Manufacture of Slow-Release Matrix Granules by Wet Granulation with an Aqueous Dispersion of Quaternary Poly(meth)acrylates in the Fluidized Bed

ABSTRACT

Slow-release matrix granules were manufactured in the fluidized bed using an aqueous dispersion of quaternary poly(meth)acrylates (Eudragit® RS 30 D) as binder for granulation. A factorial design was carried out to investigate the influence of the following parameters, spraying rate, applied polymer amount, and inlet air temperature, on various granule properties. Prerequisites for a slow release of the model drug theophylline are high spraying rate, high amount of polymer, and low inlet air temperature. No considerable decrease of the drug release rate can be achieved without a subsequent curing of the dry granules. A clear correlation exists between the moisture content of the fluidized bed, indicated by the terminal moisture content (TMC), and the mean dissolution time for 80% of the drug (MDT₈₀).     

Dry separation of particulate iron ore using density-segregation in a gas–solid fluidized bed

A gas–solid fluidized bed has been used to separate particulate iron ore (+250–500 μm in size) by segregating the particles by density. The ore particles were put into a cylindrical column of inner diameter of 100 mm and bed height of 50 mm, and were fluidized at a given air velocity u₀/u_mf = 1.2–3.2 for 10 min. u₀ and u_mf are the superficial air velocity and the minimum fluidization air velocity, respectively. The bulk density of the ore particles after fluidization was measured as a function of height through the bed in 5 mm increments (the 50 mm height was divided into 10 layers) to investigate the density-segregation. The size of the particles in each of the 10 layers was also measured to investigate size-segregation. It was found that both density-segregation and size-segregation occurred as a function of height through the bed after fluidization at u₀/u_mf = 2.0. However, the segregation did not occur near the bottom of the bed for lower u₀/u_mf and did not occur near the top of the bed for larger u₀/u_mf. The origin of the segregation-dependence on the air velocity was discussed considering the air bubbles size and the fluidizing intensity at upper and lower sections of the bed. The Fe content of the 10 layers at u₀/u_mf = 2.0 was measured to calculate the Fe-grade and Fe-recovery. The ore-recovery was also calculated using the weight of ore particles as a function of height through the bed. The feed Fe-grade (before separation) was 52.1 wt%. If the ore particles in the bottom half of the bed were regarded as the product, the Fe-grade was 59.0 wt%, and the Fe-recovery and the ore-recovery were 68.5 wt% and 60.5 wt%, respectively.     

Manufacture of slow-release matrix granules by wet granulation with an aqueous dispersion of quaternary poly(meth)acrylates in the fluidized bed

Slow-release matrix granules were manufactured in the fluidized bed using an aqueous dispersion of quaternary poly(meth)acrylates (Eudragit® RS 30 D) as binder for granulation. A factorial design was carried out to investigate the influence of the following parameters, spraying rate, applied polymer amount, and inlet air temperature, on various granule properties. Prerequisites for a slow release of the model drug theophylline are high spraying rate, high amount of polymer, and low inlet air temperature. No considerable decrease of the drug release rate can be achieved without a subsequent curing of the dry granules. A clear correlation exists between the moisture content of the fluidized bed, indicated by the terminal moisture content (TMC), and the mean dissolution time for 80% of the drug (MDT₈₀).     

Improved chemical stability of ascorbic acid and thiamine nitrate in L-HPC granules

The stability of drugs in extruded granules prepared with low substituted hydroxypropylcellulose (L-HPC) and water was investigated using ascorbic acid (AA) and thiamine nitrate (TN) as model drugs. d-Mannitol was used as the control additive for a comparison with L-HPC. The percentage of AA remaining after storage at 60 °C for 14 days in a closed glass bottle was 57% in d-mannitol granules and 89% in L-HPC granules, showing higher stability of AA in L-HPC granules. On powder X-ray diffraction measurement, AA in L-HPC and d-mannitol granules was in an amorphous state. The loss on drying (LOD) (1 g, 105 °C, 2 h) of the granules containing both AA and TN was higher in L-HPC granules (1.96%). The moisture content around AA and TN in granules was calculated. The contents were 1.36% and 4.67% in L-HPC and d-mannitol granules, respectively. Furthermore, the water activities at 25–40 °C were measured in L-HPC and d-mannitol granules, being lower in L-HPC granules at all measurement temperatures. These findings suggested that the superior storage stability of AA in granules prepared with L-HPC was due to L-HPC-induced reduction of the moisture content around AA and TN and water activity of the granules.     

