Granule Size Fractions Research Articles

The distribution of components in the different size fractions of granules prepared from binary mixtures.

Boric acid, sulphanilamide and citric acid have been mixed separately with lactose and then granulated by massing and screening. The granules have been fractionated by sieving and each fraction has been analysed for lactose content. The effect of premixing time, massing time, binder volume and ratio of components on the distribution of lactose between size fractions of granules prepared from lactose: boric acid mixtures has been investigated. Uneven distribution of lactose has been found for all blends examined. There is a premixing time and massing time that gives the optimum distribution of lactose for any given blend and binder volume. Increased binder volume in some cases improves granule uniformity. The proportion of lactose in the blend has a major effect on the distribution of this component in the granules, as does the particle size of the lactose. Granules prepared from blends of lactose with sulphanilamide and with citric acid were also examined for lactose distribution.

The synergistic effect of Landolphia owariensis latex and Eudragit® L-100-coated capsules on the in vitro controlled release of metronidazole for possible colon targeting

The overall objective of this present investigation was to determine the synergistic potentiality of Landolphia owariensis latex (LOL) and Eudragit® L-100 as hydrophobic polymeric agents in ensuring controlled drug release for possible colon-targeted delivery of metronidazole. Metronidazole granules were prepared by the wet granulation method and manually encapsulated. The entire capsule surface was first coated with Eudragit® L-100 (primary coating). Secondly half (50%) or five-sixth (5/6 or 83%) of the capsule surface was coated atop the primary coating with LOL (secondary coating). Two different granule size fractions were isolated and compared. Parallel gradient in vitro drug release studies were carried out in media of pH 1.2, 6.8 and 7.4, respectively. The dissolution data were subjected to kinetic treatment. Results showed that the least quantity of drug release took place at pH 1.2 followed by pH 6.8, with greatest drug release taking place at pH 7.4. Capsule surface coated with LOL significantly (P<0.05) affected drug release and time of release. Matrix former(binder) concentration had no significant (P<0.05) effect on drug release, but particle size did. More than one drug release mechanisms were operational and most capsules with 50% surface coated with LOL recorded higher Dissolution efficiency (DE) but lower Mean dissolution time (MDT) than those of 83%. In conclusion, the use of Eudragit® L-100 and LOL as primary and secondary capsule coatings respectively have demonstrated competence in controlling drug release and thus may hold promise at preferentially targeting metronidazole to the colon against amebic diseases.

Image analysis by pulse coupled neural networks (PCNN)—a novel approach in granule size characterization

A biologically inspired spiking neural network model, the pulse coupled neural network (PCNN), has been applied for the first time in bulk particle characterization, and specifically in the characterization of pharmaceutical granule size distributions. The PCNN was trained on surface images of pharmaceutical granule beds, and the adjustable parameters (radius neuron interconnection, r0, linking weight coefficient, beta, local threshold potential, VTheta, and number of iterations) were successfully optimized using design of experiments. As demonstrated with size fractions of granules, it was found that the PCNN produced granule size-dependent signals. In general, a first highest and relatively narrow peak located in the region of two to twelve iterations corresponded to smaller particle size, while larger particles resulted in wider peaks and in highest (not first) peak at a range between 13 and 25 iterations. Better predictions, i.e. lower RMSEP (root mean squared error of prediction) values, were obtained using high beta value, low r0 and VTheta values, while the number of iterations had to exceed 110 and the optimized model (RMSEP lower than 5) corresponded to PCNN variables: r0=1, beta=0.4, VTheta=2, and number of iterations=150. The coefficient of determination (R2) of the model was 0.94 and the predicted variation (Q2) was 0.91, while the Pearson correlation coefficient between the predicted and the measured mean particle size by sieving for eight test batches was 0.98. These findings could be characterized as promising and encouraging for the further use of image analysis by PCNNs in pharmaceutical bulk particle size and shape characterization.

