changes can be obtained by detection of local gloss variation and average gloss. Published: January 13, 2006     

Terminal settling velocity and physical properties of pollen grains in still air

Numerical simulation of wind pollination requires knowledge of pollen grain physical parameters such as size, shape factor, bulk density, and terminal settling velocity. The pollen grain parameters for Japanese cedar, Japanese cypress, short ragweed, Japanese black pine, and Japanese red pine were assessed for dry condition. Terminal settling velocities of dry pollen grains in still air were measured using image analysis of scattered light tracks in a dark settling tube. The measurement system was validated by comparing results to those obtained for standard microspheres of known size and density. Dry pollen grain shape factors indicate the resemblance of particles to spheres, except for pine pollen. Circularity factors of dry pine pollen grains were 0.90–0.86, suggesting more irregular shape than those of other pollen species. Aerodynamic diameters of dry pollen grains were calculated based on the terminal settling velocity. Aerodynamic diameters of Japanese cedar, Japanese cypress, and short ragweed closely resembled the projected area equivalent diameters, suggesting that aerodynamic behaviors of these pollen grains can be managed simply in numerical simulations. However, aerodynamic diameters of dry pine pollen grains were nearly 30 % smaller than projected area equivalent diameters. Sacci on dry pine pollen can reduce the terminal settling velocity through low density and shape effects attributed to their non-sphericity, engendering aerodynamic diameter smaller by more than 10 µm from area equivalent diameters.     

Bed expansion characteristics of liquid fluidized particles with attached microbial growth

The bed expansion behavior of liquid fluidized beds of char particles coated with attached microbial growth of denitrifying mixed bacteria was studied experimentally to obtain an expression that relates the bed expansion to the liquid velocity for liquid fluidized beds of composite particles. As for liquid beds of homogeneous spheres, the bed voidage and the liquid velocity v_z for liquid fluidized beds of biomass-coated particles were found to be related as v_z/V_i = ∈ⁿ. The correlations recommended by Richardson and Zaki for homogeneous spheres are found to be satisfactory for the estimation of the constant n, but only under certain conditions for the constant V_i.     

Optimization of solid state fermentation of sugar cane by aspergillus niger considering particles size effect

The protein enrichment of sugar cane by solid state fermentation employing Aspergillus niger was optimized in a packed bed column using a two Factor Central Composit Design α = 2, considering as independent factors the particles diameter corresponding to different times of grinding for a sample and the air flow rate. It was significative for the air flow rate (optimum 4.34 VKgM) and the particle diameter (optimum 0.136 cm). The average particle size distribution, shape factor, specific surface, volume-surface mean diameter, number of particles, real and apparent density and hollowness for the different times of grinding were determined, in order to characterize the samples.     

The sedimentation potential and the boycott effect

The sedimentation potential or the Dorn effect occurs when heavy particles fall in a liquid. An electrode near the bottom of the vessel acquires a potential difference with respect to another identical electrode placed near the upper surface of the solution. The Boycott phenomenon enhances the sedimentation in inclined vessels. In this investigation, fixed erythrocytes at 2-3% concentration were studied. The shapes include discs, oblate spheroids, spheres and spindles. From the sedimentation potentials, the zeta potentials were calculated and compared with those determined by laser Doppler velocity. By using a technique of reduced variables, it is shown that all of the data could be placed on a single curve, combining particle flexibility, shape, concentration and angle of inclination.     

Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel^® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.Key words: content uniformity, homogeneity, low-dose API, powder coating, ultrasound     

Functionality comparison of 3 classes of superdisintegrants in promoting aspirin tablet disintegration and dissolution

The aims of this study are (1) to compare the disintegration efficiency, and (2) to develop a discriminating test model for the 3 classes of superdisintegrants represented by Ac-Di-Sol, Primojel, and Polyplasdone XL10. Using a digital video camera to examine the disintegration process of tablets containing the same wt/wt percentage concentration of the disintegrants, Ac-Di-Sol was found to disintegrate tablets rapidly into apparently primary particles; Primojel also apparently disintegrated tablets into primary particles but more slowly; Polyplasdone XL10 disintegrated tablets rapidly but into larger masses of aggregated particles. The differences in the size distribution generated in the disintegrated tablets likely contribute to the drug dissolution rate differences found for aspirin tablets with similar disintegration rates. The aspirin tablet matrix is proposed as a model formulation for disintegrant efficiency comparison and performance consistency testing for quality control purposes. Published: December 12, 2005     

Chemometric evaluation of pharmaceutical properties of antipyrine granules by near-infrared spectroscopy