Antioxidant capacity of spray-dried plant extracts: Experiments and simulations

The effects of different inlet air temperatures (70–150 °C) have been studied on the antioxidant retention and yields of a spray-dried bioactive solution (Hibiscus sabdariffa L.) from a Buchi B-290 spray dryer and compared with plug-flow spray drying simulations. Antioxidant retention has been tested using the Oxygen Reducing Antioxidant Capacity assay (ORAC). Experimentally, a peak yield of between 65% and 70% of the solids fed to the dryer has been found at an outlet gas temperature of 60–65 °C and an inlet air temperature of 110 °C, regardless of the batch of material or the liquid feed rate. The varying outlet gas temperatures did not significantly affect the antioxidant retention of the sample, and the simulations demonstrate that this result is due to the competing effects of increasing air temperature and decreasing water activity (at higher inlet air temperatures) on the degradation kinetics. These results suggest that it is more important to obtain greater product yields rather than minimising the degradation amount in this spray-drying situation.     

Influence of air bubble size on float–sink of spheres in a gas–solid fluidized bed

The float–sink of density adjusted spheres of different diameter (10–40 mm) in a gas–solid fluidized bed was investigated at various bed heights (50–200 mm). The maximum density of floating spheres (ρ_float) and the minimum density of sinking spheres (ρ_sink) were determined by the float–sink experiments. The fluidized bed density (ρ_fb) was measured using the height and cross section of the fluidized bed and total weight of the fluidized media. The diameter of air bubbles at the bed surface was measured at each bed height, and was normalized by the sphere diameter. It was found that the value of ρ_fb–ρ_float approaches zero as the normalized bubble diameter decreases from 4 to 0.5 regardless of the sphere diameter. The value of ρ_sink–ρ_fb for sphere diameter = 10 mm approaches zero as the normalized bubble diameter decreases from 4 to 1.5, whereas the value for sphere diameter = 20–40 mm rises from zero as the normalized bubble diameter decreases from 1.5 to 0.5. The float and sink of spheres basically tend to follow the fluidized bed density with decreasing the normalized bubble diameter. However, relatively larger spheres do not sink based on the density difference as the normalized bubble diameter decreases, which may be due to that the fluidized bed viscosity becomes larger as the normalized bed diameter decreases.     

Enteric coating process of diclofenac sodium pellets in a fluid bed coater with a wurster insert: Influence of process variables on coating performance and release profile

The objective of this work was to study the coating process of diclofenac sodium pellets, with the commercial aqueous coating suspension for enteric release – Acryl-Eze® MP, in a fluid bed coater with a Wurster insert. Coating experiments were performed following a 2² factorial design to determine the influence of process variables on coating performance, measured by the two response variables: efficiency (η_%) and agglomeration index (m_agg%). Both response variables were found to be affected by inlet temperature and suspension flow rate with a 95% confidence level. This work also studied the release of diclofenac sodium coated and uncoated pellets in HCl 0.1 N and pH 6.8 phosphate buffer media. Results showed that the release of diclofenac sodium during the buffer stage was affected by the prior exposure to the HCl 0.1 N medium and a polymer weight gain above 9.7% (2.7 mg/cm²), was needed to modify the release in such a way that it remained below 10% for the first 120 min in HCl 0.1 N and above 75% in pH 6.8 for the next 45 min. Neither the drug content nor the release profiles were significantly affected by storage at 40 °C and 75% relative humidity.     

Experimental study on a two-stage rotary desiccant cooling system

The objectives of this study were to evaluate the performance of a novel two-stage rotary desiccant cooling (TSRDC) system and to obtain useful data and experiences for practical application. Newly developed compound desiccant (silica gel–haloids) was adopted in the system. An experimental set-up was built and used to test the system performance under three typical environmental conditions. System performances were evaluated in terms of moisture removal D and thermal coefficient of performance COP_th. It has found that the required regeneration temperature of TSRDC system is low and COP_th of the system is high. Regeneration temperatures from 65 °C to 80 °C, 65 °C to 75 °C and 80 °C to 90 °C were recommended for each environmental condition. In addition, the effects of some important operating parameters, such as inlet temperature and humidity ratio of process and regeneration air, on system performance were also investigated in this study.     