Surface effects in the acetylation of granular potato starch

The occurrence of surface effects in the acetylation of granular potato starch with acetic anhydride to degrees of substitution 0.04–0.2 was studied by two different approaches. The first approach involved the fractionation of granular starch acetates into five different size classes and analysis of their acetate content. Alternatively, two narrow size fractions of potato starch acetate granules were surface-peeled by chemical gelatinization in 5 M CaCl 2, and the remaining cores were analyzed for acetyl content at different peeling levels. It was established that true surface peeling occurs in this medium and that the ester linkages are stable under the conditions applied. Both approaches led to the conclusion that the acetylation of potato starch granules is accompanied by a pronounced surface effect. The surface peeling method allows determination of the extent of substitution as a function of the radial position in the starch granule.

Discrimination of granulocyte subtypes from light scattering: theoretical analysis using a granulated sphere model

We perform extensive simulations of light scattering by a granulated sphere in the size and refractive index range of human granulated leucocytes using the discrete dipole approximation. We calculate total and depolarized side scattering signals as a function of the size and refractive indices of cell and granules, and the granule volume fraction. Using typical parameters derived from the literature data on granulocyte morphology, we show that differences between experimentally measured signals of two granulocyte subtypes can be explained solely by the difference in their granule sizes. Moreover, the calculated depolarization ratio quantitatively agrees with experimental results. We also use the Rayleigh-Debye-Gans approximation and its second order extension to derive analytical expressions for side scattering signals. These expressions qualitatively describe the scaling of signals with varying model parameters obtained by rigorous simulations, and even lead to quantitative agreement in some cases. Finally, we show and discuss the dependence of extinction efficiency and asymmetry parameter on size and volume fraction of granules.

ESSENTIAL FACTORS INFLUENCING TUNNELING GIANT MAGNETORESISTANCE OF GRANULAR FILMS

A series of ferromagnetic-insulator granular films were prepared at room temperature with a spc350 multi-target magnetron controlled sputtering system and all of the tunneling giant magnetoresistences were measured with the conventional four probes method. Experimental results revealed that TMR depends strongly on the magnetic granule, matrix and the size distribution of magnetic granules. Accordingly, a modified phenomenological theory is presented to investigate comprehensively the effect of the magnetic granule, matrix and the size distribution of magnetic granules on the TMR. In this theory, the size distribution of granules was described by the log-normal function and all granules can be divided into three categories which have different contributions on TMR by two critical sizes: D1(T) as the critical size distinguishing superparamagnetic granules from single domain ferromagnetic granules and D2(T) as the critical size distinguishing the single domain from the multi-domain. The calculated results, including TMR versus applied magnetic field, measured temperature, granule size or volume fraction, are in agreement with the experiments when the single domain ferromagnetic granules play a key role in TMR for granular films, which indicates that our modified model is reasonable.

Granule size affects the acetyl substitution on amylopectin populations in potato and sweet potato starches

Specific enzymatic degradation in combination with chromatographic and spectrometric techniques was used to understand acetyl group distribution over the amylopectin populations of differently sized granule fractions from potato and sweet potato starches. The hydrolysates obtained after α-amylase, ß-amylase, pullulanase, and the combination of pullulanase, α-amylase and amyloglucosidase treatment were investigated by high-performance size-exclusion chromatography (HPSEC), high-performance anion-exchange chromatography (HPAEC) and Maldi-Tof-MS (Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometry). The acetyl groups were found to be located near the branching point, in the external chain and in the internal chain regions. The acetyl group distributions were different for amylopectin from different granule size fractions. Higher DP (degree of polymerization) fragments were present in the digests of acetylated amylopectin populations of the small size granule starches. Our studies confirmed that acetyl groups were unevenly distributed over the amylopectin populations.

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.

Starch Granule Size Strongly Determines Starch Noodle Processing and Noodle Quality

ABSTRACTChemical compositions, physical properties, and suitability for starch noodle making of different granule size fractions from potato and sweet potato starches were studied. The ash content, amylose content, phosphorus content, gel firmness, and freeze‐thaw stability of small‐size granule fractions(&lt; 20 μm) were significantly different from those of the large‐size granule fractions. The processibility and the qualities evaluated by objective and subjective methods of both dried and cooked starch noodles made from small‐size granule fractions were significantly better than those made from their initial starch preparations and much better than those made from the large‐size granule fractions.