The purpose of this research was to apply near-infrared (NIR) spectroscopy with chemometrics to predict the change of pharmaceutical properties of antipyrine granules during granulation by regulation of the amount of water added. The various kinds of granules (mean particle size, 70–750 μm) were obtained from the powder mixture (1 g of antipyrine, 6 g of hydroxypropylcellulose, 140 g of lactose, and 60 g of potato starch) by regulation of the added water amount (11–19 wt/wt%) in a high-speed mixer. The granules were characterized by mean particle size, angle of repose, compressibility, tablet porosity, and tablet hardness as parameters of pharmaceutical properties. To predict the pharmaceutical properties, NIR spectra of the granules were measured and analyzed by principal component regression, (PCR) analysis. The mean particle size of the granules increased from 81 μm to 650 μm with an increase in the amount of water, and it was possible to make larger spherical granules with narrow particle size distribution using a high-speed mixer. Angle of repose, compressibility, and porosity of the tablets decreased with an increase of added water, but tablet hardness increased. The independent calibration models to evaluate particle size, angle of repose, and tablet porosity and hardness were established by using PCR based on NIR spectra of granules, respectively. The correlation coefficient constants of calibration curves for prediction of mean particle size, angle of repose, tablet porosity, and tablet hardness were 0.9109, 0.8912, 0.7437, and 0.8064, respectively. It is possible that the pharmaceutical properties of the granule, such as mean particle size, angle of repose, tablet porosity, and tablet hardness, could be predicted by an NIR-chemometric method.     

Size, composition and distribution of particles related to wind induced resuspension in a shallow tropical lagoon

The size, composition and distribution of particles in the watercolumn were surveyed in a shallow area (1 m depth) of a tropicallagoon (Cte d'Ivoire) during a sequence of wind-induced resuspension.Water samples were collected hourly near the surface duringone tidal cycle. Three characteristic periods were distinguished:a calm period with low wind speed (average 1.2 m s^–1 awindy period with wind speed >3 m^–1 s (range between4 and 6 m s^–1) inducing sediment resuspension and a relaxationperiod during the decrease of wind velocity. From the analysisof several parameters (particle size and volume, bacteria. pico-and nanophytoplankton, ciliates and detritus), sediment resuspensioncaused a regular injection of particles from the bed. The finestparticles (1.5–6 µm: chlorophytes such as Chiorellaspp., picocyanobacteria such as Synechococcus) were the firstto be affected by wind-induced turbulence, whereas large particles(6–12 µm: diatoms. cyanobacteria such as Lyngbiaspp.) were dispersed into the water column at the highest windspeed. The fate of the different seston components differedaccording to their size. Therefore, wind-induced resuspensioncould greatly influence the food web organization through thequantity, quality and size of edible particles available ata given time.     

MOVEMENT OF EELWORMS

Tracks were plotted of about 300 individual eelworms comprising six species among water droplets on a glass surface. Measurements of the tracks indicated that the product of length and activity of an eelworm divided by its speed was a constant. This supports the hypothesis that the speed of an eelworm among water droplets is a function of its length and activity. This principle can only be applied to movement in soil where the length of the eelworm is less than about three times the particle diameter. Under such conditions the eelworms move in thin films or water droplets over particles. Among smaller-sized particles the speed of the eelworms is influenced by particle size. With increasing eelworm length there is an increase in soil particle size for maximum mobility.     

Interfacial feeding behavior and particle flow patterns ofAnopheles quadrimaculatus larvae (Diptera: Culicidae)

The interfacial feeding behavior, mouthpart movements, and particle flow patterns of Anopheles quadrimaculatuslarvae were investigated, using videotape recordings, high-speed microcinematography, SEM, and laboratory experiments. While positioned at the water surface, larvae demonstrated 12 behaviors associated with movements of the head. In one of these, a larva rotated its head 180° and directed its mouthparts against the air-water interface. The larva rapidly extended and retracted its lateral palatal brushes (LPBs) at a rate of 5 cycles/s (5 Hz), creating currents and allowing for the collection of particles. Particles moved toward the head at a velocity of 4.31 mm/s, in discrete stops and starts, as the LPBs beat. Our analyses determined that particle movement toward the mouth was governed by very low Reynolds numbers (0.002–0.009). This finding indicated that viscous forces predominated in Anophelesfeeding and no inertial movement of particles occurred. According to this model, the LPBs cannot intercept particles directly, but function as paddles for particle entrainment. We did not observe the pharynx to function in particle filtration but, rather, in food bolus formation. We propose that the maxillary pilose area and midpalatal brush function as interception structures. It appeared that the LPBs do not break the surface film to feed, but collect particles from the surface microlayers. A plume of uningested particles emerged from the sides of the cibarium and descended into the water column. The plume consisted of alternately clear and dark, lenticular laminae formed beneath the larval head during the collecting filtering feeding mode. A comparison of particle sizes from surface microlayers and gut contents of fourth instars showed that larvae ingested mainly small particles in the range of 1.5 to 4.5 pm in diameter. The potential significance of interfacial feeding by anopheline larvae in their aquatic environment is discussed.     

Tablet formulation containing meloxicam and β-cyclodextrin: Mechanical characterization and bioavailability evaluation

The purpose of this research was to evaluate β-cyclodextrin (β-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of β-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of β-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an A_L-type diagram with inclusion complex of 1∶1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of β-CD in the formulations up to 30%. The mean pharmacokinetic parameters (C_max, K_e, and area under the curve [AUC]_0−∞) were significantly increased in presence of β-CD. These results suggest that β-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, β-CD is particularly useful for improving the oral bioavailablity of meloxicam.