Sinking and recirculation of large intruders in vertically vibrated granular beds

A series of experiments are described in which air-immersed grains within different containers are exposed to vertical vibrations. When the peak acceleration relative to gravity exceeded Γ = 6 at 49 Hz), tilted cavitating beds were formed. Then, when a large, low-density object was put onto the free surface, the vigorous granular convection dragged it into the bed. The large object was not being dragged into the bed at Γ > 6 when the air pressure inside the container fell well below1 Torr. These findings, as well as those from computer simulations, confirm the key role played by large air cavities such as swallow holes in submerging large, low-density objects into a granular bed.     

Investigation on resistance to attrition of coated particles by response surface methodology

The purpose of the present study is to obtain better understanding of the influence of the coating thickness, h, coating formulation, T_g, and fluid bed temperature, T_bed, variables on the resistance to attrition of the coated sodium benzoate reference particles. Three reference coating materials (T_g = 50 – 125 – 150 °C) have been sprayed by using top spray fluid bed coater. Per each coating formulation three different coating levels (h = 1% – 5% – 9% w/w) have been obtained. The coating processes were performed at three different fluid bed temperatures (T_bed = 40 – 55 – 70 °C). The experiments have been designed according to the response surface methodology (RSM). Both single effects and interactions between single effects on the resistance to attrition (response variable) calculated by means of repeated impact tester were evaluated. From statistical analysis, the coating quantity appears to have a predominant effect on the resistance to attrition of the coated particle in these studied ranges of variables. This relationship is linear and positive, which means that an increasing quantity leads to more resistance to attrition. The interaction coating thickness – coating formulation, the interaction between the fluid bed temperature and the coating formulation and the coating formulation as well as the interaction costing thickness – fluid bed temperature were found to be very significant. On the contrary, no direct effect of the fluid bed temperature on the resistance to attrition is detected.     

Assessment of powder flow characteristics in incoherent soup concentrates

Soup mixtures represent specific flow characteristics while particles of different sizes and properties form a homogeneous mixture. In such mixtures, particle–particle interactions differ with addition of different fat types. This study was done to present a characterization and comparison of the cohesion index, powder flow speed dependency and caking properties of four different aggregates of fat particles with three different moisture contents, used in various compositions of powdered soup concentrates. ESEM micrographs have shown that different fat types bind particles differently. The moisture content of cream soup concentrates has a significant influence on cake height ratio of all cycles – more moisture causes higher cake height ratios (from r_s = 0.86 to r_s = 0.76; p < 0.05). Cream soup concentrates cake strength values are also significantly influenced by the mixtures moisture content – higher moisture content samples showed higher cake strength values (r_s = 0.73, p < 0.05). There is a significant correlation between compaction coefficients of all speeds and cake height ratios of all cycles for the cream soup concentrates. Combination of measuring techniques (Powder Flow Analyzer, ESEM and Mastersizer) together with Spearman’s Rank Order Correlation, as a method of non-parametric statistics, provides parturient results in characterization of extremely non-homogenous powder mixtures.     

Formation mechanisms of a dust-removal air curtain in a fully-mechanized excavation face and an analysis of its dust-removal performances based on CFD and DEM

A high concentration of dust in a fully-mechanized excavation face is a serious threat to the safety of production underground and miners’ health. This paper discusses the use of a novel air curtain generator and proposes a novel dust control and prevention technique. Based on the k-ε two-equation turbulence model, Hertz-Mindlin model and the CFD-DEM coupled interface compiled with C++ language, this paper firstly constructs a simulation model of the coupling between airflows and dust in a fully-mechanized excavation face, and then simulates the airflow fields and dust fields under forced/exhaust ventilation conditions with and without a novel air curtain generator being utilized. The results show that when only the forced/exhaust ventilation was used, a high concentration of dust spread throughout the entire tunnel space and no effective air curtain was formed. Furthermore, after the air curtain generator was turned on, as the radial-to-axial forced air ratio (P_FQ) increased, the horizontal vortex in the front of the head-on section weakened gradually, and the originally disordered airflows behind the heading machine moved uniformly towards the head-on section. As the P_FQ further increased, the distance (d) between the formed air curtain and head-on section decreased overall; through a curve fitting, this relationship can be written as: d = ?5.247 ln(P_FQ) + 13.569. When the P_FQ > 5:5, the average negative-pressure-induced dust-exhaust capacity increased, the distance between the formed air curtain and the head-on section decreased, and the re-entrainment of dust did not take place in a straightforward manner. Finally, some field measurements were carried out in order to validate the simulated results, with the subsequent comparison showing that the numerical simulated results were basically accurate.     