Evaluation of size distribution of starch granules in selected wheat varieties by the Low Angle Laser Light Scattering method

&amp;nbsp; &amp;nbsp; The distribution of the size of wheat starch granules using the method LALLS (Low Angle Laser Light Scattering), followed by the evaluation of the effect of variety, experimental site and intensity of cultivation on the vol. % of the starch A (starch granules &amp;gt; 10 &amp;mu;m) was determined. The total starch content and crude protein content in dry matter of flour T530 in selected collection of five winter wheat varieties were determined. Vol. % of the starch A in evaluated collection of wheat varieties varied between 65.31 and 72.34%. The effect of a variety on the vol. % of starch A seemed to be more marked than the effect of site and intensity of cultivation. The highest vol. % of starch A reached evaluated varieties from the quality group C, i.e. varieties unsuitable for baking utilisation (except variety Contra with high total content of starch in dry matter of flour T530, but relatively low vol. % of starch A). A low vol. % of starch A was also found in the variety Hana (very good variety for baking utilisation). Certain variety differences followed from the evaluation of distribution of starch fractions of starch granules, forming starch A. In the case of varieties Hana, Contra and Siria higher representation of fractions up to 30 &amp;mu;m was recorded, while starch A in the varieties Estica andVersailleswas formed in higher degree by size fractions of starch granules over 30 &amp;mu;m and particularly size fraction &amp;gt; 50 &amp;mu;m was greatest in these varieties of all evaluated samples. With increasing total starch content in dry matter of flour T530 the crude protein content decreased; the vol. % of starch A not always increased proportionally with increasing total starch content.

Sulfate formation and extraction from Red soil treated with micronized elemental sulfur fertilizer and incubated in closed and open systems

Two extractants, 0.01 M CaCl2 and 0.01 M Ca(H2PO4)2, and two incubation systems, closed and open, were used to investigate the influence of granule dispersion and granule size on formation in a Red soil treated with a new micronized, granular S0 fertilizer at rates of 500 and 3000 mg kg−1 of S0. Sulfate production was significantly greater with dispersed micronized particles than for either the 1 to 2 mm or 2 to 4 mm intact granule size fractions. Increasing the dosage of S0 resulted in much greater formation from all particle sizes of S0. Quantities of extracted by 0.01 M Ca(H2PO4)2 generally exceeded those removed by 0.01 M CaCl2 in both the closed and open incubation systems. Levels of extractable recovered in the open incubation procedure were consistently much greater than those in closed incubation. In open incubation, extractable varied from 0.66 to 36.79 mg S/100 g soil and 1.35 to 65.02 mg S/100 g soil, respectively, for the 0.01 M CaCl2 and 0.01 M Ca(H2PO4)2 leaching solutions. With closed incubation, recoveries ranged from 0.15 to 12.08 mg S/100 g soil and 0.21 to 31.74 mg S/100 g soil in the 0.01 M CaCl2 and 0.01 M Ca(H2PO4)2 extracts, respectively. The average oxidation percentages measured by 0.01 M Ca(H2PO4)2 extraction were 27.9%, and 36.7% greater than those occurring with 0.01 M CaCl2 extraction, in closed and open incubation, respectively. Oxidation percentages for the dispersed S0 particles were significantly higher than for intact fertilizer S0 granules, which increased significantly with decreasing granule size. Oxidation percentages were significantly greater at the lower dosage rate of S0 fertilizer. Highly significant linear function relationships between cumulative formed by oxidation of S0 and the time of open incubation were found.

Microstructure/hardness relationship in a dual composite

Double cemented (DC) carbide [1–3] is a novel dual composite composed of granules of conventional cemented carbide (WC + Co) dispersed in a metal matrix, typically cobalt (see Fig. 1). This concept of a “composite-within-a-composite” facilitates microstructural design to optimize properties for different applications. Properties of the overall composite are variable through control of granule and matrix properties, granule size and volume fraction, typically 70 to 90%. Granule properties are controlled by the grade of cemented carbide granules, i.e., Co content and WC particle size. Matrix properties are controlled by the matrix metal employed, modifiable through alloying or heat treatment. Studies to date have shown that this microstructural flexibility can achieve unusual combinations of properties, such as improved toughness and wear resistance compared to conventional cemented carbide, due to the larger metal matrix mean free path [2]. The particulate nature of the granules enables fairly conventional powder processing. DC carbide is currently being introduced in oil well drill bit inserts and should have use in many other applications requiring combined wear resistance and toughness. This material is also an ideal model for systematically investigating the microstructure/property relationships of a particulate reinforced dual composite, a design concept readily extendable to other metal and ceramic systems. Prior studies by others have investigated particulate dual composites containing lower volume fractions of cemented carbide granules in steel matrices [3–7] to improve wear and thermal shock resistance. Several

The filling of granules into hard gelatine capsules

Four different granule size fractions of Sorbitol instant® were filled into hard gelatine capsules on a tamp filling (Bosch) and a dosator nozzle machine (Zanasi) to allow comparison of the filling principles. An acceptable filling performance was always achieved and was independent of the machine type employed. Tamp filling was found to be slightly better for the coarser granule size fractions, because it does not seem to rely on a firm plug formation. A direct relationship between the angle of internal flow ( Varthalis and Pilpel, 1976) and the coefficient of fill weight variation was found for both systems. Using the dosator nozzle machine, the plug formed was always denser than the maximum bulk density, whereas on the tamp filling machine for smallest granule size the maximum plug density could not be achieved with the settings employed. The results suggest that in situations where a low plug density is an essential prerequisite for drug dissolution and bioavailability the tamp filling machine appears the more suitable filling principle. However, if a greater extent of compression is required in order to fill large dose drugs or to use a smaller capsule size, the dosator nozzle principle might work more successfully for granules.

Giant magnetoresistance of magnetic granular films in an effective medium theory

We have investigated the transport properties in magnetic granular films based on an extended effective medium theory. It is shown that the magnetoresistance of this system depends strongly on the size, shape and volume fraction of magnetic granules. Our results are in agreement with the experimental observations.

Effect of Several Cellulosic Binders and Method of Their Addition on the Properties and Binder Distribution of Granules Prepared in an Agitating Fluidized Bed.

A model system consisting of lactose-cornstarch was used to examine the effect of five cellulosic binders [hydroxypropylcellulose (HPC)(6cP), hydroxypropylmethylcellulose 2910 (HPMC)(3, 6, 15cP) and methylcellulose (MC)(15cP)] on the particle size distribution of granules prepared in an agitating fluidized bed under fixed operating conditions. The distribution of binder in different size fractions of granules was also determined by measuring the contents of methoxyl and hydroxypropoxyl groups. When the binders were added by the solution method, higher solution viscosity resulted in the granule size being increased, with almost equivalent binder distributions in different size fractions. The granules prepared by the dry mixing method with HPC (6cP) or HPMC (3cP) also showed a good correlation between median particle size and binder level, though the binders were concentrated in the coarse-sized particle fractions of the granules. The results are consistent with our previous findings on wet granulation with a fluidized bed. When a trace amount of water-soluble dye was mixed with the granulating liquid or powder components to examine the granulation mechanism in both the solution and the dry mixing methods of binder addition, the dye distributions were more uniform than the binder distributions, especially in the dry mixing method. This suggests that the solubility of binders or dye in water is a critical factor determining their distribution in the different size fractions of the granules.

Melt pelletization in a high shear mixer. IX. Effects of binder particle size

Lactose monohydrate was melt pelletized in an 8-1 high shear mixer. The meltable binders were polyethylene glycol (PEG) 3000, 6000, and 8000 used as flakes, coarse powder, and fine powder, and PEG 10000 and 20000 used as flakes and coarse powder. The distribution of the binder in different granule size fractions was dependent on the binder particle size. The binder particle size was reflected in the initial granule size at high binder viscosities. The fine powders gave rise to the lowest agglomerate growth rate, whereas a difference in growth rate between the flakes and the coarse powders was seen only at the highest viscosities.