Entropy generation in a heat exchanger working with a biological nanofluid considering heterogeneous particle distribution

Entropy generation rates considering particle migration are evaluated for a biologically produced nanofluid flow in a mini double-pipe heat exchanger. The nanofluid is used in tube side and hot water flows in annulus side. Silver nanoparticles synthesized through plant extract method from green tea leaves are utilized. Particle migration causes non-uniform concentration distribution, and non-uniformity intensifies by increase in Reynolds number and concentration. The results indicate that at high concentrations and Reynolds numbers, particle migration can have a great effect on entropy generation rates. For water inlet temperature of 308 K, the contribution of friction in nanofluid entropy generation is much more than that of heat transfer. However, as the water inlet temperature increases to 360 K, the heat transfer contribution increases such that at low Reynolds numbers, the thermal contribution exceeds the frictional one. For total heat exchanger, Bejan number is smaller than 0.2 at water inlet temperature of 308 K, while Bejan number has a large value at water inlet temperature of 360 K. Furthermore, entropy generation at the wall has an insignificant contribution, such that for Re = 1000 and φ_m = 1%, the total entropy generation rates for the nanofluid, wall, and water are 0.098810, 0.000133, and 0.041851 W/K, respectively.     

A method to predict nuclei size distributions for use in models of wet granulation

Models of granulation and agglomeration are becoming more sophisticated and accurate, but nucleation is poorly understood. Models of granulation processes typically either use simplistic nucleation assumptions; complex multi-phase simulations or deliberately focus on the final granulation stages only. Here, we validate a simple method to generate nuclei size distributions using the dimensionless spray flux parameter, for future use in granulation models in the drop controlled regime.Dimensionless spray flux describes the spray density in the spray zone, which is closely related to the Poisson distribution. A simple model to estimate the nuclei size distribution at a range of spray flux conditions was compared with data generated in a previous study. The simulations were in reasonable agreement with experimental data at low penetration time and low spray flux (Ψ_a < 0.3) but diverged when either the spray flux was >0.5. For a longer penetration time system, the simulations and experimental results agreed up to Ψ_a = 0.5. Multi-modal experimental results could not be modeled. Spray flux derived models of nuclei size distributions are useful nucleation granulation models, provided that the simulations are restricted to the drop controlled regime (Ψ_a < 0.1) and extended to higher spray fluxes with caution.     

Exergy analysis and performance of a counter flow Ranque–Hilsch vortex tube having various nozzle numbers at different inlet pressures of oxygen and air

An experimental investigation is made to determine the effects of the orifice nozzle number and the inlet pressure on the heating and cooling performance of the counter flow Ranque–Hilsch vortex tube when air and oxygen used as a fluid. The orifices used at these experiments are made of the polyamide plastic material. The thermal conductivity of polyamide plastic material is 0.25 W/m °C. Five orifices with nozzle numbers of 2, 3, 4, 5 and 6 have been manufactured and used during the experiments. For each one of the orifices (nozzle numbers) when used with two different fluids, inlet pressures were adjusted from 150 kPa to 700 kPa with 50 kPa increments, and the exergy efficiency was determined. During the experiments, a vortex tube is used with an L/D ratio of 15, and cold mass fraction is held constant at 0.5. As a result of the experimental study, it is determined that the temperature gradient between the hot and cold fluid is decreased with increasing of the orifice nozzle number.     

Study on the genotoxicity of HA/ZrO2 composite particles in vitro

To evaluate the genotoxicity of the HA/ZrO₂ composite particles by using the micronucleus test (MNT) in vitro. HA/ZrO₂ composite particles prepared by sintering at high temperature and pressure, that used powder of HA and ZrO₂ of different proportions, were compared with pure HA particles and pure ZrO₂ particles. The effect of the composite particles on cell proliferation of rabbit mesenchymal stem cells, and its the genotoxicity to rabbit mesenchymal stem cells were detected by MNT method. The MTT test showed that both pure HA particles and composite particles which contained HA promoted cell proliferation of rabbit mesenchymal stem cells, while pure ZrO₂ particles did not, and there was a significant difference (P < 0.05). The MNT test showed no significant difference between the HA group and the negative control group (P > 0.05), but a significant difference between the HA group and the positive control group (P < 0.05). The difference between the ZrO₂ group and the negative control group was significant (P < 0.01), while the difference between the ZrO₂ group and the positive control group was insignificant (P > 0.05). The genotoxicity of the HA/ZrO₂ composite particle increased with a higher proportion of ZrO₂ and an increase in the concentration of the composite, and the 30 wt.% HA/70% ZrO₂ composite with 200 μg/mL concentration showed significant genotoxicity (P < 0.01).     