Effect of Process Variables on the Properties and Binder Distribution of Granules Prepared by a High-Speed Mixer.

A model system consisting of lactose-cornstarch-microcrystalline cellulose with hydroxypropyl methylcellulose 2910 (HPMC 3cP) as a binder was used to estimate the effects of process variables (granulation time, amount of granulating water and impeller speed) on the particle size distribution of granules prepared in a high-speed mixer using a dry mixing method of binder addition. The distribution of binder in different size fractions of granules was also determined by measuring the contents of methoxyl group. The binder content interpolated at the median particle size was close to the theoretical value calculated from the formulation. Longer granulation time, greater amount of granulating water and higher impeller speed increased the granule size and strength. An expanded binder distribution was seen at higher impeller speed. At extremely short granulation time (1 mins), the granules were friable and the binder content in the larger size fraction of the granules changed during fluid-bed and tray drying because of insufficient binder dissolution or granular compaction. Binder behavior during wet granulation seems to be closely related to the observed differences in granule strength.

Effect of Several Cellulosic Binders on Particle Size Distribution in Fluidized Bed Granulation.

A model system consisting of lactose-cornstarch was used to examine the effect of five cellulosic binders [hydroxypropylcellulose (HPC) (6 cP), hydroxypropylmethylcellulose 2910 (HPMC) (3, 6, 15 cP) and methylcellulose (MC) (15 cP)] on the particle size distribution of granules prepared in a fluidized bed under fixed operating conditions. The distribution of binder in different size fractions of granules was also determined by measuring the contents of methoxyl and hydroxypropoxyl groups. When the binders were added by the solution method, higher solution viscosity resulted in the granule size being increased without any increase in the percentage of coarse (>500 μm) particles generated. The granules prepared by the dry mixing method with HPC (6 cP) or HPMC (3 cP) also showed a good correlation between median particle size and binder level. The other binders did not show such a correlation, as higher concentrations of the binders were present in the medium-sized particle fractions of the granules at higher binder levels, and partly aggregated was the observed binder in these granules. The results support our previous conclusion, in a study of wet granulation with a high-speed mixer, that analysis of granule size dependency of binder content is useful for evaluating the effectiveness of binders added by dry mixing.

Effect of Crystallinity of Microcrystalline Cellulose on Granulation in High-shear Mixer.

Granulation was carried out using binary mixtures of microcrystalline cellulose (MCC) and cornstarch (CS); water was used as granulating liquid. The effect of crystallinity of MCC on granulation was examined using MCC pulverized by a jet mill (J-MCC) and a vibrational rod mill (R-MCC). Crystallinity of J-MCC was nearly equal to that of intact MCC (I-MCC), but that of R-MCC was remarkably low due to the mechanochemical effect. The growth rate of granules with R-MCC was greater than those with I-MCC and J-MCC; the latter two had a grnule having a core (MCC and CS) around which CS was layered. R-MCC provided granules in which CS and abraded MCC were homogeneously mixed. In addition, R-MCC remarkably decreased the difference in drug content among the size fractions of granules compared with I-MCC. These results suggest that the decrease in crystallinity of MCC may increase the tendency of its abrasion by shear force of impeller, because of an increase of the fragile amorphous region swollen by added water; this, in turn, results in a difference in the growth mechanism and in a greater growth rate.

Rapid Separation and Measurement of Particle Size Distribution of Starch Granules by Sedimentation/Steric Field‐Flow Fractionation

ABSTRACTSedimentation/steric field‐flow fractionation (Sd/StFFF) is introduced as a new technique for the size analysis of starch granules. Sd/StFFF provides both high speed and high resolution, and narrow size fractions of starch granules can be collected from the eluting stream for further characterization by microscopy or other techniques. The sedimentation FFF instrument was calibrated and applications were made to 12 starch samples derived from wheat, durum wheat, corn, oat, tapioca, and potato. The instrument response curve (the fractogram) and the size distribution curves for several of these samples were recorded. The mode or bimodal diameters and the percentages of A‐and B‐granules were compiled.