Effect of V2O5 additive to 0.4SrTiO3–0.6La(Mg0.5Ti0.5)O3 ceramics on sintering behavior and microwave dielectric properties

The effect of V₂O₅ addition on the microwave dielectric properties and the microstructures of 0.4SrTiO₃–0.6La(Mg_0.5Ti_0.5)O₃ ceramics sintered for 5 h at different sintering temperature were investigated systematically. It was found that the sintering temperature was effectively lowered about 200 °C by increasing V₂O₅ addition content. The grain sizes, bulk density as well as microwave dielectric properties were greatly dependent on sintering temperature and V₂O₅ content. The 4ST–6LMT ceramics with 0.25% V₂O₅ sintered at 1400 °C for 5 h in air exhibited optimum microwave dielectric properties of ɛ_r = 50.7, Q × f = 15049.6 GHz, T_f = −1.7 ppm/°C.     

Dry dense medium separation of iron ore using a gas–solid fluidized bed

The dry dense medium separation of iron ore based on floating and sinking of ore particles in a gas–solid fluidized bed was investigated using zircon sand as the fluidized medium. The float-sink of ore particles with mean size D_ave = 23.6 mm was investigated as the fluidizing air velocity and the float-sink time were varied. It was found that gangue with density less than 2850 kg/m³ which float is able to be separated from valuable ore with density greater than 2850 km/m³ which sink. The set point (density where half the particles float and half the particles sink) decreases with increasing the air velocity, and that the float-sink separation is completed within 2 min. The influence of different sized ore particles in the float-sink experiments was also investigated. As a result, the iron ore with D_ave ? 17.6 mm are successfully separated. As D_ave decreases below 17.6 mm, the ore particles with density near the set point tend to scatter in the fluidized bed without floating or sinking, resulting in separation efficiency which decreases with decreasing D_ave. This indicates that the size of the ore particles is one of the major factors to achieve high separation efficiency.     

On the synthesis and dielectric studies of (1 − x)Bi(Mg1 / 2Zr1 / 2)O3 − xPbTiO3 piezoelectric ceramic system

Scandium free piezoelectric ceramics of the composition (1 − x)Bi(Mg_1 / 2Zr_1 / 2)O₃ − xPbTiO₃ (BMZ − xPT) were fabricated by the solid state reaction method. Dielectric and structural properties were measured and phase diagram was constructed from the temperature dependent dielectric and impedance data. The morphotropic phase boundary (MPB) was found to be located in the range 0.55 < x < 0.60 with paraelectric–ferroelectric phase transition temperature, T_C (∼ 280 °C). The ceramics near the MPB showed high room temperature dielectric constant (∼ 1387). The room temperature values of the remanent polarization (P_r) and coercive filed (E_C), were ∼ 29 μC/cm² and ∼ 23 kV/cm, respectively.     

Dopant influence on BST ferroelectric solid solutions family

Solid solutions of the Ba_1−xSr_xTiO₃ (BST) type are very attractive for applications in information technology, but also in microwaves for such electrically controlled devices as phase shifters, tunable filters, steerable antennas, varactors, etc. A family of solid solutions with x = 25, 50, 75, 90% was prepared by standard powder technology-solid state reaction and sintered at 1230 °C and 1260 °C. Dielectric permittivity and loss at low (1 kHz) and high frequency (1 ÷ 2 GHz) were measured on a large temperature range − 200 °C ÷ + 200 °C. The influence of Sr content and of 1 wt.% MgO and 1 wt.% MnO₂ doping on the complex dielectric constant was studied. The dielectric permittivity at high frequencies and room temperature considerably decreases with the increase of Sr content. Similarly, low frequency measurements showed a severe and almost linear decrease of the Curie Point with the increase of Sr fraction. At low Sr content, the measured ceramic densities slowly decrease with Sr fraction and represent about 92% of the X-ray density ρ(g/cm³) ≈ 5.99–0.99·x. At x = 90% Sr concentration, very low-density ceramics were obtained with both sintering temperatures.